Neuroprotective effects of vitamin C and garlic on glycoconjugates changes of cerebellar cortex in lead-exposed rat offspring.

The deteriorating effects of Lead (Pb) on central nervous system (CNS) such as cerebellum has been demonstrated in previous studies. Glycoconjugates with the important role in CNS development may be affected by Pb-exposure. Utilization of antioxidant agents and herbal plants has attracted a great deal of attention on attenuating neurotoxicants-induced damage. Thus, in this study the neuroprotective effects of vitamin C and garlic on content of glycoconjugates of cerebellar cortex in Pb-exposed animals were investigated. Wistar pregnant rats were divided into: control (C), Pb-exposed (Pb) (1500 ppm lead acetate in drinking water), Pb plus vitamin C (Pb + Vit C) (500 mg/kg) intraperitoneally, Pb plus garlic (Pb + G) (1 mL /100 g body weight fresh garlic juice via gavage), Pb plus vitamin C and garlic (Pb + Vit C + G), and sham groups (Sh). Finally, levels of Pb in blood were measured in both rats and offspring on postnatal day 50 (PND50). Also, the cerebellums were removed for measuring Pb-levels and performing lectin histochemistry. Blood and cerebellar Pb-levels were increased in Pb-exposed group compared to control group (P < 0.001), whereas they were decreased significantly in Pb + Vit C, Pb + G, and Pb + Vit C + G groups (P < 0.01). By using MPA, UEA-1, and WGA lectin histochemistry, Pb-exposed group showed weak staining intensity compared to other groups. Besides, significant decrease was observed in the density of lectin-positive neurons of Pb-exposed group compared to the control group (P < 0.001). Moreover, strong staining intensity and high lectin-positive neurons were found in Pb + Vit C, Pb + G and Pb + Vit C + G groups than Pb-exposed group (P < 0.001). The present study revealed that Pb-exposure can result in alteration in the cerebellar glycoconjugates contents and co-administration of vitamin C and garlic could attenuate the adverse effects of Pb. The findings of this study revealed the ameliorating effects of vitamin C and garlic against Pb, suggesting the potential use of vitamin C and garlic as preventive agents in Pb poisoning.

Fetal exposure to mercury and lead from intrauterine blood transfusions.

BACKGROUND: Mercury (Hg) and lead (Pb) exposure during childhood is associated with irreversible neurodevelopmental effects. Fetal exposure to Hg and Pb from intrauterine blood transfusion (IUBT) has not been reported. METHODS: Fetal exposure was estimated based on transfusion volume and metal concentration in donor packed red blood cell (PRBCs). As biomarkers to quantify prenatal exposure are unknown, Hg and Pb in donor PRBCs were compared to estimated intravenous (IV) RfDs based on gastrointestinal absorption. RESULTS: Three pregnant women received 8 single-donor IUBTs with volumes ranging from 19 to 120 mL/kg. Hg and Pb were present in all donor PRBC units. In all, 1/8 IUBT resulted in Hg dose five times higher than the estimated IV RfD. Median Pb dose in one fetus who received 5 single-donor IUBTs between 20-32 weeks gestation was 3.4 µg/kg (range 0.5-7.9 µg/kg). One donor unit contained 12.9 µg/dL of Pb, resulting in a fetal dose of 7.9 µg/kg, 40 times higher than the estimated IV RfD at 20 weeks gestation. CONCLUSION: This is the first study documenting inadvertent exposure to Hg and Pb from IUBT and quantifying the magnitude of exposure. Screening of donor blood is warranted to prevent toxic effects from Hg and Pb to the developing fetus.

From the Cover: 7,8-Dihydroxyflavone Rescues Lead-Induced Impairment of Vesicular Release: A Novel Therapeutic Approach for Lead Intoxicated Children.

