Blood Manganese Concentrations Research Articles

Association between whole blood essential trace elements and cognitive function in older adults

BackgroundEssential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. ObjectivesWe aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. MethodsA population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. ResultsThe association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: β = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: β = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 μg/L) increase of Se was positively associated with the MMSE score (β = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. ConclusionsThe nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.

Association of blood manganese concentrations with 24-h based brachial and central blood pressure, and pulse-wave velocity.

Potential environmental determinants of BP and hypertension in older adults are far less known than their lifestyle risk factors. Manganese (Mn) is an essential element for life that may induce changes in blood pressure (BP), but the direction of the association is unclear. We aimed to examine the association of blood manganese (bMn) with 24-h-based brachial, central BP (cBP), and pulse-wave velocity (PWV). With this purpose, we analyzed data from 1009 community-living adults aged >65 years without BP medication. bMn was measured using inductively-coupled plasma-mass spectrometry and 24-h BP with validated devices. The association of bMn (median: 6.77 μg/L; IQR: 5.59–8.27) with daytime brachial and central systolic (SBP) and with diastolic BP (DBP) was non-linear, with BP increases up to around the median of Mn and then stabilization or slight rightward decrease. Mean BP differences (95% confidence interval) comparing Mn Q2 to Q5 (vs Q1 quintile) for brachial daytime SBP were 2.56 (0.22; 4.90), 3.59 (1.22; 5.96), 3.14 (0.77; 5.51) and 1.72 (−0.68; 4.11) mmHg, respectively; and 2.22 (0.70, 3.73), 2.55 (1.01, 4.08), 2.45 (0.91; 3.98), and 1.68 (0.13; 3.24), respectively, for DBP. Daytime central-pressures showed a similar dose-response relationship with bMn as daytime brachial-pressures. The association with nighttime BP was linearly positive for brachial BPs, and only increasing for Q5 for cBP. Regarding PWV, a tendency to significant linear increase along bMn levels was observed (p-trend = 0.042). The present findings extend the scarce evidence on the association between Mn and brachial BP to 2 other vascular parameters, suggesting Mn levels as a candidate risk factor for increasing levels of both brachial and cBPs in older adults, yet further research is needed with larger cohort studies in adults at all age ranges.

Diet and Blood Concentrations of Essential and Non-Essential Elements among Rural Residents in Arctic Russia

Nutrition is an essential factor for human health. Earlier research has suggested that Arctic residents are vulnerable to environmental toxic exposures through traditional foods. Although Russia is the largest Arctic country, the evidence on the topic from the Russian part of the Arctic is scarce. We studied associations between blood concentrations of essential and non-essential elements and traditional food consumption in 297 adults from seven rural settlements in the Nenets Autonomous Area, Northwest Russia. Blood arsenic concentration was positively associated with consumption of rainbow smelt, pink salmon, Arctic char and navaga fish. Frequent consumption of northern pike was associated with increased concentration of blood mercury. Blood mercury and arsenic concentrations were significantly associated with blood selenium. We also observed positive associations between blood lead levels and the frequency of goose consumption. Moreover, subjects who reported to be hunters had higher blood levels of lead, suggesting contamination of goose meat with fragments of shotgun shells. Blood cobalt and manganese concentrations were inversely associated with serum ferritin levels. Positive associations between blood levels of manganese and lead were observed. Moreover, blood lead concentrations were significantly associated with cadmium, mercury, copper, and zinc. Our results corroborate earlier findings on the traditional foods as source of non-essential elements for the Arctic residents. Observed correlations between the levels of lead and other elements warrant further research and may have potential implications for the studies on the associations between essential elements and health outcomes.

Electrochemical Determination of Manganese in Whole Blood with Indium Tin Oxide Electrode

In this work, we demonstrate accurate and precise measurement of manganese (Mn) concentration in human whole blood with indium tin oxide (ITO) electrode using square wave stripping voltammetry. While an essential trace metal for human health, elevated levels of Mn due to environmental or occupational exposure have been associated with severe neuromotor dysfunction characterized by parkinsonism and cognitive dysfunction making the monitoring of Mn in whole blood necessary. Pediatric populations are particularly susceptible to Mn given their developing brain and potential long-term impacts on neurodevelopment. The current gold standard for whole blood Mn measurements is by ICP-MS, which is costly and time consuming. The electrochemical detection with ITO working electrode in this work showed a limit of detection of 0.5 μg l−1 and a linear range of 5 to 500 μg l−1, which encompasses the physiological Mn levels in human whole blood (5–18 μg l−1). Our results of Mn measurement in whole blood show an average precision of 96.5% and an average accuracy of 90.3% compared to ICP-MS for both the normal range (5–18 μg l−1) and the elevated levels (>36 μg l−1) that require medical intervention. These results demonstrate the feasibility of Mn measurements in human blood with electrochemical sensors.

