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Biomedical subjects

D O Carpenter

Publications and source records attributed to D O Carpenter.

At least 37 records · Page 2Linked to original sources
PubMed2000

In vivo and in vitro exposure to PCB 153 reduces long-term potentiation.

We examined the effects of gestational and lactational exposure to polychlorinated biphenyl (PCB) 153 (2,4,5,2',4',5'-hexaCB) on the magnitude of long-term potentiation (LTP) observed in the CA1 region of hippocampal brain slices prepared from rats at 30 days of age. We compared these actions to those observed when PCB 153 is dissolved in normal Krebs-Ringer solution and perfused on slices from control rats of the same age. In vivo exposure was at three dose levels (1. 25, 5, and 20 mg/kg/day) from gestational day 3 through weaning at postnatal day 21. Although responses to low-frequency stimulation of the Schaffer collateral pathway in exposed animals were not different from controls, significantly reduced LTP was induced after tetanic stimulation, even at the lowest dose studied. We observed a comparable depression of LTP when control slices were perfused with Krebs-Ringer that had been equilibrated with PCB 153 in a generator column. Neither in vivo nor in vitro exposure significantly altered the input-output curves obtained before tetanic stimulation, but both suppressed the increase in response observed in controls after tetanic stimulation. Because LTP is thought to be correlated with learning ability, these observations may provide at least a partial mechanism to explain the reduction of intelligence quotient observed in humans exposed to PCBs early in development.

Animals↗
PubMed2000

The assessment of risk to acquired hypothyroidism from exposure to PCBs: a study among Akwesasne Mohawk women.

PCBs are a family of 209 chemical compounds, each of which consists of two benzene rings and 1 to 10 chlorine atoms. Their long-term stability and dispersion into the environment and the food chain have caused concern about their impact on humans and the environment. Native American communities are believed to be at particularly high risk of such exposure since they typically are more dependent than other populations on local fish and game as a food source. We have evidence for a significant excess in incidence and prevalence of hypothyroidism among Mohawks, particularly older women, as compared to other populations. The goal of the current project is to compare serum PCB concentrations to indicators of thyroid function in controls and patients with demonstrated thyroid dysfunction. Studies on experimental animals (rats) have shown significant depression of circulating levels of T4 and moderate reductions in levels of T3 after exposure to PCBs. We are conducting a retrospective observational case-control study. The participants are Mohawk women 30 years of age and older. Controls are participants in an ongoing environmental epidemiology study, whose thyroid hormone tests show a normal function. Our study aims to investigate the association between long-term exposure to PCBs and acquired hypothyroidism, to identify the critical exposure routes and to develop and apply toxic equivalents for thyroid disease for the various PCB congeners. PCB exposure is assessed by ultra-trace, congener-specific determination in blood specimen using GC/ECD. The study is currently ongoing. We have analyzed 46 samples of cases and 75 samples of controls.

Adult↗
PubMed1999

Carnosine and taurine protect rat cerebellar granular cells from free radical damage.

Carnosine and taurine have been suggested to protect excitable tissues against oxidative stress. We have investigated the protection of cerebellar granule cells (neurons) by these compounds against free radicals generated by kainic acid (KA), and 3-morpholinosydnonimine hydrochloride (SIN-1) treatment. Carnosine decreased free radical levels in KA and SIN-1 treated cells, and increased cell viability. The KA effect, but not that of SIN-1, was dependent on the presence of external Ca2+ ions. Taurine increased cell viability, but did not decrease free radical levels. These results suggest that there are multiple pathways leading to cell death, not all of which involve decreases in intracellular free radical levels, and also indicate that multiple mechanisms of cellular defense exist against oxidative stress.

Animals↗
PubMed1999

Sources of reactive oxygen species production in excitotoxin- stimulated cerebellar granule cells.

Reactive oxygen species (ROS) production in rat cerebellar granule cells in the presence of the excitotoxins N-methyl-d-aspartate (NMDA) and kainic acid (KA) and by the protein kinase C activator phorbol myristate acetate (PMA) was Ca2+-dependent and resulted in decreased cell viability. Exposure of stimulated cells to rotenone (a respiratory chain inhibitor) did not decrease ROS levels and did not affect short-term cell viability. In cells stimulated by NMDA and KA, exposure to indomethacin (a cyclooxygenase inhibitor) and nialamide (a monoamine oxidase inhibitor) caused a decrease in ROS levels and increased cell viability occurred in NMDA-treated cells. In contrast, PMA-stimulated neurons did not show decreased ROS levels when exposed to indomethacin and nialamide. These studies suggest that there is a multiplicity of routes for Ca2+-dependent ROS production in neurons but that ROS generation by cyclooxygenase and monoamine oxidase is not controlled by protein kinase C.

