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At least 19 recordsLinked to original sources
USGS1970

Testing of selected pharmacological agents for capturing waterfowl [Annual Progress Report]

The response of game-farm mallards (Frost strain) to seven pharmacological immobilizing agents was evaluated in Phase I of a planned four-phase study. A limited amount of testing was also done with wild mallards. Single dosages were administered to determine the mean effective dose (ED50) and mean lethal dose (LD50), The therapeutic index, or safety factor (LD50/ED50), and palatability were also established. Optimum dosage rates of compounds administered orally on baits were not considered in this phase of the study. Compounds were-administered by intubation and calculated in terms of mg/kg. All except one compound produced narcosis within 5 minutes at the effective dose rate.Immobilization periods for the seven compounds ranged from 7-24 minutes, and recovery periods from 1.0-6.5 hours. Such wide variations in actions of the compounds can be attributed to a compound's rate of absorption, the ease with which it passes the blood-brain barrier, its solubility in tissues, and its rate of metabolism in the liver and kidneys. Length of both the immobilization and recovery periods were extended when dosages were increased. There was no delayed mortality among survivors with any of the seven compounds at either the ED50 or LD50. Females were generally more sensitive to the anesthetizing agents than males. The ED50 for wild mallards was substantially higher than that for the experimental game-farm birds for the two compounds on which this was tested.Tribromoethanol (Avertin of Winthrop Laboratories) satisfied all test criteria an Phase I and will be subjected to more intensive investigation in ensuing tests. Thiopental sodium (Pentothal of Amdal Company) and pentobarbital sodium (Nembutal of Abbott Laboratories) were judged to be marginal. Although their therapeutic indexes were good (5.00), recovery periods were prolonged and toxic convulsions occurred at medium to high dose rates as the LD50 was approached.Alpha-chloralose (Fisher Scientific) proved least promising of the seven compounds, mainly because of its unacceptable therapeutic index (2.25) and because it possesses prolonged induction and recovery periods. Two new experimental drugs, methoxymol and metomidate (Pitman-Moore), appeared effective and safe when administered by intubation but produced a taste aversion when added to bait. Rejection because of taste was also a problem with secobarbital (Seconal of Elanco Products), and its therapeutic index of 2.75 was unacceptable. Monitoring of heart and respiratory rates, and body temperature by telemetry showed promise as a technique for determining physiological response to drug action.

Report↗
USGS1996

Embryotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): Theembryonic vasculature is a physiological target for TCDD-induced DNA damage and apoptotic cell death in medaka (Orizias latipes)

Vertebrate embryos are extremely sensitive to environmental contaminants known as planar halogenated hydrocarbons (PHHs). The physiological targets that mediate PHH-induced embryotoxicity are not known. We have characterized embryotoxicity in medaka ( Orizias latipes ) caused by 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD), the prototypic PHH. DNA degradation in cells of the embryonic vasculature and loss of functional integrity of the medial yolk vein were demonstrated in TCDD-exposed embryos. Pharmacological intervention with piperonyl butoxide inhibited TCDD-induced DNA degradation, restored the functional integrity of the medial yolk vein, and protected against the embryotoxicity of TCDD. Treatment of TCDD-exposed embryos with the antioxidant N -acetylcysteine also provided significant protection against the embryotoxicity of TCDD. These results demonstrate that DNA damage and consequent cell death in the embryonic vasculature are key physiological mediators of TCDD-induced embryotoxicity.

