José A. Menezes-Filho

Manganese exposure and cognitive deficits: A growing concern for manganese neurotoxicity

This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on childrens cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age.

High levels of hair manganese in children living in the vicinity of a ferro-manganese alloy production plant

Manganese (Mn) is an essential element, but an effective toxic at high concentrations. While there is an extensive literature on occupational exposure, few studies have examined adults and children living near important sources of airborne Mn. The objective of this study was to analyze hair Mn of children living in the vicinity of a ferro-manganese alloy production plant in the Great Salvador region, State of Bahia, Brazil and examine factors that influence this bioindicator of exposure. We examined 109 children in the age range of 1-10 years, living near the plant. Four separate housing areas were identified a priori on the bases of proximity to the emission sources and downwind location. A non-exposed group (n=43) of similar socio-economic status was also evaluated. Mn hair (MnH) concentration was measured by graphite atomic absorption spectrometry (GFAAS). Possible confounding hematological parameters were also assessed. Mean MnH concentration was 15.20 microg/g (1.10-95.50 microg/g) for the exposed children and 1.37 microg/g (0.39-5.58 microg/g) for the non-exposed. For the former, MnH concentrations were 7.95+/-1.40 microg/g (farthest from the plant), 11.81+/-1.11 microg/g (mid-region), 34.43+/-8.66 microg/g (closest to the plant) and 34.22+/-9.15 microg/g (directly downwind). Multiple regression analysis on log transformed MnH concentrations for the exposed children derived a model that explained 36.8% of the variability. In order of importance, area of childrens residence, gender (girls>boys) and time of mothers residence in the area at the birth of the child, were significantly associated with MnH. Post hoc analyses indicated two groupings for exposure areas, with those living closest to and downwind of the plant displaying higher MnH concentrations compared to the others. The contribution of the time the mother lived in the community prior to the childs birth to the childrens current MnH suggests that in utero exposure may play a role. A study of neurobehavioral performance with respect to Mn exposure in these children is currently underway.

Elevated airborne manganese and low executive function in school-aged children in Brazil

Exposure to airborne manganese (Mn) has been associated with neurotoxic effects, including motor and cognitive deficits. The main deficits related to excessive exposure to Mn are predominantly the dysfunction of fronto-striatal and dopaminergic circuits observed in animal experimental studies, which are involved in attention, working memory and motor function. The present study aims to assess the association between elevated Mn exposure and performance on executive function and attention neuropsychological tests in children living in two communities near a ferro-manganese alloy plant. Seventy children aged between 7 and 12 years with no history of neurologic disease and an estimated IQ >68 (Vocabulary and Block Design subtests) that had lived near the iron-Mn production alloy plant for at least 1.5 years were included. Participants were assessed for cognitive functioning with neuropsychological measures for sustained attention (Test of Visual Attention - TAVIS-3R), cognitive flexibility (WCST), and verbal and visual working memory (WISC-III Digit Span subtest and Corsi Block). Manganese hair (MnH) levels were used as a biomarker of exposure. Mean scores among study participants were lower than general population norms/averages for block design, digit span, reaction time and commission errors. The median MnH level was 11.48 (range 0.52-55.74) μg/g, and no difference between sexes was observed. Spearmans correlation analysis showed a significant inverse correlation between MnH levels and estimated IQ (rho=-0.448, p=0.0001), Vocabulary (rho=-0.272, p=0.02), Block Design (rho=-0.485, p=0.00002) and Digit Span (rho=-0.410, p=0.0004). Multiple regression analyses detected inverse associations between log MnH and scores on estimated IQ (β=-9.67; 95%CI=-16.97 to -2.37), Block Design (β=-2.50; 95%CI=-3.91 to -1.10) and Digit Span Total (β=-2.59; 95%CI=-4.13 to -1.05) standardized scores and the number of correct answers in forward and backward Digit Span methods, after adjusting for covariates (β=-1.32=95%CI=-2.23 to -0.40; β=-1.09 95%CI=-2.02 to -0.16, respectively). The results suggest that airborne Mn exposure may be associated with lower IQ and neuropsychological performance in tests of executive function of inhibition responses, strategic visual formation and verbal working memory. Executive function is dependent on the fronto-striatal circuit, which may be disrupted by Mn accumulation in the brain.