Analysis of Whole Blood and Urine Trace Elements in Children with Autism Spectrum Disorders and Autistic Behaviors

The relationship between trace elements and neurological development is an emerging research focus. We performed a case–control study to explore (1) the differences of 13 trace elements chromium (Cr), manganese (Mn), cobalt (Co), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), stannum (Sn), stibium (Sb), mercury (Hg), titanium (TI), and plumbum (Pb) concentration in whole blood and urine between autism spectrum disorder (ASD) children and their typical development peers, and (2) the association between the 13 trace elements and core behaviors of ASD. Thirty ASD subjects (cases) and 30 age-sex-matched healthy subjects from Baise City, Guangxi Zhuang Autonomous Region, China, were recruited. Element analysis was carried out by inductively coupled plasma-optical emission spectrometry. Autistic behaviors were assessed using Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Children Neuropsychological and Behavior Scale (CNBS). The whole blood concentrations of Mo (p = 0.004), Cd (0.007), Sn (p = 0.003), and Pb (p = 0.037) were significantly higher in the ASD cases than in the controls. Moreover, Se (0.393), Hg (0.408), and Mn (− 0.373) concentrations were significantly correlated between whole blood and urine levels in ASD case subjects. There were significant correlations between whole blood Sb (0.406), Tl (0.365), Mo (− 0.4237), Mn (− 0.389), Zn (0.476), and Se (0.375) levels and core behaviors of ASD. Although the mechanism of trace element imbalance in ASD is unclear, these data demonstrate that core behaviors of ASD may be affected by certain trace elements. Further studies are recommended for exploring the mechanism of element imbalance and providing corresponding clinical treatment measures.

Occupational Exposure to Manganese Among Welders: Association Between Airborne Manganese Concentration and Blood Manganese Levels

Background: Manganese (Mn) is an essential element for the human body, but it can cause adverse effects on the Central Nervous System at high doses. Exposure to manganese fumes during welding can harm welders' health. Objectives: The current study aimed to measure manganese produced by shielded metal arc welding (SMAW) in the breathing zone air and blood of welders and investigate the relationship between manganese concentrations in air and blood. Methods: In this descriptive-analytical cross-sectional study, 35 welders were enrolled as the exposed group and 40 office workers as the control group. Manganese concentration in air was measured according to NIOSH method 7301. Air and blood sample analyses were carried out by ICP-OES. Statistical analysis was performed with MINITAB 17. Data were analyzed using Pearson correlation coefficient, one-sample t-test, paired t-test, and logistic regression. The significance level was set at P < 0.05. Result: The mean concentration of welding respirable particles and manganese fumes were 9.56 ± 1.67 and 0.45 ± 0.08 mg/m3, three and 22 times the exposure limit recommended by ACGIH, respectively. Average manganese was significantly higher in the welders’ blood (0.16 ± 0.02 µg/mL) than in the controls’ blood (0.04 ± 0.002 µg/mL). There were strong and significant correlations between the welding respirable particles and manganese concentration in welders’ breathing zone and blood manganese levels. Also, with each year of work experience, the manganese concentration in the welders’ blood increased by 1.5%. Conclusions: Welders are at risk of contamination with manganese. Manganese exposure reduction through more efficient ventilation systems, reducing welder’s exposure time, staff training, and appropriate respiratory protection equipment should be applied to reduce manganese exposure among welders and prevent health complications.

Cord Blood Manganese Concentrations in Relation to Birth Outcomes and Childhood Physical Growth: A Prospective Birth Cohort Study.

