RESUMEN
Epidermal growth factor receptor-dependent mechanisms have been implicated in growth signal transduction pathways that contribute to cancer development, including dermal carcinogenesis. Detection of the extracellular domain of the epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a potential biomarker for monitoring this effect in vivo. Arsenic is a known human carcinogen, producing skin and other malignancies in populations exposed through their drinking water. One such exposed population, which we have been studying for a number of years, is in Bangladesh. The purpose of this study was to examine the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent assay in the serum samples from 574 individuals with a range of arsenic exposures from drinking water in the Araihazar area of Bangladesh. In multiple regression analysis, serum EGFR ECD was found to be positively associated with three different measures of arsenic exposure (well water arsenic, urinary arsenic and a cumulative arsenic index) at statistically significant levels (pAsunto(s)
Arsénico
, Biomarcadores/sangre
, Exposición a Riesgos Ambientales/análisis
, Factor de Crecimiento Epidérmico/sangre
, Fragmentos de Péptidos/sangre
, Contaminación del Agua/análisis
, Adulto
, Factores de Edad
, Anciano
, Bangladesh
, Índice de Masa Corporal
, Exposición a Riesgos Ambientales/efectos adversos
, Factor de Crecimiento Epidérmico/química
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Factores de Riesgo
, Factores Sexuales
, Enfermedades de la Piel/inducido químicamente
, Enfermedades de la Piel/patología
, Abastecimiento de Agua/análisis
RESUMEN
This study documents the response of 6500 rural households in a 25 km(2) area of Bangladesh to interventions intended to reduce their exposure to arsenic contained in well water. The interventions included public education, posting test results for arsenic on the wells, and installing 50 community wells. Sixty-five percent of respondents from the subset of 3410 unsafe wells changed their source of drinking water, often to new and untested wells. Only 15% of respondents from the subset of safe wells changed their source, indicating that health concerns motivated the changes. The geo-referenced data indicate that distance to the nearest safe well also influenced household responses.
Asunto(s)
Intoxicación por Arsénico/prevención & control , Monitoreo del Ambiente/métodos , Conductas Relacionadas con la Salud , Educación en Salud , Conocimientos, Actitudes y Práctica en Salud , Salud Rural , Contaminantes Químicos del Agua/análisis , Abastecimiento de Agua/análisis , Intoxicación por Arsénico/epidemiología , Bangladesh/epidemiología , Monitoreo Epidemiológico , Femenino , Sistemas de Información Geográfica , Política de Salud , Humanos , Entrevistas como Asunto , Masculino , Evaluación de Programas y Proyectos de Salud , Análisis de Regresión , Seguridad , Contaminantes Químicos del Agua/envenenamiento , Abastecimiento de Agua/normasRESUMEN
A comparison of field and laboratory measurements of arsenic in groundwater of Araihazar, Bangladesh, indicates that the most widely used field kit correctly determined the status of 88% of 799 wells relative to the local standard of 50 microg/L As. Additional tests showthatthe inconsistencies, mainly underestimates in the 50-100 microg/L As range, can be avoided by increasing the reaction time from 20 to 40 min. Despite this limitation, the field data already compiled for millions of wells by the Bangladesh Arsenic Mitigation and Water Supply Project, in combination with information on well location and depth, should prove to be extremely useful to prioritize interventions in thousands of affected villages.
Asunto(s)
Arsénico/análisis , Monitoreo del Ambiente/normas , Contaminantes del Agua/análisis , Abastecimiento de Agua , Bangladesh , Humanos , Control de Calidad , Reproducibilidad de los Resultados , Medición de RiesgoRESUMEN
In vivo bone lead measurements with 109Cd-based K-shell X-ray fluorescence (XRF) have been used to assess long-term lead exposure in adults. Tibia lead levels were measured in 210 children (106 boys, 104 girls) of 11-12(1/2) years of age in a lead smelter town and in a control (nonexposed) town. Tibia lead levels, methodological uncertainties, and models of some of the factors influencing them are presented. 109Cd-based K-shell XRF tibia lead methodological uncertainty in children is comparable to that in adults.
