Blood Mn Levels Research Articles

Pathophysiological studies of aging Slc39a14 knockout mice to assess the progression of manganese-induced dystonia-parkinsonism

Over the last decade, several clinical reports have outlined cases of early-onset manganese (Mn)-induced dystonia-parkinsonism, resulting from loss of function mutations of the Mn transporter gene SLC39A14. Previously, we have performed characterization of the behavioral, neurochemical, and neuropathological changes in 60-day old (PN60) Slc39a14-knockout (KO) murine model of the human disease. Here, we extend our studies to aging Slc39a14-KO mice to assess the progression of the disease. Our results indicate that 365-day old (PN365) Slc39a14-KO mice present with markedly elevated blood and brain Mn levels, similar to those found in the PN60 mice and representative of the human cases of the disease. Furthermore, aging Slc39a14-KO mice consistently manifest a hypoactive and dystonic behavioral deficits, similar to the PN60 animals, suggesting that the behavioral changes are established early in life without further age-associated deterioration. Neurochemical, neuropathological, and functional assessment of the dopaminergic system of the basal ganglia revealed absence of neurodegenerative changes of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), with no changes in DA or metabolite concentrations in the striatum of Slc39a14-KO mice relative to wildtype (WT). Similar to the PN60 animals, aging Slc39a14-KO mice expressed a marked inhibition of potassium-stimulated DA release in the striatum. Together our findings indicate that the pathophysiological changes observed in the basal ganglia of aging Slc39a14-KO animals are similar to those at PN60 and aging does not have a significant effect on these parameters.

Performance and mineral status of laying hens fed diets with different levels of glyphosate

Concern has been raised about the potential influence of glyphosate on livestock health and performance due to its antimicrobial and mineral-chelating properties. The present study investigated potential effects of feeding diets amended with glyphosate (as a commercial product, Glyphomax HL, or as pure isopropylamine salt, IPA) to laying hens (layers). At the age of 22 weeks, a total of 320 Lohmann LSL-Lite layers started on one of four treatment diets: Control (CON), 20 mg glyphosate/kg as Glyphomax HL (GM20), 20 mg glyphosate/kg as IPA (IPA20) and 200 mg glyphosate/kg as IPA (IPA200). The EU-defined maximum residue level (MRL) of glyphosate for several feed crops is 20 mg/kg. The layers were housed in 32 enriched cages for 27 weeks. Glyphosate levels in the diets (mg/kg feed) were analysed to 0.03 for CON, 19.3 for GM20, 18.5 for IPA20 and 191.7 for IPA200. Using preselected contrasts, there were no clear effects of diet glyphosate amendment on average egg weight, egg mass, feed intake, feed conversion ratio and rate of lay, while post hoc contrasts suggested that diet glyphosate concentrations above 20 mg/kg may reduce rate of lay by 0.9%-point. Mineral levels of Mg, Ca, Mn, Fe, Cu and Zn in blood as well as indicators of welfare measured by plumage scoring and by a novel object test were not significantly affected by treatment. Glyphosate levels in blood serum (µg/L) were 0.29 for CON, 22.5 for GM20, 25.0 for IPA20 and 128.9 for IPA200. Glyphosate levels in egg yolk and egg white (ng/g) were respectively 0.26 and 0.01 for CON, 20.1 and 0.20 for GM20, 21.4 and 0.25 for IPA20 and 223.3 and 3.09 for IPA200. Glyphosate concentrations in blood serum, egg yolk and egg white reflected diet concentrations. The glyphosate degradation product, AMPA, followed the same trend as glyphosate in all analysed compartments. In conclusion, there were no clear adverse effects of glyphosate-amended diets on performance, welfare indicators and mineral status of Lohmann LSL-Lite layers even at a level approximately 10x higher than the MRL for soybeans and other common feed crops (20 mg glyphosate per kg feed). However, post hoc contrasts suggested that diet glyphosate concentrations above 20 mg/kg may reduce rate of lay by 0.9%-point. Moreover, the layers exposed down to 0.03 mg of glyphosate per kg feed produced eggs with residues of this pesticide.