Gestational exposure to manganese (Mn), an essential trace element, is associated with fetal and childhood physical growth. However, it is unclear which period of growth is more significantly affected by prenatal Mn exposure. The current study was conducted to assess the associations of umbilical cord-blood Mn levels with birth outcomes and childhood continuous physical development. The umbilical cord-blood Mn concentrations of 1179 mother–infant pairs in the Sheyang mini birth cohort were measured by graphite furnace atomic absorption spectrometry (GFAAS). The association of cord-blood Mn concentrations with birth outcomes, and the BMI z-score at 1, 2, 3, 6, 7 and 8 years old, were estimated separately using generalized linear models. The relationship between prenatal Mn exposure and BMI z-score trajectory was assessed with generalized estimating equation models. The median of cord-blood Mn concentration was 29.25 μg/L. Significantly positive associations were observed between Mn exposure and ponderal index (β, regression coefficient = 0.065, 95% CI, confidence interval: 0.021, 0.109; p = 0.004). Mn exposure was negatively associated with the BMI z-score of children aged 1, 2, and 3 years (β = −0.383 to −0.249, p < 0.05), while no significant relationships were found between Mn exposure and the BMI z-score of children at the age of 6, 7, and 8 years. Prenatal Mn exposure was related to the childhood BMI z-score trajectory (β = −0.218, 95% CI: −0.416, −0.021; p = 0.030). These results indicated that prenatal Mn exposure was positively related to the ponderal index (PI), and negatively related to physical growth in childhood, which seemed most significant at an early stage.

Clinical relevance of environmental manganese exposure with liver stiffness and steatosis detected by transient elastography in adults.

Global manganese pollution to air and water is a significant threat to human health. The associations between manganese and liver stiffness and steatosis have not been reported in epidemiological studies. This study aimed to explore the clinical relevance of blood manganese with liver stiffness and steatosis in adults from the 2017-2018 National Health and Nutrition Examination Survey (N = 4,192). Subjects with excessive alcohol consumption and hepatitis B or C infection were excluded. Liver stiffness and steatosis were detected by transient elastography. Logistic regression and restricted cubic splines were adopted to explore the non-linear dose-response relationships. In multivariate analysis, while higher blood manganese concentrations were not associated with liver stiffness in the total sample and in males, an increased odds of significant liver fibrosis was found with higher blood manganese concentrations (tertile 3 vs. tertile 1) in females [odds ratios (95% confidence intervals): 2.34 (1.32-4.14), P trend < 0.01] and in other races [1.47 (1.05-2.05), P trend = 0.03]. Higher blood manganese concentrations were associated with liver steatosis in the total sample [1.33 (1.04-1.70), P trend = 0.03], in females [1.58 (1.02-2.44), P trend = 0.04], in other races [1.91 (1.50-2.43), P trend < 0.01], and in obese subjects [2.29 (1.13-4.65), P trend = 0.02]. Dose-response analysis showed that the departures from non-linear relationships between blood manganese concentrations and significant liver fibrosis (Pnon-linearity = 0.30) and steatosis (Pnon-linearity = 0.47) were not significant, suggesting that the observed associations were linear. In conclusion, higher blood manganese concentrations were positively associated with liver stiffness and steatosis, and the associations were mainly observed in females, in races other than Non-Hispanic White, and in obese subjects.

Association Between manganese and cognitive function in US general population

BACKGROUND AND AIM: Manganese has neurotoxicity when chronically exposed to it. The symptom is similar with Parkinson`s syndrome, but the impairment of cognitive function occur faster in neurotoxicity by manganese exposure. This study investigated the association between manganese exposure and cognitive function in the general population of the elderly in the United States. METHODS: The data used in this study was National Health and Nutrition Examination Survey, collected from 2011 to 2014. The subject for this study were 1626 persons aged 60 years or older, for whom blood manganese and iron concentration measured and cognitive function evaluated. Cognitive function was evaluated through the following tests. 1)Consortium to Establish a Registry for Alzheimer's disease (CERAD), 2) the Animal Fluency test, 3) the Digit Symbol Substitution Test (DSST). We used chi-square test or ANOVA to estimate differences in the demographic characteristics of participants. Multivariable linear regression was used to examine the associations between the quartile group of the blood manganese concentration and the score of cognitive function tests, and adjusted with age, sex, race, BMI, smoking, alcohol intake, serum heavy metals. test for trend was, assuming the association to be linear. RESULTS:The animal fluency test score was significantly lower in the Q4 of blood manganese concentration compared to Q1 (β=-1.04 (95% CI -1.97,-0.11)), while not showing meaningful difference in the Q2 and Q3. And no significant differences was observed in CERAD and DSST. No linear trend was observed among quartile groups of blood manganese concentration in all cognitive function tests. CONCLUSIONS:We found a negative relationship between Blood manganese and one cognitive function tests. But the association was inconsistent in other two tests and we couldn`t find any trend among all tests. Further study for general population should be conducted for clarifying the effect of low dose chronic manganese exposure to cognitive function. KEYWORDS: NHANES, Cognitive function, Manganese

Interaction of Blood Manganese Concentrations with GSTT1 in Relation to Autism Spectrum Disorder in Jamaican Children.