Toxicology and Applied Pharmacology↗
USGS1990

Toxicokinetics of PAHs in Hexagenia

The accumulation kinetics of two waterborne polycyclic aromatic hydrocarbons (PAHs), benzo[a]pyrene (BAP) and phenanthrene (PHE), were studied in the mayfly nymph ( Hexagenia limbata ). The uptake clearance decreased while the bioconcentration of BAP increased with an increase in weight of the H. limbata nymph. The relationship between uptake clearance and bioconcentration for PHE was variable, and bioconcentration was greater for the heavier animals. Two kinetic models were used to evaluate the effect of nymph weight on disposition of PAHs: (a) the amount-uptake clearance model, similar to models most frequently used in environmental toxicology; and (b) a clearance-volume model, similar to models used in clinical pharmacology. The two models gave similar predictive results but were different in a few cases. These differences in common parameter estimation probably resulted from methodologies used and high data variability rather than the models themselves, since they are mathematically equal. Some of the parameters are unique to each of the models and are defined and described. The clearance of oxygen from water is inversely and linearly related to the weight of the mayfly nymphs, but oxygen clearances were always much less than the uptake clearances of the PAHs. The high PAH uptake clearance compared to oxygen clearance implies a greater surface area or efficiency for PAH accumulation from water.

Environmental Toxicology and Chemistry↗
USGS2010

Coral reef diseases in the Atlantic-Caribbean

Coral reefs are the jewels of the tropical oceans. They boast the highest diversity of all marine ecosystems, aid in the development and protection of other important, productive coastal marine communities, and have provided millions of people with food, building materials, protection from storms, recreation and social stability over thousands of years, and more recently, income, active pharmacological compounds and other benefits. These communities have been deteriorating rapidly in recent times. The continuous emergence of coral reef diseases and increase in bleaching events caused in part by high water temperatures among other factors underscore the need for intensive assessments of their ecological status and causes and their impact on coral reefs.

Book chapter↗
USGS2005

Mathematical analysis demonstrates that interferons-β and -γ Interact in a multiplicative manner to disrupt herpes simplex virus replication

Several studies suggest that the innate interferons (IFNs), IFN- α and IFN- β , can act in concert with IFN- γ to synergistically inhibit the replication of cytomegalovirus and herpes simplex virus type 1 (HSV-1). The significance of this observation is not yet agreed upon in large part because the nature and magnitude of the interaction between IFN- α/β and IFN- γ is not well defined. In the current study, we resolve this issue by demonstrating three points. First, the hyperbolic tangent function, tanh ( x ), can be used to describe the individual effects of IFN- β or IFN- γ on HSV-1 replication over a 320,000-fold range of IFN concentration. Second, pharmacological methods prove that IFN- β and IFN- γ interact in a greater-than-additive manner to inhibit HSV-1 replication. Finally, the potency with which combinations of IFN- β and IFN- γ inhibit HSV-1 replication is accurately predicted by multiplying the individual inhibitory effects of each cytokine. Thus, IFN- β and IFN- γ interact in a multiplicative manner. We infer that a primary antiviral function of IFN- γ lies in its capacity to multiply the potency with which IFN- α/β restricts HSV-1 replication in vivo. This hypothesis has important ramifications for understanding how T lymphocyte-secreted cytokines such as IFN- γ can force herpesviruses into a latent state without destroying the neurons or leukocytes that continue to harbor these viral infections for the lifetime of the host.

Journal of Theoretical Biology↗
USGS2017

A regional assessment of chemicals of concern in surface waters of four Midwestern United States national parks

Anthropogenic chemicals and their potential for adverse biological effects raise concern for aquatic ecosystem health in protected areas. During 2013–15, surface waters of four Midwestern United States national parks were sampled and analyzed for wastewater indicators, pharmaceuticals, personal care products, and pesticides. More chemicals and higher concentrations were detected at the two parks with greater urban influences (Mississippi National River and Recreation Area and Indiana Dunes National Lakeshore) than at the two more remote parks (Apostle Islands National Lakeshore and Isle Royale National Park). Atrazine (10–15 ng/L) and N,N-diethyl-meta-toluamide (16–120 ng/L) were the only chemicals detected in inland lakes of a remote island national park (Isle Royale National Park). Bisphenol A and organophosphate flame retardants were commonly detected at the other sampled parks. Gabapentin and simazine had the highest observed concentrations (> 1000 ng/L) in three and two samples, respectively. At the two parks with urban influences, metolachlor and simazine concentrations were similar to those reported for other major urban rivers in the United States. Environmental concentrations of detected chemicals were often orders of magnitude less than standards or reference values with three exceptions: (1) hydrochlorothiazide exceeded a human health-based screening value in seven samples, (2) estrone exceeded a predicted critical environmental concentration for fish pharmacological effects in one sample, and (3) simazine was approaching the 4000 ng/L Maximum Contaminant Level in one sample even though this concentration is not expected to reflect peak pesticide use. Although few environmental concentrations were approaching or exceeded standards or reference values, concentrations were often in ranges reported to elicit effects in aquatic biota. Data from this study will assist in establishing a baseline for chemicals of concern in Midwestern national parks and highlight the need to better understand the sources, pathways, and potential adverse effects to aquatic systems in national parks.

