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Tissue Concentrations (tissue + concentration)
Selected AbstractsChlorinated hydrocarbons in flatfishes from the Southern California, USA, BightENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2000Kenneth Schiff Abstract Alhough inputs of chlorinated hydrocarbon compounds to the Southern California Bight (SCB) are presently low, historical deposits represent a source of bioaccumulation potential to sediment-associated fauna. To assess this bioaccumulation potential, 14 chlorinated hydrocarbon classes were measured in livers of three species of flatfish collected from 63 randomly selected sites on the coastal shelf between Point Conception and the United States,Mexico international border. Tissue contamination was widespread throughout the SCB, but was limited to just two chlorinated hydrocarbon classes. Virtually 100% of Pacific sanddab (Citharichthys sordidus) and longfin sanddab (Citharichthys xanthostigma) populations were estimated to be contaminated with dichlorodiphenyltrichloroethane (total DDT = sum of o,p, and p,p, isomers of DDT + dichlorodiphenyldichloroethylene [DDE] + dichlorodiphenyldichloroethane [DDD]) and/or polychlorinated biphenyls (total PCBs). Total DDT also contaminated the majority (64%) of the Dover sole (Microstomus pacificus) population in the SCB. Total PCB measurements in tissues of SCB flatfish were dominated by 12 congeners (52, 66, 87, 101, 105, 118, 128, 138, 153, 170, 180, and 187), which averaged 95% of the combined mass of the 27 congeners analyzed. Sediment concentrations (normalized by total organic carbon content) accounted for most of the variability observed in tissue concentrations (normalized by lipid content) for 8 of these 12 congeners and total PCBs. Normalized sediment concentrations were also significantly correlated to normalized tissue concentrations for total DDT and p,p,-DDE. Tissue concentrations measured in this study from reference areas of the SCB were compared to tissue concentrations measured from reference areas in studies conducted in 1977 and 1985. Total DDT and total PCB liver concentrations were found to have decreased one to two orders of magnitude in Pacific and longfin sanddabs between 1985 and 1994. Total DDT and total PCB liver concentrations decreased 5- to 35-fold in Dover sole between 1977 and 1994. [source] Human skin permeation of ,8 -tetrahydrocannabinol, cannabidiol and cannabinolJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2004Audra L. Stinchcomb ABSTRACT The purpose of this study was to quantify the in-vitro human skin transdermal flux of ,8 -tetrahydrocannabinol (,8 -THC), cannabidiol (CBD) and cannabinol (CBN). These cannabinoids are of interest because they are likely candidates for transdermal combination therapy. Differential thermal analysis and in-vitro diffusion studies with human tissue were completed for the compounds. Heats of fusion, melting points and relative thermodynamic activities were determined for the crystalline compounds, CBD and CBN. Flux, permeability, tissue concentration and lag times were measured in the diffusion experiments. CBN had a lower heat of fusion and corresponding higher calculated relative thermodynamic activity than CBD. Ethanol concentrations of 30 to 33% significantly increased the transdermal flux of ,8 -THC and CBD. Tissue concentrations of ,8 -THC were significantly higher than for CBN. Lag times for CBD were significantly smaller than for CBN. The permeabilities of CBD and CBN were 10-fold higher than for ,8 -THC. Combinations of these cannabinoids with ethanol will be further studied in transdermal patch formulations in vitro and in vivo, as significant flux levels of all the drugs were obtained. CBD, the most polar of the three drugs, and other more polar cannabinoids will also be the focus of future drug design studies for improved transdermal delivery rates. [source] Quantification of metabolites in breast cancer patients with different clinical prognosis using HR MAS MR spectroscopyNMR IN BIOMEDICINE, Issue 4 2010Beathe Sitter Abstract Absolute quantitative measures of breast cancer tissue metabolites can increase our understanding of biological processes. Electronic REference To access In vivo Concentrations (ERETIC) was applied to high resolution magic angle spinning MR spectroscopy (HR MAS MRS) to quantify metabolites in intact breast cancer samples. The ERETIC signal was calibrated using solutions of creatine and TSP. The largest relative errors of the ERETIC method were 8.4%, compared to 4.4% for the HR MAS MRS method using TSP as a standard. The same MR experimental procedure was applied to intact tissue samples from breast cancer patients with clinically defined good (n,=,13) and poor (n,=,16) prognosis. All samples were examined by histopathology for relative content of different tissue types and proliferation index (MIB-1) after MR analysis. The resulting spectra were analyzed by quantification of tissue metabolites (,-glucose, lactate, glycine, myo-inositol, taurine, glycerophosphocholine, phosphocholine, choline and creatine), by peak area ratios and by principal component analysis. We found a trend toward lower concentrations of glycine in patients with good prognosis (1.1,µmol/g) compared to patients with poor prognosis (1.9,µmol/g, p,=,0.067). Tissue metabolite concentrations (except for ,-glucose) were also found to correlate to the fraction of tumor, connective, fat or glandular tissue by Pearson correlation analysis. Tissue concentrations of ,-glucose correlated to proliferation index (MIB-1) with a negative correlation factor (,0.45, p,=,0.015), consistent with increased energy demand in proliferating tumor cells. By analyzing several metabolites simultaneously, either in ratios or by metabolic profiles analyzed by PCA, we found that tissue metabolites correlate to patients' prognoses and health status five years after surgery. This study shows that the diagnostic and prognostic potential in MR metabolite analysis of breast cancer tissue is greater when combining multiple metabolites (MR Metabolomics). Copyright © 2010 John Wiley & Sons, Ltd. [source] Thellungiella halophila, a salt-tolerant relative of Arabidopsis thaliana, possesses effective mechanisms to discriminate between potassium and sodiumPLANT CELL & ENVIRONMENT, Issue 1 2004V. VOLKOV ABSTRACT Thellungiella halophila is a salt-tolerant close relative of Arabidopsis thaliana. Significant mRNA similarity was confirmed by hybridization of T. halophila mRNA with the A. thaliana GeneChip ATH1. To establish a platform