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Sample records for juvenile animal toxicity

  1. Juvenile animal toxicity study designs to support pediatric drug development.

    PubMed

    Cappon, Gregg D; Bailey, Graham P; Buschmann, Jochen; Feuston, Maureen H; Fisher, J Edward; Hew, Kok Wah; Hoberman, Alan M; Ooshima, Yojiro; Stump, Donald G; Hurtt, Mark E

    2009-12-01

    The objective of juvenile animal toxicity studies of pharmaceuticals is to obtain safety data, including information on the potential for adverse effects on postnatal growth and development. Studies in juvenile animals may assist in identifying postnatal developmental toxicities or other adverse effects that are not adequately assessed in the routine toxicity evaluations and that cannot be safely or adequately measured in pediatric clinical trials. Unlike the traditional reproductive and developmental toxicology studies that have been discussed in the accompanying reports, the design requirements for toxicity studies in juvenile animals are not explicitly defined in regulatory guidance. However, studies in juvenile animals can be useful in providing safety information necessary to enable pediatric clinical trials in pediatric patients or when there are special concerns for toxicities that cannot be safely or adequately measured in clinical trials. These juvenile animal toxicity studies are designed on a case-by-case basis. General design considerations and examples of study designs for assessment of juvenile animal toxicity are discussed.

  2. [Molecular Identification and Toxicity of Pufferfish Juveniles Contaminating Whitebait Products].

    PubMed

    Kiriake, Aya; Ohta, Akira; Okayama, Sakurako; Matsuura, Keiichi; Ishizaki, Shoichiro; Nagashima, Yuji

    2016-01-01

    Catches of whitebait, sardine fry, sometimes contains other marine animals, including fishes, mollusks, and crustaceans, and therefore boiled and dried whitebait products may contain these marine animals if sorting is incomplete. In September 2014, contamination of boiled and dried whitebait products with pufferfish juveniles became a serious food safety concern, as tiger pufferfish Takifugu rubripes juveniles are toxic and contain tetrodotoxin (TTX). The toxicity of the juveniles of other pufferfish species, however, is unclear. To evaluate the food safety of whitebait products contaminated with pufferfish juveniles, we identified the species and toxicity of pufferfish juveniles contaminating whitebait products processed between July and September, 2014. Nucleotide sequence analysis of 16S rRNA or cytochrome b gene fragments of the mitochondrial DNA indicated that partial sequences of the polymerase chain reaction products of 15 specimens were identical with those of Lagocephalus spadiceus, and partial sequence from 2 specimens were identical with those of Takifugu vermicularis. We analyzed TTX by liquid chromatography-tandem mass spectrometry. TTX was not detected in the L. spadiceus specimens and was below the quantification limits (30 ng/g) in a T. vermicularis specimen. Based on whitebait product manufacturer's research, 795 individuals and 27.2 g of pufferfish juveniles were detected in 8,245 kg whitebait product. Thus, the ratio of pufferfish to whitebait product was estimated to be 0.096 individual/kg whitebait product and 0.0033 g/kg whitebait product, respectively.

  3. Chronic juvenile toxic epidemic syndrome.

    PubMed Central

    Izquierdo, M; Mateo, I; Rodrígo, M; Mena, C; Sebastián, M; Conde, J; Gómez-Reino, J J

    1985-01-01

    The clinical manifestations in 21 children with chronic toxic epidemic syndrome (TES) and musculoskeletal manifestations were analysed and compared with those of the adult population. The sex ratio (2.5:1, F/M) was different from the one found in adults (6:1, F/M). The neuromuscular syndrome, the scleroderma-like picture, the pulmonary hypertension, and the Raynaud's phenomenon characteristic of TES were similar to those in adults but milder in children. The less severe vascular endothelial lesions found on microscopic examination might explain the better prognosis in this age group. Images PMID:3977416

  4. Juvenile animal cruelty and firesetting behaviour.

    PubMed

    Baglivio, Michael T; Wolff, Kevin T; DeLisi, Matt; Vaughn, Michael G; Piquero, Alex R

    2016-09-04

    There is a view that young people presenting with an animal cruelty and firesetting combination represent a uniquely risky group, but prior work has relied on samples with insufficient power. What is the prevalence of the co-occurrence of animal cruelty and firesetting behaviour among young delinquents? What other features correlate with this? We measured the prevalence of animal cruelty and firesetting among 292,649 juvenile offenders and used rare events logistic regression to examine demographic, criminal, mental health and family histories as correlates. The prevalence of animal cruelty was 0.59%, accounting for 1732 young people, and of firesetting 1.56% (n = 4553). The co-occurrence of these behaviours was rare: 0.17% (n = 498), but approximately twice that expected by chance based on the prevalence of each behaviour individually (0.59% × 1.56% = 0.009%). Rates were higher in males, older youths and Whites. Among historical variables, criminal history was the strongest correlate, followed by mental health problems, then familial and individual indicators. As only male gender and being a victim of sexual abuse increased the odds of evidencing both animal cruelty and firesetting behaviour substantially above the odds for each behaviour individually, there thus appears to be little that is unique to the co-occurrence. Our findings suggest that sensitivity to the occurrence of each is the best way forward, with rather familiar assessments and interventions offering some hope of reducing these seriously damaging behaviours. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  5. [Selenium toxicity in domestic animals].

    PubMed

    Mihajlović, M

    1992-01-01

    The earliest written report of selenium poisoning is thought to be the description by Marco Polo of a necrotic hoof disease of horses that occurred in China in 13. century. However recognition of Se as toxic principle come in the early 1930s. Severity of Se poisoning depends on chemical forms of the element, species of animals and routes of administration. The soluble Se salts (Na2SeO3 and Na2SeO4) appear to be among the more toxic compounds; the Se inherent in grains and selenoamino acids (selenomethionine and selenocystine) appear to have relative moderate toxicity; the poorly soluble forms (e.g., elemental Se, Na2Se, SeS2 and diphenyl selenide) are among the least toxic of the Se compounds. In general, toxicity of Se compounds are substantially less when they are administered orally than when they are given parenterally. Rosenfeld and Beath described three clinical types of Se intoxication: acute selenosis, subacute selenosis (i.e., blind staggers type), and chronic selenosis (i.e., alkali disease type). Acute poisoning occurs when high Se content plants are consumed in large quantities within short period. Accidental acute poisoning occurs as consequence of errors in formulation of a Se supplemented diet. The most characteristic sign of acute selenosis is garlic breath due to the pulmonary excretion of volatile Se metabolites. Other signs include lethargy, excessive salivation, vomiting, dyspnea, muscle tremors and respiratory distress. Pathological findings are: congestion of the liver and kidney, fatty degeneration and focal necrosis of the liver, endocarditis and myocarditis. Subacute selenosis ("blind staggers") occurs as a consequence of exposure to large doses of Se over a longer period of time and manifests with neurological signs (e.g., blindness, ataxia, disorientation) and respiratory distress. This form of selenosis is most frequently observed in grazing animals that have consumed Se-accumulated plants. Chronic selenosis ("alkali disease") comes

  6. Animal Abuse and Youth Violence. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Ascione, Frank R.

    The forms of abuse that animals are subjected to are similar to the forms of abuse children experience, such as physical abuse, serious neglect, and psychological abuse. This document describes psychiatric, psychological, and criminal research linking animal abuse to violence perpetrated by juveniles and adults. Particular attention is given to…

  7. Real life juvenile toxicity case studies: the good, the bad and the ugly.

    PubMed

    De Schaepdrijver, Luc; Rouan, Marie-Claude; Raoof, Araz; Bailey, Graham P; De Zwart, Loeckie; Monbaliu, Johan; Coogan, Timothy P; Lammens, Lieve; Coussement, Werner

    2008-09-01

    With the growing experience in the conduct of juvenile toxicity studies for multiple classes of compound, the 'case-by-case' approach has become under much more pressure. Instead, a general screen or 'standard design' is now commonly expected by regulatory authorities with more routine inclusion of neurological and reproductive assessments. Minor modifications or additions can be made to the design to address specific questions according to the class of drug or intended clinical use. This drift from a 'case-by-case' approach to a 'standard design' approach is present within certain reviewing divisions of the FDA, often requesting by default a rodent and non-rodent juvenile animal study. However, juvenile animal studies should be designed thoughtfully to fulfil a purpose based on scientific rationale, with each endpoint carefully considered in terms of practicality and interpretability of data generated. Only when using the appropriate strategy and design may juvenile studies add value by (1) identifying potential safety or pharmacokinetic issues for drugs intended for paediatric use, (2) suggesting additional clinical endpoints and (3) adding new information to the product label. As the knowledge from juvenile animal studies in various species grows, a better understanding of the significance/relevance of findings will be achieved.

  8. Comparative juvenile safety testing of new therapeutic candidates: relevance of laboratory animal data to children.

    PubMed

    Anderson, Tim; Khan, Nasir K; Tassinari, Melissa S; Hurtt, Mark E

    2009-01-01

    Differences in drug response in patients of various ages including children and the elderly are common, often leading to challenges in optimizing dosages and duration of use. For example, developmental changes in renal function can dramatically alter the plasma clearance of compounds with extensive renal elimination and thus can enhance renal and systemic toxicity of these drugs. Preclinical and clinical research of new therapeutics is initially focused on adults, and provides little relevant information for children especially those who are still going through skeletal and organ development. The organ systems in the pediatric population that can be most susceptible are lungs, brain, kidneys, immune, skeletal, and reproductive systems. Considering that significant differences can exist between adult and juvenile populations that may affect drug safety, major regulatory agencies around the world are encouraging and sometimes requiring companies to generate preclinical juvenile animal data to predict for potential drug toxicity in children. However, data generated from such studies are useful only if obtained using the most appropriate species at the most relevant age considering comparability of specific organ system development in question. Other factors in the design of juvenile safety studies should include the indication, existing toxicological data and likely route of human exposure. This report will discuss these factors with a focus on reviewing species-specific developmental schedules for specific target organs and relevance of preclinical data in the design and conduct of clinical pediatric studies. Specific examples will be used to discuss the relationship of preclinical juvenile toxicity observations to risk assessment in humans.