Indiana, Michigan, Minnesota, Wisconsin↗
USGS2025

Leveraging invasive mussel contaminant survey data for stepwise prioritization of chemicals of potential concern in the Great Lakes basin

Historical and ongoing anthropogenic activities coupled with advancements in analytical techniques have led to the detection of large numbers of contaminants in the Laurentian Great Lakes. Consequently, identifying and prioritizing chemicals likely to cause ecological harm represents a challenge for natural resource managers. Previous prioritization efforts have focused on contaminants in sediment, water, and passive samplers, which may not be representative of compounds that bioaccumulate in aquatic organisms. Consequently, this study adopted a stepwise method to prioritize chemicals of potential concern detected in dreissenid mussels from samples collected across the Great Lakes from 2009–2018. The stepwise method considered environmental fate, detection frequency, and exceedance of toxicity quotients based on ecotoxicological effect concentrations. Overall, 153 compounds out of 267 analyzed were detected in dreissenid mussels, 47 of which had water quality effect concentrations, 56 had apical effect concentrations (Tier 1 ECOTOX or apical screening), 17 had nonapical effect concentrations (Tier 2 ECOTOX, Cytotoxic Burst, and ToxCast) and 33 had estimated effect concentrations (quantitative structure-activity relationship, estimated screening, and pharmacological potency). Of the compounds with water quality effect concentrations, nine were designated as high priority, including the herbicide atrazine and five polycyclic aromatic hydrocarbons that were previously identified as potentially hazardous within other matrices. Similar contaminants were identified as high priority in a related study of native unionid mussels in the Great Lakes. A total of 27 compounds were low priority, suggesting that these contaminants do not warrant further action based on this dataset. Overall, these findings will facilitate the development of management strategies to mitigate the effects of contaminants on aquatic organisms within the Great Lakes.

Great Lakes basin↗
USGS2019

Functional characterization and osmoregulatory role of the Na+/K+/2Cl--cotransporter (NKCC1) in the gill of sea lamprey (Petromyzon marinus), a basal vertebrate

The present study provides molecular and functional characterization of Na+/K+/2Cl- cotransporter (nkcc1/NKCC1) in the gills of sea lamprey, the most basal extant vertebrate with an osmoregulatory strategy. We report the full-length peptide sequence for the lamprey NKCC1, which we show to group strongly with and occupy a basal position among other vertebrate NKCC1 sequences. Lamprey nkcc1 mRNA were present in many tissues but was 5-fold higher in the gill than any other tissue. NKCC1 protein was only detected in the gill. Gill mRNA and protein abundances of NKCC1 and Na+/K+-ATPase (NKA) were significantly upregulated (20- to 200-fold) in late metamorphosis in freshwater, coinciding with the development of salinity tolerance, and were upregulated an additional 2-fold after acclimation to seawater. Immunohistochemistry revealed that NKCC1 in the gill is found in filamental ionocytes that develop during metamorphosis. Lamprey treated with bumetanide, a widely used pharmacological inhibitor of NKCC1, exhibited higher plasma Cl- and osmolality and reduced muscle water content after 24 h in seawater, but had no effect in FW. This work provides the first functional characterization of NKCC1 as having a functional role mechanism for branchial salt secretion in lampreys, providing evidence that this mode of Cl- secretion has been present among vertebrates for ~550 million years.