Effects of individual amino acid mutations of zinc transporter ZIP8 on manganese- and cadmium-transporting activity

Zinc (Zn) transporter ZIP8, encoded by SLC39A8, is a unique transporter that can transport divalent manganese (Mn) and cadmium (Cd) in addition to Zn. Recently, associations between various human diseases and variant forms of ZIP8 have been reported. Four amino acid residues, V33, G38, S335, and I340, of human ZIP8 (hZIP8) are mutated in patients with congenital disorders of glycosylation (CDG), whose blood Mn levels are extremely low. Many genome-wide association studies have reported that the A391T mutation of hZIP8 caused by rs13107325 is associated with a wide range of diseases. However, the roles of individual mutations of hZIP8 on metal-transporting activity remain elusive. We established DT40 cells respectively expressing the four mutant hZIP8s and compared the Mn- and Cd-transporting activity between the mutants and wild-type hZIP8. Among the four mutations observed in the ZIP8-mutated CDG patients, the S335T and I340 N mutations in the predicted transmembrane domain 5 (TMD5) completely abolished Mn- and Cd-transporting activity, while V33 M or G35R mutations at the N-terminus did not. We also examined the A391T mutation, which slightly reduced metal transporting activity. Finally, we examined the effects of artificial mutations in the metal-binding motif EEXXH in the TMD5. Replacing EEXXH with HEXXH, which exists in most ZIP transporters, abolished the Mn- and Cd-transporting activity of hZIP8, indicating that glutamic acid in this motif plays a critical role in the unique affinity of ZIP8 for Mn and Cd. Thus, the utilization of DT40 cells enabled us to clarify the different functions of each residue of hZIP8 on metal transport.

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.

Relationship of Blood and Urinary Manganese Levels with Cognitive Function in Elderly Individuals in the United States by Race/Ethnicity, NHANES 2011-2014.

Manganese (Mn) is an essential metal with a biphasic relationship with health outcomes. High-level exposure to Mn is associated with manganism, but few data explore the effects of chronic, lower-level Mn on cognitive function in adults. We sought to determine the relationship between blood/urinary manganese levels and cognitive function in elderly individuals using 2011–2014 data from the National Health and Nutrition Examination Survey (NHANES). Weighted multivariate regression models were used to determine correlations, adjusting for several covariates. Blood Mn was inversely associated with the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) immediate learning of new verbal information (p-value = 0.04), but lost significance after adjusting for medical history (p-value = 0.09). In addition, blood Mn was inversely associated with Animal Fluency scores after adjusting for all covariates. Urinary Mn was inversely associated with CERAD immediate learning after adjusting for all covariates (p-value = 0.01) and inversely associated with the Digit Symbol Substitution Test scores (p-value = 0.0002), but lost significance after adjusting for medical history (p-value = 0.13). Upon stratifying by race/ethnicity, other Races and Non-Hispanic (NH)-Blacks had significantly higher blood Mn levels when compared to NH-Whites. Collectively, these findings suggest that increased blood and urinary Mn levels are associated with poorer cognitive function in an elderly US population.

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.

Longitudinal analyses of maternal and cord blood manganese levels and neurodevelopment in children up to 3 years of age: The Japan Environment and Children’s Study (JECS)

Manganese (Mn) is an essential trace metal and a neurotoxicant. Adverse effects of Mn exposure on the neurodevelopment of children have been reported. However, there is limited information on the effects of maternal exposure during pregnancy. We aimed to investigate the association between maternal and cord blood Mn levels and neurodevelopment in children aged between 6months and 3years using data from a Japanese nationwide birth cohort study. We used the data of 63,767 mother-child pairs with maternal blood Mn measurements recorded during the second and third trimester and of 3,787 mother-child pairs with cord blood Mn measurements. Neurodevelopment was assessed using the Japanese version of the Ages and Stages Questionnaires, third edition (J-ASQ-3), which was completed by parents or guardians at 6months, 1year, 1.5years, 2years, 2.5years, and 3years of age. The median maternal and cord blood Mn levels were 15.2 and 44.5ng/g, respectively. After adjusting for covariates, both maternal and cord blood Mn levels were negatively associated with J-ASQ-3 scores. Maternal blood Mn levels were negatively associated with gross motor function scores at all ages except for that at 1.5years (adjusted β: -0.55 to -1.23 for a two-fold increase in maternal Mn levels). The risk of developmental delay (score below the cut-off) in gross motor function increased at the same time points (adjusted odds ratio: 1.08 to 1.13). In the subgroup, cord blood Mn levels were negatively associated with gross motor function scores at 1, 2, and 2.5years (adjusted β: -1.84 to -3.27). Maternal blood Mn levels during pregnancy and cord blood Mn levels were negatively associated with neurodevelopment in children up to 3years of age. Excessive maternal and fetal exposure to Mn may have adverse effects on neuromotor function in children.