Animals↗
PubMed1999

Carnosine protects against excitotoxic cell death independently of effects on reactive oxygen species.

The role of carnosine, N-acetylcarnosine and homocarnosine as scavengers of reactive oxygen species and protectors against neuronal cell death secondary to excitotoxic concentrations of kainate and N-methyl-D-aspartate was studied using acutely dissociated cerebellar granule cell neurons and flow cytometry. We find that carnosine, N-acetylcarnosine and homocarnosine at physiological concentrations are all potent in suppressing fluorescence of 2',7'-dichlorofluorescein, which reacts with intracellularly generated reactive oxygen species. However, only carnosine in the same concentration range was effective in preventing apoptotic neuronal cell death, studied using a combination of the DNA binding dye, propidium iodide, and a fluorescent derivative of the phosphatidylserine-binding dye, Annexin-V. Our results indicate that carnosine and related compounds are effective scavengers of reactive oxygen species generated by activation of ionotropic glutamate receptors, but that this action does not prevent excitotoxic cell death. Some other process which is sensitive to carnosine but not the related compounds is a critical factor in cell death. These observations indicate that at least in this system reactive oxygen species generation is not a major contributor to excitotoxic neuronal cell death.

Animals↗
PubMed1999

Hazardous wastes in eastern and central Europe: technology and health effects.

Issues of hazardous waste management are major concerns in the countries of eastern and central Europe. A National Institute of Environmental Health Sciences-supported conference was held in Prague, Czech Republic, as a part of a continuing effort to provide information and promote discussion among the countries of eastern and central Europe on issues related to hazardous wastes. The focus was on incineration as a means of disposal of hazardous wastes, with discussions on both engineering methods for safe incineration, and possible human health effects from incineration by-products. Representatives from government agencies, academic institutions, and local industries from 14 countries in the region participated along with a few U.S. and western European experts in this field. A series of 12 country reports documented national issues relating to the environment, with a focus on use of incineration for hazardous waste disposal. A particularly valuable contribution was made by junior scientists from the region, who described results of environmental issues in their countries.

Environmental Health↗
PubMed1999

The electrogenic sodium pump activity in Aplysia neurons is not potential dependent.

We have investigated the potential dependence of the electrogenic sodium pump in Aplysia neurons by recording the potential and current induced by sudden change of the artificial sea water from one containing K+ at various concentrations to K+ -free sea water in the presence or absence of ouabain. Both K+ free sea water and ouabain block sodium transport and result in a significant depolarization due to removal of a maintained outward current that is a result of transport of more Na+ out of the cell than K+ into the cell during pump operation. In the presence of ouabain there is, however, an inward current induced by changing external K+ concentration from zero to some value between 1 and 20 mM, and this current is greater with a greater K+ concentration gradient. The current induced by change from zero to 1 mM K+ does not show any potential dependence, although those currents induced by higher K+ concentrations are potential dependent. We conclude that the activity of the electrogenic sodium pump is not potential dependent, but that the potential independence is obscured if higher concentrations of K+ are used to activate the electrogenic sodium pump.

Animals↗
PubMed1998

Vitamin E enhances Ca(2+)-mediated vulnerability of immature cerebellar granule cells to ischemia.

The effects of vitamin E on lipid peroxidation, intracellular free Ca2+ concentration ([Ca2+]i), and cell death were investigated in the postischemic immature cerebellum. Deprivation of oxygen and glucose for 10-min in a suspension of freshly dissociated granule cells from the cerebellum of 9-day-old male rat pups resulted in a recovery-induced consumption of cell nonenzymatic antioxidants (ascorbic acid, glutathione, and alpha-tocopherol) and development of membrane lipid peroxidation as measured by the thiobarbituric acid method. The rate of lipid peroxidation of the postischemic cells was stimulated, not reduced, by treatment of the cells with vitamin E (5-30 microM alpha-tocopherol phosphate). In flow-cytometric studies a 10-min period of ischemia resulted in a small increase in intracellular calcium concentration, lipid peroxidation products and cell death, but in the presence of alpha-tocopherol the same treatment caused a dramatic increase in cell death, accompanied by a large increase in [Ca2+]i and lipid peroxidation products. Pretreatment of the cells with a mixture of three antioxidants (vitamin C/rutin/ubiquinol-10, 10/5/1) or nickel (Ni2+) reduced the alpha-tocopherol-induced increases in [Ca2+]i, and cell death. Hydrogen peroxide (1 mM) and the water-soluble analogue of vitamin E, trolox (50 microM), mimicked the effect of vitamin E on lipid peroxidation in the postischemic cells. Pretreatment of the cells with the intracellular Ca2+ chelator BAPTA-AM, reduced both the alpha-tocopherol-induced increase in [Ca2+]i and cell death. The effect of vitamin E on [Ca2+]i was age dependent and decreased abruptly during maturation of the cerebellum between the first and second weeks of life. Results of in vitro treatment of the immature cerebellar cells with the water-soluble form of vitamin E (alpha-tocopherol phosphate) suggest that, after consumption of cellular co-antioxidants, vitamin E may be converted to an alpha-tocopheroxyl radical, which act as a toxic prooxidant as cellular bioenergetics deteriorate.