  9. Cyanide toxicity in juvenile pigs and its reversal by a new prodrug, sulfanegen sodium.

    PubMed

    Belani, Kumar G; Singh, Harpreet; Beebe, David S; George, Preeta; Patterson, Steven E; Nagasawa, Herbert T; Vince, Robert

    2012-05-01

    Cyanide (CN) toxicity is a serious clinical problem and can occur with sodium nitroprusside (SNP) administration, accidental smoke inhalation, industrial mishaps, and bio-terrorism. In this study, we induced severe CN toxicity independently with SNP or sodium cyanide (NaCN) in a juvenile pig model to demonstrate reversal of severe CN toxicity with a new antidote, sulfanegen sodium, a prodrug of 3-mercaptopyruvate. SNP study: A pilot study in 11 anesthetized, mechanically ventilated juvenile pigs allowed us to determine the dose of SNP to induce CN toxicity. Blood CN, serum lactates, and blood gases were monitored. CN toxicity was defined as the occurrence of severe lactic acidosis accompanied by significant elevation in blood CN levels. Based on this pilot study, 8 anesthetized pigs received a high-dose i.v. infusion of SNP (100 mg/h) for 2 hours to induce CN toxicity. They were then randomized to receive either sulfanegen sodium or placebo. Four pigs received 3 doses of sulfanegen sodium (2.5 g i.v.) every hour after induction of severe CN toxicity, and 4 pigs received placebo. NaCN study: A pilot study was conducted in 4 spontaneously ventilating pigs sedated with propofol plus ketamine to demonstrate hemodynamic and metabolic stability for several hours. After this, 6 pigs were similarly sedated and given NaCN in bolus aliquots to produce CN toxicity ultimately resulting in death. Hemodynamics and metabolic variables were followed to define peak CN toxicity. In another group of 6 pigs, severe CN toxicity was induced by this method, and at peak toxicity, the animals were given sulfanegen sodium (2.5 g i.v.) followed by a repeat dose 60 minutes later in surviving animals. SNP study: The pilot study demonstrated the occurrence of a significant increase in blood CN levels (P < 0.05) accompanied by severe lactic acidemia (P < 0.05) in all pigs receiving a high dose of SNP. Administration of the sulfanegen antidote resulted in progressive significant reduction in

  10. The evolution of juvenile animal testing for small and large molecules.

    PubMed

    Baldrick, Paul

    2013-11-01

    Recent formalised regulatory requirements for ensuring safe use of new drugs in children has increased the requirement, when considered relevant, to perform juvenile animal testing before commencing paediatric clinical trials. A key goal of this work is to identify or examine for a developmental or toxicity finding not seen in other toxicology testing. With our current knowledge, this paper examines what types of testing are occurring, what novel findings are being seen and their relevance in the safety evaluation process. Furthermore, trends for now and the future in the type of juvenile animal testing will be described including a need for more focused study designs and more published data on modern cross-species postnatal development. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Toxicity of atrazine to the juvenile hard clam, Mercenaria mercenaria.

    PubMed

    Lawton, Jennifer C; Pennington, Paul L; Chung, Katy W; Scott, Geoffrey I

    2006-11-01

    The herbicide atrazine is one of the most heavily used pesticides in the United States. The effects of atrazine on the clam Mercenaria mercenaria were evaluated in aqueous and sediment laboratory assays. Juvenile clams of approximately 1mm in size were used for all experiments. An acute aqueous bio-assay was used to determine the 96-h LC(50) for the juvenile clams. A chronic aqueous bioassay was conducted at lower atrazine concentrations over a 10-day exposure period to examine both lethal and sublethal (dry mass, shell size, and condition index) endpoints. A chronic sediment bioassay examined mortality and sublethal endpoints in a 10-day exposure. The acute 96-h LC(50) was 5608 microg/L with 95% confidence intervals ranging from 5003 to 6287 microg/L. Results of the chronic aqueous assay indicated both lethal and sublethal (reduced shell size) effects at high atrazine concentrations. In the 10-day chronic aqueous assay, the no observable effect concentration was 500 microg/L, the lowest observable effect concentration was 1000 microg/L, and the maximum allowable toxicant concentration (MATC) was 707 microg/L. There were no significant effects of atrazine in the chronic sediment exposure. Safe concentrations for the aqueous experiments were estimated by applying an uncertainty factor of 10 to the calculated MATC values. While there were adverse effects of atrazine at high concentrations, these results suggest that atrazine is not directly toxic to M. mercenaria at environmentally relevant concentrations.

  12. Juvenile animal abuse: Practice and policy implications for PNPs.

    PubMed

    Muscari, Mary

    2004-01-01

    Animal abuse has long been recognized as a sign of family violence and a warning sign of future aggression in children and adolescents. As leaders in youth violence prevention, pediatric nurse practitioners need to be aware of the prevalence and types of juvenile animal cruelty and its relationship to human violence. In doing so, they can champion for health care and related policies for this disturbing problem, described by Ascione as an underreported and understudied issue that may add to the understanding and prevention of youth violence."[One of the most dangerous things that can happen to a child] is when the child who kills or tortures [an animal] is not caught, or if caught is not punished." -Anthropologist Margaret Mead

  13. Juvenile animal studies for the development of paediatric medicines: a description and conclusions from a European Medicines Agency workshop on juvenile animal testing for nonclinical assessors.

    PubMed

    Silva-Lima, Beatriz; Due Theilade-Thomsen, Mette; Carleer, Jacqueline; Vidal, Jean-Marc; Tomasi, Paolo; Saint-Raymond, Agnes

    2010-12-01

    A workshop organised by the European Medicines Agency involved assessors and experts present in a Nonclinical Working Group evaluating juvenile animal studies for Paediatric Investigation Plans in collaboration with the Paediatric Committee and the Safety Working Party of the Committee for Human Medicinal Products. The objective of the workshop was to analyse which juvenile animal studies proposals were received and agreed by the Paediatric Committee, to check consistency and how to apply the existing European guideline on juvenile animal studies. A comparison of main organ system development in man vs. animal species was presented to guide the review and to support species selection and protocol design. An analysis of juvenile animal studies included in finalised PIP's was also presented. Out of 109 paediatric investigation plans finalised between November 2008 and March 2009, 43 included one or more juvenile animal studies. In most cases the preferred species was the rat; one species only was requested to be studied (20/22), but in a minority two species were required (2/22). When deciding on the characteristics of the juvenile animal studies, such as age of animals at study start, the age of the children targeted by the medicine was considered. It is expected that the increasing experience gained by Applicants and Regulators will allow further refining the criteria for these juvenile animal studies. Further research on this topic is highly encouraged in the European Regulatory framework. © 2010 Wiley-Liss, Inc.

  14. Animal alternatives for whole effluent toxicity testing ...

    EPA Pesticide Factsheets

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicity based effluent assessments and subsequent discharge controls became globally important, when it was recognized that physical and chemical measurements alone did not protect the environment from potential impacts. Consequently, various strategies using different toxicity tests, whole effluent assessment techniques (incorporating bioaccumulation potential and persistence) plus supporting analytical tools have been developed over 30 years of practice. Numerous workshops and meetings have focused on effluent risk assessment through ASTM, SETAC, OSPAR, UK competent authorities, and EU specific country rules. Concurrent with this drive to improve effluent quality using toxicity tests, interest in reducing animal use has risen. The Health and Environmental Sciences Institute (HESI) organized and facilitated an international workshop in March 2016 to evaluate strategies for concepts, tools, and effluent assessments and update the toolbox of for effluent testing methods. The workshop objectives were to identify opportunities to use a suite of strategies for effluents, and to identify opportunities to reduce the reliance on animal tests and to determine barriers to implementation of new methodologie

  15. Animal alternatives for whole effluent toxicity testing ...

    EPA Pesticide Factsheets

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicity based effluent assessments and subsequent discharge controls became globally important, when it was recognized that physical and chemical measurements alone did not protect the environment from potential impacts. Consequently, various strategies using different toxicity tests, whole effluent assessment techniques (incorporating bioaccumulation potential and persistence) plus supporting analytical tools have been developed over 30 years of practice. Numerous workshops and meetings have focused on effluent risk assessment through ASTM, SETAC, OSPAR, UK competent authorities, and EU specific country rules. Concurrent with this drive to improve effluent quality using toxicity tests, interest in reducing animal use has risen. The Health and Environmental Sciences Institute (HESI) organized and facilitated an international workshop in March 2016 to evaluate strategies for concepts, tools, and effluent assessments and update the toolbox of for effluent testing methods. The workshop objectives were to identify opportunities to use a suite of strategies for effluents, and to identify opportunities to reduce the reliance on animal tests and to determine barriers to implementation of new methodologie

  16. Chronic oral DDT toxicity in juvenile coho and chinook salmon

    USGS Publications Warehouse

    Buhler, Donald R.; Rasmusson, Mary E.; Shanks, W.E.

    1969-01-01

    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.

  17. The effects of chronological age and size on toxicity of zinc to juvenile brown trout

    EPA Science Inventory

    A series of toxicity tests were conducted to investigate the role of chronological age and organism weight on zinc tolerance in juvenile brown trout (Salmo trutta). Four different incubation temperatures were used to control the maturation of the juveniles prior to zinc exposure...

  18. The effects of chronological age and size on toxicity of zinc to juvenile brown trout

    EPA Science Inventory

    A series of toxicity tests were conducted to investigate the role of chronological age and organism weight on zinc tolerance in juvenile brown trout (Salmo trutta). Four different incubation temperatures were used to control the maturation of the juveniles prior to zinc exposure...

  19. Effect of test conditions on the toxicity of copper to juvenile unionid mussels

    SciTech Connect

    Keller, A.E.; Ruessler, D.S.; Kernaghan, N.J.

    1999-07-01

    During the past twenty years, unionid mussels have declined in both abundance and diversity throughout the eastern United States. As a result, there has been an increased call to evaluate the toxicity of various pollutants to unionids in an attempt to separate habitat-caused losses from those precipitated by aquatic contaminants. Few toxicity data for unionids were available until recently because unionids are not easily cultured and no test method had been developed for these animals. Therefore, water quality criteria developed by the USEPA in the 1970s and 1980s were derived from data lacking any information on unionid mussel sensitivities. The Tennessee Valley Authority (TVA) has advocated the use of a 9-day toxicity test method its scientists developed in the late 1980s. This method, which requires the use of silt, an algal mixture for food and daily changes of water, is not only more labor intensive, it also introduces sources of variation with the use of silt and algae, as well as being substantially different from the standard 96-h fathead minnow or zooplankton tests. The evaluation of TVA's suggested test conditions indicate that the use of a 16L:8D light regime, with or without silt or algae did not result in a change in the toxicity of dissolved copper to juvenile Utterbackia imbecillis mussels compared to that recorded using TVA's test conditions.