Association between the blood manganese (Mn) and hemoglobin in patients undergoing maintenance hemodialysis

Background and aimsManganese (Mn) and iron metabolism are closely related. Iron metabolism disorders often lead to anemia in patients undergoing maintenance hemodialysis (MHD). Here, we aimed to investigate the relationship between blood Mn and hemoglobin (Hb) in patients undergoing MHD. MethodsPatients undergoing MHD in September 2019 were included in a cross-sectional study. Clinical and demographic data and blood samples were collected before hemodialysis sessions, and blood levels of Mn were measured by inductively coupled plasma mass spectrometry. Both multivariable linear and binary logistic regression analyses were performed to study the relationship between the blood Mn and Hb. ResultsA total of 144 patients undergoing MHD were enrolled in the study. The patients had a mean age of 64.33 ± 13.39 years, median vintage of 33.50 (16.25–57.50) months. Among them, 66 were females (45.8%). The median blood Mn level was 13.55 µg/L (IQR:9.92–17.48). Ninety-nine patients were anemic (68.8%). The mean Hb level was 99.83 ± 19.68 g/L. The patient group with high blood Mn had a high proportion of females, and these patients had high levels of RBC, hemoglobin, Hct, UIBC, serum TCHOL, and serum LDL, yet short dialysis vintage, low prevalence of anemia, low levels of serum ferritin, serum iron, and TSAT. Following adjustment for confounding factors, we found that low blood Mn level was independently associated with lower Hb level and anemia in patients undergoing MHD by multivariate linear and multivariate binary logistic regression, respectively, in different models. ConclusionWhilst our study showed that high levels of blood Mn were independently associated with high hemoglobin in patients undergoing MHD, further multicenter studies with large sample sizes are still required.

BTBD9 attenuates manganese-induced oxidative stress and neurotoxicity by regulating insulin growth factor signaling pathway.

Manganese (Mn) is an essential mineral, but excess exposure can cause dopaminergic neurotoxicity. Restless legs syndrome (RLS) is a common neurological disorder, but the etiology and pathology remain largely unknown. The purpose of this study was to identify the role of Mn in the regulation of an RLS genetic risk factor BTBD9, characterize the function of BTBD9 in Mn-induced oxidative stress and dopaminergic neuronal dysfunction. We found that human subjects with high blood Mn levels were associated with decreased BTBD9 mRNA levels, when compared with subjects with low blood Mn levels. In A549 cells, Mn exposure decreased BTBD9 protein levels. In Caenorhabditis elegans, loss of hpo-9 (BTBD9 homolog) resulted in more susceptibility to Mn-induced oxidative stress and mitochondrial dysfunction, as well as decreased dopamine levels and alternations of dopaminergic neuronal morphology and behavior. Overexpression of hpo-9 in mutant animals restored these defects and the protection was eliminated by mutation of the forkhead box O (FOXO). In addition, expression of hpo-9 upregulated FOXO protein levels and decreased protein kinase B levels. These results suggest that elevated Mn exposure might be an environmental risk factor for RLS. Furthermore, BTBD9 functions to alleviate Mn-induced oxidative stress and neurotoxicity via regulation of insulin/insulin-like growth factor signaling pathway.

Validation of blood arsenic and manganese assessment from archived clotted erythrocyte fraction in an urban cohort of mother-child dyads