Animals↗
PubMed1998

PCBs reduce long-term potentiation in the CA1 region of rat hippocampus.

Prenatal exposure to polychlorinated biphenyls (PCBs) has been associated with a lower IQ in childhood. We have examined the effects of acute exposure to PCB mixtures and two single congeners on synaptic transmission between Schaffer collaterals and CA1 neurons of the rat hippocampus as well as posttetanic potentiation (PTP), paired pulse facilitation (PPF), and long-term potentiation (LTP). PTP and PPF represent transient increases in transmitter release immediately after stimulation, while LTP is a measure of long-term changes in synaptic plasticity that has been related to learning and memory. LTP, but neither PTP nor PPF, was reduced by Aroclor 1016 in a dose-dependent fashion at concentrations that had little effect on general synaptic transmission. The more highly chlorinated Aroclor 1254 at low concentrations specifically blocked LTP, but at higher concentrations also reduced synaptic transmission. The mono-ortho PCB congener 2,4,4'-trichlorobiphenyl and the coplanar congener 3,3',4,4'-tetrachlorobiphenyl also blocked LTP without effect on PTP or PPF. We conclude that PCBs selectively impair the process of LTP in CA1 neurons of the hippocampus.

Animals↗
PubMed1998

Environmental pollution and child health in central and Eastern Europe.

For the last 50 years, the economic and industrial development of the nations of Central and Eastern Europe has been achieved at the cost of environmental degradation. The health risks posed by this pollution to children and the steps necessary to ameliorate such risks are only beginning to be investigated. At a recent conference in Poland, sponsored in part by the National Institute of Environmental Health Sciences, participants from 11 countries in the region, together with scientists from Western Europe and the United States, met to share information regarding pediatric environmental health in Central and Eastern Europe, to consider methodologic issues in the design and conduct of such studies, and to discuss preventive strategies. This report summarizes the deliberations, outlines problem areas such as heavy metals and air pollution, delineates research and training needs to help Central and Eastern Europeans deal more effectively with such problems, and recommends specific future actions and collaborative efforts.

Air Pollution↗
PubMed1998

Human health and chemical mixtures: an overview.

Unlike laboratory animals, people are rarely exposed to a single hazardous chemical. However, most of the information documenting adverse human health effects from environmental and occupational contaminants has come from studies focused on exposure to single chemicals, and there is little information available on how two or more contaminants affect humans. Most information on the effects of mixtures comes from animal systems and limited investigations of isolated human cells in culture, even though the study of mixtures in such systems has also been neglected. Two or more compounds may show additive, antagonistic, or synergistic interactions or may act on totally different systems and thus not interact. Furthermore, even a single chemical may have multiple effects and affect more than one organ system. Effects may vary with age, and metabolites may have totally different actions from the parent compound. This paper will review the variety of health effects in humans that may result from environmental contaminants and discuss how such contaminants may interact with each other. We will also present examples on how different contaminants interact from toxicologic studies of polychlorinated biphenyls performed as part of our Albany, New York, Superfund Basic Research Program project.

Animals↗
PubMed1998

Polychlorinated biphenyls and human health.

Polychlorinated biphenyls (PCBs) were manufactured and used widely for many years. Because they are very persistent in both the environment and biological systems, there has been significant global contamination. This review presents a summary of known or suspected health effects of various PCB congeners, documented on the basis of both human and animal studies. As our knowledge increases several important points become apparent. PCBs interfere with many biological functions, including the immune system, the nervous system, and several endocrine system, and the fetus appears to be particularly vulnerable to these actions. PCBs cause certain cancers in animals. PCBs are mixtures of multiple congeners, differing on the basis of the numbers and positions of chlorines around the biphenyl ring, and it is becoming increasingly apparent that different congeners may have very different actions. These observations suggest that the potential human health hazards from PCB exposure have been underappreciated.