American Journal of Physiology - Regulatory, Integ↗
USGS2025

A Cftr-independent, Ano1-rich seawater-adaptive ionocyte in sea lamprey gills

All ionoregulating marine fishes examined to date utilize seawater-type ionocytes expressing the apical Cl- channel, cystic fibrosis transmembrane conductance regulator (Cftr) to secrete Cl − . We performed transcriptomic, molecular, and functional studies to identify Cl − transporters in the seawater-type ionocytes of sea lamprey ( Petromyzon marinus ). Gill cftr expression was minimal or undetectable in larvae and post-metamorphic juveniles. We identified other Cl − transporters highly expressed in the gills and/or upregulated following metamorphosis and further investigated two candidates that stood out in our analysis, a Ca 2+ -activated Cl − channel, anoctamin 1 ( ano1 ), and the Clc chloride channel family member 2 ( clcn2 ). Of these, ano1 was expressed 10-100 times more than clcn2 in the gills; moreover, ano1 was upregulated during seawater acclimation, while clcn2 was not. Using an antibody raised against sea lamprey Ano1, we did not detect Ano1 in the gills of larvae, found elevated levels in juveniles and observed a 4-fold increase in juveniles after seawater acclimation. Ano1 was localized to seawater-type branchial ionocytes but, surprisingly, was localized to the basolateral membrane. In vivo pharmacological inhibition experiments demonstrated that a DIDS-sensitive mechanism was critical to the maintenance of osmoregulatory homeostasis in seawater- but not freshwater-acclimated sea lamprey. Taken together, our results provide evidence of a Cftr-independent mechanism for branchial Cl − secretion in sea lamprey that leverages Ano1-expressing ionocytes. Once further characterized, the Cftr-independent, Ano1-rich ionocytes of sea lamprey could reveal novel strategies for branchial Cl − secretion, whether by Ano1 or some other Cl − transporter, not previously known in ionoregulating marine organisms.

Journal of Experimental Biology↗
USGS2004

High doses of corticosteroid suppress resistance to Ichthyophonus in starry flounder

Application of pharmacological doses of the corticosteroid dexamethasone phosphate to starry flounder Platichthys stellatus resulted in a predisposition to clinical ichthyophoniasis and a progression from latent Ichthyophonus infections to patent, histologically identifiable infections. Among Ichthyophonus -challenged starry flounder, the prevalences of clinical infections and histologically identifiable infections were significantly greater in two groups that received dexamethasone (100% and 31%, respectively) than in the respective control groups (8% and 0%). Proliferation of Ichthyophonus infections in corticosteroid-treated groups may have resulted from suppression of the cellular immune response that typically follows corticosteroid application; however, further studies are needed to determine whether these effects occur at lower, physiological concentrations of corticosteroids.

Journal of Aquatic Animal Health↗
USGS2007

Potential ecotoxicological significance of elevated concentrations of strontium in eggshells of passerine birds

We investigated the occurrence and potential ecotoxicological significance of elevated concentrations of strontium (Sr) in eggshells of nine passerine birds from four regions in Arizona. Concentrations of Sr in eggshells ranged from 70 to 1360 µg g −1 dry weight (overall mean = 684 ± 345 SD µg g −1 dw) for the four regions. 23% of the eggshells had Sr concentrations greater than 1000 µg g −1 dw. To our knowledge, these are among the highest levels of Sr that have been reported in bird eggshells in North America. Of the nine species, Brown-headed Cowbirds ( Molothrus ater ) had the greatest concentrations of Sr. There was a significant positive correlation between Sr and calcium (Ca), and between barium (Ba) and Ca. Ca, Sr, and Ba interact with each other and can exert similar chemical and pharmacological effects. Mean ( n ≥ 3) eggshell∶egg ratios for Sr varied with species and ranged from 6.1∶1 to 40.2∶1; ratios for individual eggs reached 92.7∶1. Mean Sr/Ca values ranged from 1.3 × 10 −3 to 3.0 × 10 −3 and mean eggshell thickness ranged from 83 ± 6 to 120 ± 9 µm for all species. Eggshell thickness was not significantly correlated with Sr for any species but tended to increase with Sr concentrations. We postulate that high concentrations of Sr in the shell could affect later-stage embryos by possible interference with Ca metabolism and bone growth, resulting in reduced hatching success and potential minor beak deformities.