Exposure to arsenic (As) and manganese (Mn) from contaminated food, drinking water and dust are linked to a host of adverse health effects. The recent discovery of unmonitored community exposures to hazardous levels of metals, as seen in the Flint Water Crisis and East Chicago, have demonstrated a need for novel biomonitoring methods utilizing samples other than whole blood. Here, we present a method utilizing clotted erythrocyte fraction samples, a blood component commonly archived in biorepositories, to predict whole blood levels of As and Mn. This method would allow for innovative retrospective assessments of environmental exposures in previously unused samples. Whole blood and clotted erythrocyte fraction samples were simultaneously collected from 84 participants in the Airborne Exposure to Semivolatile Organic Pollutants (AESOP) cohort study of mother-child dyads in East Chicago. Clotted erythrocyte fraction samples were prepared by alkaline dilution and subsequently analyzed using inductively coupled plasma-mass spectrometry. A strong linear relationship was observed between whole blood and clotted erythrocyte fraction with Pearson correlation coefficients (r, p < 0.001) of 0.74, and 0.82 for As and Mn, respectively. Modeled whole blood Mn levels predicted from clotted erythrocyte fractions evaluated at a test threshold representing the NHANES median of 9.7 μg/L, were found to have diagnostic sensitivity of 88% and specificity of 71%. Clotted erythrocyte partitioning of As was tested on a wide range of oral gavage doses using a rat model. Results from this investigation demonstrate clotted erythrocyte fraction samples are a viable alternative biological sample for retrospective public health surveillance of environmental exposure to As and Mn.

Bone manganese is a sensitive biomarker of ongoing elevated manganese exposure, but does not accumulate across the lifespan

Studies have established associations between environmental and occupational manganese (Mn) exposure and executive and motor function deficits in children, adolescents, and adults. These health risks from elevated Mn exposure underscore the need for effective exposure biomarkers to improve exposure classification and help detect/diagnose Mn-related impairments. Here, neonate rats were orally exposed to 0, 25, or 50 mg Mn/kg/day during early life (PND 1–21) or lifelong through ∼ PND 500 to determine the relationship between oral Mn exposure and blood, brain, and bone Mn levels over the lifespan, whether Mn accumulates in bone, and whether elevated bone Mn altered the local atomic and mineral structure of bone, or its biomechanical properties. Additionally, we assessed levels of bone Mn compared to bone lead (Pb) in aged humans (age 41–91) living in regions impacted by historic industrial ferromanganese activity. The animal studies show that blood, brain, and bone Mn levels naturally decrease across the lifespan without elevated Mn exposure. With elevated exposure, bone Mn levels were strongly associated with blood Mn levels, bone Mn was more sensitive to elevated exposures than blood or brain Mn, and Mn did not accumulate with lifelong elevated exposure. Elevated early life Mn exposure caused some changes in bone mineral properties, including altered local atomic structure of hydroxyapatite, along with some biomechanical changes in bone stiffness in weanlings or young adult animals. In aged humans, blood Mn ranged from 5.4 to 23.5 ng/mL; bone Mn was universally low, and decreased with age, but did not vary based on sex or female parity history. Unlike Pb, bone Mn showed no evidence of accumulation over the lifespan, and may not be a biomarker of cumulative long-term exposure. Thus, bone may be a useful biomarker of recent ongoing Mn exposure in humans, and may be a relatively minor target of elevated exposure.

Blood manganese and nonalcoholic fatty liver disease: A cohort-based case-control study

Background & aimsAs both a toxic and essential trace element in humans, limited research focuses on the association between blood manganese (Mn) and nonalcoholic fatty liver disease (NAFLD). We aimed to assess blood Mn concentration and its relationship with NAFLD among adults in Northern China. MethodsWe conducted a cohort-based case-control study among 1816 patients with NAFLD (970 males and 846 females) and 1111 healthy controls (598 males and 513 females). We used the restricted cubic splines method to investigate the potential non-linear relationship and logistic regression models to analyze the association between blood Mn and NAFLD. ResultsThe median (p25, p75) of blood Mn concentration in males was 10.08 (8.42,11.98) μg/L, higher than that in females [9.79 (8.01,12.04)] μg/L, P = 0.011. Compared with the tertile 1 group of Mn in males, the odds ratio (95 % confidence interval) of NAFLD for tertile 2 and tertile 3 group was 0.82 (0.61,1.10) and 0.64 (0.47,0.87), respectively. The reverse correlation was consistent in patients with different fibrosis severity determined by fibrosis-4 score. The protective association was more evident in those with triglycerides ≥1.7 mmol/L [odds ratio (95 % confidence interval) of tertile 3 vs. tertile 1: 0.40 (0.22,0.75)]. We found a non-significant U-shaped relationship between Mn and NAFLD in women. ConclusionThere may exist sex differences for the association between blood Mn and NAFLD. Higher blood Mn may be a potential protective factor for NAFLD in males. The subjects with TG ≥ 1.7 mmol/L would benefit more from higher blood Mn levels.

