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Biomedical subjects

R L Bornschein

Publications and source records attributed to R L Bornschein.

At least 37 records · Page 2Linked to original sources

Influence of social factors on lead exposure and child development.

A brief overview of current views of child development is provided, with particular attention given to the role the child's physical and social environment plays in influencing the developmental process. Examples from the recent literature are used to illustrate how these factors can influence lead exposure and most importantly how they might interact with lead to ameliorate or exacerbate possible lead effects. An example is provided which demonstrates that failure to control adequately and to adjust the data statistically to correct for the influence of these factors can lead one erroneously to attribute cognitive and behavioral changes to lead. Finally, data from the Cincinnati Prospective Lead Study are presented to illustrate the application of structural equation modeling as a means for unraveling the complex web of sociodemographic, environmental and behavioral influences on childhood lead exposure. The latter analysis indicates that for children less than 24 months of age, lead-containing dust in the home and on the children's hands are important determinates of their blood lead levels. This relationship is influenced by the amount of maternal involvement with their child and other indices of interaction between the child and primary caregiver.

Child↗

Contribution of social and developmental factors to lead exposure during the first year of life.

The social and developmental correlates of early lead exposure were explored in an interim analysis of data from an ongoing longitudinal investigation in Cincinnati. Regardless of the apparent net availability of lead in the infant's physical environment, parental behavior was still significantly associated with infant blood lead levels. However, this was only the case after infants in the study reached 6 months of age and beyond when prewalking progression and early walking made parental management all the more critical. Future lead screening and abatement programs should include supports for the caretaker-child relationship.

Child Development↗

Toxicological considerations in the assessment of lead exposure.

Many uncertainties remain today concerning effects of lead on the nervous system, particularly in regard to levels of lead exposure causing minimal brain dysfunction in children. Past studies in children have failed to define adequately the nature of the effect, the critical period and duration of exposure and the role of other factors in rendering the developing organism susceptible to lead. Prospective studies now underway should contribute greatly to the resolution of these issues. The studies propose to monitor both lead exposure and behavior at fixed intervals from birth for up to five years. The index of exposure in all studies is blood lead concentration. Test batteries vary considerably among studies, but most propose to include the Bayley Scales and the McCarthy Scales. These design features should greatly facilitate comparison of results across the studies. In the design of animal studies certain standardized features across studies also seem desirable, particularly concerning the characterization of lead exposure. Repeat measures of blood lead concentration in rats receiving lead via dams' milk and via water after weaning indicate that the response of individual animals is extremely variable, both as to the pattern of lead build-up and as to the degree of exposure. It is to be expected that biological responses would vary accordingly. It also follows that dose-response and dose-effect relationships in animal studies should be analyzed taking into account this problem. Data analysis should consider the dose and response of each animal individually. In the design of dosage regimens the profile of blood lead levels in adults and young children reported in the literature are useful guidelines in the design of exposure regimens. Many studies are concerned with non-behavioral aspects of lead toxicity e.g. disposition of neurotransmitters, morphological features of brain maturation and alterations in blood-brain barrier function. It would be extremely useful to relate the findings to some fairly standardized behavioral endpoint as well as to well-defined blood lead profiles.

Adult↗

Drug induced activity in lead-exposed mice.

Three interrelated studies were conducted to examine the locomotor activity of lead-exposed mice. The effects of lead were examined as a function of the dose and duration of exposure. Exposure during the first three weeks occurred via the maternal milk supply. Exposure following weaning was achieved via the water supply. Mice received challenges with various pharmaceutical agents, including d-amphetamine, methylphenidate, apomorphine and phenobarbital. The spontaneous activity prior to injection and the drug-induced activity were monitored. Lead-exposed mice usually displayed spontaneous activity which was indistinguishable from that of the control animals. In only one set of observations did lead exposure result in a modest increase in spontaneous activity. The drug-induced activity varied in a complex manner as a function of the magnitude and duration of the lead exposure. Depressed body weight, which was concurrent with high lead exposure (0.5% Pb(Ac)2) was also a significant parameter affecting both the spontaneous and drug-induced activity.

Age Factors↗

Evaluation of teratogenicity and behavioral toxicity with inhalation exposure of maternal rats to trichloroethylene.

Female rats were exposed by inhalation to trichloroethylene (TCE) vapors at a concentration of 1800 +/- 200 ppm to determine whether exposure before mating and during pregnancy is more detrimental to reproductive outcome than exposure either before mating alone or during pregnancy alone. Four treatment groups were utilized in a two by two factorial design: exposure to TCE for 2 weeks before mating and during the first 20 days of pregnancy; TCE before mating and filtered air during pregnancy; filtered air before mating and TCE during pregnancy; and filtered air before and during pregnancy. Significant elevations in skeletal and soft tissue anomalies, indicative of developmental delay in maturation rather than teratogenesis, were observed in the group exposed during pregnancy alone. The mixed function oxidase enzymes, ethoxycoumarin and ethoxyresorufin, indicative of cytochrome P-450 and P-448 activities, respectively, were measured in maternal and fetal livers, as well as livers of non-pregnant females, and showed variable levels of activity not uniformly related to treatment or pregnancy. Behavioral evaluation of offspring indicated a lack of treatment effect in tests of general activity levels at 10, 20 and 100 days of age. However, a reduction in postnatal body weights was seen in offspring from mothers with pregestational exposure. No results indicative of treatment-related maternal toxicity, embryotoxicity, severe teratogenicity or significant behavioral deficits were obtained in any of the treatment groups.