Childhood lead (Pb2+) intoxication is a public health problem of global proportion. Lead exposure during development produces multiple effects on the central nervous system including impaired synapse formation, altered synaptic plasticity, and learning deficits. In primary hippocampal neurons in culture and hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF) signaling. The objective of this study was to determine if activation of TrkB, the cognate receptor for BDNF, would rescue Pb2+-induced impairments of vesicular release. Rats were chronically exposed to Pb2+ prenatally and postnatally until 50 days of age. This chronic Pb2+ exposure paradigm enhanced paired-pulse facilitation of synaptic potentials in Schaffer collateral-CA1 synapses in the hippocampus, a phenomenon indicative of reduced vesicular release probability. Decreased vesicular release probability was confirmed by both mean-variance analysis and direct 2-photon imaging of vesicular release from hippocampal slices of rats exposed to Pb2+in vivo. We also found a Pb2+-induced impairment of calcium influx in Schaffer collateral-CA1 synaptic terminals. Intraperitoneal injections of Pb2+ rats with the TrkB receptor agonist 7,8-dihydroxyflavone (5 mg/kg) for 14-15 days starting at postnatal day 35, reversed all Pb2+-induced impairments of presynaptic transmitter release at Schaffer collateral-CA1 synapses. This study demonstrates for the first time that in vivo pharmacological activation of TrkB receptors by small molecules such as 7,8-dihydroxyflavone can reverse long-term effects of chronic Pb2+ exposure on presynaptic terminals, pointing to TrkB receptor activation as a promising therapeutic intervention in Pb2+-intoxicated children.

Engaging the for-profit sector in community-based participatory research: lessons from the ground.

BACKGROUND: Principles of community engagement articulated by leading governmental public health and research organizations are widely accepted. Academics seeking to partner effectively with communities have a variety of guidelines to access, and resources to assist community-based organizations (CBOs) exist. However, experiences related to inclusion of nontraditional partners from the for-profit private industry sector, utilizing participatory approaches, are not documented. OBJECTIVES: This paper describes the perspective of community and academic participants on partnership development with a for-profit environmental engineering firm. Challenges related to building a transdisciplinary, crosssector partnership are highlighted. METHODS: Results are reported using the National Institute for Environmental Health Sciences Partnerships for Environmental Public Health (PEPH) evaluation manual. Five activities pursued in early phases of research are described. CONCLUSIONS: Community members and scholars recognize that complex public health problems warrant transdisciplinary and cross-sector effort. Efforts to build CBPR partnerships with for-profit industry may benefit from a stepwise approach.

Unknown risk: co-exposure to lead and other heavy metals among children living in small-scale mining communities in Zamfara State, Nigeria.

The lead poisoning crisis in Zamfara State, Northern Nigeria has been called the worst such case in modern history and it presents unique challenges for risk assessment and management of co-exposure to multiple heavy metals. More than 400 children have died in Zamfara as a result of ongoing lead intoxication since early in 2010. A review of the common toxic endpoints of the major heavy metals advances analysis of co-exposures and their common pathologies. Environmental contamination in Bagega village, examined by X-ray fluorescence of soils, includes lead, mercury, cadmium, arsenic and manganese. Co-exposure risk is explored by scoring common toxic endpoints and hazard indices to calculate a common pathology hazard risk ranking of Pb > As > Hg >> Cd > Mn. Zamfara presents an extreme picture of both lead and multiple heavy metal mortality and morbidity, but similar situations have become increasingly prevalent worldwide.

Primary prevention of pediatric lead exposure requires new approaches to transfusion screening.

OBJECTIVE: To facilitate further assessment of transfusion-associated lead exposure by designing a procedure to test packed red blood cells (pRBCs) prepared for transfusion. STUDY DESIGN: The relationship between pRBCs and whole blood lead concentration was investigated in 27 samples using a modified clinical assay. Lead concentrations were measured in 100 pRBC units. RESULTS: Our sample preparation method demonstrated a correlation between whole blood lead and pRBC lead concentrations (R(2) = 0.82). In addition, all 100 pRBC units tested had detectable lead levels. The median pRBC lead concentration was 0.8 µg/dL, with an SD of 0.8 µg/dL and a range of 0.2-4.1 µg/dL. In addition, after only a few days of storage, approximately 25% of whole blood lead was found in the supernatant plasma. CONCLUSION: Transfusion of pRBCs is a source of lead exposure. Here we report the quantification of lead concentration in pRBCs. We found a >20-fold range of lead concentrations in the samples tested. Pretransfusion testing of pRBC units according to our proposed approach or donor screening of whole blood lead and selection of below-average units for transfusion to children would diminish an easily overlooked source of pediatric lead exposure.

Environmental lead exposure and otoacoustic emissions in Andean children.