Using data from 266 age- and sex-matched pairs of Jamaican children with autism spectrum disorder (ASD) and typically developing (TD) controls (2-8years), we investigated whether glutathione S-transferase theta 1 (GSTT1) modifies the association between blood manganese concentrations (BMC) and ASD. After adjusting conditional logistic regression models for socioeconomic status and the interaction between GSTT1 and GSTP1 (glutathione S-transferase pi 1), using a recessive genetic model for GSTT1 and either a co-dominant or dominant model for GSTP1, the interaction between GSTT1 and BMC was significant (P = 0.02, P = 0.01, respectively). Compared to controls, ASD cases with GSTT1-DD genotype had 4.33 and 4.34 times higher odds of BMC > 12 vs. ≤ 8.3μg/L, respectively. Replication in other populations is warranted.

The effects of occupational exposure to manganese fume on neurobehavioral and neurocognitive functions: An analytical cross-sectional study among welders.

This study aimed to measure concentrations of manganese fume in breathing zone (BZ) and blood among welders to assess neurocognitive and neurobehavioral functions among them. In this study 38 welders and 27 administrative employees participated. Q16 questionnaire was used to evaluate neurobehavioral symptoms. The computerized Stroop test and Continuous Performance Test (CPT) were used to assess neurocognitive functions. Sampling and analysis of manganese fumes in the BZ and blood samples were performed according to NIOSH-7300 and NIOSH-8005 methods, respectively. Average concentration of manganese in the welders' BZ and blood was 0.81 ± 0.21 mg/m3 and 18.33 ± 5.84 µg/l. Frequency of neurobehavioral symptoms was significantly higher in welders compared with control group. Spearman correlation test showed a moderate correlation between Mn concentrations in the BZ and blood Mn levels (rs = 0.352). There were statistical moderate and strong correlations between the frequency of neurobehavioral symptoms and manganese concentrations in the BZ (r=0.504) and blood Mn levels (r=0.643).The Pearson correlation coefficient (r=0.433-0.690) obtained on the psychological tests showed a moderate to strong correlation between manganese concentrations in the welders' BZ and blood and some indices of the Stroop test and CPT. The results of this study can confirm the effect of manganese inhalation on creating neurobehavioral and neurocognitive impairments in welders.

Biomarkers of cytogenetic disorders under the external environmental isolated exposure of manganese and stable strontium from drinking water

In blood of children underwent to the long-term isolated exposure of manganese and stable strontium with drinking water exceeding the acceptable level by up to 1.4 times the elevated concentrations of mentioned metals in blood were shown to be formed in relation to reference level by 2,0-4,4 times. The developing at that mutagenic effect was proved to have the dependence on the level of manganese and stable strontium concentration in blood and is pronounced in the increased rate of cells with cytogenetic anomalies on the background of the enhancement of the proliferative activity, destructive changes in the cell population and oxidative responses at the cell DNA level. The activity of genetic instability and processes of DNA oxidation in the somatic cells in children under the exposure to manganese has more pronounced character in comparison to given indices under the exposure to the stable strontium.

Changes in blood pressure associated with lead, manganese, and selenium in a Bangladeshi cohort

BackgroundHeavy metal contamination is widespread in Bangladesh. Previous studies have observed lead increases blood pressure over time. However, the role of other metal contaminants and essential micronutrients, which could also adversely affect blood pressure or act as protective factors, is understudied. ObjectivesWe therefore evaluated the associations of lead, manganese, and selenium with blood and pulse pressure trajectories. MethodsWe prospectively followed placebo-assigned participants nested within a randomized trial for the prevention of arsenic-related skin cancer (n = 255). Blood lead, manganese, and selenium were measured at baseline; blood pressure was measured at baseline and at 3 biennial follow-up examinations. Mixed-effect linear regression models were used to estimate associations with average annual changes in systolic, diastolic, and pulse pressure. ResultsIn models simultaneously adjusted for baseline blood lead, manganese, and selenium concentrations in addition to other potential confounders, lead was linearly associated with increases in systolic blood pressure, but not with diastolic blood pressure or pulse pressure. A non-linear association was observed for manganese, such that mid-range concentrations were associated with decreases in systolic, diastolic, and pulse pressure. Baseline selenium concentrations in the highest quartile were also associated with longitudinal decreases in both systolic and diastolic blood pressure, while null associations were observed with pulse pressure. In exploratory analyses, the combination of mid-range manganese and high selenium concentrations completely offset lead-associated increases in blood and pulse pressure. ConclusionsThe results indicate a direct, linear association of lead exposure with systolic blood pressure, and manganese and selenium exposures within certain ranges may have a blood pressure-lowering effect in this population.

