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Biomedical subjects

R F Seegal

Publications and source records attributed to R F Seegal.

15 recordsLinked to original sources
PubMed1991

Comparison of effects of Aroclors 1016 and 1260 on non-human primate catecholamine function.

Adult male non-human primates, Macaca nemestrina, were orally-exposed to corn oil or corn oil containing either Aroclor 1016 or 1260 at doses of 0.8, 1.6 or 3.2 mg/(kg.day) for 20 weeks. Brain concentrations of biogenic amines and individual PCB congeners were determined following exposure. Aroclor 1016 significantly decreased concentrations of dopamine and its metabolites in the caudate, putamen, substantia nigra and hypothalamus but did not alter neurotransmitter or metabolite concentrations in the globus pallidus and hippocampus. Total PCB concentrations ranged from 1 to 5 ppm with only three congeners detected (2,4,4'; 2,4,2',4' and 2,5,2',5') making up, on average, 72%, 18% and 7% respectively of the total residue in brain. There were no discernible differences in the congener make-up between brain regions. Aroclor 1260 reduced dopamine concentrations in the caudate, putamen and hypothalamus but produced no effects in the substantia nigra, globus pallidus or hippocampus. Aroclor 1260 concentrations ranged from 18 to 28 ppm with the highest levels found in the hippocampus. Of the congeners that made up more than 5% of the total residue in brain, all were hexa- and heptachlorinated di-ortho-substituted congeners. There were no discernible differences in congener make-up between brain regions. We conclude that: (1) ortho-substituted non-planar congeners are responsible for the observed changes in neurochemical function; (2) both Aroclor 1016 and Aroclor 1260 decrease dopamine concentrations by similar mechanisms; and (3) based on differences in brain concentrations of Aroclor 1260 congeners compared to Aroclor 1016 congeners, lightly-chlorinated congeners are more effective in reducing central dopamine concentrations than are the more highly chlorinated congeners.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Sub-chronic exposure of the adult rat to Aroclor 1254 yields regionally-specific changes in central dopaminergic function.

Laboratory rats were exposed to chow adulterated with either 500 or 1000 ppm Aroclor 1254 for 30 days. Analysis of biogenic amines and their metabolites in the dorsal frontal cortex, lateral olfactory tract, striatum, basal hypothalamus, hippocampus and brainstem revealed significant decreases in dopamine concentrations and metabolism in only the striatum and lateral olfactory tract. Concentrations of individual PCB congeners in the striatum, lateral olfactory tract and hippocampus were measured by gas chromatography with electron capture detection. Neither total concentration nor variations in concentrations of individual congeners between regions could explain this regional specificity. The susceptibility of the striatum and lateral olfactory tract to insult by PCBs may be due to their innervation by midbrain dopaminergic neurons which have been shown to be particularly sensitive to insult from environmental, infectious and pharmacologic agents.

Acetone↗
PubMed1990

Lightly chlorinated ortho-substituted PCB congeners decrease dopamine in nonhuman primate brain and in tissue culture.

Exposure of the nonhuman primate, Macaca nemestrina, to Aroclor 1016, a commercial mixture of 26 lightly chlorinated PCB congeners, decreased dopamine concentrations in the caudate, putamen, substantia nigra, and hypothalamus. Only three ortho-substituted nonplanar PCB congeners (2,4,4', 2,4,2',4', and 2,5,2',5') were detected in these brain regions, suggesting that these congeners may be responsible for the observed decreases in dopamine. The ability of these and other PCB congeners to alter dopamine function was tested directly by applying them to dopamine-synthesizing cells in culture, PC-12 pheochromocytoma cells. In vitro testing demonstrated that these three congeners reduced cellular dopamine concentrations while planar, dioxin-like congeners, e.g., 3,4,3',4' and 3,4,5,3',4', did not. Thus, these ortho-substituted nonplanar congeners may be directly responsible for the observed changes in in vivo neurochemistry. Furthermore, these results suggest that the observed decreases in both in vivo and in vitro dopamine concentrations may occur through a novel mechanism and not through the Ah-receptor complex thought to mediate immunotoxic and hepatotoxic changes following exposure to dioxin and dioxin-like PCBs.