  20. Cadmium toxicity assessment in juveniles of the Austral South America amphipod Hyalella curvispina.

    PubMed

    Giusto, Anabella; Somma, Lucas A; Ferrari, Lucrecia

    2012-05-01

    Hyalella curvispina is representative of zoobenthic communities in Austral South America. It is taxonomically close to Hyalella azteca and abundant in fresh water bodies of the pampasic region of Argentina. It is usually used as test organism in ecotoxicological studies at a regional level, and there is a strong concern to increase the knowledge of both their biology and their sensitivity to different toxic agents. The aim of the present work was to assess the effects of cadmium on H. curvispina juveniles exposed to concentrations expected in the water bodies of the distribution area of the species. Survival, growth and cadmium body burden were evaluated in aqueous and solid matrices under fixed experimental conditions. Animals were exposed in ten-day static toxicity bioassays to 2.5, 5.25 and 11.25 μg Cd/L for the aqueous-phase bioassays, and to 0.85, 2.8 and 5.6 mg Cd/Kg dry sediment for the solid-phase bioassays. In water only assays, the animals exposed to 11.25 μg Cd/L showed a significant decrease in survival and growth. In the sediment bioassays, no effect was observed on survival, and weight was significantly reduced at the highest concentration. Cadmium uptake was concentration dependent for both assay matrices and one order of magnitude higher in the aqueous medium than in the solid matrix. Results indicate that juveniles of H. curvispina are sensitive to cadmium concentrations expected in their environment and thus confirm their importance as test organisms for ecotoxicity assessment in water bodies within the distribution area of the species.

  1. Effect of temperature on heavy metal toxicity to juvenile crayfish, Orconectes immunis (Hagen).

    PubMed

    Khan, M A Q; Ahmed, S A; Catalin, Bogdon; Khodadoust, A; Ajayi, Oluwaleke; Vaughn, Mark

    2006-10-01

    The acute toxicity of four selected heavy metals to juvenile crayfish Orconectes immunis (Hagen) (1-2 g wet body wt. each) at room temperature increased in the following order: cadmium (x3) < copper (x10) < zinc (x2) < lead. The toxicity of these metals to crayfish acclimated at 17, 20, 23/24, and 27 degrees C increased with temperature (by 7-20% between 20 and 24 degrees C and 14-26% between 20 and 27 degrees C) as judged by the lowering of LT(50) (time to kill 50% of test animals at a fixed concentration) values. A 4 degrees C rise in temperature (from 20 to 24 degrees C), which increased the toxicity of copper by about 7%, increased the rate of oxygen consumption by about 34%. Heavy metals inhibited the rate of oxygen consumption at all temperatures. In 20 degrees C-acclimated crayfish, copper caused about 17% inhibition of oxygen consumption compared to about 7-12% by other metals including the most toxic cadmium. A 3-4 degrees C rise in temperature tripled the inhibitory effect of copper (20%), cadmium and zinc (26 and 18%, respectively), but not of lead, on oxygen consumption. A 7 degrees C-rise in temperature (from 20 to 27 degrees C) increased the inhibitory effect of heavy metals, including lead, on oxygen consumption by up to 54% in the case of copper. The data indicate that rising global temperatures (currently 0.60 degrees C) associated with climate change can have the potential to increase the sensitivity of aquatic animals to heavy metals in their environment.

  2. Intra- and interlaboratory variability in acute toxicity tests with glochidia and juveniles of freshwater mussels (Unionidae)

    USGS Publications Warehouse

    Wang, N.; Augspurger, T.; Barnhart, M.C.; Bidwell, Joseph R.; Cope, W.G.; Dwyer, F.J.; Geis, S.; Greer, I.E.; Ingersoll, C.G.; Kane, C.M.; May, T.W.; Neves, R.J.; Newton, T.J.; Roberts, A.D.; Whites, D.W.

    2007-01-01

    The present study evaluated the performance and variability in acute toxicity tests with glochidia and newly transformed juvenile mussels using the standard methods outlined in American Society for Testing and Materials (ASTM). Multiple 48-h toxicity tests with glochidia and 96-h tests with juvenile mussels were conducted within a single laboratory and among five laboratories. All tests met the test acceptability requirements (e.g., ???90% control survival). Intralaboratory tests were conducted over two consecutive mussel-spawning seasons with mucket (Actinonaias ligamentina) or fatmucket (Lampsilis siliquoidea) using copper, ammonia, or chlorine as a toxicant. For the glochidia of both species, the variability of intralaboratory median effective concentrations (EC50s) for the three toxicants, expressed as the coefficient of variation (CV), ranged from 14 to 27% in 24-h exposures and from 13 to 36% in 48-h exposures. The intralaboratory CV of copper EC50s for juvenile fatmucket was 24% in 48-h exposures and 13% in 96-h exposures. Interlaboratory tests were conducted with fatmucket glochidia and juveniles by five laboratories using copper as a toxicant. The interlaboratory CV of copper EC50s for glochidia was 13% in 24-h exposures and 24% in 48-h exposures, and the interlaboratory CV for juveniles was 22% in 48-h exposures and 42% in 96-h exposures. The high completion success and the overall low variability in test results indicate that the test methods have acceptable precision and can be performed routinely. ?? 2007 SETAC.

  3. Toxicity of oil and dispersed oil on juvenile mud crabs, Rhithropanopeus harrisii.

    PubMed

    Anderson, Julie A; Kuhl, Adam J; Anderson, A Nikki

    2014-04-01

    In order to simulate an offshore oil spill event, we assessed the acute toxicity of the non-dispersed and the chemically dispersed water-accommodated fraction (WAF) of crude oil using Louisiana sweet crude and Corexit(®) 9500A with juvenile Harris mud crabs (Rhithropanopeus harrisii), an important Gulf of Mexico benthic crustacean. The chemical dispersion of crude oil significantly increased acute toxicity of the WAF in juvenile mud crabs compared to naturally dispersed oil. The majority of the mortality in the chemically dispersed treatments occurred within 24 h. While higher concentrations of chemically dispersed WAF had no survivors, at lower concentrations surviving juvenile crabs displayed no long-term effects. These results suggest that if the juvenile crabs survive initial exposure, acute exposure to dispersed or non-dispersed crude oil may not induce long-term effects.

  4. Estimating survival rates of uncatchable animals: the myth of high juvenile mortality in reptiles.

    PubMed

    Pike, David A; Pizzatto, Lígia; Pike, Brian A; Shine, Richard

    2008-03-01

    Survival rates of juvenile reptiles are critical population parameters but are difficult to obtain through mark-recapture programs because these small, secretive animals are rarely caught. This scarcity has encouraged speculation that survival rates of juveniles are very low, and we test this prediction by estimating juvenile survival rates indirectly. A simple mathematical model calculates the annual juvenile survival rate needed to maintain a stable population size, using published data on adult survival rates, reproductive output, and ages at maturity in 109 reptile populations encompassing 57 species. Counter to prediction, estimated juvenile survival rates were relatively high (on average, only about 13% less than those of conspecific adults) and highly correlated with adult survival rates. Overall, survival rates during both juvenile and adult life were higher in turtles than in snakes, and higher in snakes than in lizards. As predicted from life history theory, rates of juvenile survival were higher in species that produce large offspring, and higher in viviparous squamates than in oviparous species. Our analyses challenge the widely held belief that juvenile reptiles have low rates of annual survival and suggest instead that sampling problems and the elusive biology of juvenile reptiles have misled researchers in this respect.

  5. Toxic effects of cannabis and cannabinoids: Animal data.

    PubMed

    Beaulieu, Pierre

    2005-01-01

    The present article reviews the main toxic effects of cannabis and cannabinoids in animals. Toxic effects can be separated into acute and chronic classifications. Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis. Chronic toxicity involves lesions of airway and lung tissues, as well as problems of neurotoxicity, tolerance and dependence, and dysregulations in the immune and hormonal systems. Animal toxicity data, however, are difficult to extrapolate to humans.

  6. Toxicity of polybrominated biphenyls (PBBs) in Domestic and laboratory animals.

    PubMed Central

    Damstra, T; Jurgelski, W; Posner, H S; Vouk, V B; Bernheim, N J; Guthrie, J; Luster, M; Falk, H L

    1982-01-01

    The composition, environmental fate, and effects of the polybrominated biphenyls (Firemaster BP-6 or FF-1) involved in the accidental contamination of cattle feed in Michigan in 1973 are reviewed. Toxic effects referred to in this report are limited to those occurring in domestic and laboratory animals and include general toxicity, neurobehavioral toxicity, immunotoxicity, reproductive toxicity, mutagenicity and carcinogenicity. The absorption, distribution, biotransformation and elimination of these polybrominated biphenyls are discussed along with the interactions with other chemicals and drugs. PMID:6282577

  7. Arsenic Toxicity to Juvenile Fish: Effects of Exposure Route, Arsenic Speciation, and Fish Species

    EPA Science Inventory

    Arsenic toxicity to juvenile rainbow trout and fathead minnows was evaluated in 28-day tests using both dietborne and waterborne exposures, both inorganic and organic arsenic species, and both a live diet and an arsenic-spiked pellet diet. Effects of inorganic arsenic on rainbow...

  8. Arsenic Toxicity to Juvenile Fish: Effects of Exposure Route, Arsenic Speciation, and Fish Species

    EPA Science Inventory

    Arsenic toxicity to juvenile rainbow trout and fathead minnows was evaluated in 28-day tests using both dietborne and waterborne exposures, both inorganic and organic arsenic species, and both a live diet and an arsenic-spiked pellet diet. Effects of inorganic arsenic on rainbow...

