Lead,Zinc, and Erythrocyte δ-Aminolevulinic Acid Dehydratase: Relationships in Lead Toxicity

A lead-intoxicated patient with extremely high blood lead levels and unexpectedly mild symptoms was studied prior to and following treatment with calcium disodium edetate (ethylenediaminetetraacetic acid) and then prior to and following oral administration of zinc sulfate. During chelation therapy, erythrocyte (5)-aminolevulinic acid dehydratase (ALAD) activity decreased as blood lead levels fell. Urinary excretion of zinc increased and was more than 3.5 times greater than that of lead. The ratio of blood lead to serum zinc was greatest (1.47) when ALAD activity was lowest. Oral administration of zinc sulfate following chelation therapy resulted in a significant increase in mean ALAD activity. In vitro additions of zinc chloride to the patient’s erythrocytes resulted in reactivation of ALAD activity. These studies suggest that zinc is an important element in the ALAD system in man. Zinc may play a protective role in lead toxicity, and zinc supplementation may be a useful adjunct to chelation therapy for lead toxicity.     

Effect of Lead on δ-Aminolevulinic Acid Dehydratase Activity in Red Blood Cells

Reduction of δ-aminolevulinic acid dehydratase (ALA-D) activity in the red blood cells has proved to be the most sensitive test for lead poisoning.

The regeneration of ALA-D, after cessation of lead exposure, was studied in 31 men who had worked in a storage battery plant. At the same PbB the ALA-D activity was found to be slightly higher in those whose exposure had terminated than in those with continuing exposure.

Regeneration was faster in those men with a shorter exposure to lead and a lower PbB at cessation of exposure.     

Different Behaviors of Erythrocyte δ-Aminolevulinic Acid Dehydratase

Different characteristics of erythrocyte δ-aminolevulinic acid dehydratase (ALA-D) between the workers with the history of occupational lead exposure and normals are described.

In the blood of lead workers, when the hemolysates are heated at 60 C for five minutes, the activity of the erythrocytes ALA-D increases up to about 3.6-fold of an initial level, and as a result of heating the optimum in pH-activity curve changes from pH 6.0 to pH 6.6, which is similar to the optimum pH of normal ALA-D. On the contrary, in normal blood, the optimum in the pH-activity curve is but little changed, even though the erythrocyte ALA-D activity is increased up to about 1.3-fold of the initial level by heating the hemolysates at 60 C for five minutes.     

Effect of Lead on δ-Aminolevulinic Acid Dehydrase Activity in Red Blood Cells

The activity of δ-aminolevulinic acid dehydrase (ALAD) in red blood cells diminishes in lead poisoning. The variation of ALAD activity with the concentration of lead in the blood and the variation of ALAD activity with the concentration of δ-aminolevulinic acid in the urine are both exponential and the correlations inverse. In a study of ALAD in, inter alia, traffic workers, enzymatic activity proved normal. It may, therefore, be assumed that there is almost no risk of lead poisoning by air pollution in the area studied (center of a town with about 250,000 inhabitants). Determination of ALAD activity in erythrocytes is considered a suitable method for demographic studies of exposure to lead. The test is too sensitive for routine follow-up of the degree of lead intoxication in occupationally exposed workers.     

Lead in Feathers and δ-Aminolevulinic Acid Dehydratase Activity in Three Raptor Species from an Unpolluted Mediterranean Forest (Southeastern Spain)

This paper presents the levels of lead found in the feathers of adult and blood of nestlings of booted eagle (Hieraaetus pennatus), European buzzard (Buteo buteo), and goshawk (Accipiter gentilis) sampled in the 1999 and 2000 breeding seasons in a Mediterranean forest of the Province of Murcia (Southeastern Spain) located far from potential sources of metal contamination. Levels of -aminolevulinic acid dehydratase activity (-ALAD) in blood were also measured in the nestlings. Lead concentrations ranged from 1.1 to 11.21 g/dl in blood of nestlings and from 0.35 to 1.66 mg/kg d.w. in the feathers of their parents. A significant relationship was found between blood -ALAD and lead ( = –568), showing a negative correlation with blood lead levels even at lead concentrations below 5 g/dl. This fact suggests the usefulness of this enzymatic biomarker for low lead exposure in forest raptors. There were also positive relationships between the lead concentrations in blood of nestlings and those in feathers of their parents ( = 0.817), suggesting the usefulness of feathers for biomonitoring environmental exposure to lead.     

Prenatal Exposure to Lead, δ-Aminolevulinic Acid,and Schizophrenia: Further Evidence

Background

A previously conducted study of prenatal lead exposure and schizophrenia using δ-aminolevulinic acid, a biologic marker of Pb exposure, in archived maternal serum samples collected from subjects enrolled in the Childhood Health and Development Study (1959–1966) based in Oakland, California, suggested a possible association between prenatal Pb exposure and the development of schizophrenia in later life.

