Lead Content of Sindoor, a Hindu Religious Powder and Cosmetic: New Jersey and India, 2014-2015.

OBJECTIVES: To assess the extent of lead content of sindoor, a powder used by Hindus for religious and cultural purposes, which has been linked to childhood lead poisoning when inadvertently ingested. METHODS: We purchased 95 samples of sindoor from 66 South Asian stores in New Jersey and 23 samples from India and analyzed samples with atomic absorption spectrophotometry methods for lead. RESULTS: Analysis determined that 79 (83.2%) sindoor samples purchased in the United States and 18 (78.3%) samples purchased in India contained 1.0 or more micrograms of lead per gram of powder. For US samples, geometric mean concentration was 5.4 micrograms per gram compared with 28.1 micrograms per gram for India samples. The maximum lead content detected in both US and India samples was more than 300 000 micrograms per gram. Of the examined US sindoor samples, 19% contained more than 20 micrograms per gram of lead (US Food and Drug Administration [FDA] limit); 43% of the India samples exceeded this limit. CONCLUSIONS: Results suggested continued need for lead monitoring in sindoor in the United States and in sindoor carried into the United States by travelers from India, despite FDA warnings.

Excessive fructose intake causes 1,25-(OH)(2)D(3)-dependent inhibition of intestinal and renal calcium transport in growing rats.

We recently discovered that chronic high fructose intake by lactating rats prevented adaptive increases in rates of active intestinal Ca(2+) transport and in levels of 1,25-(OH)2D3, the active form of vitamin D. Since sufficient Ca(2+) absorption is essential for skeletal growth, our discovery may explain findings that excessive consumption of sweeteners compromises bone integrity in children. We tested the hypothesis that 1,25-(OH)2D3 mediates the inhibitory effect of excessive fructose intake on active Ca(2+) transport. First, compared with those fed glucose or starch, growing rats fed fructose for 4 wk had a marked reduction in intestinal Ca(2+) transport rate as well as in expression of intestinal and renal Ca(2+) transporters that was tightly associated with decreases in circulating levels of 1,25-(OH)2D3, bone length, and total bone ash weight but not with serum parathyroid hormone (PTH). Dietary fructose increased the expression of 24-hydroxylase (CYP24A1) and decreased that of 1α-hydroxylase (CYP27B1), suggesting that fructose might enhance the renal catabolism and impair the synthesis, respectively, of 1,25-(OH)2D3. Serum FGF23, which is secreted by osteocytes and inhibits CYP27B1 expression, was upregulated, suggesting a potential role of bone in mediating the fructose effects on 1,25-(OH)2D3 synthesis. Second, 1,25-(OH)2D3 treatment rescued the fructose effect and normalized intestinal and renal Ca(2+) transporter expression. The mechanism underlying the deleterious effect of excessive fructose intake on intestinal and renal Ca(2+) transporters is a reduction in serum levels of 1,25-(OH)2D3. This finding is significant because of the large amounts of fructose now consumed by Americans increasingly vulnerable to Ca(2+) and vitamin D deficiency.

Radiation-induced reductions in transporter mRNA levels parallel reductions in intestinal sugar transport.

