PubMed Health⌕ Search

Biomedical subjects

David O Carpenter

Publications and source records attributed to David O Carpenter.

At least 19 recordsLinked to original sources
PubMed2006

PCBs, PCDD/Fs, and organochlorine pesticides in farmed Atlantic salmon from Maine, eastern Canada, and Norway, and wild salmon from Alaska.

Farmed Atlantic salmon (Salmo salar) from Maine and eastern Canada, wild Alaskan Chinook salmon (Oncorhynchus tshawytscha), and organically farmed Norwegian salmon samples were analyzed for the presence of polychlorinated biphenyls (PCBs), dioxin-like PCBs, polychlorinated dibenzo-p-dioxins (PCDDs), dibenzo-p-furans (PCDFs), and chlorinated pesticides. PCDD and PCDF congeners were not detected in > 80% of the samples analyzed. Total PCB concentrations (7.2-29.5 ng/g, wet weight, ww) in the farmed salmon were significantly higher than those in the wild Alaskan Chinook samples (3.9-8.1 ng/g, ww). Concentrations of PCBs, WHO PCB TEQs, and chlorinated pesticides varied significantly by region. PCB and WHO PCB TEQ concentrations in farmed salmon from eastern Canada were lower than those reported in samples collected two years earlier, possibly reflecting recent industry efforts to lower contaminant concentrations in feed. Organically farmed Norwegian salmon had the highest concentrations of PCBs (mean: 27 ng/g, ww) and WHO PCB TEQs (2.85 pg/g,ww); their TEQ values are in the higher range of those reported in farmed salmon from around the world. Removal of skin from salmon fillets resulted in highly variable reductions of lipids and contaminants, and in some skin-off samples, contaminant levels were higher, suggesting that skin removal does not protect the consumer from health risks associated with consumption of farmed salmon.

Alaska↗
PubMed2006

Modulatory effects of Aroclors 1221 and 1254 on bone turnover and vertebral histology in intact and ovariectomized rats.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. Two PCB mixtures, Aroclors 1221 and 1254 have been suggested to have estrogenic and anti-estrogenic properties, respectively. We have examined whether these PCB mixtures modulate bone turnover and vertebral histology in intact and ovariectomized (ovx) rat models. Thirty-two adult female rats were divided into four groups subcutaneously receiving 4% DMSO (control), A1221 (10 mg/kg), A1254 (10 mg/kg) oestradiol (E2, 30 microg/kg). These compounds were injected to the animals for a period of 6 weeks at two daily intervals. In the second model, rats (n=32) were ovx and allowed to recover for a period of 3 weeks. Control group received vehicle (4% DMSO) alone. Remaining rats were divided into three groups and injected (s.c.) with A1221, A1254 and E2 for 5 weeks. Urine samples were collected prior to end of the experiments. Then, all animals were decapitated. Serum parathyroid hormone (PTH), calcitonin and osteocalcin levels were determined by immunoradiometric method. Serum concentrations of alkaline phosphatase (ALP), calcium and inorganic phosphate were determined by enzymatic-colorimetric method. Urinary deoxypyridinoline (DPD) was measured by ELISA. Lumbar vertebrae (L2) of all animals were dissected out and processed for light microscopy. Levels of urinary DPD were significantly lowered in E2 -treated intact rats (p<0.001). Ovx significantly increased urinary DPD excretion (p<0.01) compared to intact control values. Administration of A1221 and A1254 had no significant effects in intact rats, however, they significantly reduced (p<0.05) and increased (p<0.001) urinary DPD levels in ovx rats, respectively. Neither of the PCB mixtures significantly changed serum osteocalcin and ALP levels in intact or ovx rats (except A1221 increased ALP in intact model, p<0.01). Both PCB mixtures had differential effects on serum PTH, calcitonin, calcium and inorganic phosphate concentrations. Treatment with A1221 reversed the adverse effects of ovariectomy on L2 histology. However, A1254 produced necrotic areas in vertebral bone, and this effect was expanded in ovx animals. Our findings suggest that both Aroclor compounds interfere with bone turnover mechanisms, particularly in ovx rats.

Alkaline Phosphatase↗
PubMed2006

Effects of melatonin on synaptic transmission and long-term potentiation in two areas of mouse hippocampus.