Objectives

In the present study we extend these findings using samples collected from the New England cohort of the National Collaborative Perinatal Project (1959–1966). Using similar methods, in this study we found results that suggest a comparable association in this cohort.

Methods

We pooled matched sets of cases and controls from both the California and New England sites using a multilevel random-intercept logistic regression model, accounting for matching and site structure as well as adjusting for maternal age at delivery and maternal education.

Results

The estimated odds ratio for schizophrenia associated with exposure corresponding to 15 μg/dL of blood Pb was 1.92 (95% confidence interval, 1.05–3.87; p = 0.03).

Conclusion

Although several limitations constrain generalizability, these results are consistent with previous findings and provide further evidence for the role of early environmental exposures in the development of adult-onset psychiatric disorders.     

Antagonistic Effect In Vivo of Zinc on Inhibition of δ -Aminolevulinic Acid Dehydratase by Lead

δ-aminolevulinic acid dehydratase (ALAD) is an enzyme involved in the biosynthesis of heme, in which it catalyzes the condensation of two molecules of δ-aminolevulinic acid to one molecule of porphobilinogen. It is a sulfhydryl enzyme, which means, among other tilings, that its activity is inhibited by many heavy metals. In the present investigation rabbits were given either zinc or lead or both. Zinc had a strong activating effect on ALAD in vivo, and the inhibitory effect of lead was almost completely eliminated. A close positive correlation was found between ALAD in the red blood cells and zinc in the plasma, but there was no correlation between ALAD and zinc in the red blood cells. These observations are of particular interest in the light of recent findings, suggesting that zinc is an essential metal for ALAD.     

δ-Aminolevulinic Acid Dehydratase Single Nucleotide Polymorphism 2 and Peptide Transporter 2*2 Haplotype May Differentially Mediate Lead Exposure in Male Children

Child low-level lead (Pb) exposure is an unresolved public health problem and an unaddressed child health disparity. Particularly in cases of low-level exposure, source removal can be impossible to accomplish, and the only practical strategy for reducing risk may be primary prevention. Genetic biomarkers of increased neurotoxic risk could help to identify small subgroups of children for early intervention. Previous studies have suggested that, by way of a distinct mechanism, δ-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD₂) and/or peptide transporter 2*2 haplotype (hPEPT2*2) increase Pb blood burden in children. Studies have not yet examined whether sex mediates the effects of genotype on blood Pb burden. Also, previous studies have not included blood iron (Fe) level in their analyses. Blood and cheek cell samples were obtained from 306 minority children, ages 5.1 to 12.9 years. ²⁰⁸Pb and ⁵⁶Fe levels were determined with inductively coupled plasma–mass spectrometry. General linear model analyses were used to examine differences in Pb blood burden by genotype and sex while controlling for blood Fe level. The sample geometric mean Pb level was 2.75 μg/dl. Pb blood burden was differentially higher in ALAD₂ heterozygous boys and hPEPT2*2 homozygous boys. These results suggest that the effect of ALAD₂ and hPEPT2*2 on Pb blood burden may be sexually dimorphic. ALAD₂ and hPEPT2*2 may be novel biomarkers of health and mental health risks in male children exposed to low levels of Pb.     

Persistent Increase of Blood Lead Level and Suppression of δ-ALAD Activity in Northern Bobwhite Quail Orally Dosed With Even a Single 2-mm Spent Lead Shot

Birds that display grit ingestion behavior are potentially at risk of lead (Pb) poisoning from mistaken ingestion of spent Pb shot pellets. The majority of available studies designed to assess such risk have used unspent shot pellets rather than field-obtained spent shot, which is oxidized and otherwise changed by weathering. Available studies also often administered more or heavier shot pellets to a bird than it might be expected to ingest. The current study dosed northern bobwhite quail (Colinus virginianus) weighing 194.6?±?23.1?g (female birds) and 199.3?±?12.2?g (male birds) with one to three spent no. 9 Pb shot collected from a skeet range, with particular interest in the toxicity that may occur from ingestion of a single 2-mm, 50?mg shot. An 8?week post-dosing clinical observation period was employed, over which feed consumption, body weight, blood Pb levels, and a battery of blood physiological parameters were made. Weight loss occurred in the birds, including male birds dosed with one Pb pellet. Erythrocyte delta aminolevulinic acid dehydratase (δ-ALAD) levels were decreased for the duration of the study across exposures and to levels associated with injury in wild bird populations. Decreased ALAD was particularly severe in female birds dosed with one Pb pellet and was still 92?% decreased at 8?weeks after dosing. Together, these results suggest that inadvertent ingestion of a single no. 9 Pb shot pellet can adversely affect the health of northern bobwhite quail.     