More than a century ago, ionizing radiation was observed to damage the radiosensitive small intestine. Although a large number of studies has since shown that radiation reduces rates of intestinal digestion and absorption of nutrients, no study has determined whether radiation affects mRNA expression and dietary regulation of nutrient transporters. Since radiation generates free radicals and disrupts DNA replication, we tested the hypotheses that at doses known to reduce sugar absorption, radiation decreases the mRNA abundance of sugar transporters SGLT1 and GLUT5, prevents substrate regulation of sugar transporter expression, and causes reductions in sugar absorption that can be prevented by consumption of the antioxidant vitamin A, previously shown by us to radioprotect the testes. Mice were acutely irradiated with (137)Cs gamma rays at doses of 0, 7, 8.5, or 10 Gy over the whole body. Mice were fed with vitamin A-supplemented diet (100x the control diet) for 5 days prior to irradiation after which the diet was continued until death. Intestinal sugar transport was studied at days 2, 5, 8, and 14 postirradiation. By day 8, d-glucose uptake decreased by approximately 10-20% and d-fructose uptake by 25-85%. With increasing radiation dose, the quantity of heterogeneous nuclear RNA increased for both transporters, whereas mRNA levels decreased, paralleling reductions in transport. Enterocytes of mice fed the vitamin A supplement had > or = 6-fold retinol concentrations than those of mice fed control diets, confirming considerable intestinal vitamin A uptake. However, vitamin A supplementation had no effect on clinical or transport parameters and afforded no protection against radiation-induced changes in intestinal sugar transport. Radiation markedly reduced GLUT5 activity and mRNA abundance, but high-d-fructose diets enhanced GLUT5 activity and mRNA expression in both unirradiated and irradiated mice. In conclusion, the effect of radiation may be posttranscriptional, and radiation-damaged intestines can still respond to dietary stimuli.

Elevated blood lead concentrations and vitamin D deficiency in winter and summer in young urban children.

BACKGROUND: It is widely recognized that blood lead concentrations are higher in the summer than in winter. Although the effects of some environmental factors such as lead in dust on this phenomenon have been studied, relationships to sunlight-induced vitamin D synthesis have not been adequately investigated. Vitamin D status is influenced by the diet, sunlight exposure, age, skin pigmentation, and other factors, and may modify gastrointestinal lead absorption or release of lead stored in bones into the bloodstream. OBJECTIVE AND METHODS: We collected paired blood samples from 142 young, urban African-American and Hispanic children in the winter and summer to study the seasonal increase in blood lead and its relationships to vitamin D nutrition, age, and race. RESULTS: A winter/summer (W/S) increase in blood lead concentrations of 32.4% was found for children 1-3 years of age. There was a smaller W/S increase of 13.0% in children 4-8 years of age. None of the 51 Hispanic children had an elevated blood lead concentration (> or = 10 microg/dL) during the winter, and only one had an elevated summertime concentration. In contrast, elevated blood lead concentrations were frequent in the 91 African-American children, especially those 1-3 years of age. For the latter, the percentage with elevated blood lead levels increased from 12.2% in winter to 22.5% in summer. A 1.2% W/S increase in serum 25-hydroxy-vitamin D (serum 25-OH-D) concentrations was found for children 1-3 years of age. However, in children 4-8 years of age the W/S increase in serum 25-OH-D was much larger-33.6%. The percentages of children with low (< 16 microg/L) serum 25-OH-D concentrations were 12.0% in winter and 0.7% in summer and were consistently greater in African-American than in Hispanic children. The seasonal increases in blood lead and serum 25-OH-D in children 4-8 years of age were significantly associated. CONCLUSION: The higher summertime serum 25-OH-D concentrations for the 4- to 8-year-old children are likely caused by increased sunlight-induced vitamin D synthesis and may contribute to the seasonal increase in blood lead. Age and race are key factors that affect blood lead and vitamin D nutrition, as well as their interactions, in young urban children.

Vitamins A, C, and E May Reduce Intestinal 210Po Levels after Ingestion.

Damage to the gut mucosa is a probable contributory cause of death from ingested Po. Therefore, medical products are needed that can prevent, mitigate, and/or repair gastrointestinal (GI) damage caused by high-LET radiation emitted by Po. The present studies investigated the capacity of a diet highly enriched with vitamins A, C, and E (vitamin ACE) to protect against intestinal mucosal damage indicated by functional reductions in nutrient transport caused by orally ingested Po. Mice were gavaged with 0 or 18.5 kBq Po-citrate and fed a control or vitamin ACE-enriched diet (the latter beginning either 96 h before or immediately after gavage). Mouse intestines significantly retained Po on day 8 post-gavage. The concentration of Po in intestinal tissues was significantly (p<0.05) lower in all vitamin ACE groups compared to control. There were borderline significant Po-induced reductions in intestinal absorption of D-fructose. The combination of vitamins A, C, and E may reduce Po incorporation in the intestines when given before, or enhance decorporation when provided after, Po gavage.