  9. Clinical neurologic indices of toxicity in animals.

    PubMed Central

    O'Donoghue, J L

    1996-01-01

    The fundamental structures and functions of the nervous systems of animals and humans are conserved in many ways across species. These similarities provide a basis for developing common neurologic examinations for a number of species of animals and also provide a basis for developing risk assessments across species for neurologic end points. The neurologic examination requires no expensive equipment and can be conducted in the field or wherever impaired animals are identified. The proper conduct of neurologic examinations in animals assumes that the examiner has a fundamental understanding of the normal structure and function of the nervous system as well as knowledge about the spontaneous disease background of the species being studied. PMID:9182039

  10. Effects of ammonia on juvenile unionid mussels (Lampsilis cardium) in laboratory sediment toxicity tests

    USGS Publications Warehouse

    Newton, Teresa J.; Allran, John W.; O'Donnell, Jonathan A.; Bartsch, Michelle; Richardson, William B.

    2003-01-01

    Ammonia is a relatively toxic compound generated in water and sediments by heterotrophic bacteria and accumulates in sediments and pore water. Recent data suggest that unionid mussels are sensitive to un-ionized ammonia (NH3) relative to other organisms. Existing sediment exposure systems are not suitable for ammonia toxicity studies with juvenile unionids; thus, we modified a system to expose juveniles to ammonia that was continuously infused into sediments. This system maintained consistent concentrations of ammonia in pore water up to 10 d. Juvenile Lampsilis cardium mussels were exposed to NH3 in pore water in replicate 96-h and 10-d sediment toxicity tests. The 96-h median lethal concentrations (LC50s) were 127 and 165 μg NH3-N/L, and the 10-d LC50s were 93 and 140 μg NH3-N/L. The median effective concentrations (EC50s) (based on the proportion affected, including dead and inactive mussels) were 73 and 119 μg NH3-N/L in the 96-h tests and 71 and 99 μg NH3-N/L in the 10-d tests. Growth rate was substantially reduced at concentrations between 31 and 76 μg NH3-N/L. The lethality results (when expressed as total ammonia) are about one-half the acute national water quality criteria for total ammonia, suggesting that existing criteria may not protect juvenile unionids.

  11. HMX: Acute Toxicity Tests in Laboratory Animals.

    DTIC Science & Technology

    1985-07-30

    Nutrition expanded Rat and Mouse Maintenance Diet No. 1 (Appendix 1) but were deprived of food for a 16 h period prior to dosing. Water was available...humidity was 57% (extremes of 52%-74%). The animals were fed on BP Nutrition expanded Rat and Mouse Maintenance Diet No. 1 but were deprived of food for a... Nutrition expanded Rat and Mouse Maintenance Diet No. 1. Food and water were avail- able ad libitum throughout the study. c) Method The application site

  12. Acute silver toxicity in aquatic animals is a function of sodium uptake rate.

    PubMed

    Bianchini, Adalto; Grosell, Martin; Gregory, Sean M; Wood, Chris M

    2002-04-15

    On the basis of these facts about freshwater fish and invertebrates: (i) the Na+ turnover is a physiological process associated with the gill membranes; (ii) the key mechanism of acute silver toxicity consists of reduction in Na+ uptake by blockade of gill Na+,K+-ATPase; (iii) the mass-specific surface area of the gills depends on animal body mass; and (iv) the gill surface is also the major site of Na+ loss by diffusion, we hypothesized that whole body Na+ uptake rate (i.e., turnover rate) and secondarily body mass would be good predictors of acute silver toxicity. Results obtained from toxicological (LC50 of AgNO3) and physiological (22Na uptake rate) tests performed on juvenile fish (rainbow trout, Oncorhynchus mykiss), early juvenile and adult crayfish (Cambarusdiogenes diogenes), and neonate and adult daphnids (Daphnia magna) in moderately hard water of constant quality support the above hypothesis. Therefore, sensitivity to AgNO3, in terms of either total measured silver or free Ag+, was reliably predicted from the whole body Na+ uptake rate in animals with body mass ranging over 6 orders of magnitude (from micrograms to grams). A positive log-log correlation between acute AgNO3 toxicity and body mass of the same species was also observed. Furthermore, the whole body Na+ uptake rate was inversely related to body mass in unexposed animals. The combination of these last two results explains why the small animals in this study were more sensitive to Ag+ than the larger ones. Taken together, these results clearly point out the possibility of incorporating the Na+ uptake rate into the current version of the Biotic Ligand Model to improve the predictive capacity of this model. In the absence of information on Na+ uptake rate, then body mass may serve as a surrogate.

  13. Acute toxicity and synergism of cadmium and zinc in white shrimp, Penaeus setiferus, Juveniles

    SciTech Connect

    Vanegas, C.; Espina, S.; Botello, A.V.; Villanueva, S.

    1997-01-01

    Toxic effects of individual heavy metals on decapod crustaceans have been reported frequently, but little information exists concerning interactions. Among the non-essential heavy metals, cadmium is one of the most hazardous elements in the aquatic environment; on the other hand, zinc is an essential element, but toxic when present in greater than trace amounts. Biological effects of cadmium in aquatic organisms are complex due to the interactions with both environmental variables and other toxic agents. In decapod crustaceans, the toxicity of cadmium and zinc is modified by salinity, temperature, hypoxia, calcium ion concentrations and life-cycle stage. Heavy metal pollution has increased in the coastal waters of the Gulf of Mexico, particularly in shrimp habitat. This study examined the toxicity of cadmium and zinc to white shrimp juveniles and looked at the interaction of the metals. 16 refs., 2 tabs.

  14. Aliskiren toxicity in juvenile rats is determined by ontogenic regulation of intestinal P-glycoprotein expression

    SciTech Connect

    Hoffmann, Peter; Beckman, David; McLean, Lee Anne; Yan, Jing-He

    2014-02-15

    Juvenile rat toxicity studies with the direct renin inhibitor aliskiren were initiated to support treatment in the pediatric population. In Study 1, aliskiren was administered orally to juvenile rats at doses of 0, 30, 100 or 300 mg/kg/day with repeated dosing from postpartum day (PPD) 8 to PPD 35/36. In-life, clinical pathology, anatomic pathology, and toxicokinetics evaluations were performed. In Study 2, single oral doses of aliskiren (0, 100 or 300 mg/kg) were given to 14-, 21-, 24-, 28-, 31- or 36-day-old rats; in-life data and toxicokinetics were evaluated. Study 3 was a single dose (3 mg/kg i.v.) pharmacokinetic study in juvenile rats on PPD 8, 14, 21 and 28. In Study 4, naïve rats were used to investigate ontogenic changes of the multidrug-resistant protein 1 (MDR1) and the organic anion transporting polypeptide (OATP) mRNA in several organs. Oral administration of aliskiren at 100 and 300 mg/kg caused unexpected mortality and severe morbidity in 8-day-old rats. Aliskiren plasma and tissue concentrations were increased in rats aged 21 days and younger. Expression of MDR1 and OATP mRNA in the intestine, liver and brain was significantly lower in very young rats. In conclusion, severe toxicity and increased exposure in very young rats after oral administration of aliskiren are considered to be the result of immature drug transporter systems. Immaturity of MDR1 in enterocytes appears to be the most important mechanism responsible for the high exposure. - Highlights: • Aliskiren was orally administered to juvenile rats. • Unexpected severe toxicity and acute mortality occurred in rats aged 8 days. • Toxicity was associated with increased aliskiren plasma and tissue exposure. • Developmental changes of exposure correlated with ontogeny of transporters. • Immaturity of MDR1 in enterocytes causes increased exposure in very young rats.

  15. Toxicity assessment of molindone hydrochloride, a dopamine D2/D5 receptor antagonist in juvenile and adult rats.

    PubMed

    Krishna, Gopala; Gopalakrishnan, Gopa; Goel, Saryu

    2017-06-01

    Neuroleptic drug molindone hydrochloride is a dopamine D2/D5 receptor antagonist and it is in late stage development for the treatment of impulsive aggression in children and adolescents who have attention deficient/hyperactivity disorder (ADHD). This new indication for this drug would expand the target population to include younger patients, and therefore, toxicity assessments in juvenile animals were undertaken in order to determine susceptibility differences, if any, between this age group and the adult rats. Adult rats were administered molindone by oral gavage for 13 weeks at dose levels of 0, 5, 20, or 60 mg/kg-bw/day. Juvenile rats were dosed for 8 weeks by oral gavage at dose levels of 0, 5, 25, 50, or 75 mg/kg-bw/day. Standard toxicological assessments were made using relevant study designs in consultation with FDA. Treatment-related elevation in serum cholesterol and triglycerides and decreases in glucose levels were observed in both the age groups. Organ weight changes included increases in liver, adrenal gland and seminal vesicles/prostate weights. Decreases in uterine weights were also observed in adult females exposed to the top two doses with sufficient exposure. In juveniles, sexual maturity parameters secondary to decreased body weights were observed, but, were reversed. In conclusion, the adverse effects noted in reproductive tissues of adults were attributed to hyperprolactinemia and these changes were not considered to be relevant to humans due to species differences in hormonal regulation of reproduction. On the whole, there were no remarkable differences in the toxicity profile of the drug between the two age groups.

  16. Exposure to the toxic dinoflagellate Alexandrium catenella modulates juvenile oyster Crassostrea gigas hemocyte variables subjected to different biotic conditions.

