Prediction of response of blood lead to airborne and dietary lead from volunteer experiments with lead isotopes

To predict the response of blood lead to airborne and dietary lead requires knowledge of the rate of uptake of lead into the body from lung and gut, its subsequent partitioning between compartments, the stay time in those compartments, and its redistribution or excretion. Tracer studies with volunteers have shown no differences in systemic distribution of inorganic lead between tissues whether it is taken by inhalation, ingestion or injection. Lead is rapidly transferred from plasma to red cells, and there is slower movement thence into liver and other soft tissues, to bone, and to excreta. Work at Harwell and elsewhere with 203Pb has shown that the initial rapid distribution leaves rather over half the assimilated lead attached to red cells. The result is remarkably consistent, and applies also to dogs and baboons. The renal clearance (Vu) (ratio of U to CB, or daily urinary output expressed as mass of blood having the same lead content), and also the endogenous faecal clearance excretion rate (Vf), have been measured on human subjects with 203Pb. The results are consistent with Vu, as measured with stable lead, with many results giving Vu about 0.1 kg d-1. However, there is evidence that Vu increases when CB is elevated above the normal. This may explain the nonlinear relation between uptake of lead and the corresponding CB, which has been observed in humans exposed to environmental lead. Vf is about half Vu, and a similar result applies to calcium. The clearance rate Va of 203Pb from blood to bone has been measured, and a variety of human and animal data in the literature has been reviewed to support this result. Combined with bone turnover rates (from data on 90Sr), the postulated inputs to bone give estimates of skeletal burdens which agree with post-mortem results. The results are combined in a compartment model. The retention of lead aerosol in the lung, and uptake from the gut are then considered, with use made of radioactive tracer (203Pb), stable isotopic tracer (204Pb) and total lead measurements. Here there is great diversity of results. Particle size affects the fractional lung retention and the site of retention, which in turn affects the fractional uptake to blood. Presence or absence of food in the stomach when lead is ingested greatly affects the fractional gut uptake. Finally, a limited selection of results of volunteer exposures to stable lead in air or diet are reviewed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Learning to lead

A successful research career requires not only an aptitude for science but also the mastering of other skills including communication, management, and grant writing. A growing number of programs at universities and research institutes aim to teach these crucial skills to graduate students, postdoctoral fellows, and junior faculty.     

Nutrition of lead

At the levels to which human beings are exposed in the workplace as well as in the general environment, lead has been shown to be a toxic element in most of its chemical forms, whether it is inhaled or ingested in water or food. The four main sources of contamination of food are soil, industrial pollution, agricultural technology and food processing. Reasonable quantities of the metal can be stored by humans in a relatively inert form in bone; lead has an affinity for bone and acts by replacing calcium. Gastrointestinal lead absorption and retention, the major pathway of lead intake, has been shown to vary widely depending on the chemical environment of the gastrointestinal lumen, age and iron stores (nutritional status of the subject). Studies in animals have shown that certain substances bind lead and increase its solubility, thus enhancing its absorption. These dietary components consist of sodium citrate, ascorbate, amino acids, vitamin D, protein and fat, and lactose. Data suggest a three-compartmental pool for lead metabolism: (1) blood; (2) soft tissue (hair, nails, sweat, salivary, gastric, pancreatic and biliary secretions); and (3) skeleton. Lead absorption occurs primarily in the duodenum where lead enters the epithelial mucosal cells. The total bodily amount of lead does not affect lead absorption; lead does not have a feedback mechanism which limits absorption. In the adult rat, lead absorption from the intestinal lumen appears to proceed by both active transport and passive diffusion. Bile is an important route of excretion in the gut.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influences of thiamin on lead intoxication,lead deposition in tissues and lead hematological responses of Tilapia zillii

1. Lead levels in the blood, kidney, liver, brain and muscle of fish receiving only lead were elevated markedly over the values of both controls and thiamin-treated fish.2. No statistical difference was observed between the lead levels in bone samples of both fish receiving only lead and thiamin-treated fish.3. In contrast to the fish receiving only lead the fish treated with thiamin appeared to be healthy and had no lead poisoning signs.4. Over the period of study, hemoglobin content and red blood cell counts of fish receiving only lead showed significant decreases from the values of both controls and fish treated with thiamin.5. Hematocrit values and white blood cell counts were uninfluenced by either lead exposure or thiamin treatment at all intervals.6. The data suggest that thiamin can serve as a promising natural chelator to prevent fish mortality, not only in short term, but also in prolonged exposure.     

Metabolic interactions between lead and copper in rats ingesting lead acetate

The effects of Pb ingestion with and without concurrent dietary Cu supplementation were determined on parameters associated with Cu deficiency in rats fed a nutritionally adequate diet. Groups of weanling male Sprague-Dawley rats were fed a purified (AIN-′76) diet and given Pb (0 or 500 ppm) and Cu (0, 6, or 12 ppm) as the acetate salt in deionized drinking water for 5 wk. A Pb-induced Cu deficiency resulted that was characterized by decreased levels of Cu in tissue and blood, decreased activities of the Cu-dependent enzymes, ceruloplasmin (serum) and Superoxide dismutase (erythocytes), and increased concentration of Fe in liver. These effects of Pb were prevented completely or in part by concurrent Cu supplementation. The Pb-induced decrease in hemoglobin and hematocrit values and the decrease in weight gain were not prevented by Cu supplementation of the diet and can therefore be assumed to be the direct result of a toxic effect of Pb. Although Pb ingestion resulted in decreased concentration of Cu in blood and tissue, additional dietary Cu had no effect on Pb levels.     