Asunto(s)
Exposición a Riesgos Ambientales/estadística & datos numéricos , Monitoreo del Ambiente/normas , Plomo/análisis , Probabilidad , Tibia/metabolismo , Niño , Femenino , Humanos , Masculino , Espectrometría por Rayos XRESUMEN
Iron homeostasis is tightly regulated, as cells work to conserve this essential but potentially toxic metal. The translation of many iron proteins is controlled by the binding of two cytoplasmic proteins, iron regulatory protein 1 and 2 (IRP1 and IRP2) to stem loop structures, known as iron-responsive elements (IREs), found in the untranslated regions of their mRNAs. In short, when iron is depleted, IRP1 or IRP2 bind IREs; this decreases the synthesis of proteins involved in iron storage and mitochondrial metabolism (e.g. ferritin and mitochondrial aconitase) and increases the synthesis of those involved in iron uptake (e.g. transferrin receptor). It is likely that more iron-containing proteins have IREs and that other IRPs may exist. One obvious place to search is in Complex I of the mitochondrial respiratory chain, which contains at least 6 iron-sulfur (Fe-S) subunits. Interestingly, in idiopathic Parkinson's disease, iron homeostasis is altered, and Complex I activity is diminished. These findings led us to investigate whether iron status affects the Fe-S subunits of Complex I. We found that the protein levels of the 75-kDa subunit of Complex I were modulated by levels of iron in the cell, whereas mRNA levels were minimally changed. Isolation of a clone of the 75-kDa Fe-S subunit with a more complete 5'-untranslated region sequence revealed a novel IRE-like stem loop sequence. RNA-protein gel shift assays demonstrated that a specific cytoplasmic protein bound the novel IRE and that the binding of the protein was affected by iron status. Western blot analysis and supershift assays showed that this cytosolic protein is neither IRP1 nor IRP2. In addition, ferritin IRE was able to compete for binding with this putative IRP. These results suggest that the 75-kDa Fe-S subunit of mitochondrial Complex I may be regulated by a novel IRE-IRP system.
Asunto(s)
Hierro/metabolismo , Mitocondrias/enzimología , NADH NADPH Oxidorreductasas/metabolismo , Regiones no Traducidas 5' , Animales , Secuencia de Bases , Células COS , Clonación Molecular , Cartilla de ADN , ADN Complementario , Complejo I de Transporte de Electrón , Humanos , NADH NADPH Oxidorreductasas/química , NADH NADPH Oxidorreductasas/genética , Conformación de Ácido NucleicoRESUMEN
Maternal smoking during pregnancy elevates risk for later child behavior problems. Because prior studies considered only Western settings, where smoking co-occurs with social disadvantage, we examined this association in Yugoslavia, a different cultural setting. Mothers enrolled in pregnancy as the low-exposure group in a prospective study of lead exposure were interviewed about health, including smoking history. A total of 199 children were assessed on the Child Behavior Checklist (CBCL) at ages 4, 4 1/2, and 5 years. Average cumulative blood lead (BPb) was determined from serial samples taken biannually since delivery. Longitudinal analyses were derived from 191 children with available data on behavior and covariates. Smoking was unrelated to social adversity. Controlling for age, gender, birthweight, ethnicity, maternal education, and Home Observation for Measurement of the Environment (HOME) Acceptance, smoking was associated with worse scores on almost all subscales; BPb concentration was related to small increases in the Delinquency subscale. Daughters of smokers received significantly higher scores on Somatic Complaints compared to daughters of nonsmokers, consistent with other work relating biological factors and internalizing problems in young girls. Because the present smoking/child behavior associations persist after control for individual and social factors also related to behavior problems, possible biological mediators are considered.
Asunto(s)
Conducta Infantil , Plomo , Trastornos Mentales/epidemiología , Efectos Tardíos de la Exposición Prenatal , Fumar , Adulto , Peso al Nacer , Estudios de Casos y Controles , Preescolar , Comparación Transcultural , Escolaridad , Femenino , Humanos , Recién Nacido , Plomo/sangre , Edad Materna , Trastornos Mentales/etiología , Embarazo , YugoslaviaRESUMEN
To investigate associations between the timing of lead (Pb) exposure on early intelligence, we examined the results of psychometric evaluations at ages 3, 4, 5, and 7 years, from 442 children whose mothers were recruited during pregnancy from a smelter town and a non-lead-exposed town in Yugoslavia. We compared the relative contribution of prenatal blood lead (BPb) with that of relative increases in BPb in either the early (0-2 years) or the later (from 2 years on) postnatal period to child intelligence measured longitudinally at ages 3 and 4 (McCarthy GCI), 5 (Wechsler Preschool and Primary Scale of Intelligence-Revised, WPPSI-R IQ), and 7 (Wechsler Intelligence Scale for Children-version III, WISC-III IQ), controlling for: Home Observation for Measurement of the Environment (HOME) quality; maternal age, intelligence, education, and ethnicity; and birthweight and gender. Elevations in both prenatal and postnatal BPb were associated with small decrements in young children's intelligence.