    PubMed

    Lassudrie, Malwenn; Soudant, Philippe; Nicolas, Jean-Louis; Miner, Philippe; Le Grand, Jacqueline; Lambert, Christophe; Le Goïc, Nelly; Hégaret, Hélène; Fabioux, Caroline

    2016-04-01

    The Pacific oyster Crassostrea gigas is an important commercial species cultured throughout the world. Oyster production practices often include transfers of animals into new environments that can be stressful, especially at young ages. This study was undertaken to determine if a toxic Alexandrium bloom, occurring repeatedly in French oyster beds, could modulate juvenile oyster cellular immune responses (i.e. hemocyte variables). We simulated planting on commercial beds by conducting a cohabitation exposure of juvenile, "specific pathogen-free" (SPF) oysters (naïve from the environment) with previously field-exposed oysters to induce interactions with new microorganisms. Indeed, toxic Alexandrium spp. exposures have been reported to modulate bivalve interaction with specific pathogens, as well as physiological and immunological variables in bivalves. In summary, SPF oysters were subjected to an artificial bloom of Alexandrium catenella, simultaneously with a cohabitation challenge. Exposure to A. catenella, and thus to the paralytic shellfish toxins (PSTs) and extracellular bioactive compounds produced by this alga, induced higher concentration, size, complexity and reactive oxygen species (ROS) production of circulating hemocytes. Challenge by cohabitation with field-exposed oysters also activated these hemocyte responses, suggesting a defense response to new microorganism exposure. These hemocyte responses to cohabitation challenge, however, were partially inhibited by A. catenella exposure, which enhanced hemocyte mortality, suggesting either detrimental effects of the interaction of both stressors on immune capacity, or the implementation of an alternative immune strategy through apoptosis. Indeed, no infection with specific pathogens (herpesvirus OsHV-1 or Vibrio aesturianus) was detected. Additionally, lower PST accumulation in challenged oysters suggests a physiological impairment through alteration of feeding-related processes. Overall, results of this

  17. Acute toxicity of triazine pesticides to juvenile signal crayfish (Pacifastacus leniusculus).

    PubMed

    Velisek, Jozef; Kouba, Antonin; Stara, Alzbeta

    2013-01-01

    Crustacea are at high risk of toxic effects of agricultural pesticides. Currently, many questions regarding the toxicity of triazine herbicides to crayfish remain unresolved. The aim of this research was to evaluate the acute toxicity of atrazine, hexazinone, metribuzine, prometryne, simazine, and terbutryne to juvenile signal crayfish (Pacifastacus leniusculus). Acute toxicity tests were performed in accordance with standardized guidelines for testing of chemicals, OECD no. 203, using a semistatic test system. Signal crayfish juveniles (n=672) of 49.0-81.5 mg weight and 12.8-16.0 mm total length were used for the bioassay. Mortalities were recorded daily to 96 h. Each pesticide was tested at concentrations of 1, 10, 40, 70, and 100 mg.l-1. Percent mortalities were analyzed by linear regression, and median lethal concentration (LC50) values were computed using probit analysis EKO-TOX 5.2 software. 96hLC50 values for juvenile signal crayfish were 12.1 mg.l-1 for atrazine, 13.9 mg.l-1 for terbutryne, 14.4 mg.l-1 for prometryne, 19.5 mg.l-1 for hexazinone, 30.6 mg.l-1 for metribuzine, and 77.9 mg.l-1 for simazine. Atrazine showed the greatest toxicity to signal crayfish. The present study demonstrated that triazines are toxic to signal crayfish. Signal crayfish is more sensitive than the fish for atrazine, hexazine, metribuzine, and for these triazines signal crayfish can be used as a bio-indicator of environmental contamination.

  18. Acute toxicity of copper, ammonia, and chlorine to glochidia and juveniles of freshwater mussels (Unionidae)

    USGS Publications Warehouse

    Wang, N.; Ingersoll, C.G.; Hardesty, D.K.; Ivey, C.D.; Kunz, J.L.; May, T.W.; Dwyer, F.J.; Roberts, A.D.; Augspurger, T.; Kane, C.M.; Neves, R.J.; Barnhart, M.C.

    2007-01-01

    The objective of the present study was to determine acute toxicity of copper, ammonia, or chlorine to larval (glochidia) and juvenile mussels using the recently published American Society for Testing and Materials (ASTM) Standard guide for conducting laboratory toxicity tests with freshwater mussels. Toxicity tests were conducted with glochidia (24- to 48-h exposures) and juveniles (96-h exposures) of up to 11 mussel species in reconstituted ASTM hard water using copper, ammonia, or chlorine as a toxicant. Copper and ammonia tests also were conducted with five commonly tested species, including cladocerans (Daphnia magna and Ceriodaphnia dubia; 48-h exposures), amphipod (Hyalella azteca; 48-h exposures), rainbow trout (Oncorhynchus mykiss; 96-h exposures), and fathead minnow (Pimephales promelas; 96-h exposures). Median effective concentrations (EC50s) for commonly tested species were >58 ??g Cu/L (except 15 ??g Cu/L for C. dubia) and >13 mg total ammonia N/L, whereas the EC50s for mussels in most cases were 40 ??g/L and above the FAV in the WQC for chlorine. The results indicate that the early life stages of mussels generally were more sensitive to copper and ammonia than other organisms and that, including mussel toxicity data in a revision to the WQC, would lower the WQC for copper or ammonia. Furthermore, including additional mussel data in 2007 WQC for copper based on biotic ligand model would further lower the WQC. ?? 2007 SETAC.

  19. Use of transgenic animals in understanding molecular mechanisms of toxicity.

    PubMed

    Wolf, C R; Henderson, C J

    1998-06-01

    Understanding molecular mechanisms of chemical toxicity and the potential risks of drugs to man is a pivotal part of the drug development process. With the dramatic increase in the number of new chemical entities arising from high throughput screening, there is an urgent need to develop systems for the rapid evaluation of potential drugs so that those agents which are most likely to be free of adverse effects can be identified at the earliest possible stage in drug development. The complex mechanisms of action of chemical toxins has made it extremely difficult to evaluate the precise toxic mechanism and also the relative role of specific genes in either potentiating or ameliorating the toxic effect. This problem can be addressed by the application of genetic strategies. Such strategies can exploit strain differences in susceptibility to specific toxic agents or, with the rapidly developing technologies, can exploit the use of transgenic animals where specific genes can be manipulated and subsequent effects on chemical toxicity evaluated. Transgenic animals can be exploited in a variety of ways to understand mechanisms of chemical toxicity. For example, a human gene encoding a drug metabolizing enzyme can be directly introduced and the effects on toxic response evaluated. Alternatively, specific genes can be deleted from the mouse genome and the consequences on toxicological response determined. Many toxic chemical agents modulate patterns of gene expression within target cells. This can be used to screen for responses to different types of toxic insult. In such experiments the promotor of a stress-regulated gene can be ligated to a suitable reporter gene, such as lacZ, or green fluorescent protein, and inserted into the genome of an appropriate test species. On administration of a chemical agent, cells which are sensitive to the toxic effects of that chemical will express the reporter, which can then be identified using an appropriate assay system. This latter

  20. Mitigation of nitrite toxicity by increased salinity is associated with multiple physiological responses: A case study using an economically important model species, the juvenile obscure puffer (Takifugu obscurus).

    PubMed

    Wang, Jun; Tang, Hengxing; Zhang, Xingxing; Xue, Xiaofeng; Zhu, Xuexia; Chen, Yafen; Yang, Zhou

    2017-09-13

    Nitrite is a common pollutant in water and is highly toxic to aquatic animals. To reveal the mechanism of salinity in attenuating nitrite toxicity to fish, we measured the physiological responses of juvenile Takifugu obscurus exposed to nitrite concentrations (0, 10, 20, 50, and 100 mg/L) under different salinity levels (0, 10, and 20 ppt) for 96 h. Salinity increased the survival rates of juvenile T. obscurus exposed to nitrite. Changes in key hematological parameters, antioxidant system, malondialdehyde, Na(+)/K(+)-ATPase, and HSP70 indicated that nitrite induced considerable damage to juveniles; salinity mitigated the harmful effects. This finding reflects similar changing trends in both antioxidants and their gene expressions among different tissues. We applied an overall index, an integrated biomarker response (IBR), that increased under high-nitrite condition but recovered to the normal levels under salinity treatment. Analysis of the selected detection indices and IBR values showed that the overall mitigating effect of salinity on nitrite toxicity seems to be at sub-cellular level and associated with complicated physiological responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Biomonitoring toxicity of natural sediments using juvenile Hyalella curvispina (Amphipoda) as test species: evaluation of early effect endpoints.

    PubMed

    Giusto, Anabella; Salibián, Alfredo; Ferrari, Lucrecia

    2014-03-01

    The utility of early effect endpoints as biomarkers of ecotoxicity of natural sediments in water-sediment static system was investigated. The particular goal was to evaluate the ecotoxicity of the sediment samples from La Choza stream, located in upper basin of the Reconquista river, the second most polluted river of Argentina. Native juveniles Hyalella curvispina were used as test organisms evaluating survival, growth, oxidative stress parameters (SOD; CAT, TBARS) and the electron transport system (ETS) activity as early toxic effect. This study used methodologies and techniques that allow the assessment of sediment pollution with a native species as test organism and provided data to discuss the viability of sublethal endpoints as tools for freshwater sediment assessment. In spring and in summer two ten-day series of whole-sediment assays were conducted simultaneously: (a) standard assays and (b) biomarkers assays. A control sediment was ran simultaneously in which no--effect on survival was measured. In summer there was a significant increase in length and biomass in both exposed and control groups. In spring an inhibitory effect on growth and an increase in oxidative damage with a concomitant rise in antioxidant defenses, was observed in animals exposed to La Choza sediment. ETS measurement indicated a significant depression of metabolic activity of amphipods exposed to contaminated sediments. The measured biomarkers represent the first record for juvenile H. curvispina exposed to polluted natural sediments under standardized laboratory conditions. The used bioanalytical tools demonstrated higher sensitivity and a more accurate assessment of the effects than those obtained by the standard tests of survival and growth. We propose their adoption in biomonitoring of freshwater sediment toxicity.

  2. Non-animal Replacements for Acute Toxicity Testing.

    PubMed

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. 2015 FRAME.

  3. Contrasting sensitivities to fluoride toxicity between juveniles and adults of the aquatic snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca).

    PubMed

    Aguirre-Sierra, Aránzazu; Alonso, Alvaro; Camargo, Julio A

    2011-05-01

    In contrast to aquatic vertebrates, there is scarce available information on the contrasting tolerance to fluoride of different life stages and/or sizes of aquatic invertebrates. The purpose of this study was to assess the likely differences in sensitivity between juveniles and adults of the aquatic snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca) to short-term (4 days) toxicity of fluoride ion (F(-)). LC50 and EC50 values for juveniles were significantly lower than those for adults at 24, 48, 72 and 96 h. Based on our results, the use of fluoride data of bioassays with juveniles should provide more protective water quality criteria than data from adult stage.