Abnormalities, Drug-Induced↗

Brain lipofuscin concentration and oxidant defense enzymes in lead-poisoned neonatal rats.

Neonatal rats were given aqueous lead acetate intragastrically from d 2-20 of life at doses of 0, 10, 50, and 225 mg Pb/kg.d. Blood Pb concentrations on d 21 were (mean +/- SE) 23 +/- 3 (control), 63 +/- 19, 246 +/- 55, and 994 +/- 223 microgram/100 ml, and brain Pb concentrations were 14 +/- 2, 60 +/- 5, 114 +/- 15, and 275 +/- 26 microgram/100 g, respectively. Growth was significantly depressed only in rats given the highest dose of Pb (225 mg/kg.d). Solvent-extractable lipofuscin pigment concentration of brain tissue progressively decreased over the 21-d duration of the experiment but was not significantly altered at any dose of Pb. Brain glutathione peroxidase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities were stimulated on d 20 at the maximal dose of Pb, but the activities of brain superoxide dismutases and catalase were not altered by Pb exposure. Locomotor activity was significantly increased in the male animals on d 20, but only at the highest dose of Pb. These results indicate that Pb toxicity in neonatal rats is not associated with accelerated in vivo lipid peroxidation in the brain, but that certain oxidant defense mechanisms in the brain are stimulated by Pb.

Aging↗

Behavioral deficits in adult rats following neonatal lead exposure.

Rats exposed to lead via the maternal milk were tested at maturity on three different visual discrimination tasks. Starting at parturition the dams were given either tap water, 0.20% sodium acetate, 0.02% lead acetate, or 0.20% lead acetate in the drinking water. At weaning, the pups from all the groups were placed on normal chow and tap water. At 20 days of age, the concentration of lead in the blood and brain of the high lead-exposed offspring was approximately 6 times that of controls (11 microgram% vs 66 microgram%). A significant deficit was found in the ability of the high lead-exposed group to acquire a simultaneous visual discrimination task conducted in an operant chamber. No significant differences were observed in the ability of lead-exposed rats to acquire either a successive visual discrimination task or a cued go/no-go discrimination. Thee results suggest that early lead exposure can affect certain behavioral processes and that the effects may persist even after the rat has reached maturity.

Animals↗

Behavioral effects of low level neonatal lead exposure.

Rats exposed to lead via maternal milk were tested at various stages of development on a number of behavioral tasks. Beginning at paturition, the dams were given either tap water, 0.02%, or 0.10% lead acetate in the drinking water. Pups from all three groups were weaned to normal chow and tap water at 21 days of age. The mean lead concentration of the dam's blood and of neonatal (20 days of age) brain and blood were all below 50 microgram/100 ml. No significant differences were found between the high lead-exposed group and controls in general as measured by wheel running over a 21 day period beginning at 30 days of age. However, there was a significant difference in wheel running behavior during the first three hr of testing. Both lead-exposed groups were found to display significantly less aggressive behavior as measured by the shock-elicited aggression test. Low level lead exposure had no discernable effect on the acquisition and subsequent reversal of a successive brightness discrimination task. Lead exposure under these conditions appears to affect some aspects of emotional behavior, while having little effect on general activity or cognitive function.

Aggression↗

Diurnal variations in the analgesic effectiveness of morphine in mice.

Response to thermal stimulation and the analgesic effectiveness of morphine during various phases of the diurnal cycle were assessed by the hotplate method. Saline treated controls exhibited shortest reaction times during the last quarter of the light-phase and first quarter of the dark phase. Longest reaction times were recorded during the last quarter of the dark phase. Doses of 4, 8, 16, and 32 mg/kg of morphine was administered IP at the peak and trough of the pain sensitivity rhythm. The ED50 (95% C.L.) during the last quarter of the light phase was found to be 14.60 (10.6-20.0) mg/kg while during the last quarter of the dark phase the ED50 was found to be 5.85 (4.5-7.7) mg/kg. In a second experiment, independent groups of ten mice each were injected SC with 8 mg/kg of morphine at three hr intervals over a 48 hr test session. Peak analgesic activity was obtained in the group injected during the last quarter of the dark phase while minimal analgesic effectiveness was obtained during the third quarter of the light phase. Central administration of morphine via the intraventricular route yielded the same relationship, i.e., maximal analgesic effectiveness during the last quarter of the dark phase.