Asunto(s)
Inteligencia/efectos de los fármacos , Plomo/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Análisis de Varianza , Niño , Desarrollo Infantil/efectos de los fármacos , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Plomo/sangre , Estudios Longitudinales , Masculino , Embarazo , Estudios Prospectivos , Pruebas Psicológicas , Factores de Tiempo , YugoslaviaRESUMEN
OBJECTIVE: To investigate associations between lead exposure and early motor development. STUDY DESIGN: We conducted standardized assessments of motor function (Bruininks-Oseretsky Test of Motor Proficiency and Beery Developmental Test of Visual-Motor Integration) at age 54 months in 283 children whose mothers were recruited in pregnancy from a smelter town and a non-lead-exposed town in Yugoslavia and who have been monitored twice yearly since birth. Blood lead concentration (BPb) was summarized in a measure reflecting the average of the child's semiannual serial log BPbs through 54 months. RESULTS: Multiple regression showed that taken together, anthropometric measures (birth weight, body mass index) and markers of a stimulating and organized home life (HOME scale, parental education and intelligence, availability of siblings) explained a significant 10% to 18% of the variance in motor functioning. Beyond these contributions, BPb was significantly associated with poorer fine motor and visual motor function but was unrelated to gross motor coordination. CONCLUSIONS: Modest associations between early lead exposure and fine motor and visual motor functioning appear even after statistical adjustment is done for other contributors to motor development. Associations with BPb are specific to these areas of motor skill; gross motor development was unaffected.
Asunto(s)
Desarrollo Infantil , Plomo/sangre , Destreza Motora , Preescolar , Exposición a Riesgos Ambientales , Femenino , Humanos , Masculino , Embarazo , Estudios Prospectivos , YugoslaviaRESUMEN
Recent studies suggest that manganese-induced neurodegenerative toxicity may be partly due to its action on aconitase, which participates in cellular iron regulation and mitochondrial energy production. This study was performed to investigate whether chronic manganese exposure in rats influenced the homeostasis of iron in blood and cerebrospinal fluid (CSF). Groups of 8-10 rats received intraperitoneal injections of MnCl2 at the dose of 6 mg Mn/kg/day or equal volume of saline for 30 days. Concentrations of manganese and iron in plasma and CSF were determined by atomic absorption spectrophotometry. Rats exposed to manganese showed a greatly elevated manganese concentration in both plasma and CSF. The magnitude of increase in CSF manganese (11-fold) was equivalent to that of plasma (10-fold). Chronic manganese exposure resulted in a 32% decrease in plasma iron (p<0.01) and no changes in plasma total iron binding capacity (TIBC). However, it increased CSF iron by 3-fold as compared to the controls (p<0.01). Northern blot analyses of whole brain homogenates revealed a 34% increase in the expression of glutamine synthetase (p<0.05) with unchanged metallothionein-I in manganese-intoxicated rats. When the cultured choroidal epithelial cells derived from rat choroid plexus were incubated with MnCl2 (100 microM) for four days, the expression of transferrin receptor mRNA appeared to exceed by 50% that of control (p<0.002). The results indicate that chronic manganese exposure alters iron homeostasis possibly by expediting unidirectional influx of iron from the systemic circulation to cerebral compartment. The action appears likely to be mediated by manganese-facilitated iron transport at brain barrier systems.