  4. Soil bioretention protects juvenile salmon and their prey from the toxic impacts of urban stormwater runoff.

    PubMed

    McIntyre, J K; Davis, J W; Hinman, C; Macneale, K H; Anulacion, B F; Scholz, N L; Stark, J D

    2015-08-01

    Green stormwater infrastructure (GSI), or low impact development, encompasses a diverse and expanding portfolio of strategies to reduce the impacts of stormwater runoff on natural systems. Benchmarks for GSI success are usually framed in terms of hydrology and water chemistry, with reduced flow and loadings of toxic chemical contaminants as primary metrics. Despite the central goal of protecting aquatic species abundance and diversity, the effectiveness of GSI treatments in maintaining diverse assemblages of sensitive aquatic taxa has not been widely evaluated. In the present study we characterized the baseline toxicity of untreated urban runoff from a highway in Seattle, WA, across six storm events. For all storms, first flush runoff was toxic to the daphniid Ceriodaphnia dubia, causing up to 100% mortality or impairing reproduction among survivors. We then evaluated whether soil media used in bioretention, a conventional GSI method, could reduce or eliminate toxicity to juvenile coho salmon (Oncorhynchus kisutch) as well as their macroinvertebrate prey, including cultured C. dubia and wild-collected mayfly nymphs (Baetis spp.). Untreated highway runoff was generally lethal to salmon and invertebrates, and this acute mortality was eliminated when the runoff was filtered through soil media in bioretention columns. Soil treatment also protected against sublethal reproductive toxicity in C. dubia. Thus, a relatively inexpensive GSI technology can be highly effective at reversing the acutely lethal and sublethal effects of urban runoff on multiple aquatic species.

  5. Developmental toxicity of indium: embryotoxicity and teratogenicity in experimental animals.

    PubMed

    Nakajima, Mikio; Usami, Makoto; Nakazawa, Ken; Arishima, Kazuyoshi; Yamamoto, Masako

    2008-12-01

    Indium, a precious metal classified in group 13 (IIIB) in the periodic table, has been used increasingly in the semiconductor industry. Because indium is a rare metal, technology for indium recycling from transparent conducting films for liquid crystal displays is desired, and its safety evaluation is becoming increasingly necessary. The developmental toxicity of indium in experimental animals was summarized. The intravenous or oral administration of indium to pregnant animals causes growth inhibition and the death of embryos in hamsters, rats, and mice. The intravenous administration of indium to pregnant animals causes embryonic or fetal malformation, mainly involving digit and tail deformities, in hamsters and rats. The oral administration of indium also induces fetal malformation in rats and rabbits, but requires higher doses. No teratogenicity has been observed in mice. Caudal hypoplasia, probably due to excessive cell loss by increased apoptosis in the tailbud, in the early postimplantation stage was considered to account for indium-induced tail malformation as a possible pathogenetic mechanism. Findings from in vitro experiments indicated that the embryotoxicity of indium could have direct effects on the conceptuses. Toxicokinetic studies showed that the embryonic exposure concentration was more critical than the exposure time regarding the embryotoxicity of indium. It is considered from these findings that the risk of the developmental toxicity of indium in humans is low, unless an accidentally high level of exposure or unknown toxic interaction occurs because of possible human exposure routes and levels (i.e. oral, very low-level exposure).

  6. Acute toxicity of an acid mine drainage mixing zone to juvenile bluegill and largemouth bass

    USGS Publications Warehouse

    Henry, T.B.; Irwin, E.R.; Grizzle, J.M.; Wildhaber, M.L.; Brumbaugh, W.G.

    1999-01-01

    The toxicity of an acid mixing zone produced at the confluence of a stream that was contaminated by acid mine drainage (AMD) and a pH-neutral stream was investigated in toxicity tests with juvenile bluegill Lepomis macrochirus and largemouth bass Micropterus salmoides. Fish mortalities in instream cages located in the mixing zone, below the mixing zone, and upstream in both tributaries were compared to determine relative toxicity at each site. In all tests and for both species, significantly higher mortality was observed in the mixing zone than at any other location, including the acid stream, which had lower pH (2.9-4.3). The mixing zone was defined chemically by rapid precipitation of dissolved aluminum and iron, which arrived from the low-pH stream, and by the presence of white precipitates, which were attached to the substratum and which extended below the confluence. Possible seasonal changes in mixing zone toxicity were investigated by conducting field tests with bluegill in June, July, and August 1996 and in January 1997 and by conducting field tests with largemouth bass in April and May 1997. Toxicity was not significantly different at the extremes of temperature, pH, and metal concentration that occurred in June and July, as compared with January. Toxicity was significantly lower in August; however, elevated stream discharge during the August test may have disturbed mixing zone characteristics. High toxicity in AMD mixing zones may lower the survival of fishes in streams, reduce available habitat, and impede movements of migratory fish.

  7. Non-animal methodologies within biomedical research and toxicity testing.

    PubMed

    Knight, Andrew

    2008-01-01

    Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues

  8. Utilization of animal studies to determine the effects and human risks of environmental toxicants (drugs, chemicals, and physical agents).

    PubMed

    Brent, Robert L

    2004-04-01

    Toxicology studies using animals and in vitro cellular or tissue preparations have been used to study the toxic effects and mechanism of action of drugs and chemicals and to determine the effective and safe dose of drugs in humans and the risk of toxicity from chemical exposures. Studies in pregnant animals are used to determine the risk of birth defects and other reproductive effects. There is no question that whole animal teratology studies are helpful in raising concerns about the reproductive effects of drugs and chemicals, but negative animal studies do not guarantee that these agents are free from reproductive effects. There are examples in which drug testing was negative in animals (rat and mouse) but was teratogenic in the human (thalidomide), and there are examples in which a drug was teratogenic in an animal model but not in the human (diflunisal). Testing in animals could be improved if animal dosing using the mg/kg basis were abandoned and drugs and chemicals were administered to achieve pharmacokinetically equivalent serum levels in the animal and the human. Because most human teratogens have been discovered by alert physicians or epidemiology studies, not animal studies, animal studies play a minor role in discovering teratogens. In vitro studies play an even less important role, although they are helpful in describing the cellular or tissue effects of the drugs or chemicals. One cannot determine the magnitude of human risks from these in vitro studies. Performing toxicology studies on adult animals is performed by pharmaceutical companies, chemical companies, the Food and Drug Administration, many laboratories at the National Institutes of Health, and scientific investigators in laboratories throughout the world. Although a vast amount of animal toxicology studies are performed on pregnant animals and numerous toxicology studies are performed on adult animals, there is a paucity of animal studies using newborn, infant, and juvenile animals. This

  9. Chronic toxicity of copper and ammonia to juvenile freshwater mussels (Unionidae)

    USGS Publications Warehouse

    Wang, N.; Ingersoll, C.G.; Greer, I.E.; Hardesty, D.K.; Ivey, C.D.; Kunz, J.L.; Brumbaugh, W.G.; Dwyer, F.J.; Roberts, A.D.; Augspurger, T.; Kane, C.M.; Neves, R.J.; Barnhart, M.C.

    2007-01-01

    The objectives of the present study were to develop methods for conducting chronic toxicity tests with juvenile mussels under flow-through conditions and to determine the chronic toxicity of copper and ammonia to juvenile mussels using these methods. In two feeding tests, two-month-old fatmucket (Lampsilis siliquoidea) and rainbow mussel (Villosa iris) were fed various live algae or nonviable algal mixture for 28 d. The algal mixture was the best food resulting in high survival (???90%) and growth. Multiple copper and ammonia toxicity tests were conducted for 28 d starting with two-month-old mussels. Six toxicity tests using the algal mixture were successfully completed with a control survival of 88 to 100%. Among copper tests with rainbow mussel, fatmucket, and oyster mussel (Epioblasma capsaeformis), chronic value ([ChV], geometric mean of the no-observed-effect concentration and the lowest-observed-effect concentration) ranged from 8.5 to 9.8 ??g Cu/L for survival and from 4.6 to 8.5 ??g Cu/L for growth. Among ammonia tests with rainbow mussel, fatmucket, and wavy-rayed lampmussel (L. fasciola), the ChV ranged from 0.37 to 1.2 mg total ammonia N/L for survival and from 0.37 to 0.67 mg N/L for growth. These ChVs were below the U.S. Environmental Protection Agency 1996 chronic water quality criterion (WQC) for copper (15 ??g/L; hardness 170 mg/L) and 1999 WQC for total ammonia (1.26 mg N/L; pH 8.2 and 20??C). Results indicate that toxicity tests with two-month-old mussels can be conducted for 28 d with >80% control survival; growth was frequently a more sensitive endpoint compared to survival; and the 1996 chronic WQC for copper and the 1999 chronic WQC for total ammonia might not be adequately protective of the mussel species tested. However, a recently revised 2007 chronic WQC for copper based on the biotic ligand model may be more protective in the water tested. ?? 2007 SETAC.

  10. Acute and chronic toxicity of technical-grade pesticides to glochidia and juveniles of freshwater mussels (Unionidae).

    PubMed

    Bringolf, Robert B; Cope, W Gregory; Eads, Chris B; Lazaro, Peter R; Barnhart, M Christopher; Shea, Damian

    2007-10-01

    Chemical contaminants are among many potential factors involved in the decline of freshwater mussel populations in North America, and the effects of pesticides on early life stages of unionid mussels are largely unknown. The objective of this study was to determine the toxicity of technical-grade current-use pesticides to glochidia and juvenile life stages of freshwater mussels. We performed acute toxicity tests with glochidia (five species) and juveniles (two species) exposed to a suite of current-use pesticides including herbicides (atrazine and pendimethalin), insecticides (fipronil and permethrin), and a reference toxicant (NaCl). Because of limited availability of test organisms, not all species were tested with all pesticides. Toxicity tests with fungicides (chlorothalonil, propiconazole, and pyraclostrobin) were performed with one species (Lampsilis siliquoidea). Lampsilis siliquoidea glochidia and juveniles were highly sensitive to the fungicides tested but the technical-grade herbicides and insecticides, at concentrations approaching water solubility, were not acutely toxic to this or the other unionid species. In a 21-d chronic test with four-month-old juvenile L. siliquoidea, the 21-d median effective concentration (EC50) with atrazine was 4.3 mg/L and in atrazine treatments >or=3.8 mg/L mussel growth was significantly less than controls. The relatively high sensitivity of L. siliquoidea to chlorothalonil, propiconazole, and pyraclostrobin is similar to that reported for other aquatic organisms commonly used for toxicity testing. The relative risk associated with acute exposure of early life stages of mussels to technical-grade atrazine, pendimethalin, fipronil, and permethrin is likely low; however, survival and growth results with juvenile L. siliquoidea indicate that chronic exposure to high concentrations (>/=3.8 mg/L) of atrazine may have the potential to impact mussel populations and warrants further investigation.