We have examined the effects of melatonin on synaptic transmission and long-term potentiation (LTP) in the Schaffer Collateral-CA1 and the mossy fiber-CA3 pathways in mouse hippocampus brain slices. Melatonin (0.1-1 mM) application had different actions on both the field excitatory postsynaptic potentials (fEPSPS) and LTP in the CA1 as compared to the CA3. In CA1, 0.1 mM melatonin blocked LTP, while 1 mM melatonin also depressed the fEPSP. In CA3, neither 0.1 nor 1 mM melatonin altered the fEPSP, whereas both concentrations only slightly reduced LTP. These results demonstrate that melatonin significantly alters synaptic transmission and LTP in the CA1 but has only modest actions in CA3.

Animals↗
PubMed2006

Childhood asthma and indoor allergens in Native Americans in New York.

BACKGROUND: The objective of this study was to assess the correlation between childhood asthma and potential risk factors, especially exposure to indoor allergens, in a Native American population. METHODS: A case-control study of St. Regis Mohawk tribe children ages 2-14 years, 25 diagnosed with asthma and 25 controls was conducted. Exposure was assessed based on a personal interview and measurement of mite and cat allergens (Der p 1, Fel d 1) in indoor dust. RESULTS: A non-significant increased risk of childhood asthma was associated with self-reported family history of asthma, childhood environmental tobacco smoke exposure, and air pollution. There was a significant protective effect of breastfeeding against current asthma in children less than 14 years (5.2 fold lower risk). About 80% of dust mite and 15% of cat allergen samples were above the threshold values for sensitization of 2 and 1 mug/g, respectively. The association between current asthma and exposure to dust mite and cat allergens was positive but not statistically significant. CONCLUSION: This research identified several potential indoor and outdoor risk factors for asthma in Mohawks homes, of which avoidance may reduce or delay the development of asthma in susceptible individuals.

Adolescent↗
PubMed2006

Exposure to persistent organic pollutants and hypertensive disease.

Previous research suggests that exposure to persistent organic pollutants (POPs) increases the risk of chronic diseases such as hypertension. We identified the zip codes of more than 800 waste sites contaminated with POPs and other pollutants, based on which we classified zip codes of upstate New York into three groups: "POPs sites", zip codes containing hazardous waste sites with POPs; "other waste sites", zip codes containing hazardous waste sites but not with POPs; and "clean sites", zip codes without any known hazardous waste sites. Age, gender, race, and zip code of residence of patients diagnosed with hypertension (ICD-9 codes 401-404) were identified using the New York Statewide Planning and Research Cooperative System (SPARCS) for the years 1993-2000. A generalized linear model, the negative binomial model, was used to assess the effect of living in a zip code with a hazardous waste site on the discharge rate of hypertension. After control for the aforementioned covariates, we found a statistically significant elevation of 19.2% (95% CI = 8.5%, 31%) in hypertension discharge rate for "POPs sites" and a 10% elevation in discharge rates for "other waste sites" as compared to "clean sites". In a subset of "POPs sites" where people have higher income, smoke less, exercise more and have healthier diets, there was still a 13.9% elevation of hypertension discharge rate as compared to "clean sites". The results support the hypothesis that living near hazardous waste sites, particularly sites containing POPs, may constitute a risk of exposure and of developing hypertension.

Adult↗
PubMed2006

Cerebellar granule cell death induced by aluminum.

Using flow cytometry of acutely isolated cerebellar granule cell neurons, we have determined the effects of Al (III) on viability, membrane potential, intracellular calcium concentration and generation of reactive oxygen species (ROS). Al (III) killed granule cells in a time- and concentration-dependent fashion when monitored by use of the DNA-binding dye, propidium iodide. The threshold concentration was about 50 micromolar, and cell death at 100 micromolar was apparent after 30 min exposure and increased over time. Cell death was accompanied by cell swelling and a decrease in membrane potential, and was not dependent on external calcium concentration. While exposure to Al (III) was accompanied by an increase in ROS and an elevation of intracellular calcium concentration, calcium chelators and ROS scavengers did not reduce cell death. The action of Al (III) was not accompanied by activation of caspase-3 or an increase in annexin-V binding, both indicators of apoptosis. In the presence of intracellular O,O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid (BAPTA) and absence of extracellular calcium there was still a fluo-3 signal, which likely reflects an accumulation of intracellular Al (III). These observations suggest that the cell death is subsequent to intracellular accumulation of Al (III) and subsequent perturbation of cellular metabolism.

Aluminum↗
PubMed2005

Lipid composition and contaminants in farmed and wild salmon.