for future molecular comparison of the two species several physiological mechanisms, which may confer high salt tolerance to T. halophila, were investigated. Determination of ion content in shoots and roots of A. thaliana and T. halophila indicated different strategies of ion uptake and translocation from root to shoot in the two species. During salt stress T. halophila accumulated less sodium than A. thaliana. Tissue concentrations of sodium and potassium showed negative correlation in A. thaliana but not in T. halophila. Electrophysiological experiments proved high potassium/sodium selectivity of root plasma membrane channels in T. halophila. In particular, voltage-independent currents were more selective for potassium in T. halophila than in A. thaliana. Single cell sampling of T. halophila leaves during salt exposure revealed increased concentrations of sodium and decreased concentrations of potassium in epidermal cells suggesting that this cell type could function to ensure storage of sodium and exchange of potassium with the rest of leaf. Application of salt resulted in a sharp drop of transpiration in A. thaliana. By contrast, transpiration in T. halophila responded more slowly and was only slightly inhibited by salt treatment, thus maintaining high water uptake and ion transport. [source] The Role of Platelet-activating Factor in the Mammalian Female Reproductive TractREPRODUCTION IN DOMESTIC ANIMALS, Issue 6 2008U Tiemann Contents Platelet-activating factor (PAF) is a potent lipid mediator produced by various cell types of mammals and is involved in an inflammatory-like process with increased vascular permeability. Platelet-activating factor exerts its actions through the activation of specific PAF receptors (PAF-R) found in cells and tissues of the female reproductive tract. The aim of this article was summarized briefly in the current research on the role of PAF in female reproductive functions. Platelet-activating factor has been implicated in processes of ovulation, implantation and parturition because of its angiogenic and growth factor properties. This factor is influenced by ovarian steroid hormones in bringing about changes in the uterus and is a candidate molecule for initial embryo,maternal dialogue. Tissue concentrations of PAF are regulated by the equilibrium between biosynthesis and degradation by PAF-acetylhydrolase (PAF-AH). Antagonists of PAF interfere with ovulation and implantation. Platelet-activating factor, its receptor, and PAF-AH activity play an important role in the maintenance of pregnancy. [source] Subcellular distribution of zinc in Daphnia magna and implication for toxicityENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2010Wen-Xiong Wang Abstract We examined the subcellular partitioning of zinc (Zn) in Daphnia magna both under acute and chronic exposures. In the acute Zn toxicity tests, the daphnids were exposed to different Zn concentrations for 48,h or to one lethal concentration (1,000,µg/L) for different durations (time to death for up to 47,h). Significant mortality of daphnids was observed when the newly accumulated Zn concentration reached a threshold level of approximately 40,µg/g wet weight (or 320,µg/g dry wt), approximately 3.5 times higher than the background tissue concentration (92,µg/g dry wt). Chronic exposure (14 d) to Zn resulted in nonobservable effect on survivorship and growth at newly accumulated tissue concentration of over 40,µg/g wet weight. With increasing Zn acute exposure, more Zn was partitioned into the cellular debris fraction, indicating that this fraction was presumably the first targeted site of binding for Zn upon entering the animals. The importance of other subcellular fractions either decreased accordingly or remained comparable. We found that the metal-sensitive fraction (Zn distribution in the organelles and heat-denatured proteins) did not predict the acute Zn toxicity in Daphnia. During chronic exposure, however, no major change of the subcellular partitioning of Zn with increasing Zn exposure was documented. Zinc was mainly found in the organelles and heat-stable protein fractions during chronic exposure, suggesting that any subcellular repartitioning occurred primarily during acute exposure. Metallothioneins were induced upon chronic Zn exposure, but its induction evidently lagged behind the Zn accumulation. Our present study showed that the subcellular fractionation approach could not be readily used to predict the acute and chronic toxicities of Zn in Daphnia. A tissue-based Zn accumulation approach with a threshold Zn tissue concentration was better in predicting acute Zn toxicity. Environ. Toxicol. Chem. 2010; 29:1841,1848. © 2010 SETAC [source] Circulating EM66 is a highly sensitive marker for the diagnosis and follow-up of pheochromocytomaINTERNATIONAL JOURNAL OF CANCER, Issue 8 2006Johann Guillemot Abstract We have previously demonstrated that measurement of tissue concentration of the novel secretogranin II-derived peptide EM66 may help to discriminate between benign and malignant pheochromocytomas. The aim of the present study was to characterize EM66 in plasma and urine of healthy volunteers and pheochromocytoma patients, in order to further evaluate the usefulness of this peptide as a circulating marker for the management of the tumors. HPLC analysis of plasma and urine samples demonstrated that the EM66-immunoreactive material coeluted with the recombinant peptide. In healthy volunteers, plasma and urinary EM66 levels were, respectively, 2.6 (1.9,3.7) ng/ml and 2.9 (1.9,4.6) ng/ml. In patients with pheochromocytoma, plasma EM66 levels were 10-fold higher than those of healthy volunteers (26.9 (7.3,44) ng/ml), and returned to normal values after removal of the tumor. In contrast, urinary EM66 levels were not significantly different from those of healthy volunteers (3.2 (2.2,3.9) ng/ml). Measurement of total or free plasma metanephrines and 24 hr urinary metanephrines in our series of patients revealed that these tests, taken separately, are less sensitive than the EM66 determination. Pheochromocytes in primary culture secreted high levels of EM66, suggesting that the chromaffin tumor was actually responsible for the increased plasma peptide concentrations in the patients. These data indicate that EM66 is secreted in the general circulation and that elevated plasma EM66 levels are correlated with the occurrence of pheochromocytoma. Thus, EM66 is a sensitive plasma marker that should be considered as a complementary tool in the management of pheochromocytoma. © 2005 Wiley-Liss, Inc. [source] High