Studies relating sensory hearing impairment to lead (Pb) exposure in children have presented inconsistent results. The objective of this study was to measure distortion product otoacoustic emissions (DPOAE), sounds emanating from the outer hair cells of the inner ear, in Pb-exposed children to determine the effects of Pb poisoning on the inner ear. DPOAE were recorded for 9 f(2) frequencies from 1187 to 7625 Hz on 102 ears of 53 Pb-exposed children (aged 6-16 yr) residing in Pb-contaminated environments in the Andes Mountains of Ecuador where Pb glazing of ceramics is the primary livelihood. Blood lead (PbB) levels ranged from 4.2 to 94.3 µg/dl (mean: 37.7; SD: 25.7; median: 36.4). The median PbB level was markedly higher than the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) 10-µg/dl action level. Spearman rho correlation analyses of the relation between PbB level and DPOAE amplitude and between PbB level and DPOAE signal-to-noise ratio revealed no significant associations at any of the f(2) frequencies tested. In addition, no significant correlation (Spearman rho) between PbB level and hearing sensitivity for 6 pure-tone test frequencies from 1000 to 8000 Hz was found. Although the study group was found to have abnormally elevated PbB levels, in contrast to some earlier reports, the results of the current study showed no consistent Pb-induced sensory effects on the cochlea of Pb-intoxicated children.

An academic-community outreach partnership: building relationships and capacity to address childhood lead poisoning.

BACKGROUND: Although academic institutions are rich resources for improving public health, academic partnerships with community organizations can be challenging. We describe a successful academic-community partnership composed of the Dartmouth Toxic Metals Research Program, the Manchester (New Hampshire) Health Department, and the Greater Manchester Partners Against Lead Poisoning (GMPALP). OBJECTIVE: Partners collaborated to translate science and best practices into social action and policy change to address childhood lead poisoning. METHODS: Using the evolution of a childhood lead poisoning prevention initiative, we discuss how an academic-community relationship can be created and sustained. LESSONS LEARNED: Our experience demonstrates that broad-based partnerships are enhanced by the attributes of community-based participatory research (CBPR). We observe that engaging in community collaborations that are not driven by research eliminates potential conflicts for academic and community partners. CONCLUSION: We identify four core values, namely, (1) adaptability, (2) consistency, (3) shared authority, and (4) trust, as being constructive when working in such partnerships.

Higher infant blood lead levels with longer duration of breastfeeding.

OBJECTIVE: To determine whether longer breastfeeding is associated with higher infant lead concentrations. STUDY DESIGN: Data were analyzed from 3 studies of developmental effects of iron deficiency in infancy: Costa Rica (1981-1984), Chile (1991-1996), and Detroit (2002-2003). The relation between duration of breastfeeding and lead levels was assessed with Pearson product-moment or partial correlation coefficients. RESULTS: More than 93% of the Costa Rica and Chile samples was breastfed (179 and 323 breastfed infants, respectively; mean weaning age, 8-10 months), as was 35.6% of the Detroit sample (53 breastfed infants; mean weaning age, 4.5 months). Lead concentrations averaged 10.8 microg/dL (Costa Rica, 12-23 months), 7.8 microg/dL (Chile, 12 months), and 2.5 microg/dL (Detroit, 9-10 months). Duration of breastfeeding as sole milk source and total breastfeeding correlated with lead concentration in all samples (r values = 0.14-0.57; P values = .06-<.0001). CONCLUSIONS: Longer breastfeeding was associated with higher infant lead concentration in 3 countries, in 3 different decades, in settings differing in breastfeeding patterns, environmental lead sources, and infant lead levels. The results suggest that monitoring lead concentrations in breastfed infants be considered.

The politics of lead toxicology and the devastating consequences for children.

At virtually every step in the history of the uncovering of lead's toxic qualities, resistance was shown by a variety of industrial interests to the association of lead and toxicity. During the first half of the last century, three primary means were used to undermine the growing body of evidence: first, the lead industry sought to control lead research by sponsoring and funding university research. In the 1920s, the General Motors Company, with the aide of DuPont and Standard Oil Companies, established the Kettering Labs, a research unit at the University of Cincinnati which, for many decades was largely supported by industry funds. In the same decade, the lead industry sponsored the research of Joseph Aub at Harvard who worked on neurophysiology of lead. A second way was to shape our understanding of lead itself, portraying it as an indispensable and healthful element essential for all modern life. Lead was portrayed as safe for children to use, be around, and even touch. The third way that lead was exempted from the normal public health measures and regulatory apparatus that had largely controlled phosphorus poisoning, poor quality food and meats and other potential public health hazards was more insidious and involved directly influencing the scientific integrity of the clinical observations and research. Throughout the past century tremendous pressure by the lead industry itself was brought to bear to quiet, even intimidate, researchers and clinicians who reported on or identified lead as a hazard. This article will draw on our previous work and add new documentation of the trajectory of industry attempts to keep out of the public view the tremendous threat of lead poisoning to children.