Asunto(s)
Cloruros/farmacología , Homeostasis/efectos de los fármacos , Hierro/metabolismo , Compuestos de Manganeso/farmacología , Animales , Glutamato-Amoníaco Ligasa/metabolismo , Hierro/sangre , Hierro/líquido cefalorraquídeo , Masculino , Manganeso/sangre , Manganeso/líquido cefalorraquídeo , Metalotioneína/metabolismo , Concentración Osmolar , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Transferrina/genética , Factores de Tiempo , Transferrina/análisisRESUMEN
The symptoms of Mn-induced neurotoxicity resemble those of Parkinson's diseases. Since iron (Fe) appears to play a pivotal role in pathophysiology of Parkinson's disease, we set out to test the hypothesis that alterations in Fe-requiring enzymes such as aconitase contribute to Mn-induced neurotoxicity. Mitochondrial fractions prepared from rat brain were preincubated with MnCl2 in vitro, followed by the enzyme assay. Mn treatment significantly inhibited mitochondrial aconitase activity (24% inhibition at 625 microM to 81% at 2.5 mM, p<0.05). The inhibitory effect was reversible and Mn-concentration dependent, and was reversed by the addition of Fe (0.05-1 mM) to the reaction mixture. In an in vivo chronic Mn exposure model, rats received intraperitoneal injection of 6 mg/kg Mn as MnCl2 once daily for 30 consecutive days. Mn exposure led to a region-specific alteration in total aconitase (i.e. , mitochondrial+cytoplasmic): 48.5% reduction of the enzyme activity in frontal cortex (p<0.01), 33.7% in striatum (p<0.0963), and 20.6% in substantia nigra (p<0.139). Chronic Mn exposure increased Mn concentrations in serum, CSF, and brain tissues. The elevation of Mn in all selected brain regions (range between 3.1 and 3.9 fold) was similar in magnitude to that in CSF (3.1 fold) rather than serum (6. 1 fold). The present results suggest that Mn alters brain aconitase activity, which may lead to the disruption of mitochondrial energy production and cellular Fe metabolism in the brain.
Asunto(s)
Aconitato Hidratasa/antagonistas & inhibidores , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Manganeso/farmacología , Mitocondrias/enzimología , Neurotoxinas/farmacología , Animales , Encéfalo/metabolismo , Ácido Cítrico/metabolismo , Interacciones Farmacológicas , Hierro/farmacología , Manganeso/antagonistas & inhibidores , Manganeso/metabolismo , Mitocondrias/efectos de los fármacos , RatasRESUMEN
A primary rat choroidal epithelial cell culture system was developed to investigate mechanisms of heavy metal toxicity on the blood-cerebrospinal fluid (CSF) barrier. Epithelial cells were dissociated from choroidal tissue by pronase digestion and cultured in standard DMEM culture media supplemented with 10% fetal bovine serum and 10 ng epithelial growth factor per ml. The procedure yielded 2-5 x 10(4) cells from pooled plexuses of three to four rats, and a viability of 77-85%. The cultures displayed a dominant polygonal type of epithelial cells, with a population doubling time of 2-3 d. The cultures were of distinct choroidal epithelial origins. For example, immunocytochemical studies using monospecific rabbit anti-rat TTR polyclonal antibody revealed a strong positive stain of transthyretin (TTR), a thyroxine transport protein exclusively produced by the choroidal epithelia. Also, reverse-transcriptase polymerase chain reaction (PCR) confirmed the presence of specific TTR mRNA in the cultures. The cultures were further adapted to grow on a freely permeable membrane sandwiched between two culture chambers. The formation of an impermeable confluent monolayer occurred within 5 d after seeding and was verified by the presence of a steady electrical resistance across the membrane (80 +/- 10 ohm per cm2). The epithelial barriers appeared to actively transport [125I]-thyroxine from the basal to apical chamber. These results suggest that this primary cell culture system possesses typical choroidal epithelial characteristics and appears to be a suitable model for in vitro mechanistic investigations of blood-CSF barrier.
Asunto(s)
Plexo Coroideo/citología , Células Epiteliales/citología , Animales , Transporte Biológico , Barrera Hematoencefálica , Bovinos , Células Cultivadas , Femenino , Masculino , Conejos , Ratas , Ratas Sprague-DawleyRESUMEN
For a prospective study of lead exposure and early development, we recruited pregnant women from a lead smelter town and from an unexposed town in Yugoslavia and followed their children through 7 years of age. In this paper we consider associations between lifetime lead exposure, estimated by the area under the blood lead (BPb) versus time curve (AUC7), and intelligence, with particular concern for identifying lead's behavioral signature. The Wechsler Intelligence Scales for Children-Version III (WISC-III) was administered to 309 7-year-old children, 261 of whom had complete data on intelligence, blood lead, and relevant sociodemographic covariates (i.e., Home Observation for the Measurement of the Environment (HOME), birth weight, gender, sibship size, and maternal age, ethnicity, intelligence, and education). These showed anticipated associations with 7-year intelligence, explaining 41-4% of the variance in Full Scale, Performance, and Verbal IQ. Before covariate adjustment, AUC7 was unrelated to intelligence; after adjustment, AUC7 explained a significant 2.8%-4.2% of the variance in IQ. After adjustment, a change in lifetime BPb from 10 to 30 micro/dl related to an estimated decrease of 4.3 Full Scale IQ points; estimated decreases for Verbal and Performance IQ were 3.4 and 4.5 points, respectively. AUC7 was significantly and negatively related to three WISC-III factor scores: Freedom from Distractibility, Perceptual Organization, and Verbal Comprehension; the association with Perceptual Organization was the strongest. Consistent with previous studies, the IQ/lead association is small relative to more powerful social factors. Findings offer support for lead's behavioral signature; perceptual-motor skills are significantly more sensitive to lead exposure than are the language-related aspects of intelligence.