Case of elevated blood lead in a South Asian family that has used Sindoor for food coloring.

After a routine blood testing, a local pediatrician discovered that a 13-month-old boy had an elevated blood lead level (BLL) of 57 microg/dL. Since the baby was mostly breast-fed, the pediatrician did a blood test on the mother, and the result showed a BLL of 85 microg/dL. As the mother denied any history of pica behavior, the pediatrician suspected a source of lead to which the entire family might have been exposed and tested the father's BLL. The results showed a BLL of 95 microg/dL, and the pediatrician informed the poison center. The subsequent epidemiological investigation revealed that the parents had used a product called Sindoor for food coloring. Laboratory analyses showed that the product contains more than 57.8% of acid-extractable lead by weight. Given the extremely high content of Pb in this product, Sindoor poses a serious risk of lead poisoning if it is used for food coloring.

High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation.

We examined nutrient transport in the intestines of mice exposed to chronic low-LET 137Cs gamma rays. The mice were whole-body irradiated for 3 days at dose rates of 0, 0.13 and 0.20 Gy/h, for total dose delivery of 0, 9.6 or 14.4 Gy, respectively. The mice were fed either a control diet or a diet supplemented with high levels of vitamins A, C and E. Our results showed that nutrient transport was perturbed by the chronic irradiation conditions. However, no apparent alteration of the macroscopic intestinal structures of the small intestine were observed up to day 10 after initiating irradiation. Jejunal fructose uptake measured in vitro was strongly affected by the chronic irradiation, whereas uptake of proline, carnosine and the bile acid taurocholate in the ileum was less affected. D-glucose transport did not appear to be inhibited significantly by either 9.6 or 14.4 Gy exposure. In the 14.4 Gy irradiated groups, the diet supplemented with high levels of vitamins A, C and E increased intestinal transport of fructose compared to the control diet (day 10; t test, P = 0.032), which correlated with elevated levels of vitamins A, C and E in the plasma and jejunal enterocytes. Our earlier studies with mice exposed acutely to 137Cs gamma rays demonstrated significant protection for transport of fructose, glucose, proline and carnosine. Taken together, these results suggest that high levels of vitamins A, C and E dietary supplements help preserve intestinal nutrient transport when intestines are irradiated chronically or acutely with low-LET gamma rays.

Blood lead concentrations and pregnancy outcomes.

In this study, the authors related blood lead concentrations to Apgar scores, birth weight, gestational age, small-for-gestational age, and hypertension in pregnancy (HIP)/toxemia. Data and blood were collected 4 times during pregnancy from 705 women, aged 12-34 yr. Blood lead concentrations, measured by atomic absorption spectrophotometry, were related to reproductive outcomes, abstracted from medical records. Average blood lead concentrations were 1.2 microgram/dl (standard error = +/- 0.03). Maternal blood lead concentrations were related significantly to HIP/toxemia--before and after adjusting for age, calcium intake, and race/ethnicity (p < .03). Longitudinal regression analyses revealed that blood lead concentrations in women with HIP/toxemia changed by 0.02 microgram/dl for every 0.01 microgram/dl change in women without HIP/toxemia. Maternal blood lead concentration and its change were not significantly associated with other reproductive outcomes. Low levels of maternal blood lead concentrations were significantly associated with HIP/toxemia.

The effects of local vanadium treatment on angiogenesis and chondrogenesis during fracture healing.