Determination of Manganese in Human Whole Blood with Indium Tin Oxide Electrochemical Point-of-Care Sensor

Manganese (Mn) is one of the most common elements in the earth’s crust, and its compounds are widely used in consumer products including gasoline, cell phone batteries, fertilizer, pigments, fireworks, etc. Although a trace metal in the human body and under tight homeostatic control, elevated levels of Mn due to occupational or environmental exposure can cause serious adverse health effects, such as manganism (a Parkinsonian-like syndrome), liver cirrhosis, and Behcet disease. The normal range of Mn in blood is 4.7-18.3 µg/L (5-20 ppb), and values greater than 36 µg/L correlate with disease. The current method for analyzing Mn in blood is via inductively coupled plasma mass spectrometry (ICP-MS) in centralized labs, which requires a venipuncture sample, can take 3-6 months for analyses, and can be costly. Electrochemical analysis can offer an attractive alternative, leading to developing a point-of-care system for Mn monitoring in blood, with the advantages of being inexpensive and easily miniaturized. Herein, we report the first Indium Tin Oxide (ITO) electrochemical microsensor capable of accurately measuring Mn levels in human blood with cathodic stripping voltammetry (CSV). As shown in Fig. 1 (a), the ITO microsensor was developed by integrating a screen-printed carbon auxiliary electrode and an Ag/AgCl reference electrode on an ITO coated glass slide (1 cm × 4 cm). A circular ITO film with 3 mm diameter was exposed and used as the working electrode. To start electrochemical analysis, blood sample was first microwave digested with nitric acid and hydrogen peroxide to release Mn2+ bound to the proteins. The acid-digested blood sample was then titrated with sodium hydroxide to pH 5. Square wave cathodic stripping voltammetry (SWCSV) with optimized parameters was carried out to construct the calibration curve in the digested & pH adjusted blood sample with the Mn concentration ranging from 1.2 ppb to 25 ppb (confirmed by ICP-MS). The voltammogram in Fig. 1(b) shows an increasing trend of peak height and area with Mn concentration; and the calibration curve in Fig. 1(c) shows a sensitivity of 38.6 nC/ppb and linearity of 0.997 from the sensor’s measurements. We used the same stripping parameters, while applying a 3-point standard addition method, to determine the Mn concentration in two blood samples. The concentrations of 10.5 ppb and 26.3 ppb from our measurements lead to an average accuracy of 90% in comparison to the ICP-MS results of 8.9 ppb and 27.6 ppb. Four 150 µl sample droplets with a total volume of 600 µl were used in the measurement. Considering the 10X dilution from the blood digestion and pH adjustment process, only 60 µl of whole blood is needed to determine the Mn level with our approach. The favorable results and the small blood volume required in this work suggests the feasibility of point-of-care monitoring Mn in blood and is expected to be very useful for monitoring Mn exposure in vulnerable populations like children. Figure 1

Associations between blood and urinary manganese with metabolic syndrome and its components: Cross-sectional analysis of National Health and Nutrition Examination Survey 2011-2016.

Manganese (Mn) may improve cardiometabolic health with its anti-oxidative ability. However, epidemiological evidence on the overall and sex-specific relationship between Mn exposure and metabolic syndrome (MetS) has been inconclusive. We evaluated the associations of urinary (n=1713) and blood (n=3335) Mn levels with the prevalence of MetS, its components (elevated waist circumference, impaired glucose metabolism, elevated blood pressure and dyslipidemia) and sex-dependent heterogeneities among participants in the United States National Health and Nutrition Examination Survey 2011-2016. After adjusting for multiple covariates and the levels of other metals (Arsenic, Barium, Cadmium, Mercury, Molybdenum, Tin and Uranium), urinary Mn at the third quartile associated with a lower odd of MetS (odds ratio [OR]=0.55, 95% confidence interval [C.I.]=0.32-0.97), elevated waist circumference (OR=0.56, 95% C.I.=0.36-0.86) and elevated fasting plasma glucose (OR=0.46, 95% C.I.=0.27-0.76) among overall participants, and lower odds of MetS (OR=0.40, 95% C.I.=0.16-0.99), elevated waist circumference (OR=0.39, 95% C.I.=0.19-0.81) and elevated fasting plasma glucose (OR=0.44, 95% C.I.=0.22-0.90) among men. The U-shaped dose-response relationship between urinary Mn and MetS (P non-linear=0.008) was observed among all participants. We did not observe the significant associations of blood Mn with the prevalence of MetS. Compared with other metals, urinary Mn played a less important role in development of MetS (posterior inclusion probabilities [PIP]=0.49 for Mn versus 0.54 to 0.91 for other metals), but the contribution of blood Mn (PIP=0.59 versus 0.60 to 0.61) was similar to other blood metals (Cadmium, Lead, Mercury and Selenium). These findings have provided new evidence of the potential roles of Mn in cardiometabolic health, and the needs to explore how Mn interacts with multiple metals in sex-specific manner.