tumor tissue concentration of urokinase plasminogen activator receptor is associated with good prognosis in patients with ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 4 2003Christer Borgfeldt Abstract The urokinase plasminogen activator (uPA) system is involved in tumor growth and metastasis. We assayed the components of the uPA system in homogenates of 64 primary epithelial ovarian tumors and 5 metastases and evaluated the association of these parameters to prognosis in the 51 malignant cases. The levels of uPA, PAI-2 and the uPA:PAI-1 complex increased with progressive loss of histological differentiation (ptrend <0.001, <0.05 and <0.001). The level of PAI-1 was higher in poorly than in well/moderately differentiated tumors (p = 0.03). The content of uPAR was lower in benign tumors as compared to borderline malignancies (p = 0.002), invasive primary tumors (p < 0.001), and metastases (p = 0.002). Surprisingly, the level of uPAR was lower in poorly differentiated as compared to both borderline (p = 0.01) and well differentiated malignant tumors (p = 0.005). Also, the level of uPAR was lower in advanced as compared to early stages of the disease (ptrend = 0.002). The median follow-up time for patients was 5.8 years. High tumor tissue levels of uPAR were associated with longer postoperative survival (HR = 0.4, 95% CI = 0.2,0.8, p = 0.01). In contrast, shorter survival was evident in patients with high tumor levels of uPA from 2 years on after operation (HR = 4.6, 95% CI = 1.2,17, p = 0.02). High tPA levels tended to be associated with shorter overall survival after 2 years (HR = 2.9, 95% 95% CI = 0.9,9.8, p = 0.08). Although high tumor tissue content of uPAR was associated with a less aggressive phenotype characterized by well differentiated histology and longer survival, low content of uPAR in the poorly differentiated tumors and metastases presumably results from increased elimination of uPAR. © 2003 Wiley-Liss, Inc. [source] Chronic Morphine Treatment and Withdrawal Increase Extracellular Levels of Norepinephrine in the Rat Bed Nucleus of the Stria TerminalisJOURNAL OF NEUROCHEMISTRY, Issue 2 2000José Antonio Fuentealba Extracellular levels of norepinephrine (NE) and glutamate (Glu) in the ventral bed nucleus of the stria terminalis (vBNST) of saline- and chronic morphine-treated rats, with or without withdrawal, were studied by means of the in vivo microdialysis technique in anesthetized rats. In addition, the tissue concentration of NE was studied at different rostrocaudal levels of the vBNST. Chronic morphine treatment significantly increased extracellular levels of NE, but not Glu, in vBNST. At 48 h after naloxone-induced morphine withdrawal there was a further significant increase in the extracellular levels of NE, but not Glu, in vBNST. The presence of UK 14304, an ,2 -adrenergic agonist, induced a significant decrease in NE extracellular levels in all experimental groups. In contrast, UK 14304 induced a significant decrease in Glu extracellular levels only in saline-treated rats. The results also show that the vBNST presents a rostrocaudal gradient of NE and contains 9.4% of total brain NE. The increase in NE extracellular levels in vBNST induced by chronic morphine treatment and the further increase in NE levels 48 h after naloxone-induced morphine withdrawal suggest that NE in vBNST may be involved in the pharmacological effects of chronic morphine and withdrawal. [source] Human skin permeation of ,8 -tetrahydrocannabinol, cannabidiol and cannabinolJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2004Audra L. Stinchcomb ABSTRACT The purpose of this study was to quantify the in-vitro human skin transdermal flux of ,8 -tetrahydrocannabinol (,8 -THC), cannabidiol (CBD) and cannabinol (CBN). These cannabinoids are of interest because they are likely candidates for transdermal combination therapy. Differential thermal analysis and in-vitro diffusion studies with human tissue were completed for the compounds. Heats of fusion, melting points and relative thermodynamic activities were determined for the crystalline compounds, CBD and CBN. Flux, permeability, tissue concentration and lag times were measured in the diffusion experiments. CBN had a lower heat of fusion and corresponding higher calculated relative thermodynamic activity than CBD. Ethanol concentrations of 30 to 33% significantly increased the transdermal flux of ,8 -THC and CBD. Tissue concentrations of ,8 -THC were significantly higher than for CBN. Lag times for CBD were significantly smaller than for CBN. The permeabilities of CBD and CBN were 10-fold higher than for ,8 -THC. Combinations of these cannabinoids with ethanol will be further studied in transdermal patch formulations in vitro and in vivo, as significant flux levels of all the drugs were obtained. CBD, the most polar of the three drugs, and other more polar cannabinoids will also be the focus of future drug design studies for improved transdermal delivery rates. [source] In vivo quantification of regional myocardial blood flow: Validity of the fast-exchange approximation for intravascular T1 contrast agent and long inversion time,MAGNETIC RESONANCE IN MEDICINE, Issue 2 2006Marlene Wiart Abstract In the present study we investigated the effects of water exchange between intra- and extravascular compartments on absolute quantification of regional myocardial blood flow (rMBF) using a saturation-recovery sequence with a rather long inversion time (TI, 176 ms) and a T1 -shortening intravascular contrast agent (CMD-A2-Gd-DOTA). Data were acquired in normal and ischemically injured pigs, with radiolabeled microsphere flow measurements used as the gold standard. Five water exchange rates (fast, 6 Hz, 3 Hz, 1 Hz, and no exchange) were tested. The results demonstrate that the fast-exchange approximation may be appropriate for rMBF quantification using the described experimental setting. Relaxation rate change (,R1) analysis improved the accuracy of the analysis of rMBF compared to the MR signal. In conclusion, the current protocol could provide sufficient accuracy for estimating rMBF assuming fast exchange and a linear relationship between signal and tissue concentration when quantification of precontrast T1 is not an option. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source] The Receptors and Role of Angiotensin II in Knee Joint Blood Flow Regulation and Role of Nitric Oxide in Modulation of Their FunctionMICROCIRCULATION, Issue 5 2003H. NAJAFIPOUR ABSTRACT Objectives: Angiotensin-converting enzyme (ACE) upregulation in the stroma cells of arthritis rheumatoid joints may produce a higher tissue concentration of angiotensin II (angII), which is a vasoconstrictor and mitogen factor that causes local hypoxia and synovial proliferation. No study in the literature has examined the role of angII in joint blood flow (JBF) regulation and the potential effect of ACE inhibitors on JBF. Methods: The study was performed on 20 Dutch white rabbits to examine the JBF response to angII, angII receptor subtypes, and the role of nitric oxide (NO) in angII effects in knee joint blood vessels. Drugs were administered locally through retrograde saphenous artery cannulation. Joint vascular resistance (JVR) was calculated by dividing the arterial blood pressure by the JBF. Results: AngII increased JVR dose dependently. The angII type 1 (AT1) receptor antagonist losartan did not change the basal JVR but completely blocked the effect of angII on JVR. N, -nitro-L-arginin methyl ester (L-NAME) increased JVR by a mean (±SEM) of 25.8 ± 8.7% (p < 0.05) but did not affect the joint vessel response to angII and losartan. Conclusions: AngII receptors are from the AT1 subtype in normal joint blood vessels, but angII plays no significant role in JBF regulation. The basal release of NO plays a role in resting JBF regulation, but NO does not affect the AT1 receptor-mediated vasoconstriction of joint blood vessels. [source] Prenatal diagnosis of free sialic acid storage disorders (SASD)PRENATAL DIAGNOSIS, Issue 8 2006Nina Aula Abstract Free sialic acid storage disorders, Salla disease (SD) and Infantile sialic acid storage disease (ISSD), are lysosomal storage diseases due to impaired function of a sialic acid transporter, sialin, at the lysosomal membrane. Several mutations of the sialin gene, SLC17A5, are known, leading either to the severe neonatal/infantile disease or to the milder, adult-type developmental disorder, Salla disease. Free sialic acid accumulation in lysosomes causes increased tissue concentration and consequently elevated urinary excretion. Prenatal diagnosis of SASD is possible either by determination of free sialic acid concentration or by mutation analysis of the SLC17A5 gene in fetal specimen, in chorionic villus biopsy particularly. Both techniques have been successfully applied in several cases, sialic acid assay more often in ISSD cases but mutation analysis preferentially in SD. Sialic acid assay of amniotic fluid supernatant or cultured amniotic fluid cells may give erroneous results and should not be used for prenatal diagnosis of these disorders. The present comments are mainly based on our experience of prenatal diagnosis of SD in Finnish families. A founder mutation in SLC17A5 gene, 115C-> T, represents 95% of the disease alleles in the Finnish SD patients, which provides a unique possibility to apply mutation analysis. Therefore, molecular studies have successfully been used in 17 families since the identification of the gene and the characterization of the SD mutations. Earlier, eight prenatal studies were performed by measuring the free sialic acid concentration in chorionic villus samples. Copyright © 2006 John Wiley & Sons, Ltd. [source] Experimental hyperhomocysteinaemia: differences in tissue metabolites between homocystine and methionine feeding in a rat modelACTA PHYSIOLOGICA, Issue 1 2009A. Pexa Abstract Aim:, Hyperhomocysteinaemia, diagnosed by serum levels, is regarded as an independent risk indicator for cardiovascular events and is associated with various diseases. The pathomechanisms seem to be partly due to concentrations of homocysteine metabolites and their effect on the cellular transmethylation processes. Methods:, We compared two common models for experimental hyperhomocysteinaemia , high methionine diet and homocystine-enriched diet , regarding their effects on tissue concentrations of homocysteine metabolites. Results:, Both diets induced hyperhomocysteinaemia without affecting renal function or vitamine status. However, the tissue contents of homocysteine and its precursors S -adenosyl-homocysteine (SAH) and S -adenosyl-methionine exhibited major differences between both models. Transmethylation potential was elevated 1.7-fold in liver of rats fed the methionine diet, whereas it was unaltered after homocystine-enriched diet. Kidneys of rats fed the methionine diet did not show any alterations in tissue content of homocysteine and its precursors, whereas in the homocystine group homocysteine and the transmethylation inhibitor SAH were elevated from 23.1 ± 10.4 to 78.0 ± 26.0 nmol g,1 and from 106 ± 4 to 170 ± 22 nmol g,1 respectively. Homocysteine tissue content was elevated in the homocystine, but not in the methionine group. Conclusions:, Alterations to homocysteine metabolism are distinct in both models. These findings may explain divergent results, which have been published for these models of hyperhomocysteinaemia and which have resulted in controversial discussions in the past. [source] Simultaneous detection of S -adenosylmethionine and S -adenosylhomocysteine in mouse and rat tissues by capillary electrophoresisELECTROPHORESIS, Issue 7-8 2003Eric O. Uthus Abstract A capillary electrophoresis method for the determination of S -adenosylmethionine (SAM) and S -adenosylhomocysteine (SAH) in rat liver and kidney and mouse liver is described. The method can also be used to determine SAM in whole blood. The method provides rapid (approximately 16 min sample to sample) resolution of both compounds in perchloric extracts of tissues. Separation was performed by using an uncoated 50 ,m ID capillary with 60 cm total length (50 cm to the detector window). Samples were separated at 22.5 kV and the separation running buffer was 200 mM glycine pH 1.8 (with HCl). The method compares favorably to HPLC methods (r,2 = 0.994 for SAM, r,2 = 0.998 for SAH) and has a mass detection limit of about 10 fmol for both SAM and SAH at a signal-to-noise ratio of 3. The method is linear over ranges of 1,100 ,M SAM and 1,250 ,M SAH. This method can be used to determine tissue concentrations of SAM and SAH, two metabolites that can provide insight into many biological processes. [source] Tissue-specific distribution and whole-body burden estimates of persistent organic pollutants in the bottlenose dolphin (Tursiops truncatus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2010Jennifer E. Yordy Abstract Most exposure assessments for free-ranging cetaceans focus on contaminant concentrations measured in blubber, and few data are available for other tissues or the factors governing contaminant distribution among