Interaction between manganese and GSTP1 in relation to autism spectrum disorder while controlling for exposure to mixture of lead, mercury, arsenic, and cadmium

BackgroundWe previously reported a significant interactive association between polymorphisms of GSTP1 and blood manganese concentrations (BMC) with autism spectrum disorder (ASD) in Jamaican children. In this paper, we investigate the same interactive association with ASD while adjusting for the mixture of four metals (lead, mercury, cadmium, and arsenic). MethodWe used data from 163 case-control pairs of children 2–8 years of age from our autism project in Jamaica, in which we collected blood for heavy metals analysis at enrollment. To minimize potential multicollinearity between concentrations of the four metals, we generated a mixture index using generalized weighted quantile sum regression, which was used in conditional logistic regression models to control for the four metals while assessing the interactive association between GSTP1 and BMC with ASD. ResultsSimilar to the findings we reported previously, we found that in co-dominant and dominant models for GSTP1, among children with the Ile/Ile genotype, those with BMC ≥ 12 μg/L had 4.6 and 4.27 times higher odds of ASD compared to those with BMC < 12 μg/L (adjusted Matched Odds Ratio (MOR) = 4.6, 95% CI: 1.21–17.42 and adjusted MOR = 4.27, 95% CI: 1.15–15.85, respectively). In the co-dominant model, for children with the Ile/Val and Val/Val genotypes, the adjusted MORs were 1.26 (95% CI: 0.32, 5.01) and 0.26 (95% CI: 0.05, 1.42), respectively. ConclusionsAfter adjusting for the mixture of four metals, the interactive association of BMC and GSTP1 with ASD remained significant with similar magnitude of associations. Results should be interpreted cautiously.

Mediating and Interacting Effects of Birth Outcomes on the Relationship between Prenatal Manganese Exposure and Cognitive Outcome among 2-3 years-old Bangladeshi Children

Background/Aim: We investigated the mediating and interacting influence of physical measurements at birth on the relationship between prenatal exposure to manganese and cognitive status among 2-3 years-old Bangladeshi children. Methods: Pregnant mothers were enrolled in a prospective birth cohort in rural Bangladesh between 2008-2011 and children followed longitudinally. Manganese was measured in umbilical cord blood metal by ICP-MS. Anthropometric measurements (weight, length, head circumference) were assessed at delivery. Cognitive status of the children was assessed by translated and culturally appropriate version of the Bayley Scales of Infant and Toddler Development Third Edition at age 20-40 months. We assessed the effect of cord blood manganese on neurodevelopment considering whether physical measures at birth mediated the association with cognitive score or whether these measures modified the association between cord blood manganese and cognitive score. Recently developed statistical approaches allow for estimating mediation and effect modification effects simultaneously. Results: 764 mother-child pairs were included. Higher cord blood manganese concentration was associated with lower cognitive score [β=-0.31, standard error (SE)=0.12, p=0.008]. Among the birth measures, mediating and modifying effects of birth length were identified. We found a significant mediation effect through birth length (β =-0.08, SE=0.03). We found evidence of interaction between manganese and birth length (β =0.11, SE=0.03) and of mediated interaction (both mediation and interaction)(β =-0.04, SE=0.01)(all p≤0.01). The overall proportion mediated by birth length was 38.2% and the proportion attributed to interaction was 21.7%. Conclusions: Our findings confirm that birth length significantly contributes to the overall effect of manganese exposure on child’s cognitive score. This suggests that manganese may have effects on global nutritional status that contributes to neurotoxicity, as opposed to effects that are specific to brain development. In addition, our analysis suggests that birth length (a marker of growth stunting) also partly modifies the effect of manganese on neurodevelopment.