Environmental exposure to manganese and other trace metal(loid)s in air: associations with cognitive and motor functions.

Background/Aim: Maliaño, Cantabria (Spain) is a 10,000 inhabitants community with elevated air-Mn from ferroalloy industrial emissions (annualarithmetic mean=781 ng/m3; reference guideline from WHO &lt;=150 ng/m3). The capital of the region (Santander, 172,000 inhabitants) is 7 km from the industrial emission source (IES). Our objective was to determine the blood levels of Mn, As and Pb in adult healthy volunteers, and to explore the associations between residence distance from the IES, blood levels, and their cognitive and motor function. Methods: Ongoing cross-sectional study analyzing the first 29 volunteers: 19 women and 10 males, mean age 47.2 years. Cognitive and motor function was assessed by 5 and 3 tests respectively. Cognitive crude scores were standardized according to NEURONORMA norms. Distance from the IES was categorized into "&lt;=1.5 km" versus "&gt;1.5 to &lt;10 km from the IES". Spearman's rho coefficient (rs) was used for correlations. Results: Means for Mn, As and Pb blood levels (µg/L) were 8.34; 8.22 and 11.65 respectively. As (rs=-0.590, p=0.001) and Pb (rs=-0.465, p=0.011) were correlated with lower distance from the IEM. Regarding cognitive function, statistically-significant mean differences were obtained for "WAIS Digit Span Backward" (1.44 points lower when living &lt;=1.5 km, p=0.017) and "Verbal Fluency Test Initial Letter P" (4.21 points lower, p=0.042). WAIS Digit Span forward (NEURONORMA) was correlated negatively with Mn levels (rs=-0.410, p=0.027). Regarding motor function, Grooved Pegboard was inversely correlated with distance (the closer the residence to the IES, the longer the time to complete the test: rs=-0.38, p=0.043), mean difference=10.32 more seconds in highly exposed. For none of the rest of analyses, significant results were obtained against the hypothesis of worse cognitive or motor function as a function of distance from the IES, or blood levels. Conclusions. Our results suggest poorer cognitive and motor function, especially in terms of proximity to IES.

Rare cases of severe life-threatening lead poisoning due to accident or chronic occupational exposure to lead and manganese: Diagnosis, treatment, and prognosis

Chronic long-term, low-dose environmental and occupational exposure to lead (Pb) has been extensively studied in large cohorts worldwide among general populations, miners, smelters, or battery workers. However, studies on severe life-threatening Pb poisoning due to accidental or chronic occupational exposure to Pb and manganese (Mn) were rarely reported. We present one case of acute severe Pb poisoning and compare it with another severe chronic occupational exposure case involving Pb and Mn. A 27-year-old woman mistakenly took a large quantity of pure Pb powder as an herbal remedy; she developed abdominal colic, severe nausea, vomiting, fatigue, and cutaneous and sclera icterus. Laboratory tests showed her blood lead level (BLL) of 173.5 µg dL-1 and urinary lead level (ULL) of 1240 µg dL-1. The patient was diagnosed with acute Pb poisoning and acute liver failure. In another chronic exposure case, a 56-year-old man worked in a Pb and Mn smelting factory for 15 years. He was brought to the emergency room with severe nausea, vomiting, and paroxysmal abdominal colic, which was intolerable during the onset of pain. His BLL was 64.8 µg dL-1 and ULL was 38 µg dL-1, but his blood and urinary Mn levels were normal. The patient was diagnosed with chronic Pb poisoning. Both patients received chelation therapy with calcium disodium ethylene-diamine-tetraacetate (CaNa2EDTA). The woman with acute severe Pb intoxication recovered well and was discharged from the hospital after treatment, and the man who survived severe Pb poisoning was diagnosed with lung cancer. Clinical manifestations of acute and chronic severe Pb poisoning are different. Chelation therapy with CaNa2EDTA is proven to be an effective life-saving therapy in both cases by reducing BLL. Occupational exposure to both Pb and Mn does not appear to increase Mn neurotoxicity; however, the probability that co-exposure to Mn may increase Pb toxicity in the same patient cannot be excluded.