tissues. The goal of this study was to provide a detailed description of the distribution of persistent organic pollutants (POPs) within the common bottlenose dolphin (Tursiops truncatus) body and assess the role of lipid dynamics in mediating contaminant distribution. Thirteen tissues (brain, blubber, heart, liver, lung, kidney, mammary gland, melon, skeletal muscle, spleen, thyroid, thymus, and testis/uterus) were sampled during necropsy from bottlenose dolphins (n,=,4) and analyzed for lipid and 85 POPs, including polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers. Significant correlations between tissue POP concentrations and lipid suggest that distribution of POPs is generally related to tissue lipid content. However, blubber:tissue partition coefficients ranged widely from 0.753 to 6.25, suggesting that contaminant distribution is not entirely lipid-dependent. Tissue-specific and whole-body contaminant burdens confirmed that blubber, the primary site of metabolic lipid storage, is also the primary site for POP accumulation, contributing >90% to the whole-body burdens. Observations also suggest that as lipid mobilizes from blubber, contaminants may redistribute, leading to elevated tissue concentrations. These results suggest that individuals with reduced blubber lipid may be at increased risk for exposure-related health effects. However, this study also provides evidence that the melon, a metabolically inert lipid-rich structure, may serve as an alternate depot for POPs, thus preventing the bulk of blubber contaminants from being directly available to other tissues. This unique physiological adaptation should be taken into consideration when assessing contaminant-related health effects in wild cetacean populations. Environ. Toxicol. Chem. 2010;29:1263,1273. © 2010 SETAC [source] Critical period of sensitivity for effects of cadmium on frog growth and development,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2009Jackson A. Gross Abstract Cadmium is a ubiquitous pollutant in aquatic environments that can alter organismal physiology and ecology. Previous experiments found that ecological Cd exposures increased the growth and development of two North American anurans. However, the generality of these effects among species, the time period over which they occur, and the mechanisms responsible remain conjectural. The goal of the present study was to determine the critical period of sensitivity of Rana pipiens exposed to ecologically relevant levels of Cd. We exposed tadpoles to Cd (0 [control], 1.0, and 10.0 ,g/L) from Gosner stage (GS) 25 to metamorphic climax. We assessed effects of Cd on amphibian length, survival, and development during premetamorphosis (GS 25,30) and prometamorphosis (GS 31,42). After 14 d of exposure, we staged tadpoles and recorded snout-vent length. Tadpoles were then pooled according to treatment and stage (GS , 29 or GS , 30) and allowed to undergo metamorphic development. Tadpoles exposed to 10 ,g/L were significantly larger and more advanced in development by 14 d. Survival to forelimb emergence exceeded 90% in all treatments, and time to metamorphic climax was not different from that in controls. Body burdens of Cd were positively correlated with increasing treatment. Early amphibian development (premetamorphosis) was shown to be the critical period of sensitivity for growth and development. Whereas the freshwater criterion for Cd appears to be protective for survival, a lack of knowledge remains about the sublethal effects of chronic exposures of metal pollutants, especially as they relate to tissue concentrations at various stages of amphibian life history. [source] Assessing exposure of sediment biota to organic contaminants by thin-film solid phase extractionENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2009Lizanne M. Meloche Abstract Differences in bioavailability among sediments are a source of variability and uncertainty in sediment quality assessment. We present three sets of studies designed to test a thin-film solid phase extraction technique for characterizing the bioavailability of organic chemicals in sediments. Laboratory studies with spiked natural sediments reveal highly reproducible thin-film extractions for chemicals with octanol,water partition coefficients between 104.5 and 108.5, with 95% equilibration times between 1 and 600 h. Studies with field-collected sediments illustrate that method detection limits are sufficiently low for field application at contaminated sites. Bioaccumulation studies with clams (Macoma balthica) show excellent correlations between thin-film and animal tissue concentrations. We conclude that thin-film extraction provides an ecologically relevant, fugacity-based measure of chemical exposure that can be expected to improve sediment quality assessments. [source] Influence of sediment ingestion and exposure concentration on the bioavailable fraction of sediment-associated tetrachlorobiphenyl in oligochaetes,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2008Arto J. Sormunen Abstract The desorption and bioavailability of 3,3,,4,4,-tetrachlorobiphenyl (PCB 77) were studied in spiked natural sediments at six concentrations. The desorption kinetics were measured in a sediment,water suspension using Tenax® resin extraction, and the bioavailability was measured by exposing Lumbriculus variegatus (Oligochaeta) to PCB 77,spiked sediment in a 14-d kinetic study. In addition, freely dissolved pore-water concentrations were measured using the polyoxymethylene solid-phase extraction method. The present study examined whether bioavailability can be defined more accurately by measuring the size of desorbing fractions and the pore-water concentrations than by using the standard equilibrium partitioning approach. The importance of ingested sediment in bioaccumulation also was investigated. Our data showed a clear, decreasing trend in the rapid-desorbing fractions and in the standard biota,sediment accumulation factors (BSAF) with increasing concentration in sediment. Desorbing fractions,refined BSAFs were more uniform across the concentration treatments, and the pore-water PCB 77 concentration predicted tissue concentrations close to observed values. In the risk assessment process, pore-water concentration or desorbing fractions would lead to more precise bioavailability estimates compared with those from the traditional equilibrium partitioning approach. The result also showed, however, that sediment-ingesting worms had access to an additional bioavailable chemical fraction that was especially evident when PCB 77 pore-water concentrations most likely approached the solubility limit. Thus, feeding may modify the bioavailable fraction that cannot be explained by simple equilibrium partitioning models. [source] Role of ethylenediaminetetraacetic acid on lead uptake and translocation by tumbleweed (Salsola kali L.)