Assessment of carcinogenic heavy metal levels in Brazilian cigarettes.

Several studies have associated high cancer incidence with smoking habits. According to IARC, lead (Pb), cadmium (Cd), arsenic (As), nickel (Ni), and chromium (Cr) are carcinogenic to humans. These metals are present in cigarettes and their levels vary according to geographical region of tobacco cultivation, fertilizer treatment, plant variety etc. This study aims to assess these metal levels in cigarettes commercialized in Brazil. Three cigarettes of each 20 different brands were individually weighed, the tobacco filling removed, and homogenized. After desiccation, samples were subjected to microwave-assisted digestion. Analyses were performed by graphite furnace atomic absorption spectrometry. Mean levels for Pb, Cd, As, Ni, and Cr were, respectively, 0.27 ± 0.054, 0.65 ± 0.091, 0.09 ± 0.024, 1.26 ± 0.449, and 1.43 ± 0.630, in micrograms per gram of tobacco. No correlation was observed between Cd and any other metal analyzed. A mild correlation (r = 0.483, p < 0.05) was observed between Pb and Cr levels. Strong significant (p < 0.01) correlations were observed between Ni and Cr (r = 0.829), Ni and As (r = 0.799), Ni and Pb (r = 0.637), and between Cr and As (r = 0.621). Chromium and Ni levels were significantly higher in cigarettes from a multinational manufacturer. Our results show a high variability in heavy metal levels in cigarettes, representing an important exposure source of smokers and passive smokers to carcinogenic substances.

Noninvasive biomarkers of manganese exposure and neuropsychological effects in environmentally exposed adults in Brazil

Manganese (Mn), an essential element to humans, in excess can cause neurotoxic damage. So far, Mn exposure assessment has no ideal biomarker. This study aims to investigate the association between Mn exposure, using noninvasive biomarkers, and neuropsychological effects in environmentally exposed adults. The residents of two communities near to a ferromanganese refinery in Bahia, Brazil were evaluated. Volunteers aged 15-55 of both sexes provided scalp hair, axillary hair, fingernail and saliva specimens for Mn determination by electrothermal absorption spectrometry. Several neuropsychological tests were used to evaluate cognitive, attention, memory, motor and executive functions. Significant correlations were observed between Mn in hair (MnH, median 8.95 μg/g), axillary hair (MnAxH,18.49 μg/g) and fingernail (MnFN, 6.91 μg/g) with the performances in several neuropsychological tests. No association was observed between manganese levels in saliva (MnSal, 4.2 μg/L) and any neuropsychological function. Multiple regression analysis detected an inverse association between Log MnH and IQ (β=-4.76 [CI 95% -9.17 to -0.36]) and between Log MnFN and visual working memory (β=-3.33 [CI 95% -6.15 to -0.52]). Direct association was observed between Log MnFN and time of completion in the cognitive flexibility task (β=56.29 [CI 95% 2.41-110.18]). The Mn biomonitoring using noninvasive biomarkers was able to detect high exposure levels, which were associated with detrimental neuropsychological effects in adults exposed to industrial emissions.

Calcium and fat metabolic balance, and gastrointestinal tolerance in term infants fed milk-based formulas with and without palm olein and palm kernel oils: a randomized blinded crossover study