Essential and non-essential trace elements among working populations in Ghana

BackgroundLead battery repair workers (LBRW) and electronic repair workers (ERW) may be exposed to inorganic components during work. This study aimed at determining essential and non-essential trace elements in male LBRW, ERW, referents and a group of female petty traders (FPT) in Kumasi (Ghana), taking into account iron status and inflammation. MethodsAltogether 64 LBRW, 64 ERW, 65 referents and 26 FPT were investigated in this cross-sectional study. Urine, whole blood and serum were collected for determination of trace elements. C-reactive protein and ferritin were determined in serum. ResultsThe LBRW had higher blood concentrations of manganese (B-Mn) and lead (B-Pb) and antimony in urine (U-Sb), and lower concentrations of cobalt in blood (B-Co). Being ERW was associated with higher concentrations of blood cadmium (B-Cd), urinary tin (U-Sn) and serum chromium (S-Cr). Concentrations of selenium (B-Se), Co and mercury (B-Hg) in whole blood and iodine in urine (U-I) were relatively high. Marginal iron status appeared to be a determinant for elevated concentrations of Co in particular, but also Mn and Cd in blood. Systemic inflammation was associated with the concentrations of copper and Se. The concentrations of Hg in whole blood were highly associated with Se and arsenic (As) in whole blood, indicating fish consumption as a common source of intake of these elements. However, Hg in whole blood was only slightly associated with Se in serum. ConclusionsThe ERW had elevated concentrations of B-Cd, S-Cr, and U-Sn, while B-Mn, B-Pb, and U-Sb concentrations were higher among the LBRW. Iron status and inflammation had substantial impact on some element concentration. This population had high concentrations of B-Se, B-Hg and B-Co and U-I.

Maternal and Cord Blood Manganese Concentrations and Early Childhood Neurodevelopment among Residents near a Mining-Impacted Superfund Site.

Background:Environmental manganese exposure has been associated with adverse neurodevelopmental outcomes among school-aged children; yet, few studies have evaluated prenatal exposure.Objectives:Our study examines associations between prenatal manganese concentrations and placental transfer of manganese with neurodevelopment in 224 2-y-old children residing near the Tar Creek Superfund Site.Methods:We collected maternal and cord blood at delivery, measured manganese using inductively coupled plasma mass spectrometry, and assessed neurodevelopment using the Bayley Scales of Infant Development-II. Associations between manganese and mental (MDI) and psychomotor (PDI) development indices were estimated in multivariable models. Placental transfer, approximated by cord/maternal manganese ratio, cord/total manganese ratio (), and by joint classification according to high or low (above or below median) maternal and cord manganese, was evaluated as a predictor of neurodevelopment.Results:Median levels [interquartile ranges (IQR)] of manganese in maternal and cord blood, respectively, were 24.0 (19.5–29.7) and . Adjusting for lead, arsenic, and other potential confounders, an IQR increase in maternal manganese was associated with (95% CI: , ) points on MDI and (95% CI: , ) points on PDI. Cord manganese concentrations were not associated with neurodevelopment scores. Cord/maternal and cord/total manganese ratios were positively associated with MDI [cord/maternal: ; cord/total: ] and PDI (cord/maternal: ; cord/total: ). Compared to mother–child pairs with low maternal and cord manganese, associations with neurodevelopment scores were negative for pairs with either high maternal, high cord, or high maternal and cord manganese.Conclusions:Maternal blood manganese concentrations were negatively associated with early childhood neurodevelopment scores in our study. Findings highlight the importance of understanding maternal exposures during pregnancy and factors influencing placental transfer. https://doi.org/10.1289/EHP925

Investigation of manganese homeostasis in dogs with anaemia and chronic enteropathy.