  11. Chronic toxicity of nonylphenol and ethinylestradiol: haematological and histopathological effects in juvenile Common carp (Cyprinus carpio).

    PubMed

    Schwaiger, J; Spieser, O H; Bauer, C; Ferling, H; Mallow, U; Kalbfus, W; Negele, R D

    2000-11-01

    In recent ecotoxicological research, there is an increasing concern about alkylphenolic industrial chemicals, such as nonylphenol (NP), because of their estrogenic properties. Data on the general fish toxicity of these wide spread aquatic pollutants are scarce. In order to evaluate sublethal toxic effects of environmentally relevant concentrations of NP, juvenile Common carp (Cyprinus carpio) were exposed to NP concentrations ranging from 1 to 15 microg NP/l over a 70-day period. Classical toxicological endpoints, such as various haematological parameters and histopathological alterations were investigated. In a comprehensive protocol, besides NP-induced effects also alterations due to a treatment with the synthetic estrogen ethinylestradiol (EE2) were evaluated. After both the NP-exposure as well as the EE2-treatment, the predominant haematological finding was a severe anaemia. Histopathological alterations in the kidney, the liver and the spleen occurred exclusively after treatment with EE2, whereas NP-exposed fish did not show any tissue lesions. Depending on the haematological parameter examined, a NOEC between 1 and 5 microg NP/l could be established. From the present findings, it is assumed, that under field conditions, the NP-induced, general toxic effects, might outbalance the relatively weak estrogenic effects of this compound and possibly might disturb ecologically relevant processes such as fish reproduction.

  12. Elevated temperatures increase the toxicity of pesticide mixtures to juvenile coho salmon.

    PubMed

    Laetz, Cathy A; Baldwin, David H; Hebert, Vincent R; Stark, John D; Scholz, Nathaniel L

    2014-01-01

    Pesticide mixtures and elevated temperatures are parallel freshwater habitat stressors for Pacific salmon in the western United States. Certain combinations of organophosphate (OP) insecticides are known to synergistically increase neurotoxicity in juvenile salmon. The chemicals interact to potentiate the inhibition of brain acetylcholinesterase (AChE) and disrupt swimming behavior. The metabolic activation and detoxification of OPs involve temperature-sensitive enzymatic processes. Salmon are ectothermic, and thus the degree of synergism may vary with ambient temperature in streams, rivers, and lakes. Here we assess the influence of water temperature (12-21°C) on the toxicity of ethoprop and malathion, alone and in combination, to juvenile coho salmon (Oncorhynchus kisutch). A mixture of ethoprop (0.9 μg/L) and malathion (0.75 μg/L) produced synergistic AChE inhibition at 12°C, and the degree of neurotoxicity approximately doubled with a modest temperature increase to 18°C. Slightly lower concentrations of ethoprop (0.5 μg/L) combined with malathion (0.4 μg/L) did not inhibit brain AChE activity but did produce a temperature-dependent reduction in liver carboxylesterase (CaE). The activity of CaE was very sensitive to the inhibitory effects of ethoprop alone and both ethoprop-malathion combinations across all temperatures. Our findings are an example of how non-chemical habitat attributes can increase the relative toxicity of OP mixtures. Surface temperatures currently exceed water quality criteria in many western river segments, and summer thermal extremes are expected to become more frequent in a changing climate. These trends reinforce the importance of pollution reduction strategies to enhance ongoing salmon conservation and recovery efforts.

  13. Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague-Dawley Rat.

    PubMed

    Filgo, Adam J; Foley, Julie F; Puvanesarajah, Samantha; Borde, Aditi R; Midkiff, Bentley R; Reed, Casey E; Chappell, Vesna A; Alexander, Lydia B; Borde, Pretish R; Troester, Melissa A; Bouknight, Schantel A Hayes; Fenton, Suzanne E

    2016-10-01

    There are currently no reports describing mammary gland development in the Harlan Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs, and other researchers in understanding and interpreting chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically stained tissues for estrogen, progesterone, and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically induced mammary gland anomalies that may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylstilbestrol, or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated, and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies.

  14. Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague Dawley Rat

    PubMed Central

    Filgo, Adam J.; Foley, Julie F.; Puvanesarajah, Samantha; Borde, Aditi R.; Midkiff, Bentley R.; Reed, Casey E.; Chappell, Vesna A.; Alexander, Lydia B.; Borde, Pretish R.; Troester, Melissa A.; Hayes Bouknight, Schantel A.; Fenton, Suzanne E.

    2016-01-01

    There are currently no reports describing mammary gland development in the Harlan Sprague Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs and other researchers in understanding and interpretation of chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically-stained tissues for estrogen, progesterone and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically-induced mammary gland anomalies which may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo p-dioxin, diethylstilbestrol or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies. PMID:27613106

  15. Animal models of peripheral neuropathy due to environmental toxicants.

    PubMed

    Rao, Deepa B; Jortner, Bernard S; Sills, Robert C

    2014-01-01

    Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy--namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves.

  16. Animal Models of Peripheral Neuropathy Due to Environmental Toxicants

    PubMed Central

    Rao, Deepa B.; Jortner, Bernard S.; Sills, Robert C.

    2014-01-01

    Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy—namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves. PMID:24615445

  17. Toxicity of sediments from lead-zinc mining areas to juvenile freshwater mussels (Lampsilis siliquoidea) compared to standard test organisms.

    PubMed

    Besser, John M; Ingersoll, Christopher G; Brumbaugh, William G; Kemble, Nile E; May, Thomas W; Wang, Ning; MacDonald, Donald D; Roberts, Andrew D

    2015-03-01

    Sediment toxicity tests compared chronic effects on survival, growth, and biomass of juvenile freshwater mussels (28-d exposures with Lampsilis siliquoidea) to the responses of standard test organisms-amphipods (28-d exposures with Hyalella azteca) and midges (10-d exposures with Chironomus dilutus)-in sediments from 2 lead-zinc mining areas: the Tri-State Mining District and Southeast Missouri Mining District. Mussel tests were conducted in sediments sieved to <0.25 mm to facilitate recovery of juvenile mussels (2-4 mo old). Sediments were contaminated primarily with lead, zinc, and cadmium, with greater zinc and cadmium concentrations in Tri-State sediments and greater lead concentrations in southeast Missouri sediments. The frequency of highly toxic responses (reduced 10% or more relative to reference sites) in Tri-State sediments was greatest for amphipod survival (25% of samples), midge biomass (20%), and mussel survival (14%). In southeast Missouri sediments, the frequency of highly toxic samples was greatest for mussel biomass (25%) and amphipod biomass (13%). Thresholds for metal toxicity to mussels, expressed as hazard quotients based on probable effect concentrations, were lower for southeast Missouri sediments than for Tri-State sediments. Southeast Missouri sites with toxic sediments had 2 or fewer live mussel taxa in a concurrent mussel population survey, compared with 7 to 26 taxa at reference sites. These results demonstrate that sediment toxicity tests with juvenile mussels can be conducted reliably by modifying existing standard methods; that the sensitivity of mussels to metals can be similar to or greater than standard test organisms; and that responses of mussels in laboratory toxicity tests are consistent with effects on wild mussel populations.

  18. Toxicity of sediments from lead-zinc mining areas to juvenile freshwater mussels (Lampsilis siliquoidea) compared to standard test organisms

    USGS Publications Warehouse

    Besser, John M.; Ingersoll, Christopher G.; Brumbaugh, William G.; Kemble, Nile E.; May, Thomas W.; Wang, Ning; MacDonald, Donald D.; Roberts, Andrew D.

    2015-01-01

    Sediment toxicity tests compared chronic effects on survival, growth, and biomass of juvenile freshwater mussels (28-d exposures with Lampsilis siliquoidea) to the responses of standard test organisms—amphipods (28-d exposures with Hyalella azteca) and midges (10-d exposures with Chironomus dilutus)—in sediments from 2 lead–zinc mining areas: the Tri-State Mining District and Southeast Missouri Mining District. Mussel tests were conducted in sediments sieved to <0.25 mm to facilitate recovery of juvenile mussels (2–4 mo old). Sediments were contaminated primarily with lead, zinc, and cadmium, with greater zinc and cadmium concentrations in Tri-State sediments and greater lead concentrations in southeast Missouri sediments. The frequency of highly toxic responses (reduced 10% or more relative to reference sites) in Tri-State sediments was greatest for amphipod survival (25% of samples), midge biomass (20%), and mussel survival (14%). In southeast Missouri sediments, the frequency of highly toxic samples was greatest for mussel biomass (25%) and amphipod biomass (13%). Thresholds for metal toxicity to mussels, expressed as hazard quotients based on probable effect concentrations, were lower for southeast Missouri sediments than for Tri-State sediments. Southeast Missouri sites with toxic sediments had 2 or fewer live mussel taxa in a concurrent mussel population survey, compared with 7 to 26 taxa at reference sites. These results demonstrate that sediment toxicity tests with juvenile mussels can be conducted reliably by modifying existing standard methods; that the sensitivity of mussels to metals can be similar to or greater than standard test organisms; and that responses of mussels in laboratory toxicity tests are consistent with effects on wild mussel populations.

  19. Toxicity of ozonated estuarine water to juvenile blue crabs (Callinectes sapidus) and Juvenile Atlantic menhaden (Brevoortia tyrannus)

    SciTech Connect

    Richardson, L.B.; Burton, D.T.

    1981-02-01

    Large quantitites of estuarine and marine water are treated with chlorine to prevent condenser system fouling at power plants. Chlorine and its residual by-products, however, are toxic to many forms of aquatic life. Ozone is one alternative oxidant which has proven to be an effective biocide and disinfectant in many fresh water applications. Ozonation of estuarine and marine waters, however, may produce residual compounds similar to those produced by chlorination. This study was initiated to provide baseline information on the toxicity of ozonated estuarine water to two representative estuarine species. The blue crab, Callinectes sapidus Rathbun, and the Atlantic menhaden, Brevoortia tyrannus Latrobe, were selected because of their wide distribution and commercial importance. The toxicity of ozone has been compared with chlorine toxicity data from the literature in an effort to examine possible similarities in toxicity.