Levels of omega-3 (n-3) and omega-6 (n-6) fatty acids and lipid-adjusted concentrations of polychlorinated biphenyls (PCBs), dioxins, toxaphene, and dieldrin were determined in 459 farmed Atlantic salmon, 135 wild Pacific salmon, and 144 supermarket farmed Atlantic salmon fillets purchased in 16 cities in North America and Europe. These were the same fish previously used for measurement of organohalogen contaminants. Farmed salmon had greater levels of total lipid (average 16.6%) than wild salmon (average 6.4%). The n-3 to n-6 ratio was about 10 in wild salmon and 3-4 in farmed salmon. The supermarket samples were similar to the farmed salmon from the same region. Lipid-adjusted contaminant levels were significantly higher in farmed Atlantic salmon than those in wild Pacific salmon (F = 7.27, P = 0.0089 for toxaphene; F = 15.39, P = 0.0002 for dioxin; F > or = 21.31, P < 0.0001 for dieldrin and PCBs, with df = (1.64) for all). Levels of total lipid were in the range of 30-40% in the fish oil/fish meal that is fed to farmed salmon. Salmon, especially farmed salmon, are a good source of healthy n-3 fatty acids, but they also contain high concentrations of organochlorine compounds such as PCBs, dioxins, and chlorinated pesticides. The presence of these contaminants may reduce the net health benefits derived from the consumption of farmed salmon, despite the presence of the high level of n-3 fatty acids in these fish.

Animals↗
PubMed2005

Effects of PCB 52 and PCB 77 on cell viability, [Ca(2+)](i) levels and membrane fluidity in mouse thymocytes.

Exposure to polychlorinated biphenyls (PCBs) is known to suppress immune system function and this action is usually ascribed to dioxin-like PCBs that act via the Ah receptor. We have studied the effects of one ortho-substituted, non-dioxin-like PCB (PCB 52) and one coplanar, dioxin-like congener (PCB 77) on properties of thymocytes acutely isolated from mice. Viability of thymocytes was dose- and time-dependently reduced by PCB 52 with a threshold concentration of about 1 microM, while there was no effect of PCB 77 on viability at concentrations less than 10 microM. Cell death was detectible within 5 min of exposure. Both congeners caused a dose-dependent increase in [Ca(2+)](i), but the threshold concentration was 1 microM for PCB 52 and 5 microM for PCB 77. However, the cell death was not due to the elevation of [Ca(2+)](i), since it was not reduced by incubation in Ca-free Tyrode's Solution. PCB 52, but not PCB 77, caused an increase in membrane fluidity at a concentration of 5 microM. These observations are consistent with previous results that suggest that ortho-substituted PCB congeners dissolve in cell membrane and cause greater disruption of function than do dioxin-like PCB congeners.

Animals↗
PubMed2005

Consumption advisories for salmon based on risk of cancer and noncancer health effects.

The levels of dioxins/furans, polychlorinated biphenyls (PCBs), and chlorinated pesticides were determined in farmed salmon for eight regions in Europe, North America, and South America, in salmon fillets purchased in 16 cities in Europe and North America, and in five species of wild Pacific salmon. Upon application of US Environmental Protection Agency (USEPA) methods for developing fish consumption advisories for cancer from mixtures of all of these substance for which USEPA has reported a cancer slope factor, the most stringent recommendation, for farmed salmon from northern Europe, was for consumption of at most one meal every 5 months in order to not exceed an elevated risk of cancer of more than 1 in 100,000. Farmed salmon from North and South America triggered advisories of between 0.4 and one meal per month. Retail market samples, in general, reflected levels found in regionally farmed fish, although much of the US salmon comes from Chile, which had somewhat lower contaminant levels than the North American farmed samples. Upon consideration of all of these organochlorine compounds as a mixture, even wild Pacific salmon triggered advisories of between one and less than five meals per month. The advisories are driven by the non-dioxin-like PCBs and pesticides and not by dioxins/furans and coplanar PCBs. For noncancer effects for contaminants where USEPA has provided a reference dose only endrin and PCBs triggered any significant advisory. For both of these in the worst case, farmed salmon from northern Europe, the advice was not more than three meals per month.

Animals↗
PubMed2005

Hazardous waste sites and stroke in New York State.

BACKGROUND: Environmental exposure to persistent organic pollutants (POPs) may lead to elevation of serum lipids, increasing risk of atherosclerosis with thromboembolism, a recognized cause of stroke. We tested the hypothesis that exposure to contaminants from residence near hazardous waste sites in New York State influences the occurrence of stroke. METHODS: The rates of stroke hospital discharges were compared among residents of zip codes containing hazardous waste sites with POPs, other pollutants or without any waste sites using information for 1993-2000 from the New York Statewide Planning and Research Cooperative System (SPARCS) database, containing the records of all discharge diagnoses for patients admitted to state-regulated hospitals. RESULTS: After adjustment for age and race, the hospitalization rate for stroke in zip codes with POPs-contaminated sites was 15% higher than in zip codes without any documented hazardous waste sites (RR 1.15, 95% CI, 1.05, 1.26). For ischemic stroke only, the RR was 1.17 (95% CI 1.04, 1.31). Residents of zip codes containing other waste sites showed a RR of 1.13 (95% CI, 1.02, 1.24) as compared to zip codes without an identified waste site. CONCLUSION: These results suggest that living near a source of POPs contamination constitutes a risk of exposure and an increased risk of acquiring cerebrovascular disease. However further research with better control of individual risk factors and direct measurement of exposure is necessary for providing additional support for this hypothesis.