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2007Guadalupe de la Rosa Abstract Tumbleweed plants (Salsola kali L.) grown in agar and liquid media demonstrated a high capacity to accumulate Pb in their different parts without affecting biomass. Whereas shoot elongation and biomass were not significantly affected by high tissue concentrations of Pb, root growth was significantly affected relative to controls. Roots, stems, and leaves demonstrated Pb concentrations of 31,000, 5,500, and 2,100 mg/kg dry weight, respectively, when plants were grown in the agar medium containing 80 mg Pb/L. Application of ethylenediaminetetraacetic acid (EDTA) to Pb-contaminated media dramatically reduced the total acquisition of Pb from both types of media. However, EDTA significantly increased the translocation of Pb from roots to the aerial parts, as evidenced by a multifold increase (23- and 155-fold for agar and liquid media, respectively) in the translocation concentration factor. The concentration of the antioxidant thiol compounds significantly increased (p < 0.05) in plants grown with uncomplexed Pb treatments relative to control plants. Scanning-electron microscopy and electron dispersive x-ray spectroscopic evaluation of leaf samples demonstrated an interesting pattern of Pb translocation in the presence or absence of EDTA. Large Pb crystals were found across the leaf tissues (palisade, spongy parenchyma, and conducting tissues) in the absence of EDTA. Lead nanoparticles also were seen when plants were grown in Pb-EDTA solution. Ultramicroscopic features of tumbleweed provide clear evidence for the unrestricted conduction of Pb from the root to the aerial parts, and this property makes the plant a good candidate for phytoremediation. [source] Toxicity and fate of two munitions constituents in spiked sediment exposures with the marine amphipod Eohaustorius estuariusENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2005Gunther Rosen Abstract The lethal toxicity of the explosive compounds 14C-labeled 2,4,6-trinitrotoluene (TNT) and nonradiolabeled hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) to the estuarine amphipod Eohaustorius estuarius was investigated in 10-d spiked sediment exposures. The 10-d median lethal concentration (LC50) was determined using the sum molar initial concentration of TNT, ami-nodinitrotoluenes (ADNTs), and diaminonitrotoluenes (DANTs), as determined by high-performance liquid chromatography (HPLC), and collectively referred to as HPLC-TNT*. Despite expectations of higher toxicity in sandy sediment (Yaquina Bay [YB], OR, USA) compared to relatively fine-grained sediment (San Diego Bay [SDB], CA, USA), LC50 values were similar: 159 and 125 ,mol/kg, for YB and SDB sediments, respectively. When expressed as the sum of TNT and all its degradation products (14C-TNT*), LC50s were approximately two times the corresponding LC50s determined by HPLC. The HPLC-TNT* fraction likely corresponds to the most bioavailable and toxic transformation products. The concentrations of 14C-TNT* in tissues were substantially higher than those for HPLC-TNT*, suggesting that compounds other than TNT and its major aminated transformation products were prevalent. Critical body residues were similar for exposures to SDB (11.7 ,mol/kg) and YB sediments (39.4 ,mol/kg), despite marked differences in the nature of compounds available for uptake in the exposure media. The critical body residues for E. estuarius are lower than those reported for other aquatic invertebrates (83,172 ,mol/kg). Unlike observations for TNT, RDX was only loosely associated with SDB sediment, with near complete recovery of the parent compound by chemical analysis. Exposure to RDX did not result in significant mortality even at the highest measured sediment concentration of 10,800 ,mol/kg dry weight, nor tissue concentrations as high as 96 ,mol/kg wet weight. The lack of RDX lethal effects in this study is consistent with results reported for other invertebrate species. [source] Approaches for linking whole-body fish tissue residues of mercury or DDT to biological effects thresholdsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2005Nancy Beckvar Abstract A variety of methods have been used by numerous investigators attempting to link tissue concentrations with observed adverse biological effects. This paper is the first to evaluate in a systematic way different approaches for deriving protective (i.e., unlikely to have adverse effects) tissue residue-effect concentrations in fish using the same datasets. Guidelines for screening papers and a set of decision rules were formulated to provide guidance on selecting studies and obtaining data in a consistent manner. Paired no-effect (NER) and low-effect (LER) whole-body residue concentrations in fish were identified for mercury and DDT from the published literature. Four analytical approaches of increasing complexity were evaluated for deriving protective tissue residues. The four methods were: Simple ranking, empirical percentile, tissue threshold-effect level (t-TEL), and cumulative distribution function (CDF). The CDF approach did not yield reasonable tissue residue thresholds based on comparisons to synoptic control concentrations. Of the four methods evaluated, the t-TEL approach best represented the underlying data. A whole-body mercury t-TEL of 0.2 mg/kg wet weight, based largely on sublethal endpoints (growth, reproduction, development, behavior), was calculated to be protective of juvenile and adult fish. For DDT, protective whole-body concentrations of 0.6 mg/kg wet weight in juvenile and adult fish, and 0.7 mg/kg wet weight for early life-stage fish were calculated. However, these DDT concentrations are considered provisional for reasons discussed in this paper (e.g., paucity of sublethal studies). [source] In situ reproduction, abundance, and growth of young-of-year and adult largemouth bass in a population exposed to polychlorinated biphenylsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2004Dudley W. Reiser Abstract We conducted a two-year field study (2000,2001) in the Housatonic River, Massachusetts (USA) to determine if we could detect in situ population-level effects on largemouth bass (Micropterus salmoides) exposed to