The status of childhood lead poisoning and prevention in Nevada, USA.

One of the first steps in addressing the problem of childhood lead poisoning is to identify the possible sources of exposure in specific communities and target high-risk populations with appropriate interventions. Due to several factors, such as lack of funding and lack of blood lead reporting, little information exists regarding the occurrence of childhood lead poisoning and the prevalence of potential exposure sources in the state of Nevada. Following the recent establishment of a Nevada-based Lead Poisoning Program, we compiled the most current information available on Nevadans, and use this knowledge to suggest future research objectives and outreach activities for the state. Accordingly, we identify the characteristics of the vulnerable Nevada populations, explore possible sources of lead exposure unique to Nevada, and summarize the existing data on childhood lead poisoning. Emerging data indicates that Nevada is an area of rapid population growth, characterized by increasing immigration from Latin America, increasing numbers of children from low-income families with no health insurance. Also, childhood lead poisoning may arise from exposure to non-paint sources of lead. After presenting the Nevada statistics, we propose and recommend a set of research and outreach strategies that best suit the needs of Nevada residents.

Identifying housing that poisons: a critical step in eliminating childhood lead poisoning.

The purpose of our study was to develop a method to identify and prioritize "high-risk" buildings in Chicago that could be targeted for childhood lead poisoning prevention activities. We defined "high-risk" buildings as those where multiple children younger than 6 years with elevated blood lead levels (BLLs) had lived and where lead hazards were previously identified on environmental inspection. By linking 1997-2003 Chicago elevated blood lead surveillance, environmental inspection, and building footprint data, we found that 49,362 children younger than 6 years with elevated BLLs lived at 30,742 buildings. Of those, 67 were "high-risk" buildings and these were associated with 994 children with elevated BLLs. On average, 15 children with elevated BLLs had lived in each building (range: 10-53, median: 13). Almost two thirds (n = 43) of the high-risk buildings had two or more referrals for inspection to the same apartment or housing unit; of those, 40 percent (n = 17) failed to maintain lead-safe status after compliance. Linking blood lead surveillance, environmental inspection, and building footprint databases allowed us to identify individual high-risk buildings. This approach prioritizes lead hazard control efforts and may help health, housing, and environmental agencies in targeting limited resources to increase lead-safe housing for children.

Dorchester Lead-Safe Yard project: a pilot program to demonstrate low-cost, on-site techniques to reduce exposure to lead-contaminated soil.

Despite a general reduction in blood lead levels in children after lead was banned in gasoline and paint, lead poisoning remains an important health problem in many older urban areas. One factor that increases risk in these places is the high levels of lead in certain residential areas. A major intervention study found that reducing lead levels in urban soils results in a reduction in exposed children's blood lead levels. Removing lead from inner-city soils or reducing exposures to lead-contaminated soils typically is expensive, technologically challenging, or beyond the ability of low-income households to undertake. This project, in conjunction with residents and community-based institutions, developed a series of in situ, low-cost, low-technology measures that worked to reduce the exposure to lead-contaminated soils in one Boston, Massachusetts, neighborhood. The project demonstrated several important results. Government, universities, residents, and community based organizations can work together effectively to reduce exposures to lead in soil. Lead-contaminated soil can be mitigated at a fraction of the cost of conventional methods in ways that increase the ability of residents, community health centers, and others to have a positive impact on their neighborhoods. A lead-safe yard program can be replicated and institutionalized by municipal home de-leading programs and other community organizations.

Combining datasets to predict the effects of regulation of environmental lead exposure in housing stock.

A model for children's blood lead concentrations as a function of environmental lead exposures was developed by combining two nationally representative sources of data that characterize the marginal distributions of blood lead and environmental lead with a third regional dataset that contains joint measures of blood lead and environmental lead. The complicating factor addressed in this article was the fact that methods for assessing environmental lead were different in the national and regional datasets. Relying on an assumption of transportability (that although the marginal distributions of blood lead and environmental lead may be different between the regional dataset and the nation as a whole, the joint relationship between blood lead and environmental lead is the same), the model makes use of a latent variable approach to estimate the joint distribution of blood lead and environmental lead nationwide.