DNA–Protein Crosslinks and Sister Chromatid Exchanges as Biomarkers of Exposure to Formaldehyde

Abstract

Formaldehyde is classified as a probable human carcinogen. DNA–protein crosslinks (DPCs) and sister chromatid exchanges. (SCEs) may represent early lesions in the carcinogenic process. The authors examined the OPCs and, SCEs in peripheral-blood lymphocytes of 12 and 13 workers exposed to formaldehyde and eight and 20 unexposed workers, respectively. The amounts of DPCs and SCEs in the exposed and the unexposed differed significantly after adjustment for smoking. There was a linear relationship between years of exposure and the amounts DPC and SCE. The authors conclude that the data indicate a possible Mechanism of carcinogenicity of formaldehyde, and that formaldehyde is mutagenic to humans. These results support the use of DPCs as a biomarker of occupational exposure to formaidehyde and to detect high risk populations for secondary prevention.     

Carbon Assimilation and Digestive Toxicity in Naïve Grass Shrimp (Palaemonetes pugio) Exposed to Dietary Cadmium

Bulletin of Environmental Contamination and Toxicology - Naïve grass shrimp Palaemonetes pugio were pulse-fed cadmium-contaminated meals containing carbon-14, fluorescent or near-infrared...     

Serum Levels of TGF-β1 and MCP-1 as Biomarkers for Progressive Coal Workers’ Pneumoconiosis in Retired Coal Workers: A Three-year Follow-up Study

Various cytokines activated by the inhalation of coal dust may mediate inflammation and lead to tissue damage. Objective of this study was to examine the relationships between coal workers’ pneumoconiosis (CWP) progression over a 3 yr period and the serum levels of cytokines in 85 retired coal workers. To investigate the relevance of serum cytokines in CWP, serum levels of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), transforming growth factor–beta1 (TGF-β1), and monocyte chemotactic protein-1 (MCP-1) as progressive CWP biomarkers were studied in relation to the progression of pneumoconiosis over a 3 yr period in 85 patients with CWP. CWP progression was evaluated through paired comparisons of chest radiographs. Median levels of TGF-β1 and MCP-1 were significantly higher in subjects with progressive CWP than in those without CWP progression. The area under the ROC curve for TGF-β1 (0.693) and MCP-1 (0.653) indicated that these cytokines could serve as biomarkers for the progression of CWP. Serum TGF-β1 levels were related to the progression of CWP (β=0.247, p=0.016). The results suggest that high serum levels of TGF-β1 and MCP-1 are associated with the progression of CWP.     

Real-Time PCR Investigation of the Dynamic Expression of Three “RNA Processing and Modification” Genes of Phanerochaete chrysosporium Exposed to Lead

The expression of three ribosome binding proteins namely; polyadenylate-binding protein, splicing factor RNPS1 and ATP-dependent RNA helicase of Phanerochaete chrysosporium exposed to lead were analyzed by real-time PCR. The mRNA level of splicing factor RNPS1 showed 2.7 (p < 0.05), 2.6 (p < 0.05) and 4.9-fold (p < 0.001) increase when the cells were exposed to 25, 50 and 100 μM lead, respectively. 50 and 100 μM lead exposure resulted in almost 2-fold (p < 0.01and p < 0.05, respectively) increase in the expression of ATP-dependent RNA helicase. Polyadenylate-binding protein mRNA levels did not reveal any significant increase when cells exposed to the concentrations of lead employed. However, the mRNA level of polyadenylate-binding protein and splicing factor RNPS1 within a period of 1 and 2 h temporal exposure to 100 μM lead showed 2.5 (p < 0.001) and 3.4-fold (p < 0.001) increase, respectively. Expression level of ATP-dependent RNA helicase was not affected from the period of exposure to this metal.     

Effect of Defriprone on Glycine and γ-amino-butyric-acid and Essential Elements in Brain of Rats Exposed to Aluminum