Animals↗
PubMed1989

Chronic exposure of primates to 60-Hz electric and magnetic fields: I. Exposure system and measurements of general health and performance.

We exposed pigtailed macaques (Macaca nemestrina) to electric (E) and magnetic (B) fields at strengths of 3 kV/m and 0.1 G, 10 kV/m and 0.3 G, and 30 kV/m and 0.9 G for three 21 day segments. These three exposure segments were preceded and followed by 21 day sham exposure segments. Additional animals received only sham exposure for five 21 day segments. Detailed description of the exposure chamber and field generation apparatus is given. We evaluated measures of animal well-being, including weight, blood chemistry, blood cell counts, and performance on a simple motor task, and performed postmortem examinations. Reliable and consistent results were obtained throughout data collection. None of the measures evaluated was significantly affected by E- and B-field exposures. Data obtained during actual exposure segments were not distinguishable from those obtained during the initial and final sham exposure segments, nor were they different from data obtained from the sham-exposed animals. Thus, field exposure had no apparent effects on general health or performance.

Animals↗
PubMed1989

Chronic exposure of primates to 60-Hz electric and magnetic fields: II. Neurochemical effects.

We exposed Macaca nemestrina (pig-tailed macaques) to electric (E) and magnetic (B) fields ranging in intensity from 3 kV/m and 0.1 G to 30 kV/m and 0.9 G for three 21-day (d) periods. Experimental animals were exposed to sham E and B fields for two 21-d periods, one prior to and one following actual exposure to E and B fields, resulting in a total of five 21-d periods. Control animals were exposed to sham E and B fields for the entire 105-d interval. At the end of each 21-d period cerebrospinal fluid (CSF) was obtained by lumbar puncture and analyzed for concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), metabolites of dopamine and serotonin neurotransmitters, respectively, by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Results are based on an examination of six experimental and four control animals. Exposure to E and B fields at all strengths was associated with a significant decline in CSF concentrations of both HVA and 5-HIAA when statistical comparisons were made against values obtained at the end of the preexposure interval. However, HVA returned to preexposure levels during the postexposure period, while 5-HIAA did not. No significant change in the concentrations of HVA or 5-HIAA was noted in the control animals. These results strongly suggest that exposure of the nonhuman primate to E and B fields can significantly affect specific biochemical estimates of nervous system function. These effects may involve alterations either in neuronal activity or in the activity of enzymes that catabolize the neurotransmitters.

Animals↗
PubMed1989

Chronic exposure of primates to 60-Hz electric and magnetic fields: III. Neurophysiologic effects.

The neurophysiologic effects of combined 60-Hz electric (E) and magnetic (B) fields, of magnitudes comparable to those produced by high-voltage powerlines, were investigated in 10 monkeys (Macaca nemestrina). Six animals (experimental group) were each exposed to three different levels of E and B fields: 3 kV/m and 0.1 G, 10 kV/m and 0.3 G, and 30 kV/m and 0.9 G. Field exposures were preceded and followed by sham exposures, during which factors of field generation were present (e.g., heat, vibration, noise, etc.) without E and B fields. Each of the five segments (i.e., the three exposure segments and the initial and final sham exposure segments) lasted 3 weeks. Animals were exposed for 18 h/day (fields on at 1600 h, off at 1000 h). Four other animals (external control group) were given sham exposure for the entire 15-week period. Auditory, visual, and somatosensory evoked potentials were recorded twice a week, during the daily 6-h field-off period. E- and B-field exposure had no effect on the early or mid-latency evoked potential components, suggesting that exposure at these levels has no effect on peripheral or central sensory afferent pathways. However, there was a statistically significant decrease in the amplitudes of late components of the somatosensory evoked potential during the 10kV/m and 0.3 G, and 30 kV/m and 0.9 G exposure levels. This result is possibly related to the opiate antagonist effect of electromagnetic field exposure reported by others.