BackgroundEffects of palm olein (POL) on calcium and fat metabolic balance and gastrointestinal (GI) tolerance have been clinically evaluated but its use in combination with palm kernel oil (PKO), and canola oil has not been similarly assessed in infants.MethodsCalcium and fat balance and GI tolerance were evaluated in 33 healthy term infants (age = 68-159d) in a randomized, double-blinded, 14d crossover trial at a day care center in Salvador, Brazil; followed by a 4d hospital ward metabolic balance study in 17 of the male subjects. The study compared two commercially available milk-based powdered formulas in Brazil; one containing POL (44% of total fat), PKO (21.7%) and canola oil (18.5%) as predominant fats (PALM), and the other containing none (NoPALM). Occasional human milk (HM) supplementation was allowed at home.ResultsFormula and HM intakes, and growth were not different (p > 0.05). Calcium absorption (%) for infants fed NoPALM (58.8 ± 16.7%; means ± SD) was higher (p = 0.023) than those fed PALM (42.1 ± 19.2%), but was not significant (p = 0.104) when calcium intake was used as a covariate. Calcium intake was higher (p < 0.001) in NoPALM versus PALM fed infants. However, calcium retention (%) was higher in infants fed NoPALM compared to PALM with (p = 0.024) or without (p = 0.015) calcium intake as a covariate. Fat absorption (%) for NoPALM was greater than PALM fed infants (NoPALM = 96.9 ± 1.2 > PALM = 95.1 ± 1.5; p = 0.020 in Study Period I). Mean rank stool consistency was softer in infants fed NoPALM versus PALM (p < 0.001; metabolic period). Adverse events, spit-up/vomit, fussiness and gassiness were not different (p > 0.05). Formula acceptability was high and comparable for both formula feedings, regardless of HM supplementation.ConclusionsTerm infants fed PALM based formula (containing palm olein, palm kernel and canola oils) demonstrated lower calcium retention and fat absorption, and less softer stool consistency versus infants fed NoPALM based formula. Study suggested formula fat differences may affect GI function in infants.Clinical trial registrationClinical Trial.Gov # (http://www.clinicaltrials.gov): NCT00941564.

Maternal blood and hair manganese concentrations, fetal growth, and length of gestation in the ISA cohort in Costa Rica

BACKGROUND Animal studies have shown that both deficiency and excess manganese (Mn) may result in decreased fetal size and weight, but human studies have reported inconsistent results. METHODS We examined the association of blood and hair Mn concentrations measured at different times during pregnancy with fetal growth among term births and length of gestation in a cohort of 380 mother-infant pairs living near banana plantations aerially sprayed with Mn-containing fungicides in Costa Rica. We used linear regression and generalized additive models to test for linear and nonlinear associations RESULTS Mean (± SD) blood Mn concentration was 24.4 ± 6.6 μg/L and geometric mean (geometric SD) hair Mn concentration was 1.8 (3.2) μg/g. Hair Mn concentrations during the second and third trimesters of gestation were positively related to infant chest circumference (β for 10-fold increase = 0.62 cm; 95% CI: 0.16, 1.08; and β = 0.55 cm; 95% CI: -0.16, 1.26, respectively). Similarly, average maternal hair Mn concentrations during pregnancy were associated with increased chest circumference (β for 10-fold increase = 1.19 cm; 95% CI: 0.43, 1.95) in infants whose mothers did not have gestational anemia, but not in infants of mothers who had gestational anemia (β = 0.39 cm; 95% CI: -0.32, 1.10; pINT=0.14). All these associations were linear. Blood Mn concentrations did not show consistent linear nor nonlinear relationships with any of the birth outcomes CONCLUSIONS Mn plays an important role in fetal development, but the extent to which environmental exposures may cause adverse health effects to the developing fetus is not well understood. Among women living near banana plantations in Costa Rica, we did not observe linear or nonlinear associations of Mn concentrations with lowered birth weight or head circumference, as reported in previous studies. However, we did find positive linear associations between maternal hair Mn concentrations during pregnancy and infant chest circumference.