Adult↗
PubMed2005

A new fast electrophysiological response measured extracellularly in a mouse hippocampal brain slice.

In a hippocampal mouse brain slice the CA1 stratum radiatum field potential evoked by electrical stimulation of the Schaffer collaterals was used to analyze the very early responses. Parallel bipolar electrodes were utilized to lower the voltage induced by the stimulating current in the recording electrode, and to keep the induced voltage within the linear range of the headstage preamplifier and the recording amplifiers. When the stimulating and recording electrodes are in saline in the same plane and same depth, the shapes of the recorded voltage and stimulating current are similar. The shape of the recorded voltage significantly changes when the recording electrode is in the stratum radiatum of CA1. The signal recorded in the first 2 ms, before the presynaptic volley, indicates the existence of a fast response shown as a positive deflection. For times slightly longer than the stimulating pulse width, the fast response overlaps with the voltage induced by the discharging of the polarization charge accumulated in the double layer capacitance at the interface between metal and saline. For times longer than about 1.4 ms the fast response and presynaptic volley are superimposed. The fast response is about 0.5 mV when the stimulating charge is 15-25 nC. The demonstration that the fast response disappears upon bath perfusion of tetrodotoxin is convincing support for its axonal origin. We postulate that this fast response represents the current source corresponding to the Schaffer collaterals excitatory sink. An undistorted recording of the first 2 ms of the sweep gives useful information about the fast neuronal activity measured extracellularly, and cannot be regarded as a simple stimulus artifact.

Action Potentials↗
PubMed2005

A comparison of the roles of protein kinase C in long-term potentiation in rat hippocampal areas CA1 and CA3.

1. Using agonists and antagonists with specificity toward various isozymes, we have examined the role of protein kinase C (PKC) in long-term potentiation (LTP) in rat hippocampal areas CA1 and CA3. 2. Agonists (indolactum V but not phorbol ester) and antagonists (sphingosine, staurosporine, chelerytherene) acting at all PKC isozymes reduce or block LTP induction at both sites. 3. However ingenol, a relatively specific agonist at the delta and epsilon isozymes, blocks LTP in the MF-CA3 pathway, but not in the SC-CA1 pathway. 4. Go6976, a relatively specific antagonist of the alpha and beta isozymes, blocks LTP in the SC-CA1 pathway at both ages tested (30- and 60-day-old animals), but blocks LTP in the MF-CA3 in 60 but not 30-day-old animals. 5. Our studies indicate that different PKC isozymes are crucial to LTP induction in these two areas of hippocampus, and that there are development changes in the profile of isozymes.

Animals↗
PubMed2005

Polychlorinated biphenyl (PCB) exposure assessment by multivariate statistical analysis of serum congener profiles in an adult Native American population.

The major determinants of human polychlorinated biphenyl (PCB) body burden include the source and route of exposure and the toxicokinetic processes occurring after uptake. However, the relative importance of each factor for individual subjects cannot currently be determined. The present study characterizes levels and patterns of PCB congeners in a large cohort of adult Akwesasne Mohawks with historical PCB exposure. Total serum PCB ranged from 0.29 to 48.32 ng/g and was higher in adult men than in women (median of 3.81 vs. 2.94 ng/g). The mean serum congener profile for the full cohort was dominated by persistent penta- to hepta-chlorinated biphenyls; several labile congeners were also prominent. In order to provide additional information on individual body burden determinants, multivariate exploratory data analysis techniques were applied to the congener-specific serum PCB data. A self-training receptor model, polytopic vector analysis (PVA), was employed to determine the number, composition, and relative proportions of independent congener patterns that contributed to the overall serum PCB profile for each Mohawk subject. PVA identified five such patterns, each of which was characterized by a unique mix of congeners. One pattern observed in a limited number of Mohawks was similar to those reported for air sampled near contaminated sediment deposits at Akwesasne and for volatilized Aroclor 1248 and is hypothesized to reflect recent inhalation exposure in these subjects. A second pattern was consistent with unaltered Aroclor 1254. A third pattern, resembling Aroclor 1262 but without labile congeners, was correlated with age and is interpreted as representing a lifetime PCB accumulation profile. The final two patterns were dominated by subsets of major persistent congeners and are hypothesized to reflect intermediate bioaccumulation profiles and/or differences in individual toxicokinetics. The results confirm the utility of a multivariate exploratory analysis approach to congener-specific PCB data and provide additional insight into the exposure and individual factors that determine PCB body burden in this population.