Arizona↗
USGS1996

In vivo/in vitro comparison of pharmacokinetics and pharmacodynamics of 3,3',4,4'-tetrachlorobiphenyl (PCB77)

The rat hepatoma cell line, H4IIE, serves as a useful tool to assess potential biological effects such as induction of cytochrome P4501A1 expression. The objectives of this study were twofold: to investigate the kinetic time course and dosimetry of PCB77 in rat hepatoma cells dosed with PCB77 and in liver of rats given ip doses of PCB77, and to compare in vitro and in vivo P4501A1 enzyme induction responses. For the 4-day time–course study, H4IIE cells were exposed with two doses of [ 14 C]PCB77 (0.9 and 3 μg/plate) and harvested at 15 and 30 min, 1, 2, 4, 8, and 12 hr, and 1, 2, 3, and 4 days. PCB77-derived radioactivity was detected in the cells as early as 15 min postdosing. For the dose–response study, the cells were dosed with various concentrations of PCB77 (0.00316–5.37 μg/plate) and harvested on Day 3 since ethoxyresorufin O -deethylase (EROD) activity in vitro reached its maximum on the third day postdosing. Time–course and dose–response studies revealed that only 1–3% of the total delivered dose was found in the cells, with the remainder in the media and adhering to the culture plates. For the dose–response study in vivo, male Fischer rats were dosed with a single ip injection of various concentrations of PCB77 (0.1–50 mg/kg body wt) and euthanized on Day 3. PCB77-derived radioactivity and EROD induction in vivo were measured. When EROD activity and PCB77-derived radioactivity in the rat hepatoma cells and in the rat liver were compared on an equivalent weight basis, there was a significant correlation ( r 2 = 0.985) between them. Prior to this study, no information on quantitative dosimetry and EROD activities of PCB77 has been reported to validate the in vitro assay with in vivo data.

Toxicology and Applied Pharmacology↗
USGS1998

Correlation of 2,3,7,8-tetrachlorodibenzo- p -dioxin-induced apoptotic cell death in the embryonic vasculature with embryotoxicity

Vertebrate embryos are particularly sensitive to 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). Identification of tissues that are susceptible to the adverse effects of TCDD is requisite for understanding the embryo toxic effects of TCDD. The objective of the present study was to quantitate the temporal appearance of and dose dependence of apoptosis in TCDD-exposed medaka embryos ( Oryzias latipes ). A fluorescent-based DNA end-labeling assay provided a sensitive method for detection of TCDD-induced apoptosis in tissue sections of medaka embryos. Apoptotic cells were readily apparent in the medial yolk vein at all observed embryonic stages in TCDD-exposed embryos. Slope-comparison analysis indicated that TCDD-induced programmed cell death in the embryonic medial yolk vein was mechanistically linked to embryo mortality. These data are consistent with the hypothesis that vascular damage contributes to the acute embryo toxic effects of TCDD. However, as sublethal concentrations of dioxin-like compounds are more typical of environmental exposures, tissue damage was also assessed in medaka fry that were exposed to low doses of TCDD during embryonic development. Cell death was detected in gill and digestive tissues in visibly healthy medaka fry that had been exposed to low doses of TCDD during embryonic development. Increased expression of cytochrome P450 1A is a major biochemical consequence of TCDD exposure and is often used as a biomarker for exposure to dioxin-like compounds. Therefore, we compared the tissue distribution of TCDD-induced P450 1A expression and TCDD-induced programmed cell death. TCDD-induced programmed cell death co-localized with TCDD-induced P450 1A expression in both embryos and in visibly healthy post-hatch fry. Our results suggest that aberrant programmed cell death may be a suitable marker for exposure of feral organisms to dioxin-like compounds.