This study quantified the effects of local intramedullary delivery of an organic vanadium salt, which may act as an insulin-mimetic on fracture healing. Using a BB Wistar rat femoral fracture model, local vanadyl acetylacetonate (VAC) was delivered to the fracture site and histomorphometry, mechanical testing, and immunohistochemistry were performed. Callus percent cartilage was 200% higher at day 7 (p < 0.05) and 88% higher at day 10 (p < 0.05) in the animals treated with 1.5 mg/kg of VAC. Callus percent mineralized tissue was 37% higher at day 14 (p < 0.05) and 31% higher at day 21 (p < 0.05) in the animals treated with 1.5 mg/kg of VAC. Maximum torque to failure was 104% and 154% higher at 4 weeks post-fracture (p < 0.05) for the healing femurs from the VAC-treated (1.5 and 3.0 mg/kg) animals. Animals treated with other VAC doses demonstrated increased mechanical parameters at 4 weeks (p < 0.05). Immunohistochemistry detected 62% more proliferating cells at days 7 (p < 0.05) and 94% more at day 10 (p < 0.05) in the animals treated with 1.5 mg/kg VAC. Results showed 100% more vascular endothelial growth factor-C (VEGF-C) positive cells and 80% more blood vessels at day 7 (p < 0.05) within the callus subperiosteal region of VAC-treated animals (1.5 mg/kg) compared to controls. The results suggest that local VAC treatment affects chondrogenesis and angiogenesis within the first 7-10 days post-fracture, which leads to enhanced mineralized tissue formation and accelerated fracture repair as early as 3-4 weeks post-fracture.

Marked changes in endogenous antioxidant expression precede vitamin A-, C-, and E-protectable, radiation-induced reductions in small intestinal nutrient transport.

Rapidly proliferating epithelial crypt cells of the small intestine are susceptible to radiation-induced oxidative stress, yet there is a dearth of data linking this stress to expression of antioxidant enzymes and to alterations in intestinal nutrient absorption. We previously showed that 5-14 days after acute γ-irradiation, intestinal sugar absorption decreased without change in antioxidant enzyme expression. In the present study, we measured antioxidant mRNA and protein expression in mouse intestines taken at early times postirradiation. Observed changes in antioxidant expression are characterized by a rapid decrease within 1h postirradiation, followed by dramatic upregulation within 4h and then downregulation a few days later. The cell type and location expressing the greatest changes in levels of the oxidative stress marker 4HNE and of antioxidant enzymes are, respectively, epithelial cells responsible for nutrient absorption and the crypt region comprising mainly undifferentiated cells. Consumption of a cocktail of antioxidant vitamins A, C, and E, before irradiation, prevents reductions in transport of intestinal sugars, amino acids, bile acids, and peptides. Ingestion of antioxidants may blunt radiation-induced decreases in nutrient transport, perhaps by reducing acute oxidative stress in crypt cells, thereby allowing the small intestine to retain its absorptive function when those cells migrate to the villus days after the insult.

Control of Alzheimer's amyloid beta toxicity by the high molecular weight immunophilin FKBP52 and copper homeostasis in Drosophila.

FK506 binding proteins (FKBPs), also called immunophilins, are prolyl-isomerases (PPIases) that participate in a wide variety of cellular functions including hormone signaling and protein folding. Recent studies indicate that proteins that contain PPIase activity can also alter the processing of Alzheimer's Amyloid Precursor Protein (APP). Originally identified in hematopoietic cells, FKBP52 is much more abundantly expressed in neurons, including the hippocampus, frontal cortex, and basal ganglia. Given the fact that the high molecular weight immunophilin FKBP52 is highly expressed in CNS regions susceptible to Alzheimer's, we investigated its role in Abeta toxicity. Towards this goal, we generated Abeta transgenic Drosophila that harbor gain of function or loss of function mutations of FKBP52. FKBP52 overexpression reduced the toxicity of Abeta and increased lifespan in Abeta flies, whereas loss of function of FKBP52 exacerbated these Abeta phenotypes. Interestingly, the Abeta pathology was enhanced by mutations in the copper transporters Atox1, which interacts with FKBP52, and Ctr1A and was suppressed in FKBP52 mutant flies raised on a copper chelator diet. Using mammalian cultures, we show that FKBP52 (-/-) cells have increased intracellular copper and higher levels of Abeta. This effect is reversed by reconstitution of FKBP52. Finally, we also found that FKBP52 formed stable complexes with APP through its FK506 interacting domain. Taken together, these studies identify a novel role for FKBP52 in modulating toxicity of Abeta peptides.