Asunto(s)
Desarrollo Infantil/efectos de los fármacos , Exposición a Riesgos Ambientales/efectos adversos , Inteligencia/efectos de los fármacos , Plomo/efectos adversos , Niño , Femenino , Humanos , Plomo/sangre , Masculino , Destreza Motora/efectos de los fármacos , Embarazo , Resultado del Embarazo , Efectos Tardíos de la Exposición Prenatal , Estudios Prospectivos , Percepción Visual/efectos de los fármacos , YugoslaviaRESUMEN
The choroid plexus, which is responsible for the maintenance of the biochemical milieu of the cerebrospinal fluid (CSF), avidly sequesters Pb. In order to test the hypothesis that chronic Pb exposure may impair choroid plexus function, male weanling Sprague-Dawley rats were exposed to Pb in drinking water at doses of 0, 50, or 250 micrograms Pb/ml (as Pb acetate) for 30, 60, or 90 days. The function of the choroid plexus was assessed as reflected by CSF concentrations of transthyretin (TTR, a major CSF protein manufactured by brain choroid plexus) and CSF essential metal ions (Ca2+, Mg2+, K+, and Na+). TTR concentrations were determined by radioimmunoassay using a monospecific rabbit anti-rat TTR polyclonal antibody, and CSF metal ions analyzed by flame atomic absorption spectrophotometry. Two-way ANOVA of CSF TTR concentrations revealed highly significant dose (p < 0.0001), time (p < 0.0223), and dose-by-time effects (p < 0.0379). Moreover, the percentage of reduction of CSF TTR was directly correlated with Pb concentrations in the choroid plexus (r = 0.703, p < 0.05). Pb exposure significantly increased CSF concentrations of Mg2+, but did not markedly altered CSF concentrations of Ca2+, K+, and Na+. Histopathologic examination under the light microscope did not show distinct alterations of plexus structure in Pb-treated rats. Since TTR is responsible for transport of thyroid hormones to the developing brain, we postulate that the depression of choroid plexus TTR production (and/or secretion) by Pb may impair brain development in young animals by depriving the CNS of thyroid hormones.
Asunto(s)
Plexo Coroideo/efectos de los fármacos , Plomo/toxicidad , Compuestos Organometálicos/toxicidad , Prealbúmina/líquido cefalorraquídeo , Administración Oral , Análisis de Varianza , Animales , Peso Corporal/efectos de los fármacos , Cationes Bivalentes/líquido cefalorraquídeo , Cationes Bivalentes/metabolismo , Cationes Monovalentes/líquido cefalorraquídeo , Cationes Monovalentes/metabolismo , Plexo Coroideo/metabolismo , Plexo Coroideo/patología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Plomo/administración & dosificación , Masculino , Metales/líquido cefalorraquídeo , Compuestos Organometálicos/administración & dosificación , Prealbúmina/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
Beverages stored in lead-crystal glass accumulate extraordinary concentrations of lead. We obtained a lead-crystal decanter manufactured with lead from Australia, where the ratio of 206Pb/207Pb is distinctly different from that in the United States. We sought to determine the bioavailability of crystal-derived lead, using the technique of stable isotope dilution in blood. We conducted a single-dose, nonrandomized cross-over study in which participants were admitted to the Clinical Research Center twice, 1 week apart. During the first admission, subjects ingested sherry obtained from the original bottle. During the second admission, they ingested sherry that had been stored in the crystal decanter and that had achieved a lead concentration of 14.2 mu mol/l. After ingesting decanter-stored sherry, mean blood lead rose significantly (p = 0.0003) from 0.10 to 0.18 mu mol/l, while mean 206Pb/207Pb fell from 1.202 to 1.137 (p = 0.0001). On average, 70% of the ingested dose of lead was absorbed. We conclude that lead derived from crystal glass is highly bioavailable; repeated ingestions could cause elevated blood lead concentration. The technique of stable isotope dilution lends itself to the study of the bioavailability of lead in other matrices, including soil.