Prenatal molybdenum exposure and infant neurodevelopment in Mexican children

Abstract Objective To evaluate the association between prenatal exposure to molybdenum (Mo) and infant neurodevelopment during the first 30 months of life. Methods We selected a random sample of 147 children who participated in a prospective cohort study in four municipalities in the State of Morelos, Mexico. The children were the products of uncomplicated pregnancies with no perinatal asphyxia, with a weight of ≥2 kg at birth, and whose mothers had no history of chronic illnesses. These women were monitored before, during, and after the pregnancy. For each of these children a maternal urine sample was available for at least one trimester of pregnancy, and urine Mo levels were determined by electrothermal atomic absorption spectrometry. Neurodevelopment was evaluated using the psychomotor (PDI) and mental development indices (MDI) of the Bayley scale. Association between prenatal exposure to Mo and infant neurodevelopment was estimated using generalized mixed effect models. Results The average urinary concentrations of Mo adjusted for creatinine varied between 45.6 and 54.0 µg/g of creatinine at first and third trimester, respectively. For each doubling increase of Mo (μg/g creatinine) during the third trimester of pregnancy, we observed a significant reduction on PDI (β = −0.57 points; P = 0.03), and no effect on MDI (β = 0.07 points; P = 0.66). Discussion As this is the first study that suggests a potential negative association between prenatal Mo exposure and infant neurodevelopment, these results require further confirmation.

Lead and cadmium in mangrove root crab (Goniopsis cruentata), in natura and at food processing stages

ABSTRACT Lead (Pb) and cadmium (Cd) were determined in mangrove root crab (Goniopsis cruentata) tissues (in natura) and in two culinary preparations by graphite furnace atomic absorption spectrometry. Mangrove root crab samples from three sampling sites along the Jaguaripe River, Bahia, Brazil, where lead-glazed ceramics are produced, and from two commercial preparations were collected or purchased in March and April 2016. Cd levels in raw and processed samples were below the methods’ limits of detection (0.016 mg kg−1), while Pb levels in the raw tissues were determined only in the gills (0.67 mg kg−1) and in the hepatopancreas (0.14 mg kg−1). However, Pb levels increased from 0.05 to 2.84 mg kg−1 in boiled/sorted muscle and in the traditional stew (with a 57-fold increase), respectively. Pb levels augmented significantly in the processed food due to migration of Pb used in the glazing of cooking ceramic utensils, surpassing the Brazilian and international safety limits.

Selenium and Zinc Status in Chronic Myofascial Pain: Serum and Erythrocyte Concentrations and Food Intake

Introduction Nutritional disorders have been reported to be important causal factors that can intensify or cause a painful response in individuals with chronic musculoskeletal pain. Aim To assess the habitual intake of and the serum and erythrocyte levels of selenium and zinc in patients with chronic myofascial pain. Materials and Methods A case-control study of 31 patients with chronic myofascial pain (group I) and 31 subjects without pain (group II). Dietary record in five days for assessing food intake were used. The serum and erythrocyte concentrations of selenium and zinc were analyzed using an atomic absorption spectrophotometry. Pain intensity was assessed using a visual analog scale. Results The group of patients with chronic myofascial pain, compared with the control group, showed a lower erythrocyte concentration of selenium (79.46 ± 19.79 μg/L vs. 90.80 ± 23.12 μg/L; p = 0.041) and zinc (30.56 ± 7.74 μgZn/gHb vs. 38.48 ± 14.86 μgZn/gHb, respectively; p = 0.004). In this study, a compromised food intake of zinc was observed in the majority of the subjects in both groups. The selenium intake was considered to be safe in 80% of the subjects in both groups; however, the likelihood of inadequate intake of this mineral was twice as high in group I (49.5% vs. 24.4%, respectively). In the logistic regression analysis, the erythrocyte concentration of zinc was associated with the presence of pain. In each additional 1 mg of Zn2+ per gram of hemoglobin, a reduction of 12.5% was observed in the risk of the individual having chronic myofascial pain (B = -0.133; adjusted OR = 0.875, 95% CI = 0.803 to 0.954, Wald = 9.187, standard error = 0.044, p = 0.002). Physical inactivity and obesity were noted more commonly in group I compared with the control group. Conclusion In this study, patients with chronic myofascial pain showed lower intracellular stores of zinc and selenium and inadequate food intake of these nutrients.