Biomedical subjects

David O Carpenter

Publications and source records attributed to David O Carpenter.

44 records · Page 3Linked to original sources

PubMed2003

The mechanism of presynaptic long-term depression mediated by group I metabotropic glutamate receptors.

1. Metabotropic glutamate receptors (mGluRs) are known to play a role in synaptic plasticity. In a study of rat hippocampal brain slices, we find that a brief perfusion of a group I mGluR agonist, (S)-3,5-dihydroxyphenylglycine (DHPG), induced a robust long-term depression (DHPG-LTD) in area CA1. 2. The action was accompanied by an enhancement of the paired-pulse facilitation (PPF) ratio. 3. At the same time DHPG enhanced ionophoretic responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), kainic acid (KA), and N-methyl-D-aspartate (NMDA) in CA1 pyramidal neurons. This was only partially reversed by washing. 4. These observations indicate that DHPG exerts two opposing actions, suppression of the synaptic transmission and facilitation of postsynaptic responses. However, the presynaptic action dominates, since the net effect of monosynaptic activation is a reduction of response. 5. Perfusion of DHPG reduced three calcium-dependent responses in CA3 pyramidal neurons, which are presynaptic to CA1 neurons. These are calcium spike width and amplitude, after-hyperpolarization (AHP), and spike frequency adaptation (SFA). 6. These results suggest that the DHPG-LTD results from modulation of the presynaptic calcium currents by group I mGluRs.

Animals↗

PubMed2003

Low birth weight and residential proximity to PCB-contaminated waste sites.

Previous investigations have shown that women exposed to polychlorinated biphenyls (PCBs) are at increased risk of giving birth to an infant with low birth weight (< 2,500 g), and that this relationship is stronger for male than for female infants. We have tested the hypothesis that residents in a zip code that contains a PCB hazardous waste site or abuts a body of water contaminated with PCBs are at increased risk of giving birth to a low-birth-weight baby. We used the birth registry of the New York State Vital Statistics to identify all births between 1994 and 2000 in New York State except for New York City. This registry provides information on the infant, mother, and father together with the zip code of the mother's residence. The 865 state Superfund sites, the 86 National Priority List sites, and the six Areas of Concern in New York were characterized regarding whether or not they contain PCBs as a major contaminant. We identified 187 zip codes containing or abutting PCB-contaminated sites, and these zip codes were the residences of 24.5% of the 945,077 births. The birth weight in the PCB zip codes was on average 21.6 g less than in other zip codes (p < 0.001). Because there are many other risk factors for low birth weight, we have adjusted for these using a logistic regression model for these confounders. After adjusting for sex of the infant, mother's age, race, weight, height, education, income, marital status, and smoking, there was still a statistically significant 6% increased risk of giving birth to a male infant of low birth weight. These observations support the hypothesis that living in a zip code near a PCB-contaminated site poses a risk of exposure and giving birth to an infant of low birth weight.

Confounding Factors, Epidemiologic↗

PubMed2003

The need for global environmental health policy.

The world economy has been growing by an average of 3.5% a year. Continued global development is sustainable if overall social assets remain constant or rise over time, including manufactured, human, and environmental capital. Sustainable development requires that society not decrease its overall assets. But unregulated global trade may result in long-term loss of environmental capital. Multilateral governance is needed. Classical business models tend to view environmental damage as an externality--an impact on a third party's welfare that is neither compensated nor appropriated. The Rio Declaration on Environment and Development clearly states that economic development must err on the side of environmental integrity. Whereas UN Environmental Program policy requires precaution in the face of scientific uncertainty, World Trade Organization policy requires scientific certainty before precaution can be used. The conflict is obvious. In fact, there is gross lack of policy coordination across institutions. This article looks at some environmental strains and concludes that trade policy must address all aspects of human welfare, not merely the economic.

Journal Article↗

PubMed2002

Understanding the human health effects of chemical mixtures.

Most research on the effects of chemicals on biologic systems is conducted on one chemical at a time. However, in the real world people are exposed to mixtures, not single chemicals. Although various substances may have totally independent actions, in many cases two substances may act at the same site in ways that can be either additive or nonadditive. Many even more complex interactions may occur if two chemicals act at different but related targets. In the extreme case there may be synergistic effects, in which case the effects of two substances together are greater than the sum of either effect alone. In reality, most persons are exposed to many chemicals, not just one or two, and therefore the effects of a chemical mixture are extremely complex and may differ for each mixture depending on the chemical composition. This complexity is a major reason why mixtures have not been well studied. In this review we attempt to illustrate some of the principles and approaches that can be used to study effects of mixtures. By the nature of the state of the science, this discussion is more a presentation of what we do not know than of what we do know about mixtures. We approach the study of mixtures at three levels, using specific examples. First, we discuss several human diseases in relation to a variety of environmental agents believed to influence the development and progression of the disease. We present results of selected cellular and animal studies in which simple mixtures have been investigated. Finally, we discuss some of the effects of mixtures at a molecular level.