Analgesia↗

Technique for assessing visual discrimination learning in mice.

An automated technique for the study of visual discrimination learning in mice has been developed. The technique utilizes a nose-poke as the operant response. The nose-poke response requires no shaping, has a relatively high operant level and can be used to measure preacquisition exploratory behavior. CD-1 mice acquired a simultaneous brightness discrimination readily but a successive brightness discrimination proved more difficult. A 20 sec intertrial interval was optimal for acquisition of the simultaneous discrimination. Reversal learning was slow. This procedure should prove useful in the study of the effects of pharmacologic and toxic agents on learning and performance in both weanlings and adult mice.

Animals↗

Lead exposure and the cognitive development of urban preschool children: the Cincinnati Lead Study cohort at age 4 years.

The purpose of this analysis was to determine if significant associations could be observed between prenatal/postnatal blood lead (PbB) levels and the cognitive development of 258 urban, inner-city children at 4 years of age. These children have been followed since birth with frequent assessments of general health, PbB, and neuropsychological status. The Kaufman Assessment Battery for Children (K-ABC) was administered at approximately 4 years of age. Higher neonatal PbB levels were associated with poorer performance on all K-ABC subscales. However, this inverse association was limited to children from the poorest families. Maternal PbB levels were unrelated to 4-year cognitive status. Few statistically significant associations between postnatal PbB levels and K-ABC scales could be found. However, the results did suggest a weak inverse relationship between postnatal PbB levels and performance on a K-ABC subscale which assesses visual-spatial and visual-motor integration skills. In these results we note both contradiction and accord with previously published prospective studies.

Child, Preschool↗

The developmental consequences of low to moderate prenatal and postnatal lead exposure: intellectual attainment in the Cincinnati Lead Study Cohort following school entry.

In a further follow-up study of the Cincinnati Lead Study Cohort, 253 children were administered the Wechsler Intelligence Scale for Children-Revised (WISC-R) at approximately 6.5 years of age. Postnatal blood lead concentrations were inversely associated with Full-Scale (FSIQ) and Performance IQ (PIQ). Following statistical adjustment for developmental co-factors such as maternal IQ and an assessment of the quality of caretaking in the home environment, a statistically significant relationship remained between postnatal blood lead concentrations and PIQ. Further statistical analyses suggested that averaged lifetime blood lead concentrations in excess of 20 micrograms/dL were associated with deficits in PIQ on the order of approximately 7 points when compared to children with mean concentrations less or equal to 10 micrograms/dL. These results are discussed in terms of their consistency with other similar studies as well as their internal consistency with earlier reports on this cohort. The findings of this investigation support recent initiatives in the United States to reduce the exposure of children to environmental lead.

Child↗

Hippocampal potentials evoked by stimulation of olfactory basal forebrain and lateral septum in the rat.

Electrophysiological characteristics of olfactory-hippocampal relations were examined because recent anatomical studies have described a substantial olfactory input to the hippocampus via the entorhinal cortex. Potentials evoked in the dorsal hippocampus of anesthetized rats by stimulation of the prepyriform cortex, pyriform cortex, diagonal band, lateral olfactory tract, anterior commissure, olfactory tubercle and anterior olfactory nucleus had similar characteristics, although latencies differed. For example, latencies were twice as long after stimulation of the obliquely oriented portion of the diagonal band than after stimulation of the prepyriform cortex. A relatively low-amplitude, initially negative wave was recorded in the subiculum, CA1 and CA2, and a relatively high-amplitude, initially positive wave was recorded in CA4 and the dentate gyrus. In CA3 negative potentials were observed at dorsal recording sites and positive potentials were recorded at more ventral sites. Peak latencies were usually two to four msec shorter for the negative than for the positive wave. Laminar distributions of responses evoked in the hippocampus by stimulation of the prepyriform cortex and diagonal band were evaluated by driving eight electrodes mounted on one carrier through the brain and were found to be strikingly similar. Maximal amplitudes of the negative wave were recorded at the level of stratum moleculare of CA1 and the subiculum, and peak amplitudes of the positive wave were associated with the hilus of the dentae gyrus. Transition from negative to positive waveforms occurred approximately at the hippocampal fissure. Although the negative and positive waves were usually elicited together, they also were separable in that only negative waves were recorded along some tracks and only positive waves along others. Also, various stimulation sites in the prepyriform cortex elicited stable high-amplitude positive waves accompanied by negative waves of varying amplitude. It is suggested that branches of the perforant path are involved in generation of the two waves and that activity in a number of olfactory structures may influence the hippocampus, probably via the perforant pathway. Thus, hippocampal potentials following prepyriform or diagnonal band stimulation were not abolished by transection of the fornix-fimbria. Dorsolateral septal stimulation evoked hippocampal responses with characteristics and distribution distinctly different from those evoked by stimulation of olfactory areas. The findings suggest that lateral septal stimulation may activate the hippocampus antidromically.

Animals↗