Animals↗
PubMed1989

Effects of Aroclor 1254 on dopamine and norepinephrine concentrations in pheochromocytoma (PC-12) cells.

Pheochromocytoma (PC-12) cells synthesize, store, release and metabolize dopamine (DA) and norepinephrine (NE) in a manner analogous to that observed in the mammalian central nervous system. These cells were used to develop and validate an alternate method to animal testing to assess the effects of a complex environmental mixture of polychlorinated biphenyls (Aroclor 1254) on cellular catecholamine function. Aroclor 1254, at concentrations of 1 to 100 ppm, significantly decreased cellular catecholamine concentrations after 6 hrs. Exposure at 100 ppm for periods of less than an hr increased cellular catecholamine concentrations while longer exposure times (i.e., 1 to 24 hr) decreased cellular catecholamine concentrations. This in vitro depletion of catecholamines is similar to that seen in vivo. Thus, PC-12 cells may be useful for neurochemical evaluation of neurotoxicants with particular reference to effects on catecholaminergic systems.

Adrenal Gland Neoplasms↗
PubMed1988

Stereotaxic microinjection of HSV-1 selectively decreases striatal dopamine concentrations in mice.

BALB/c mice were stereotaxically injected in the striatum with either the MP or MacIntyre strain of herpes simplex type 1. Three days later, at a time when the animals were free from overt signs of infection, they were killed by cervical dislocation and the striatum was rapidly removed. Concentrations of dopamine, norepinephrine, serotonin and their metabolites were subsequently determined by means of high-performance liquid chromatography with electrochemical detection. With both strains of virus, dopamine levels were reduced and the ratio of homovanillic acid to dopamine was elevated in MP-inoculated mice. Norepinephrine, serotonin and its metabolites were unaffected. Immunoperoxidase staining in separate, identically treated animals indicated that the infection was confined to the striatum and necrosis was minimal at this point in time. These results demonstrate that dopamine metabolism can be affected by herpes simplex in the absence of immunocytochemical evidence of infection of the cell bodies of dopaminergic neurons or cellular death.

Animals↗
PubMed1988

The degree of PCB chlorination determines whether the rise in urinary homovanillic acid production in rats is peripheral or central in origin.

Commercial mixtures of polychlorinated biphenyls (PCBs, Aroclor 1016, 1254, and 1260) differing in their degree of chlorination and their accumulation in the brain were employed along with a peripheral monoamine oxidase inhibitor, debrisoquin sulfate (Declinax, DS) to determine whether the rise in urinary homovanillic acid (UHVA) following exposure to these PCBs is derived from the peripheral or central nervous system. Rats were gavaged with either corn oil or corn oil containing Aroclor 1016 or a mixture of Aroclors 1254 and 1260 and 24-hr UHVA production was determined by high-performance liquid chromatography with electrochemical detection. All animals also received ip injections of DS to inhibit peripheral production of HVA. Analysis of variance indicated that, following DS treatment, 24-hr UHVA production remained significantly elevated in the Aroclor 1254/1260-exposed animals; while no significant differences between Aroclor 1016-exposed animals and controls were noted. The rise in UHVA in the Aroclor 1254/1260 group involves HVA of central origin whereas the rise in the Aroclor 1016-treated animals is only peripheral. Thus, PCBs that differ in their degree of chlorination alter dopaminergic functions in anatomically different locations.

Animals↗
PubMed1986

High-performance liquid chromatography of biogenic amines and metabolites in brain, cerebrospinal fluid, urine and plasma.