目的 探讨去铁酮(defriprone,DFP)对铝染毒大鼠脑组织中甘氨酸(Gly)、γ-氨基丁酸(GABA)两种抑制性氨基酸类神经递质及铝和必需元素影响.方法 将35只健康清洁级Wistar雄性大鼠按体重随机分为5组,分别为阴性对照组和铝单独染毒组以及铝+低、中、高剂量DFP组,每组7只,采用灌胃方式染毒,每天1次,每周连续染毒5d,间隔2d.前8周,阴性对照组给予生理盐水(1ml/d),其他4组给予AlCl3溶液(354.7mg/kg).后2周,阴性对照组与铝染毒组给予生理盐水(1ml/d);铝+DFP低、中、高剂量组分别给予不同浓度DFP溶液(13.72、27.44和54.88mg/kg),每天1次.测定脑组织中Gly、GABA及铝、铜、镁、钙和铁的含量.结果 与阴性对照组比较,铝单独染毒组和铝+各剂量DFP组大鼠脑组织中Gly和GABA的含量均较高,差异有统计学意义(P＜0.01).与铝单独染毒组比较,铝+各剂量DFP组大鼠脑组织中Gly和GABA的含量均较低,差异有统计学意义(P＜0.01).与阴性对照组比较,铝单独染毒组和铝+低、中剂量DFP组大鼠脑组织中铝含量均较高,差异有统计学意义(P＜0.01).与铝单独染毒组比较,铝+各剂量DFP组大鼠脑组织中铝含量均较低,差异有统计学意义(P＜0.01);且随着DFP剂量的升高,大鼠脑组织中的铝含量呈下降趋势.各组大鼠脑组织中铜、镁、钙和铁含量间比较,差异均无统计学意义.结论DFP可通过促进铝排出,恢复铝染毒大鼠脑组织中Gly和GABA的正常代谢,且对铜、镁、钙、铁等必需元素在脑中平衡不产生影响,对中枢神经系统具有明显保护作用.     

Lead accumulation and depression of δ-aminolevulinic acid dehydratase (ALAD) in young birds fed automotive waste oil

The effects of a 3-week dietary exposure to automotive waste crankcase oil (WCO) were examined in 1-week-old mallard (Anas platyrhynchos) ducklings and pheasant (Phasianus colchicus) chicks. Treatment groups consisted of birds exposed to 0.5, 1.5, or 4.5% WCO, to 4.5% clean crankcase oil (CCO), or untreated controls. In both species, red blood cell ALAD activity was significantly inhibited after one week by 50 to 60% in the 0.5% WCO group and by 85 to 90% in the 4.5% WCO group due to the presence of lead. Growth, hematocrit, and hemoglobin were not significantly affected at the end of three weeks. Plasma aspartate aminotransferase (AST) activity was higher in mallards after three weeks of ingesting either 4.5% WCO or 4.5% CCO, suggesting an oil-related effect due to components other than lead. Treatment had no effect on plasma concentration of uric acid, glucose, triglycerides, total protein, or cholesterol. Lead analysis showed the WCO to contain 4,200 ppm Pb and the CCO to contain 2 ppm. Tissues of mallards were examined for accumulation of lead and the order of accumulation at the end of three weeks was kidney > liver > blood ～ brain.     

Prevalence of pain and fear as barriers to vaccination in children – Systematic review and meta-analysis

BackgroundInjection-related pain and fear are common adverse reactions in children undergoing vaccination and influence vaccine acceptance. Despite the large body of literature on sources of vaccine non-compliance, there is no estimate of the prevalence of pain and fear as contributing factors. The objective was to estimate the prevalence of injection pain or fear of needles as barriers to childhood (i.e., 0–18 years) vaccination.MethodsFour databases were searched from inception for relevant English and French articles until August 2021. In addition, the references of recent systematic reviews and all articles included in the review were hand searched. Article screening and data extractions were performed in duplicate. Studies were included if they reported on injection-related pain or fear of needles in children (0–18 years) using a checklist/closed-ended question(s). Results were stratified by respondent (parents or children), type of pediatric population (general or under-vaccinated), and relative importance of barrier (pain or needle fear as primary reason or any reason for under-vaccination). Prevalence rates of pain or needle fear were combined using a random effects model. Quality of included studies was assessed using the Joanna Briggs Institute critical appraisal checklist for prevalence data. Quality across studies was assessed using GRADE.ResultsThere were 26 studies with 45 prevalence estimates published between 1995 and 2021. For parent reports (of children) and children self-reported reasons for non-compliance, prevalence rates of pain or needle fear ranged from 5 to 13% in a general population and 8 to 28% in an under-vaccinated population, with a substantial variation in the prevalence estimates. There was no difference between category of respondent or relative importance on pain or needle fear prevalence rate. A regression model demonstrated an overall prevalence rate of pain or needle fear as an obstacle to vaccination of 8% in the general population and 18.3% in the under-vaccinated population. All evidence was very low in quality.ConclusionThis is the first review to systematically quantify the prevalence and therefore, importance, of pain and needle fear as obstacles to vaccination in children around the world. Pain from injection or fear of needles were demonstrated to be sufficiently prevalent as barriers to vaccination in children to warrant attention. Addressing pain and fear has the potential to significantly improve vaccination acceptance.