Analysis of internal exposure levels of manganese, cobalt, selenium and molybdenum in blood and urine among general population in parts of Shaanxi Province

To investigate the internal exposure levels of manganese(Mn), cobalt(Co), selenium(Se) and molybdenum(Mo) in blood and urine among the general population in parts of Shaanxi Province, and thereby to analyze their population distribution characteristics. In 2017, a total of 720 subjects of general people aged 3-79 years were recruited from 5 counties in Shaanxi Province, by stratified random sampling method, blood and urine samples were collected, and the contents of Mn, Co, Se and Mo in blood and urine samples were detected by inductively coupled plasma mass spectrometry(ICP-MS). The test result were statistically analyzed according to different genders, regions and age groups. Among general people in Shaanxi Province, the median of Mn in blood and urine were separately 8. 43 and 0. 60 μg/L. The median of Mn in blood among males and females were 7. 99 and 8. 81 μg/L, the difference was statistically significant(P&lt;0. 05), the difference of blood Mn between urban and rural areas was statistically significant(P&lt;0. 05). The median of Co in blood and urine were separately 0. 13 and 0. 17 μg/L, the median of Co in blood among males and females were 0. 12 and 0. 15 μg/L, the median of Co in urine among males and females were 0. 16 and 0. 20 μg/L, the differences were statistically significant(P&lt;0. 05), the differences of blood Co and urine Co in urban and rural areas were statistically significant(P&lt;0. 05). The median of Se concentration in blood and urine were separately 73. 20 and 13. 30 μg/L, the median of Se in urine among males and females were 14. 40 and 12. 40 μg/L, the difference were statistically significant(P&lt;0. 05), the differences of blood Se and urine Se in urban and rural areas were statistically significant(P&lt;0. 05). The median of Mo concentration in blood and urine were separately 0. 60 and 50. 40 μg/L, the median of Mo in urine among males and females were 56. 60 and 43. 00 μg/L, the difference was statistically significant(P&lt;0. 05), the difference of blood Mo between urban and rural areas was statistically significant(P&lt;0. 05). Within the same gender, all indexes in whole blood(except female blood Se) were statistically significant among age groups(P&lt;0. 05). The differences of male urine Co, urine Se, urine Mo and female urine Co among age groups were statistically significant(P&lt;0. 05). Among general population in Shaanxi Province, the Mn, Co, Se and Mo levels in blood and urine are varied by gender age and area, the blood Se level is relatively low.

Blood concentrations of 50 elements in Eagle owl (Bubo bubo) at different contamination scenarios and related effects on plasma vitamin levels

Some metals and metalloids (e.g. Pb, Hg, Cd and As) are well-known for their bioaccumulation capacity and their toxic effects on birds, but concerns on other minor elements and rare earth elements (ME and REE) are growing due to their intensive use in modern technology and potential toxicity. Vitamins and carotenoids play essential roles in nestling growth and proper development, and are known to be affected by the metals classically considered as toxic. However, we are unaware of any attempts to evaluate the exposure to 50 elements and related effects in plasma vitamins and carotenoids in raptor species. The main goals of this study are: (i) to assess the exposure to 50 elements (i.e. classic toxic elements, trace elements, REE and ME) in nestling Eagle owls (Bubo bubo) inhabiting three differently polluted environments (mining, industrial and control areas) in southeastern Spain, and (ii) to evaluate how element exposure affects plasma vitamin and carotenoid levels, hematocrit and body measurements (mass and wing length) of the individuals. Our results show that local contamination in the mining area contributes to increased blood concentrations of Pb, As and Tl in nestlings, while diet differences between control and mining/industrial areas may account for the different levels of Mn, Zn, and Sr in blood, and lutein in plasma. Plasma tocopherol levels were increased in the mining-impacted environment, which may be a mechanism of protection to prevent toxic element-related oxidative stress. Plasma α-tocopherol was enhanced by 20% at blood Pb concentrations ≥8 ng/ml, and nestlings exhibited up to 56% increase in α-tocopherol levels when blood Pb concentrations reached 170 ng/ml. Tocopherol seems to be a sensitive biomarker under an exposure to certain toxic elements (e.g. Pb, As, Tl).