A method for high-performance liquid chromatographic separation and electrochemical detection of biogenic amines and metabolites in a variety of biological matrices is described. The method employs either homogenization, precipitation or dilution followed by direct injection of the samples and permits the chromatographic resolution of dopamine, norepinephrine, epinephrine, serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in brain; 3-methoxy-4-hydroxyphenylglycol, DOPAC, 5-HIAA and HVA in cerebrospinal fluid; 5-HIAA, HVA and 5-HT in plasma; and 5-HIAA and HVA in urine. Alterations in chromatographic conditions, voltammetry and in vivo pharmacological manipulations are employed to verify the identity of the putative neurotransmitter and metabolite peaks in the biological samples.

Animals↗
PubMed1986

Polychlorinated biphenyls produce regional alterations of dopamine metabolism in rat brain.

Adult male rats were gavaged with a mixture of polychlorinated biphenyls (PCBs; Aroclors 1254 and 1260) at either 500 or 1000 mg/kg body weight. Concentrations of dopamine (DA) and its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were determined in caudate nucleus and lateral olfactory tract on postgavage Days 1, 3, 7 and 14. DA and DOPAC concentrations in caudate decreased after exposure to PCBs, as did HVA/DA ratios. DA concentrations in the lateral olfactory tract were unaffected, although DOPAC/DA ratios decreased. These results demonstrate that the mature mammalian nervous system is sensitive to a brief exposure to PCBs and that regional differences exist in the neurochemical sequelae of exposure to PCBs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Regional alterations in serotonin metabolism induced by oral exposure of rats to polychlorinated biphenyls.

Adult male rats were gavaged with a mixture of Aroclors 1254 and 1260 at a dose level of either 500 or 1000 mg/kg and were killed on post-gavage days 1, 3, 7 and 14. Total PCB concentrations and concentrations of serotonin and its major central metabolite, 5-hydroxyindoleacetic acid, were determined in the dorsal frontal cortex, lateral olfactory tract, hippocampus, medial-basal hypothalamus and brainstem. Differences in the initial concentrations and redistribution patterns of PCBs were observed in the brain regions examined. Serotonin concentrations were reduced in frontal cortex and hippocampus, unaffected in hypothalamus and brainstem and elevated in lateral olfactory tract. Serotonin metabolism, estimated by determination of the metabolite to neurotransmitter ratio, was elevated in all brain areas except for the lateral olfactory tract. These results demonstrate that following a single exposure to PCBs, there are significant changes in serotonin concentrations and metabolism in the adult rat. Furthermore, there are regional brain differences with regard to PCB concentrations and the direction and magnitude of neurochemical change induced by the PCBs.

Animals↗
PubMed1985

Lumbar cerebrospinal fluid homovanillic acid concentrations are higher in female than male non-human primates.

Concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were determined in lumbar cerebrospinal fluid from intact male and female Macaca nemestrina. Concentrations of homovanillic acid, but not 5-hydroxyindoleacetic acid were significantly higher in the females under baseline conditions. Following probenecid treatment, 5-hydroxyindoleacetic acid concentrations were significantly elevated over baseline conditions in both sexes although only homovanillic acid concentrations were significantly higher in the female monkeys.

Animals↗
PubMed1985

Polychlorinated biphenyls induce regional changes in brain norepinephrine concentrations in adult rats.

Adult male rats were gavaged with a mixture of Aroclor 1254 and 1260 at a dose level of either 500 or 1000 mg/kg and were killed on post-gavage Days 1, 3, 7 and 14. Total PCB concentrations and concentrations of norepinephrine were determined in the frontal cortex, hypothalamus, hippocampus, and brainstem. Brain regions behaved differently from each other in terms of both initial concentrations and redistribution patterns of PCBs following exposure. Norepinephrine concentrations were reduced in the frontal cortex and hippocampus but were unaffected in the hypothalamus and brainstem. These results demonstrate that the mature mammalian nervous system is sensitive to a brief exposure to PCBs, that the neurological effects are reversible and dependent on the presence of PCBs in the tissue, and that there are regional brain differences with regard to PCB concentrations and direction and magnitude of neurochemical change induced by the PCBs.

Animals↗