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Biomedical subjects

P Mushak

Publications and source records attributed to P Mushak.

At least 37 records · Page 2Linked to original sources

Sexual differences in the distribution and retention of organic and inorganic mercury in methyl mercury-treated rats.

At 56 days of age, male and female Long-Evans rats received 1 mumole of 203Hg-labeled methyl mercuric chloride per kilogram sc and total, organic, and inorganic mercury contents and concentrations in tissues were determined for up to 98 days postdosing. Whole body clearance of mercury was faster in females than in males, and females attained higher peak percentages of the methyl mercury dose in kidney and brain than did males. Females had significantly higher mean percentages of the mercury dose present in the kidney and brain as organic or total mercury and in brain as inorganic mercury than did males. Males had significantly higher mean percentages of the dose present as organic or total mercury in pelt and whole body than did females. When expressed on a concentration basis, the only significant sexual difference was in the higher average concentration of organic mercury in the kidneys of females. When expressed on a tissue content basis, significant male-female differences in the kinetics (sex X time interactions) of organic mercury retention were found in kidney, brain, skeletal muscle, pelt, and whole body. Significant sex X time interactions in the concentrations of organic mercury were found in kidney, skeletal muscle, and whole body. Kinetics of retention and concentration of inorganic Hg in the pelt differed significantly for males and females. Discordance in degree of statistical significance of differences in mercury contents and concentrations reflected in part differences in relative body composition of males and females. Integrated exposures of tissues of males and females to organic or inorganic mercury were determined by fitting multiexponential retention functions to retention data. Differences in integrated exposure were estimated by the female-to-male ratio of areas under retention curves. Reconstruction of whole body organic and inorganic mercury burdens from constituent tissues indicated that integrated exposures of males and females to inorganic mercury were equal but females had a lower integrated exposure to organic mercury. Integrated exposure of liver to either form of mercury was about equal in males and females. However, the integrated exposure of the brain of females to inorganic mercury was 2.19 times that of males suggesting a sexual difference in accumulation or retention of inorganic mercury in the nervous system. These sexual differences in distribution and retention of organic and inorganic mercury after methyl mercury exposure may underlie reported sexual differences in sensitivity to the toxic effects of methyl mercury.

Animals↗

Relation of lead and social factors to IQ of low-SES children: a partial replication.

An independent replication of a previous study (Schroeder et al., 1985) of the effects of interactive social environmental factors on the relationship of lead and Stanford-Binet IQ was performed on 75 of 80 low-SES black children screened by county health departments in North Carolina. Children's mean blood lead (PbB) level was 20.8 micrograms/dl (range, 6.3 to 47.4). Multivariate regression analyses showed no significant interactions between PbB and age, sex, maternal IQ, Caldwell home environment score, or SES (Hollingshead Two-Factor Index). There was a highly significant negative relationship between both mean and maximum PbB levels with IQ, p less than .002; that is, IQ decreased linearly as PbB increased. The most accurate and precise regression model included lead, maternal IQ, home environment, and gender.

Child↗

Separating the effects of lead and social factors on IQ.

Initial evaluations of 104 low-socioeconomic status black children screened by the local community health departments in North Carolina showed significant effects of lead in the range 6-59 micrograms/dl on IQ after controlling for concomitant social factors, such as socioeconomic status, home environment, and maternal IQ. The main concomitant variable was socioeconomic status, which was multicolinear with other social factors. Five years later, when all blood lead levels were 30 micrograms/dl or less, lead effects on IQ were no longer significant. The correlation between maternal and child IQ, which had been suppressed initially in children with higher lead levels, returned to expected levels when decreases in blood lead level occurred, while concomitant variables remained stable over the 5-year period.

Child↗

5-year follow-up study of children with low-to-moderate lead absorption: electrophysiological evaluation.

Forty-nine children aged 6 to 12 years were evaluated for residual effects of lead exposure using psychometric, electrophysiological, and medical tests 5 years after initial assessment. The original range of blood lead (PbB) levels was 6-59 (mean = 28) micrograms/dl; the current range was 6-30 (mean = 14) micrograms/dl. A linear relationship between PbB and slow brain wave voltage during sensory conditioning was observed at initial evaluation and at 2-year follow-up. No significant relationship between PbB and slow wave voltage during passive conditioning was found at the 5-year follow-up, although a linear increase in slow wave negativity relative to the current PbB level during active conditioning was suggested by exploratory analyses. Another exploratory analysis revealed a significant linear relationship between the original PbB levels and the latency of waves III and V of the brainstem auditory evoked potential. The latency of both waves increased as a function of original PbB. Increased latency of these waves is suggestive of subclinical pathology of the auditory pathway rostral to the cochlear nucleus, although end-organ impairment cannot be ruled out. No threshold for the effect of Pb on auditory function was apparent.

Brain↗

Differential vulnerability of mixed and cutaneous nerves in lead neuropathy.

The prevalence of demyelinated fibers in mixed nerve (sciatic) and cutaneous nerve (sural) and the change in lead levels in various tissues over time were assessed in a model of lead neuropathy in the rat. Long-Evans rats were given drinking water containing 4% lead acetate and killed between one and 213 days of exposure. Lead levels in blood, brain, kidney, and femur increased over the 213-day period. Lead levels in sciatic nerve appeared to increase rapidly during the first few weeks of exposure and then decline to a lower plateau. The neuropathy was characterized by segmental demyelination and remyelination; neither axonal degeneration nor a microangiopathy was found. Sciatic nerve had a significantly greater prevalence of demyelinated fibers than sural nerve; the prevalence of demyelinated fibers was similar in proximal and distal sciatic nerve. The variable, brain-lead concentration times days on lead, which is an indicator of cumulative brain exposure, was the best predictor of the prevalence of demyelination. The differential involvement of sciatic and sural nerves in lead neuropathy may either indicate that Schwann cells myelinating different nerve-fiber populations have different susceptibilities to lead toxicity, or that lead preferentially enters sciatic nerve.