1558-P: Sex-Specific Associations of Blood and Urinary Manganese with Glucose Levels, Insulin Resistance, and Kidney Function among U.S. Adults: Use of 2011-2016 NHANES Data

Although the role of manganese (Mn) in the development of diabetes has been a concern, epidemiological studies directly linking Mn exposures to glucose homeostasis in a sex-dependent context are rare. We evaluated the associations of Mn levels in both blood and urine with glucose levels, insulin resistance, and kidney function among general populations and potential heterogeneities by sex. We performed a cross-sectional analysis of population-based data in the National Health and Nutrition Examination Survey (NHANES) involving 1417 adults in 2011-2016. We estimated the associations between blood and urinary Mn levels with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), insulin, and estimated glomerular filtration rate (eGFR) by using categorical and spline analyses. There were significant positive linear relationships between urinary Mn with FPG (P&amp;lt;overall=0.003, P&amp;lt;nonlinear=0.817) and HbA1c (P&amp;lt;overall=0.023, P&amp;lt;nonlinear=0.854) among women, while blood Mn levels were associated HOMA-IR (P&amp;lt;nonlinear=0.042) and insulin (P&amp;lt;nonlinear=0.014) with J-shaped dose-responses among men. For eGFR, positive linear relationships were observed with blood Mn in women (P&amp;lt;overall=0.032, P&amp;lt;nonlinear=0.549), and with urinary Mn in both men (P&amp;lt;nonlinear=0.058) and women (P&amp;lt;nonlinear=0.892). In sensitivity analysis, after excluding participants with diabetes, we still observed sex differences in the association between urinary Mn levels with FPG, HbA1c, insulin, HOMA-IR and eGFR. In summary, blood and urinary Mn levels were independently associated with glucose-related biomarkers with potential heterogeneities by sex. The findings emphasize the probable role of Mn for the glucose-related biomarkers and kidney function, and call for more studies on the risk of diabetes in a sex-specific manner. Disclosure J. Yang: None. A. Yang: None. N. Cheng: None. Y. Bai: None.

Sex-specific associations of blood and urinary manganese levels with glucose levels, insulin resistance and kidney function in US adults: National health and nutrition examination survey 2011–2016

Exposures to heavy metals play a role in the etiopathogenesis of diabetes. Epidemiological studies investigating a potential sex-specific linkage between manganese (Mn) exposures and glucose homeostasis are rare. We comprehensively estimated the associations of blood and urinary Mn levels with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), insulin, and estimated glomerular filtration rate (eGFR) among 1417 adults in the US National Health and Nutrition Examination Survey (NHANES) 2011–2016. We further examined the potential heterogeneities by sex and joint-effects of multiple metal exposures by the Bayesian kernel machine regression (BKMR). Among women, we found positive linear relationships between urinary Mn with FPG (Poverall = 0.003, Pnonlinear = 0.817) and HbA1c (Poverall = 0.023, Pnonlinear = 0.854). Among men, J-shaped relationships were observed between blood Mn with HOMA-IR (Pnonlinear = 0.042) and insulin (Pnonlinear = 0.014). For eGFR, positive linear relationships were obserned among women for blood Mn (Pnonlinear = 0.549) and among both men and women for urinary Mn levels. The joint-effects of urinary Mn with molybdenum (Mo) on FPG and HbA1c, urinary Mn with cadmium (Cd) and cesium (Cs) on eGFR, and blood Mn with Cd and lead (Pb) on eGFR were detected. In summary, blood and urinary Mn levels were independently associated with glucose levels, insulin resistance and kidney function with potential sex-dependent heterogeneities. These findings emphasize the probable role of Mn in the regulation of glucose metabolism and kidney function, and confirm the need for more studies on sex-specific risk of diabetes.