Animals↗

PubMed2002

Electrophysiologic and behavioral effects of perinatal and acute exposure of rats to lead and polychlorinated biphenyls.

Lead and polychlorinated biphenyls (PCBs) both cause a reduction of intelligence quotient and behavioral abnormalities in exposed children that have features in common with attention deficit hyperactivity disorder. We have used rats as a model to study the effects of both perinatal and acute exposure to lead or PCBs in an effort to compare and understand the mechanisms of these nervous system decrements. Long-term potentiation (LTP) is an electrophysiologic measurement that correlates well with cognitive ability. We have determined the effects of chronic perinatal exposure to lead or PCB 153 as well as acute application of these substances to isolated brain slices, with recordings in two areas of the hippocampus, CA1 and CA3. Both substances, whether chronically or acutely applied, significantly reduced LTP in CA1 in animals at age 30 and 60 days. In CA3, they reduced LTP in 30-day animals but potentiated it in 60-day animals. Although neither lead nor PCB 153 alters baseline synaptic transmission at low stimulus strengths, at higher levels they induce changes in the same direction as those of LTP. These results show surprisingly similar actions of these quite different chemicals, and the similarity of effects on chronic and acute application indicates that effects are both pharmacologic and developmental. Behavioral studies of rats exposed to PCBs from contaminated fish show hyperactivity, impulsiveness, and increased frustration relative to unexposed controls. These results demonstrate that lead and PCBs have similar effects on synaptic plasticity and behavior and suggest that the compounds may act through a common mechanism.

Adult↗

PubMedDate not supplied

Expansion of visual receptive fields in experimental glaucoma.

Glaucoma is a major cause of blindness and is characterized by death of retinal ganglion cells. In a rat model of glaucoma in which intraocular pressure is raised by cautery of episcleral veins, the somata and dendritic arbors of surviving retinal ganglion cells expand. To assess physiological consequences of this change, we have measured visual receptive-field size in a primary retinal target, the superior colliculus. Using multiunit recording, receptive-field sizes were measured for glaucomatous eyes and compared to both those measured for contralateral control eyes and to homolateral eyes of unoperated animals. Episcleral vein occlusion increased intraocular pressure. This was accompanied by a significant increase in receptive-field size across the superior colliculus. The expansion of receptive fields was proportional to both degree and duration of the increase of intraocular pressure. We suggest that this increase in the size of receptive fields of glaucomatous eyes may be related to the increase in the size of dendritic arbors of the surviving ganglion cells in retina.

Animals↗

PubMedDate not supplied

Children's environmental health in Central Asia and the Middle east.

Children in Central Asia and the Middle East bear disproportionate environmental threats to health, of which the most widespread and serious result from poverty, malnutrition, lack of access to safe drinking water and food, and exposures to toxic chemicals. Their psychological health is threatened in several parts of this region by internal wars and strife. Many, or even most, children are regularly exposed to environmental tobacco smoke. In many of these countries, children constitute very high percentages of the population. Because children constitute the future, it is critical that these threats to their health be addressed and reduced to the greatest extent possible through both provision of safe and adequate drinking water and nutrition and reduction of exposures to environmental contaminants.

Asia↗

PubMedDate not supplied

Polychlorinated biphenyls (PCBs): routes of exposure and effects on human health.

The polychlorinated biphenyls (PCBs) are synthetic organochlorine chemicals that were useful industrial products in the past, but their production was ended because they persist in both the environment and living organisms. The PCBs are mixtures of up to 209 different components (congeners), depending on the number and position of chlorines around the biphenyl ring. The PCBs are fat-soluble substances to which everyone is exposed through ingesting animal fats, inhalation, or dermal contact. Exposure to PCBs suppresses the immune system, thereby increasing the risk of acquiring several human diseases. Both ortho-substituted and coplanar (dioxin-like) congeners are tumor promoters that enhance the effects of other carcinogenic substances. PCB exposure, especially during fetal and early life, reduces IQ and alters behavior. The PCBs alter thyroid and reproductive function in both males and females and increase the risk of developing cardiovascular and liver disease and diabetes. Women are at high risk of giving birth to infants of low birth weight, who are at high lifetime risk for several diseases. As knowledge of their toxic effects has grown faster than environmental levels have declined, PCBs remain dangerous contaminants.

Chronic Disease↗