Animals↗

Potential human health effects of acid rain: report of a workshop.

This report summarizes the potential impact of the acid precipitation phenomenon on human health. There are two major components to this phenomenon: the predepositional phase, during which there is direct human exposure to acidic substances from ambient air, and the post-depositional phase, in which the deposition of acid materials on water and soil results in the mobilization, transport, and even chemical transformation of toxic metals. Acidification increases bioconversion of mercury to methylmercury, which accumulates in fish, increasing the risk to toxicity in people who eat fish. Increase in water and soil content of lead and cadmium increases human exposure to these metals which become additive to other sources presently under regulatory control. The potential adverse health effects of increased human exposure to aluminum is not known at the present time.

Acids↗

Potential impact of acid precipitation on arsenic and selenium.

The potential impact of acidic precipitation on the environmental mobility of the metalloids arsenic (As) and selenium (Se) has not been given much attention and is poorly understood. As with other elements, the interest here is the potential effect of environmental acidification on environmental behavior in ways that are relevant to human exposure to these metalloids. Available information on acid precipitation and the environmental behavior of these metalloids do, however, permit some preliminary conclusions to be drawn. Both As and Se appear to be mobilized from household plumbing into tap water by the corrosive action of soft, mildly acidic water, while surface water catchment systems in areas impacted by acidic deposition may contain elevated soluble As levels. Acidification of aquatic ecosystems that are drinking water sources may pose the prospect of enhanced release of As from sediment to water as well as reduction in water levels of Se. Acidification of ground waters, where As appears to be especially mobile, is of particular concern in this regard. The potential impact of acidic deposition on As and Se in soils cannot readily be assessed with respect to human exposure, but it would appear that the behavior of these metalloids in poorly buffered, poorly immobilizing soils, e.g., sandy soils of low metal hydrous oxide content, would be most affected. The effect is opposite for the two elements; lowered pH would appear to enhance As mobility and to reduce Se availability. Altered acidity of both soil and aquatic systems poses a risk for altered biotransformation processes involving both As and Se, thereby affecting the relative amounts of different chemical forms varying in their toxicity to humans as well as influencing biogeochemical cycling.

Acids↗

The analysis of total and form-variable tin in various media.

Methods for both total and form-variable tin analysis in biological media are reviewed. While total tin analysis was common in the past, and in some cases still is, better understanding of the toxicology and toxicokinetics of organotins in biological systems requires knowledge of specific tin forms present. Both chromatographic and non-chromatographic methods for chemical speciation of organotins in various media have been described, the former appearing to offer the most promising approaches. High performance liquid chromatography (HPLC) in tandem with tin-specific metal detection presently appears to offer the most promise.

Animals↗

Effect of triethyl tin on myelination in the developing rat.

Myelinogenesis in developing rats was studied following chronic dosing with triethyl tin (TET), at a level of 1.0 mg TET/kg body wt/day. Experiments included starved controls with body weights depressed by 17 to 40% to equal those of the TET-treated groups. Rats at ages of 16, 21, and 30 days showed decreases relative to well-nourished controls in body weight, forebrain weight, myelin yield, cerebroside level, and specific activity of brain 2',3'-cyclic nucleotide-3'-phosphohydrolase when dosed with TET. At 30 days, myelin and cerebroside yields were reduced by approximately 55%, while CNP activity was reduced by less than 20%. No differences in the forebrain myelin protein composition between control, starved, and TET animals were noted. The rate of myelin protein synthesis relative to brain total protein (assayed by incorporation of intracranially injected [3H]glycine into brain homogenate and myelin proteins) was decreased in the TET rats in proportion to the decreased yield of myelin, but no particular myelin protein was preferentially affected. Matching starved controls exhibited similar body weight decreases, less pronounced forebrain weight decreases, and little or no decrease in myelin concentration. There was a relative increase in the myelin protein synthesis rate in the starved rats, indicating preferential utilization of limited protein precursors for myelin protein synthesis. Spinal cord myelin was also decreased in the TET rats, but less severely than in the forebrain. At all ages optic, but not sciatic, nerves showed decreases in myelin concentration with TET treatment. We conclude that TET inhibits forebrain growth and CNS myelination more severely than can be accounted for by a general metabolic insult.

Animals↗

Blood lead concentrations in a remote Himalayan population.

The lead content in the air at the foothills of the Himalayas in Nepal was found to be negligible. The concentration of lead in the blood of 103 children and adults living in this region was found to average 3.4 micrograms per deciliter, a level substantially lower than that found in industrialized populations.

Adult↗

Contributions of the caregiving environment to increased lead burden of children.

Two groups of children, 12 to 30 months (n = 14) and 31 to 78 months of age (n = 12), showing increased lead burden were compared to a sample of children matched for age, sex, and socioeconomic status but showing no evidence of increased lead burden. All children were screened at a local county health department because of suspected lead exposure or as part of the Early and Periodic Screening, Diagnosis, and Treatment Program. The quality of the caregiving environment was assessed using the HOME Inventory. A measure of maternal intelligence was also obtained. For the younger children, significant deficits in maternal IQ and quality of the caregiving environment were associated with increased lead burden. In particular, the subscales of the HOME Inventory dealing with emotional and verbal responsivity of the mother and maternal involvement with the child were significantly lower for children with increased lead burden. For the older children there was no significant association between lead burden and home environment or maternal IQ. The results suggest that intellectual deficits previously attributed to lead toxicity may be related to compromised home environment.

Child↗