Lethargy is a frequent and important clinical feature of anaemia; however, it does not absolutely correlate with the severity of anaemia. Manganese is efficiently absorbed through the gastrointestinal tract via divalent metal transporter 1 (DMT1), which is also responsible for iron transport. DMT1 is upregulated in iron deficiency (ID). Increased manganese concentrations are reported in ID anaemia (IDA) in various species. Manganese is neurotoxic and therefore may contribute to lethargy observed in some anaemic patients. In addition, anaemia and ID are common in human inflammatory bowel disease. Little is known about how anaemia influences manganese metabolism in veterinary patients and how common is anaemia in dogs with chronic enteropathy (CE). If elevated manganese concentrations are found, then potentially neurotoxicity may be contributing to morbidity in these cases. The objectives of this study were to investigate the hypothesis that whole blood manganese concentrations would be increased in dogs with anaemia, particularly in dogs with confirmed IDA, and that anaemia would be common in canine CE. Medical records from 2012-2016 were reviewed for dogs with CE that were anaemic, as well as dogs with confirmed IDA, where a sample suitable for manganese analysis was held in an archive. Manganese concentration was measured in whole blood from: 11 anaemic dogs with CE, 6 dogs with IDA, 9 non-anaemic ill controls, and 12 healthy controls. Mann-Whitney U and Kruskal-Wallis tests with post-test Dunn’s multiple comparisons tests were performed, with P<0.05 considered significant. The prevalence of anaemia in canine CE was 20.6% (33/160). Manganese concentrations were significantly different between all groups (P=0.0001) and higher in non-anaemic than anaemic dogs (P=0.0078). Manganese concentrations were also higher in healthy compared to ill controls (P<0.0001), anaemic dogs with CE (P=0.0056) and to dogs with IDA (P=0.0001). No differences were observed between anaemic dogs with CE, IDA and ill controls. Although anaemia was frequently observed in canine CE, the hypothesis that dogs with anaemia would have increased manganese concentrations, possibly contributing to a lethargic state was not supported. Further research is warranted to understand the influence of anaemia on whole blood manganese.

Blood manganese concentrations in patients exposed to mercury

Nivolumab, an anti PD-1 monoclonal antibody, has been approved for the treatment of previously treated advanced or metastatic non-small-cell lung cancer (NSCLC). The aim of this study was to develop and validate an ELISA method for the quantification of nivolumab in plasma from patients with NSCLC in order to perform future pharmacokinetic/pharmacodynamic (PK/PD) studies. A home-made ELISA was developed and validated according to the general recommendations for the immunoassays. Then, the ELISA method was applied to quantify plasma trough levels (Cmin) of nivolumab (3 mg/kg every two weeks) in 27 NSCLC patients at days 14, 28 and 42 after start of treatment. Blood samples were collected just before the infusion on days 0 (baseline), 14, 28 and 42 after start of treatment. The dynamic calibration range for nivolumab assay was 5–100 μg/mL. Within- and between-day imprecision for quality controls (5, 20 and 75 μg/mL) were less than 5 and 12%, respectively. The mean (± standard deviation) nivolumab Cmin was 17.3 ± 4.8 μg/mL (coefficient of variation, CV = 27.8%), 25.0 ± 9.7 μg/mL (CV = 38.8%) and 33.0 ± 12.9 μg/mL (CV = 39.1%) on days 14, 28 and 42, respectively. IgG (p = 0.002) and ALT (p = 0.041) were independently associated with plasma nivolumab Cmin at day 42. The present ELISA method for quantification of nivolumab in plasma from NSCLC patients is sensitive and accurate enough to be used for further PK/PD investigations.

Massive intravenous manganese overdose due to compounding error: minimal role for hemodialysis

Context: Manganese-associated parkinsonism is well described in occupational settings, in chronic methcathinone users, and in patients receiving long-term total parenteral nutrition. We present a unique case of acute intravenous manganese poisoning with a systematic evaluation of hemodialysis efficacy.Case details: A 52-year-old woman was inadvertently administered a single intravenous dose of 800 mg compounded manganese chloride at an outpatient chelation center. In an attempt to minimize central nervous system (CNS) manganese deposition, she underwent urgent hemodialysis followed by five days of therapy with calcium disodium EDTA (1 g/m2 over eight hours daily). Her initial whole blood manganese concentration, obtained six hours after exposure and prior to treatment, was 120 mcg/L (2.19 micromol/L); normal <5 mcg/L (< 0.09 micromol/L). Following the first four-hour hemodialysis session her blood manganese concentration decreased to 20 mcg/L (0.36 micromol/L). Despite the fall in her blood manganese concentration, analysis of dialysate revealed a total elimination of only 604 mcg (11 micromol) manganese (∼1.4% of manganese burden). Although she remained asymptomatic, an MRI on hospital day two revealed T1 hyperintensities within the bilateral globus pallidi, consistent with manganese exposure.Discussion: Manganese poisoning is associated with irreversible neurologic toxicity. Hemodialysis did not appear to significantly enhance elimination in this case of acute intravenous manganese toxicity, beyond supportive care and calcium disodium EDTA chelation.