Asunto(s)
Utensilios de Comida y Culinaria , Exposición a Riesgos Ambientales , Vidrio , Plomo/farmacocinética , Adulto , Disponibilidad Biológica , Estudios Cruzados , Femenino , Humanos , Isótopos , Plomo/sangre , Plomo/orina , Masculino , Factores de Tiempo , VinoRESUMEN
Meso-2,3-dimercaptosuccinic acid (DMSA, or succimer) is an oral chelating agent for heavy-metal poisoning. While studying the urinary elimination of unaltered DMSA, altered DMSA (i.e., its mixed disulfides), and lead in children with lead poisoning, we observed a pattern of urinary drug elimination after meals suggestive of enterohepatic circulation. The excretion of lead in urine patterned the elimination of altered DMSA rather than the parent molecule. In addition, the half-life of elimination of DMSA via the kidney was positively associated with blood lead concentration. Two additional crossover studies of DMSA kinetics were conducted in normal adults to confirm the presence of enterohepatic circulation of DMSA after meals. In one, increases in plasma total DMSA concentration were observed after meals in all six subjects; these increases were prevented by cholestyramine administration 4, 8, and 12 hr after DMSA. In the second, the administration of neomycin also prevented increases in DMSA after meals. These studies indicate that 1) a metabolite(s) of DMSA undergoes enterohepatic circulation and that microflora are required for DMSA reentry; 2) in children, moderate lead exposure impairs renal tubular drug elimination; and 3) a metabolite of DMSA appears to be an active chelator.
Asunto(s)
Intoxicación por Plomo/metabolismo , Succímero/metabolismo , Adulto , Niño , Preescolar , Resina de Colestiramina/farmacología , Estudios Cruzados , Ingestión de Alimentos , Femenino , Humanos , Lactante , Plomo/sangre , Plomo/orina , Intoxicación por Plomo/sangre , Intoxicación por Plomo/orina , Circulación Hepática , Masculino , Neomicina/farmacología , Proyectos Piloto , Succímero/administración & dosificaciónRESUMEN
Extensive research has been devoted to the development of biomarkers of environmental and occupational exposure to lead (Pb). This body of work can serve as a paradigm for biomarker development for other chemical exposures. Early efforts focused on indirect measurements of exposure by analyzing precursors and enzymes of a biosynthetic pathway (heme) in blood and urine. However, the direct measurement of Pb in blood has become increasingly simple and reliable and is now widely accepted for pediatric surveillance programs, in part because of known associations of Pb with adverse health outcomes. Other markers of exposure include measurements of Pb in important compartments: bone Pb, tooth Pb, and chelatable Pb. In addition, the technique of stable isotope dilution is available, since Pb exists in numerous nonradioactive isotopic forms. The strengths and weaknesses of all Pb biomarkers for confirming a diagnosis or for epidemiologic research vary widely depending upon the hypothesis under investigation.
Asunto(s)
Biomarcadores/análisis , Exposición a Riesgos Ambientales , Monitoreo del Ambiente , Intoxicación por Plomo/diagnóstico , Humanos , Plomo/análisis , Plomo/sangre , Intoxicación por Plomo/prevención & controlRESUMEN
For a prospective study of lead exposure and early development, we recruited pregnant women from a smelter town and a nonlead-exposed town in Yugoslavia and followed them and their children through age 4. For 332 children seen at age 4, mean scores on the McCarthy Scales General Cognitive Index (GCI) in the exposed and nonexposed towns were 81.3 and 86.6, respectively; geometric mean blood lead concentrations (BPb) were 39.9 and 9.6 micrograms/dl, respectively. Potential confounders included the quality of the HOME environment; maternal age, intelligence, education, and language; birthweight and gender. These showed predictable associations with 4-year intelligence, accounting for 42.7% of the variance in GCI. Following adjustment for these variables and for concurrent Hgb, we found significant independent adverse associations between GCI and BPb's, measured at 6-month intervals since birth. At age 4, BPb accounted for an incremental 3.5% of the variance in GCI, such that the estimated loss in GCI associated with an increase in BPb from 10-25 micrograms/dl was 3.8 points. The Perceptual-Performance subscale of the McCarthy was most sensitive to Pb exposure, a result consistent with findings from prospective studies in Boston and Port Pirie.