elevated levels of polychlorinated biphenyls (PCBs). Calculated whole-body PCB concentrations in adult bass in 2002 averaged 121 mg/kg (range = 34,556 mg/kg). Polychlorinated biphenyl concentrations in young-of-year (YOY) composites in 2000 and 2002 averaged 28 mg/kg (range = 21,41 mg/kg) and 19 mg/kg (range = 16,24 mg/kg), respectively. Laboratory studies of fish have reported PCB toxicity at exposure levels below and within the range of those found in the Housatonic River. We evaluated five field-derived metrics: reproductive activity, relative abundance of YOY, YOY growth rates, adult growth, and adult condition to determine whether we could detect effects of PCBs in the largemouth bass population. These computed metrics, when compared with data sets assembled for numerous largemouth bass populations in North America, provided no evidence of population-level impairment. Results of this study suggest that PCB tissue concentrations associated with effects in laboratory studies do not necessarily translate to detectable effects on largemouth bass populations in their natural environment. [source] Toxicokinetics of sediment-associated polybrominated diphenylethers (flame retardants) in benthic invertebrates (Lumbriculus variegatus, oligochaeta)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2004Matti T. Leppänen Abstract Polybrominated diphenylethers (PBDEs) are ubiquitous environmental contaminants showing rapid temporal increase in some sample types. The compounds are known to biomagnify in aquatic food webs and are assumed to archive into sediments and soils. Currently, no direct evidence indicates whether sediment-associated PBDEs are available for biota. The aim of the present study was to explore the uptake and elimination of two common congeners (47 and 99) in sediment-inhabiting invertebrates to shed light on possible bioavailability of sediment-associated PBDEs. Two clean lake sediments were spiked with environmentally relevant concentrations of 14C-labeled tetra- and pentabromo diphenylether, and oligochaetes (Lumbriculus variegatus) were exposed for three or four weeks to allow kinetic accumulation calculations. Subsequent depuration tests were performed after three weeks of exposure to obtain depuration rates. Both congeners were clearly bioavailable, and only slight differences in steady-state tissue concentrations were found between the four sediment-ingesting oligochaete treatments (biota sediment accumulation factors [BSAFs], 3.0,3.7). The tetrabromo diphenylether-exposed oligochaetes that did not ingest sediment had clearly lower influx rates (0.1 vs 1,3 nmol h -1) than sediment-ingesting worms. Also, the estimated BSAF (1.8) was statistically different from that of the sediment-ingesting oligochaetes. These findings support the significance of feeding behavior in bioaccumulation of very hydrophobic organic contaminants. Depuration of both congeners was biphasic, indicating two kinetically different compartments in L. variegatus. Compartment A made up 73 to 92% of total radioactivity in tissues and had relatively fast depuration rates (half-lives, 10.5,47.5 h); the smaller compartment B had very slow depuration rates. No significant biotransformation of PBDEs was evident. The present study clearly demonstrates that the sediment-associated PBDEs, like other hydrophobic organic contaminants of environmental concern, are not totally sequestered from sediment-inhabiting oligochaetes and are subject to trophic transfer. [source] Probabilistic risk assessment of reproductive effects of polychlorinated biphenyls on bottlenose dolphins (Tursiops truncatus) from the Southeast United States coastENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2002Lori H. Schwacke Abstract High levels of polychlorinated biphenyls (PCBs) have been reported in the tissues of some species of marine mammals. The high concentrations are of concern because a growing body of experimental evidence links PCBs to deleterious effects on reproduction, endocrine homeostasis, and immune system function. Much of the recent research has focused on determining the exposure of marine mammal populations to PCBs, but very little effort has been devoted to the actual risk assessments that are needed to determine the expected impacts of the documented exposures. We describe a novel risk assessment approach that integrates measured tissue concentrations of PCBs with a surrogate dose-response relationship and leads to predictions of health risks for marine mammals as well as to the uncertainties associated with these predictions. Specifically, we use PCB tissue residue data from three populations of bottlenose dolphins (Tursiops truncatus), study the feasibility of published dose-response data from a surrogate species, and combine this information to estimate the risk of detrimental reproductive effects in female dolphins. Our risk analyses for dolphin populations near Beaufort (NC, USA), Sarasota (FL, USA), and Matagorda Bay (TX, USA) indicate a high likelihood that reproductive success, primarily in primiparous females, is being severely impaired by chronic exposure to PCBs. Excess risk of reproductive failure, measured in terms of stillbirth or neonatal mortality, for primiparous females was estimated as 60% (Beaufort), 79% (Sarasota), and 78% (Matagorda Bay). Females of higher parity, which have previously off-loaded a majority of their PCB burden, exhibit a much lower risk. [source] Importance of maternal transfer of the photoreactive polycyclic aromatic hydrocarbon fluoranthene from benthic adult bivalves to their pelagic larvaeENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2000Marguerite C. Pelletier Abstract Laboratory experiments were conducted to determine if maternal transfer of polycyclicaromatichydrocarbons (P AH) from benthic adult bivalves could result in phototoxicity to their pelagic larvae when exposed to ultraviolet light (UV). In these experiments, adult bivalves were exposed to water or sediments amended with the model photoreactive PAH, fluoranthene. Elevated adult fluoranthene tissue concentrations were correlated with embryo concentrations. Embryonic mortality was enhanced by exposure to ultraviolet light when adult tissue fluoranthene levels were greater than 5,000 ,g/g lipid. While the exposure concentrations used in this experimental system were high, ultraviolet light exposure levels were low. Also, some of the PAHs are more potent than the model compound used in this study. These results indicate that maternal transfer of photoactive PAHs from organisms living in contaminated sediments may represent a significant adverse effect to populations of benthic bivalves. [source] Technical basis for narcotic chemicals and polycyclic aromatic hydrocarbon criteria.ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2000Abstract A method is presented for developing water quality criteria (WQC) for type I narcotic chemicals in general and PAHs in particular. The criteria can be applied to any individual or mixture of narcotic chemicals using only the chemical's octanol-water partition coefficient KOW. It is derived from a database of LC50s comprising 156 chemicals and 33 species, including fish, amphibians, arthropods, mollusks, polychaetes, coelenterates, and protozoans. A target lipid model is proposed that accounts for variations in toxicity due to differing species sensitivities and chemical differences. The model is based on the idea that a target lipid is the site of action in the organism. Further, it is assumed that target lipid has the same lipid-octanol linear free energy relationship for all species. This implies that the slope of the log(LC50),log(KOW) relationship is the same for all species. However, individual species may have varying target lipid body burdens that cause toxicity. The target lipid LC50 body burdens derived from concentration data in the water only are compared to measured total lipid LC50 body burdens for five species. They are essentially equal, indicating that the target lipid concentration is equal to the total extracted lipid concentration. The precise relationship between partitioning in target lipid and octanol is established. The species-specific body burdens are used to determine the WQC final acute value, i.e., the 95-percentile level of protection. An acute-to-chronic ratio is used to compute the body burden corresponding to the WQC final chronic value, which is the procedure used to derive the U.S. Environmental Protection Agency water quality criteria. The criteria are expressed either as dissolved concentrations in the water column or as tissue concentrations. [source] Chlorinated hydrocarbons in flatfishes from the Southern California, USA, BightENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2000Kenneth Schiff Abstract Alhough inputs of chlorinated hydrocarbon compounds to the Southern California Bight (SCB) are presently low, historical deposits represent a source of bioaccumulation potential to sediment-associated fauna. To assess this bioaccumulation potential, 14 chlorinated hydrocarbon classes were measured in livers of three species of flatfish collected from 63 randomly selected sites on the coastal shelf between Point Conception and the United States,Mexico international border. Tissue contamination was widespread throughout the SCB, but was limited to just two chlorinated hydrocarbon classes. Virtually 100% of Pacific sanddab (Citharichthys sordidus) and longfin sanddab (Citharichthys xanthostigma) populations were estimated to be contaminated with dichlorodiphenyltrichloroethane (total DDT = sum of o,p, and p,p, isomers of DDT + dichlorodiphenyldichloroethylene [DDE] + dichlorodiphenyldichloroethane [DDD]) and/or polychlorinated biphenyls (total PCBs). Total DDT also contaminated the majority (64%) of the Dover sole (Microstomus pacificus) population in the SCB. Total PCB measurements in tissues of SCB flatfish were dominated by 12 congeners (52, 66, 87, 101, 105, 118, 128, 138, 153, 170, 180, and 187), which averaged 95% of the combined mass of the 27 congeners analyzed. Sediment concentrations (normalized by total organic carbon content) accounted for most of the variability observed in tissue concentrations (normalized by lipid content) for 8 of these 12 congeners and total PCBs. Normalized sediment concentrations were also significantly correlated to normalized tissue concentrations for total DDT and p,p,-DDE. Tissue concentrations measured in this study from reference areas of the SCB were compared to tissue concentrations measured from reference areas in studies conducted in 1977 and 1985. Total DDT and total PCB liver concentrations were found to have decreased one to two orders of magnitude in Pacific and longfin sanddabs between 1985 and 1994. Total DDT and total PCB liver concentrations decreased 5- to 35-fold in Dover sole between 1977 and 1994. [source] Incidence and impact of axial malformations in larval bullfrogs (Rana catesbeiana) developing in sites polluted by a coal-burning power plantENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2000William A. Hopkins Abstract Amphibian malformations have recently received much attention from the scientific community, but few studies have provided evidence linking environmental pollution to larval amphibian malformations in the field. We document an increased incidence of axial malformations in bullfrog larvae (Rana catesbeiana) inhabiting two sites contaminated with coal combustion wastes. In the polluted sites, 18 and 37% of larvae exhibited lateral curvatures of the spine, whereas zero and 4% of larvae from two reference sites had similar malformations. Larvae from the most heavily polluted site had significantly higher tissue concentrations of potentially toxic trace elements, including As, Cd, Se, Cu, Cr, and V, compared with conspecifics from the reference sites. In addition, malformed larvae from the most contaminated site had decreased swimming speeds compared with those of normal larvae from the same site. We hypothesize that the complex mixture of contaminants produced by coal combustion is responsible for the high incidence of malformations and associated effects on swimming performance. [source] Upregulation of Brain Expression of P-Glycoprotein in MRP2-deficient TR - Rats Resembles Seizure-induced Up-regulation of This Drug Efflux Transporter in Normal RatsEPILEPSIA, Issue 4 2007Katrin Hoffmann Summary:,Purpose: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood,brain barrier (BBB). MRP2 is absent in the transport-deficient (TR,) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR, rats compared with nonmutant (wild-type) Wistar rats. Methods: The expression of MRP2 and Pgp in brain and liver sections of TR, rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. Results: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR, rats. TR, rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR, rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. Conclusions: The data on TR, rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR, rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose. [source] | |||||||||||||||||||