When the lead extractor becomes the assistant for new lead implant

With the increasing number of cardiovascular implantable electronic device upgrade and vein obstruction caused by previous leads, it is important to have alternative techniques to upgrade the device with the maintenance of functioning leads.We report an 83-year old male with 13-year old one-lead dual-chamber pacemaker, ischemic cardiac disease and pre-dialytic chronic kidney disease submitted to an upgrade to cardiac resynchronization therapy. A sub-occlusion in the transition of left brachiocephalic vein and the superior vena cava was documented. Re-permeabilization was only achieved with a TightRail? rotating dilator sheath over a guidewire with successful left ventricle lead implant.     

Influences of thiamin on lead intoxication, lead deposition in tissues and lead hematological responses of Tilapia zillii.

1. Lead levels in the blood, kidney, liver, brain and muscle of fish receiving only lead were elevated markedly over the values of both controls and thiamin-treated fish. 2. No statistical difference was observed between the lead levels in bone samples of both fish receiving only lead and thiamin-treated fish. 3. In contrast to the fish receiving only lead the fish treated with thiamin appeared to be healthy and had no lead poisoning signs. 4. Over the period of study, hemoglobin content and red blood cell counts of fish receiving only lead showed significant decreases from the values of both controls and fish treated with thiamin. 5. Hematocrit values and white blood cell counts were uninfluenced by either lead exposure or thiamin treatment at all intervals. 6. The data suggest that thiamin can serve as a promising natural chelator to prevent fish mortality, not only in short term, but also in prolonged exposure.     

Are fingernail lead levels a reliable biomarker of lead internal dose?

BackgroundPotentially toxic elements, such as lead, can bioaccumulate and alter human physiology. Human biomonitoring is an essential tool to evaluate chemical exposures in different biological matrices (blood, urine, saliva, nails, and hair). Of these biological matrices, nails are favorable for their ease of sampling, transport and storage. The aim of this study was to investigate possible correlations between blood lead levels (BLL) and washed and non-washed fingernail lead levels (FLL) in 55 adults living in a lead-contaminated area.MethodVenous blood and fingernail (thumbs and forefingers) samples were collected. Nails from the left hand were washed with Triton X-100 (0.5 % m/v) and HNO₃ solution, while nails from the right hand were not submitted to the pre-analytical procedures. Samples were analyzed by graphite furnace atomic absorption spectrometry, and pairwise correlations were used to correlate lead concentrations between BLL and FLL; nails from fingers of the same hand and between washed and unwashed fingernails. Principal component analysis was performed and scatter diagrams were plotted to investigate correlations.ResultsA non-significant positive correlation was found between BLL and washed forefinger nails lead (r = 0.219, p = 0.112) and between BLL and thumbnail lead levels (r = 0.182, p = 0.191). Comparison of fingernails from the same hand (thumb and forefinger), showed that lead concentrations of non-washed nails varied widely, even on analyses of transversal fragments from the same nail. Lead levels in non-washed forefinger nails were not correlated with non-washed thumbnails (r = 0.169, p = 0.219). Conversely, washed thumb and forefinger nails were found to be correlated (r = 0.39, p = 0.003). Washed and non-washed nails were also found to be correlated (p < 0.0001).ConclusionIn conclusion, the results showed that non-washed nails are not a reliable biomarker for lead exposure. Although washing nails before analysis may reduce external contamination, the correlation of lead concentrations between fingers is poor for fingernail lead levels to serve as an internal dose biomarker to lead exposure. In addition, levels in washed nails were not significantly correlated with blood lead levels. Fingernail lead levels seem to serve as an indicator of lead exposure sources in contact with the individual, but not as a reliable biomarker of internal dose.     

Blood lead levels and cumulative blood lead index (CBLI) as predictors of late neurodevelopment in lead poisoned children

Objective: To find the best lead exposure assessment marker for children.

Methods: We recruited 11 children, calculated a cumulative blood lead index (CBLI) for the children, measured their concurrent BLL, assessed their development, and measured their bone lead level.

Results: Nine of 11 children had clinically significant neurodevelopment problems. CBLI and current blood lead level, but not the peak lead level, were significantly or marginally negatively associated with the full-scale IQ score.

Conclusion: Lead exposure at younger age significantly impacts a child’s later neurodevelopment. CBLI may be a better predictor of neurodevelopment than are current or peak blood lead levels.     

Cardiac effects of lead

Symptoms consistent with cardiac disease have been noted as part of the syndrome of lead (Pb) intoxication. All types of cardiotoxicity noted in patients have been reproduced in experimental animals exposed acutely to high concentrations of Pb, or chronically exposed to lower levels. Types of cardiac effects observed include negative inotropism and electrocardiogram abnormalities, particularly conduction defects. Neonatal rats exposed to Pb via the milk of dams provided a drinking solution of lead acetate exhibit approximately four times the sensitivity to the arrhythmogenic effect of norepinephrine as adults compared with controls. Cardiotoxicity occurs after exposure as short as the first 10 postnatal days, but is not expressed until the rats are adult. Increased sensitivity to the arrhythmogenic effect of norepinephrine was seen in Pb-exposed animals in vivo and in isolated hearts from Pb-exposed animals in vitro. Norepinephrine arrhythmogenesis in vivo was attenuated by atropine or vagotomy, which indicates vagal nerve involvement. Possible mechanisms including interference with central gamma-aminobutyric acid systems, alteration of adrenergic nerve development, and Pb-Ca interaction are discussed.     

Yersinia lead SUMO attack

Little is known about the mechanism by which Yops, proteins that Yersinia inject into the cytosol of macrophage, cause downregulation of the inflammatory response and diseases such as the plague. Now it appears that Yops are the first bacterial member of a new family of ubiquitin-like proteases.