Bone mineral density and content during weight cycling in female rats: effects of dietary amylase-resistant starch.

BACKGROUND: Although there is considerable evidence for a loss of bone mass with weight loss, the few human studies on the relationship between weight cycling and bone mass or density have differing results. Further, very few studies assessed the role of dietary composition on bone mass during weight cycling. The primary objective of this study was to determine if a diet high in amylase-resistant starch (RS2), which has been shown to increase absorption and balance of dietary minerals, can prevent or reduce loss of bone mass during weight cycling. METHODS: Female Sprague-Dawley (SD) rats (n = 84, age = 20 weeks) were randomly assigned to one of 6 treatment groups with 14 rats per group using a 2 x 3 experimental design with 2 diets and 3 weight cycling protocols. Rats were fed calcium-deficient diets without RS2 (controls) or diets high in RS2 (18% by weight) throughout the 21-week study. The weight cycling protocols were weight maintenance/gain with no weight cycling, 1 round of weight cycling, or 2 rounds of weight cycling. After the rats were euthanized bone mineral density (BMD) and bone mineral content (BMC) of femur were measured by dual energy X-ray absorptiometry, and concentrations of calcium, copper, iron, magnesium, manganese, and zinc in femur and lumbar vertebrae were determined by atomic absorption spectrophotometry. RESULTS: Rats undergoing weight cycling had lower femur BMC (p < 0.05) and marginally lower BMD (p = 0.09) than rats not undergoing weight cycling. In comparison to controls, rats fed RS2 had higher femur BMD (p < 0.01) and BMC (p < 0.05), as well as higher values for BMD and BMC measured at the distal end (p < 0.001 and p < 0.01) and femoral neck (p < 0.01 and p < 0.05). Consistent with these findings, RS2-fed rats also had higher femur calcium (p < 0.05) and magnesium (p < 0.0001) concentrations. They also had higher lumbar vertebrae calcium (p < 0.05) and magnesium (p < 0.05) concentrations. CONCLUSION: Weight cycling reduces bone mass. A diet high in RS2 can minimize loss of bone mass during weight cycling and may increase bone mass in the absence of weight cycling.

Renal and gastrointestinal potassium excretion in humans: new insight based on new data and review and analysis of published studies.

OBJECTIVES: Little is known about the relationship between the renal and gastrointestinal excretion of potassium in humans. This information is important in light of strong associations of potassium intake with hypertension and occlusive stroke. METHODS: We determined the relationship between fecal and urinary excretion of potassium under both fixed and variable potassium intakes using our unpublished archival data and published data of others. Twenty-five subjects were evaluated. RESULTS: On a fixed, low oral potassium intake (61.2 +/- 4.7 mmol/day; mean +/- SD), there was an inverse relationship between fecal and urinary potassium excretion (r = -0.66, p = 0.040). In studies in which potassium intake varied between 61-135 mmol/day, fecal and urinary potassium excretions were positively correlated (r = 0.58, p = 0.024). Considerable within-and-between-subject variation was observed in the relationship between fecal and urinary potassium excretion. CONCLUSIONS: Inter-individual variation in fecal potassium excretion may arise from both variation in dietary potassium intake and intrinsic individual differences in the renal versus gastrointestinal handling of potassium.

Tissue lead concentration during chronic exposure of Pimephales promelas (fathead minnow) to lead nitrate in aquarium water.