Asunto(s)
Anemia Ferropénica/complicaciones , Discapacidades del Desarrollo/etiología , Exposición a Riesgos Ambientales , Intoxicación por Plomo/complicaciones , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/psicología , Preescolar , Trastornos del Conocimiento/etiología , Femenino , Estudios de Seguimiento , Humanos , Hierro/uso terapéutico , Intoxicación por Plomo/psicología , Masculino , Embarazo , Estudios Prospectivos , Análisis de Regresión , Factores Socioeconómicos , Yugoslavia/epidemiologíaRESUMEN
The purpose of this paper is to discuss issues which relate to the risks and benefits of pharmacologic intervention in children with elevated blood lead (BPb) concentrations. In January, 1991, 2,3-dimercaptosuccinic acid (DMSA; succimer or CHEMET) was approved by the FDA for administration to children with blood lead concentrations of 45 micrograms/dl or higher. Thus, it is now considerably simpler to treat children with elevated BPb's. DMSA is orally actively, relatively safe and specific, and can, in some situations, be used on an out-patient basis. The author is concerned that the recent CDC statement on lead poisoning, whose aim is to reduce (by various means) children's BPb's below 10 micrograms/dl, may unintentionally encourage pediatricians to treat children with relatively low BPb's with DMSA, both for medical and legal reasons. Should children with BPb's of less than 45 ug/dl be treated, and why? The risks and benefits of treatment in such children are uncertain. A randomized, placebo controlled, double-blind drug intervention trial is needed (and justified) in order to more carefully assess the benefits and the risks associated with the treatment of lower BPb's.
Asunto(s)
Intoxicación por Plomo/tratamiento farmacológico , Humanos , Intoxicación por Plomo/sangre , Guías de Práctica Clínica como Asunto , Factores de Riesgo , Succímero/uso terapéuticoRESUMEN
For a prospective study of lead exposure, iron status, and infant development, we recruited infants living in a smelter town and a non-lead-exposed town in Kosovo, Yugoslavia. Among 392 infants assessed at age 2 years, the mean Mental Development Index (MDI), Bayley Scales of Infant Development, was 105.2. At age 2 years, geometric mean blood lead concentrations were 35.5 and 8.4 micrograms/dl, respectively, among infants from the exposed and nonexposed towns. After controlling for variables associated with MDI, we found significant independent associations for both blood lead and hemoglobin concentrations. For example, a rise in blood lead concentration at age 2 years from 10 to 30 micrograms/dl was associated with an estimated 2.5 point decrement in MDI (p = 0.03); statistically nonsignificant decrements were associated with blood lead levels measured at birth and at 6, 12, and 18 months of age. A decrease in hemoglobin concentration at 18 months of age from 12 to 10 gm/dl was associated with an estimated 3.4 point decrement in MDI (p = 0.02); the latter association was present in both towns, suggesting that it was due to iron deficiency anemia independent of lead exposure. The findings suggest that the brain is vulnerable to the effects of both lead exposure and anemia before 2 years of age. On a global basis, the developmental consequences of anemia may exceed those of lead exposure.
Asunto(s)
Anemia Hipocrómica/complicaciones , Desarrollo Infantil , Exposición a Riesgos Ambientales , Plomo/sangre , Anemia Hipocrómica/sangre , Preescolar , Cognición , Femenino , Sangre Fetal/química , Hemoglobinas/análisis , Humanos , Lactante , Masculino , Estudios Prospectivos , Factores SocioeconómicosRESUMEN
It has been suggested that the accumulation of tobacco-derived cadmium (Cd) in the placenta is responsible for the adverse effect of cigarette smoking on infant birthweight. We chose to test this hypothesis; therefore, we studied a population of nonsmoking pregnant women who were exposed to low levels of smelter-derived Cd and a group of nonexposed women. A higher mean placental Cd concentration (p less than .0007) was found in the exposed women (n = 106), compared with those who were not exposed (n = 55); the observed Cd concentrations were comparable to concentrations reported previously for smoking and nonsmoking women, respectively. Least squares multiple regression (controlling for potentially confounding variables) revealed no association between placental Cd and birthweight. It was, therefore, concluded that the effect of smoking on birthweight was not mediated through Cd.