Adolescent↗
PubMed2005

Effects of PCBs 52 and 77 on Th1/Th2 balance in mouse thymocyte cell cultures.

Polychlorinated biphenyls (PCBs) are industrial chemicals that have been released into the environment, resulting in widespread and persistent contamination. PCBs exist as 209 different congeners depending on the chlorine substitution on the biphenyl rings, and the physical properties and toxic effects of different PCB congeners are structure-dependent. We have tested an ortho-substituted, noncoplanar congener, 2,2',5,5'-tetrachlorobiphenyl (PCB 52), and a non-ortho-substituted coplanar congener, 3,3',4,4'-tetrachlorobiphenyl (PCB 77), for their effects on the T helper 1 (Th1) and T helper 2 (Th2) lymphocyte balance. The experiments were performed in 10 microg/ml concanavalin A (Con A)-stimulated and nonstimulated thymocytes for determination of cytokine production profiles. Interferon-gamma (produced by Th1 cells) and interleukin (IL)-10 (produced by Th2 cells) concentrations were measured in the supernatants at 12 and 24 hr after treatment with PCBs. PCBs 52 and 77 caused significant increases in interferon-gamma levels at 12 and 24 hr in both Con A-stimulated and nonstimulated media. IL-10 levels were significantly reduced at two interval periods by PCBs 52 and 77 in cultures with and without Con A. Our results show that the cytokine production profile was significantly shifted to Th1 by both ortho-substituted and coplanar PCB congeners in mouse thymocyte cultures.

Animals↗
PubMed2005

Quantitative analysis of the benefits and risks of consuming farmed and wild salmon.

Contaminants in farmed Atlantic and wild Pacific salmon raise important questions about the competing health benefits and risks of fish consumption. A benefit-risk analysis was conducted to compare quantitatively the cancer and noncancer risks of exposure to organic contaminants in salmon with the (n-3) fatty acid-associated health benefits of salmon consumption. Recommended levels of (n-3) fatty acid intake, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may be achieved by consuming farmed or wild salmon while maintaining an acceptable level of noncarcinogenic risk. However, the recommended level of EPA+DHA intake cannot be achieved solely from farmed or wild salmon while maintaining an acceptable level of carcinogenic risk. Although the benefit-risk ratio for carcinogens and noncarcinogens is significantly greater for wild Pacific salmon than for farmed Atlantic salmon as a group, the ratio for some subgroups of farmed salmon is on par with the ratio for wild salmon. This analysis suggests that risk of exposure to contaminants in farmed and wild salmon is partially offset by the fatty acid-associated health benefits. However, young children, women of child-bearing age, pregnant women, and nursing mothers not at significant risk for sudden cardiac death associated with CHD but concerned with health impairments such as reduction in IQ and other cognitive and behavioral effects, can minimize contaminant exposure by choosing the least contaminated wild salmon or by selecting other sources of (n-3) fatty acids.

Animals↗
PubMed2005

Emerging evidence for a similar role of glutamate receptors in the nervous and immune systems.

The role of glutamate receptors in synaptic transmission and excitotoxicity in the nervous system is well established. Recent evidence has emerged that glutamatergic mechanisms also exist in a wide variety of non-neuronal cells. In the case of thymocytes and lymphocytes, several types of glutamate receptor are expressed which can induce functional changes. This review focuses on the cellular function of NMDA-activated ionotropic and groups I and III metabotropic glutamate receptors in lymphocytes. Levels of exogenous and endogenous circulatory agonists and antagonists for lymphocyte glutamate receptors, notably homocysteine metabolites, are markedly increased in certain disease states and may be involved in disorders of the immune system. In addition to glutamate and aspartate, these compounds are active at glutamate receptors and increase the excitotoxic effects of glutamate in both neurons and lymphocytes. Increased levels of compounds acting at glutamate receptors may be risk factors for organ damage, for example in both heart and kidney disease. We conclude that glutamate is involved in signaling in immunocompetent cells and that the expression of both ionotropic and metabotropic glutamate receptors may have regulatory functions in immunocompetent cells, as well as in the nervous system. In addition, glutamate may serve as a signaling agent between the immune and nervous systems.

Animals↗