Toxicology and Applied Pharmacology↗
USGS1969

Chronic oral DDT toxicity in juvenile coho and chinook salmon

Technical and p,p′ -DDT was incorporated into test diets and fed to juvenile chinook and coho salmon for periods as long as 95 days. Pure p,p′ -DDT was slightly more toxic to young salmon than was the technical DDT mixture. Chinook salmon appeared to be 2–3 times more sensitive to a given concentration of DDT in the diet than were coho salmon. The size of the fish greatly influenced toxicity, smaller younger fish being more susceptible to a given diet than larger older fish. The dose of DDT accumulated within the median survival time ranged from 27–73 mg/kg for chinook salmon and from 56–72 mg/kg for coho salmon. The extrapolated 90-dose LD50 ( Hayes, 1967 ) for young chinook and coho salmon were 0.0275 and 0.064 mg/kg/day, respectively. Liver size decreased on prolonged feeding with DDT, and carcass lipid content was increased. A severe surface ulceration of the nose region appeared in coho salmon fed DDT over long periods. In addition, an interesting localized degeneration of the distal convoluted tubule was observed in the kidney of coho salmon receiving DDT.

Toxicology and Applied Pharmacology↗
USGS1970

Toxicity of DDT to Japanese quail as influenced by body weight, breeding condition, and sex

Controlled experiments were utilized to simulate the stresses on wild birds of breeding condition and of weight loss due to migration. Light conditions in the laboratory were manipulated to produce Japanese quail ( Coturnix coturnix japonica ) in breeding condition and not in breeding condition. Within each of these groups, some birds were partially starved before dosage and some were fully fed. Birds were then fed dietary levels of 0, 700, 922, 1214, or 1600 ppm dry weight of p,p′ -DDT for a period of 20 days or until death. Birds partially starved before dosage were more susceptible to DDT intoxication than nonstarved ones, and birds not in breeding condition were slightly more so than birds in breeding condition. Similarly, males died earlier than females, and the birds of the lighter weight strain used in the second half of the study died earlier than the birds of the heavier strain used in the first half. The heavier birds of each sex not only survived longer than lighter individuals receiving the same treatments, but they also lost a greater proportion of their weight before death. During the early portion of the dosage period, females in breeding condition were less sensitive to DDT than were females not in breeding condition and males. After 10 days on dosage, however, the cumulative mortality of females in breeding condition rapidly approached that of males and of females not in breeding condition. Food restriction prior to dosage, strains of quail, breeding conditions, and sexes resulted in weight differences and a corresponding accentuation or delay of the effects of the different levels of DDT.

Toxicology and Applied Pharmacology↗
USGS1971

Comparative acute oral toxicity of pesticides to six species of birds

Acute oral LD50 values were determined for 16 common pesticides on mallard ducks ( Anas platyrhynchos ), ring-necked pheasants ( Phasianus colchicus ), chukar partridges ( Alectoris graeca ), coturnix quail ( Coturnix coturnix japonica ), common pigeons ( Columba livia ), and house sparrows ( Passer domesticus ). Analyses of the data revealed that (1) the average sensitivity of any one species to the 16 pesticides did not differ statistically from that of any other species, and (2) at the same time, the species varied widely in their sensitivity to any given compound. The average range of the LD50 values for single chemicals in the 6 species was nearly 10-fold. With differences of this magnitude, it is recommended that extrapolation of toxicity data from one species to another be avoided.

Toxicology and Applied Pharmacology↗
USGS1972

The acute oral toxicity of 369 pesticidal, pharmaceutical and other chemicals to wild birds

The acute po toxicity of 369 chemicals was determined for 1 or more species of wild birds, always including either red-winged blackbirds or starlings. Of these, 180 chemicals were toxic to 1 or more species at 100 mg/kg or less. Statistical comparison of redwing, starling and rat data indicated that redwings were more sensitive to chemicals than starlings, and both were more sensitive than rats.

Toxicology and Applied Pharmacology↗