The fathead minnow is a useful species for evaluating the toxicity of wastewater effluents. While this fish is widely used for "survival" studies of metal toxicity, little or no work has been done on the tissue distribution of metals in fathead minnows. To determine the distribution of tissue lead, aquarium studies were conducted for several weeks with fish maintained in soft synthetic freshwater. Lead- (II) nitrate was added to three aquaria attaining concentrations of 20-30 ppb (aquarium B), 100-140 ppb (aquarium C), and roughly 200 ppb (aquarium D). Results were compared to controls (aquarium A). During the initial week, the majority of aquarium D fish died, whereas few deaths occurred in the other groups. Lead accumulation was dose- and tissue-dependent, with highest uptake by the gills. Gill concentrations of aquarium D fish averaged about 4-fold higherthan in skeleton or skin and muscle. In vitro, lead (2.5-25 ppm) caused dose-dependent reductions in the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) in gills incubated in physiological buffer. These findings demonstrate that fathead minnow gills bind and accumulate waterborne lead rapidly and preferentially and raise the possibility that gill lipid peroxidation contributes to lead toxicity at low water hardness.

Lead in breast milk and maternal bone turnover.

OBJECTIVE: Our purpose was to determine whether breast milk lead (Pb) levels are correlated with maternal blood Pb levels, bone loss, or bone turnover during reproduction. STUDY DESIGN: Data were collected prospectively at 0, 1.5, 3, 6, and 12 months after delivery in 15 lactating and 30 bottle-feeding women. Variables included breast milk Pb (inductively coupled mass spectrometry), maternal blood Pb (atomic absorption spectrophotometry), osteocalcin (radioimmunoassay), and bone mineral density change (dual-energy x-ray absorptiometry). RESULTS: Mean Pb breast milk concentrations were 6.1, 5.6, 5.9, and 4.3 ng/mL at the 1.5, 3, 6, and 12 months post partum, whereas mean maternal blood Pb concentrations were 1.4, 1.6, 1.7, and 1.4 microg/dL at 0, 3, 6, and 12 months post partum. The 5.6% bone loss and significant bone turnover were related to breast milk Pb levels but not to postpartum maternal blood Pb levels. Maternal and breast milk Pb values were modestly correlated at 1 to 2 months. CONCLUSIONS: Bone loss and bone turnover were related to breast milk Pb levels. In these women, there was no evidence that either high maternal blood or breast milk Pb concentrations are a major public health concern.

Lead exposure potentiates predatory attack behavior in the cat.

Epidemiologic studies have demonstrated that environmental lead exposure is associated with aggressive behavior in children; however, numerous confounding variables limit the ability of these studies to establish a causal relationship. The study of aggressive behavior using a validated animal model was used to test the hypothesis that there is a causal relationship between lead exposure and aggression in the absence of confounding variables. We studied the effects of lead exposure on a feline model of aggression: predatory (quiet biting) attack of an anesthetized rat. Five cats were stimulated with a precisely controlled electrical current via electrodes inserted into the lateral hypothalamus. The response measure was the predatory attack threshold current (i.e., the current required to elicit an attack response on 50% of the trials). Blocks of trials were administered in which predatory attack threshold currents were measured three times a week for a total of 6-10 weeks, including before, during, and after lead exposure. Lead was incorporated into cat food "treats" at doses of 50-150 mg/kg/day. Two of the five cats received a second period of lead exposure. Blood lead concentrations were measured twice a week and were <1, 21-77, and <20 micro g/dL prior to, during, and after lead exposure, respectively. The predatory attack threshold decreased significantly during initial lead exposure in three of five cats and increased after the cessation of lead exposure in four of the five cats (P<0.01). The predatory attack thresholds and blood lead concentrations for each cat were inversely correlated (r=-0.35 to -0.74). A random-effects mixed model demonstrated a significant (P=0.0019) negative association between threshold current and blood lead concentration. The data of this study demonstrate that lead exposure enhances predatory aggression in the cat and provide experimental support for a causal relationship between lead exposure and aggressive behavior in humans.