Animals↗
PubMed1998

Lead potentiates cytokine- and glutamate-mediated increases in permeability of the blood-brain barrier.

We have measured the transendothelial electrical resistance across the blood-brain barrier (BBB) with a microelectrode technique and determined the effects of subcutaneous injections (five injections over ten days) of lipopolysaccharide (LPS, 100 ng/g), recombinant mouse interleukin-6 (IL-6, 5 ng/g), and/or inorganic lead (lead, 2.5 5 micrograms/g) on the ion permeability of arterioles in the temporoparietal cortex of anaesthetized mice between 10 and 40 days of age. In controls the electrical resistance increased with age. It was decreased in animals treated with IL-6, but unaffected by lead at the different ages studied. In IL-6 treated mice, repeated neonatal exposure to lead (five injections between 2 and 10 days after birth) caused a delay in the increase in arteriole resistance with age. LPS injections caused a 36% increase in ion permeability of the BBB in twenty-day-old mice, and lead potentiated this effect of LPS. Intra-arterial injections of glutamate did not alter vascular resistance, but topical applications of glutamate on the cerebrum caused a reversible decrease in the resistance in mice not treated with lead, and an irreversible decrease in mice treated with lead. Injections of glutamate in the lumen of arterial vessels in the parietal and temporoparietal brain areas of mice pretreated with lead and LPS, plus a topical application of glutamate, caused depolarization of neurons in the temporoparietal cortex. These results suggest that disruption of the BBB can allow serum glutamate to penetrate the brain, causing further disruption of the BBB, and that lead irreversibly potentiates this cascade of harmful events.

Animals↗
PubMed1998

Lipopolysaccharide and interleukin-6 enhance lead entry into cerebellar neurons: application of a new and sensitive flow cytometric technique to measure intracellular lead and calcium concentrations.

The distribution of intracellular ionized lead (Pb) and calcium in dissociated cerebellar cells of ten-day-old mice was measured by flow cytometry. There are no fluorescent probes specific for lead, whereas commonly used fluorescent calcium indicators bind heavy metals with greater affinity than they do calcium, which impedes discrimination of lead- and calcium-induced fluorescence changes. Therefore, we developed a method to determine [Pb2+]i and [Ca2+]i by employing a combination of the calcium indicator fluo-3 and the heavy-metal chelator TPEN. Using these methods, we studied the effects of multiple in vivo exposure (five subcutaneous injections over 10 days) to lipopolysaccharide (LPS, 100 ng/g), recombinant mouse interleukin-6 (IL-6, 5 ng/g) and/or inorganic lead (lead, 2.5 micrograms/g) on lead and calcium concentrations. Control cells had [Cai] of 112 nM. Lead exposure alone had little effect on [Ca2+]i and resulted in a mean [Pb2+]i of about 7 pM, and did not alter cell volume. A significant fraction of cells (about 44% of living cells) from animals treated with lead plus LPS were swollen, as determined by analysis of the light scattering pattern, and there was a small increase in the number of dead cells, identified with the nucleic acid stain, 7-aminoactinomycin. While [Ca2+]i was not significantly increased in animals treated with either only LPS or IL-6, lead and calcium concentrations were increased in animals exposed to lead and LPS or IL-6 in both the non-swollen and swollen cells, with a mean value of (Pb2+)i of 32 pM and (Ca2+)i of 155 nM in cells not swollen. Electrophysiological analysis showed that LPS injections caused decreases in the membrane potential of endothelial cells of the blood-brain barrier (BBB) and lead potentiated the effect of LPS. IL-6 mimicked the effects of LPS, but was less potent. Thus these experiments indicate a synergistic interaction between lead and cytokines on biophysical properties of both neurons and endothelial cells of the BBB.

Animals↗
PubMed1998

Time series analysis of Aplysia total motion activity.

We rely on various nonparametric time series techniques to quantify several autocorrelated Aplysia total motion activity series. The effect of light on total motion activity has been removed. A general model will be proposed for total motion activity, which is found to display a circadian rhythm, and the toxic effect of PCBs on total motion activity will be assessed. No underlying assumptions are made about the form of the circadian rhythm. Several types of circadian total motion activity patterns are discovered. We form the hypothesis that different data series may be separated into three distinct groups of common patterns of circadian total motion activity. We also investigate if in fact only a single innate oscillator regulates total motion activity.

Animals↗