  20. Toxicity of un-ionized ammonia, nitrite, and nitrate to juvenile bay scallops, Argopecten irradians irradians.

    PubMed

    Widman, James C; Meseck, Shannon L; Sennefelder, George; Veilleux, David J

    2008-04-01

    Juvenile bay scallops (7.2-26.4 mm) were exposed for 72 h to different concentrations of un-ionized ammonia, nitrite, or nitrate. Using the Trimmed Spearman Karber method, 50% lethal concentrations (LC(50)) and 95% confidence limits were calculated individually for each. Un-ionized ammonia concentrations above 1.0 mg N-NH(3)/L resulted in 100% scallop mortality within 72 h. The 72-h LC(50) for un-ionized ammonia was calculated at 0.43 mg N/L. At nitrite concentrations of 800 mg N/L or higher 100% mortality was observed. The 72-h LC(50) for nitrite was calculated at 345 mg N/L. Nitrate was the least toxic, with 100% mortality observed at a concentration of 5000 mg N/L. The calculated nitrate 72-h LC(50) was 4453 mg N/L. Our results indicate that un-ionized ammonia is the most lethal nitrogenous waste component to bay scallops.

  1. Animal models of disease: feline hyperthyroidism: an animal model for toxic nodular goiter.

    PubMed

    Peterson, Mark E

    2014-11-01

    Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission. © 2014 Society for Endocrinology.

  2. The juvenile toxicity study as a tool for a science-based risk assessment in the children population group.

    PubMed

    Narciso, Laura; Catone, Tiziana; Aquilina, Gabriele; Attias, Leonello; De Angelis, Isabella; Iuliano, Maria Grazia; Tassinari, Roberta; Mantovani, Alberto; Maranghi, Francesca

    2017-09-01

    Children show unique features concerning chemical hazards and risks, due to different exposure scenarios, age-related metabolic capacity and biological susceptibility linked to post-natal development. Chemical Regulatory frameworks state the need of children risk characterization. Current testing guidelines covering post-natal development are not routinely required by regulatory applications other than pesticides and biocides. Juvenile toxicity studies are foreseen for paediatric drugs: the toxicological repeated-dose tests don't allow accurate evaluations of effects upon direct exposure of immature organism. The paper discusses a testing approach aimed to address regulatory requirements of chemical hazard identification/characterization in a children-specific perspective. Juvenile toxicity test could be performed primarily on chemicals that may have relevant modes of action and/or age-related toxicokinetic differences and/or lead to important children exposure. This could be pursued by updating existing guidelines/test protocols with triggers for endpoints relevant to juvenile toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Effects of salinity on olfactory toxicity and behavioral responses of juvenile salmonids from copper.

    PubMed

    Sommers, Frank; Mudrock, Emma; Labenia, Jana; Baldwin, David

    2016-06-01

    Dissolved copper is one of the more pervasive and toxic constituents of stormwater runoff and is commonly found in stream, estuary, and coastal marine habitats of juvenile salmon. While stormwater runoff does not usually carry copper concentrations high enough to result in acute lethality, they are of concern because sublethal concentrations of copper exposure have been shown to both impair olfactory function and alter behavior in various species in freshwater. To compare these results to other environments that salmon are likely to encounter, experiments were conducted to evaluate the effects of salinity on the impairment of olfactory function and avoidance of copper. Copper concentrations well within the range of those found in urban watersheds, have been shown to diminish or eliminate the olfactory response to the amino acid, l-serine in freshwater using electro-olfactogram (EOG) techniques. The olfactory responses of both freshwater-phase and seawater-phase coho and seawater-phase Chinook salmon, were tested in freshwater or seawater, depending on phase, and freshwater-phase coho at an intermediate salinity of 10‰. Both 10‰ salinity and full strength seawater protected against the effects of 50μg copper/L. In addition to impairing olfactory response, copper has also been shown to alter salmon behavior by causing an avoidance response. To determine whether copper will cause avoidance behavior at different salinities, experiments were conducted using a multi-chambered experimental tank. The circular tank was divided into six segments by water currents so that copper could be contained within one segment yet fish could move freely between them. The presence of individual fish in each of the segments was counted before and after introduction of dissolved copper (<20μg/L) to one of the segments in both freshwater and seawater. To address whether use of preferred habitat is altered by the presence of copper, experiments were also conducted with a submerged

  4. Rapid-behaviour responses as a reliable indicator of estrogenic chemical toxicity in zebrafish juveniles.

    PubMed

    Sárria, M P; Soares, J; Vieira, M N; Castro, L Filipe C; Santos, M M; Monteiro, N M

    2011-11-01

    Whereas biochemical and molecular parameters have been well recognised as important "signposts" of individual disturbance to endocrine disrupting chemical's (EDCs) exposure, behavioural endpoints are yet greatly overlooked as a routine tool in environmental risk assessment of EDCs. However, life histories are intimately associated with numerous inter- and intra-specific interactions, which invariably depend on the performance of effective behaviours. Within fish species, one of the most important factors influencing energy turnover earlier in the development is locomotor activity. This essential trait reflects the organism's ability to generate and coordinate the metabolic energy required for both reproductive and non-reproductive behaviours. Inappropriate movement responses due to toxic effects of contaminants may ultimately impact important ecological variables. Therefore, in the present study, the swimming bursts of zebrafish juveniles exposed for 40 d to the synthetic estrogen ethinylestradiol (EE(2)), tested at environmentally relevant concentrations (nominal concentrations of 0.5, 1 and 2 ng L(-1)), were investigated in order to address the potential of rapid-behaviour patterns as an effective response indicator of estrogenic endocrine disrupting chemical's exposure. This synthetic estrogen was selected due to its high prevalence in aquatic ecosystems, ability to mimic natural estrogens and proven record of causing negative effects in fish reproduction. The behavioural responses were compared with established endpoints used in the screening of EE(2) effects at adulthood. Results indicate that zebrafish juveniles' swimming activity was significantly decreased upon EE(2) exposure. Since reduced locomotion of zebrafish may impact foraging, predator avoidance, drift and transport, and even interfere with social and reproductive behaviours, a fitness decline of wild fish populations can ultimately be hypothesized. Furthermore, behavioural endpoints were found to

  5. Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsilis siliquoidea).

    PubMed

    Wang, Ning; Erickson, Russell J; Ingersoll, Christopher G; Ivey, Christopher D; Brunson, Eric L; Augspurger, Tom; Barnhart, M Christopher

    2008-05-01

    The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20 degrees C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity.

  6. Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsills siliquoidea)

    USGS Publications Warehouse

    Wang, N.; Erickson, R.J.; Ingersoll, C.G.; Ivey, C.D.; Brunson, E.L.; Augspurger, T.; Barnhart, M.C.

    2008-01-01

    The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20??C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity. ?? 2008 SETAC.

  7. Toxicity and toxicokinetics of perfluorooctanoic acid in humans and animals.

    PubMed

    Kudo, Naomi; Kawashima, Yoichi

    2003-05-01

    Perfluorooctanoic acid (PFOA) is an octanoic acid derivative to which all aliphatic hydrocarbons are substituted by fluorine. PFOA and its salts are commercially used in various industrial processes. The chemical is persistent in the environment and does not undergo biotransformation. It was reported that PFOA is found not only in the serum of occupationally exposed workers but also general populations. Recent studies have suggested that the biological half-life of PFOA in humans is 4.37 years based on study of occupationally exposed workers. It is increasingly suspect that PFOA accumulates and affects human health, although the toxicokinetics of PFOA in humans remain unclear. In experimental animals, PFOA seems low in toxicity. PFOA is well-absorbed following oral and inhalation exposure, and to a lesser extent following dermal exposure. Once absorbed in the body, it distributes predominantly to the liver and plasma, and to a lesser extent the kidney and lungs. PFOA is excreted in both urine and feces. Biological half-life of PFOA is quite different between species and sexes and the difference is due mainly to the difference in renal clearance. In rats, renal clearance of PFOA is regulated by sex hormones, especially testosterone. PFOA is excreted into urine by active tubular secretion, and certain organic anion transporters are though to be responsible for the secretion. Fecal excretion is also important in the elimination of PFOA. There is evidence that PFOA undergoes enterohepatic circulation resulting in reduced amounts of fecal excretion. Elucidation of the mechanisms of transport in biological systems leads to elimination and detoxification of this chemical in the human body.

  8. In-stream validation of the effects of intermittent sediment toxicity on recruitment of juvenile unionid mussels

    SciTech Connect

    Yeager, M.M.; Cherry, D.S.; Scott, J.C.; Van Hassel, J.H.

    1994-12-31

    A triad approach was used to assess sediment toxicity in the Clinch River, Virginia to determine if sediment bound toxicants are contributing to decreased recruitment of unionid mussel populations. Eleven sites in the Clinch River and one site in a tributary, which exhibited suitable mussel habitat, were included in the analysis. Physical characteristics of the sediment revealed similar particle size distribution and percent water content at the twelve sites; however, three of the sites exhibited high volatile organic compounds. Total recoverable metals analysis of lead, zinc and copper in the interstitial water showed fluctuating metal concentrations throughout the river on different sampling dates. Sediment bioassays using C. riparius, D. magna, and H. azteca identified intermittent toxicity which may be related to non-point runoff from rain events. At ten of the twelve sites, mussel density surveys indicated decreased recruitment despite apparent suitable habitat. Invertebrate community structure analysis identified eight of the twelve sites as having significantly lower total abundance than the reference side and six of the twelve sites as s supporting significantly fewer taxa. In-situ juvenile mussel testing was used to determine the degree to which toxicity may impair juvenile recruitment in unionid populations.

  9. Bioaccumulation and chronic toxicity of dietary L-selenomethionine in juvenile white sturgeon (Acipenser transmontanus).

    PubMed

    Tashjian, Diran H; Teh, Swee J; Sogomonyan, Arutyun; Hung, Silas S O

    2006-10-12

    An 8-week growth trial was conducted to determine the sensitivity of white sturgeon (Acipenser transmontanus) to the toxicological effects of elevated dietary selenium (Se). Juvenile white sturgeon were fed diets supplemented with Se in the form of L-selenomethionine (SeMet), resulting in dietary concentrations of 0.4, 9.6, 20.5, 41.7, 89.8, and 191.1 microg Se/g diet on a dry weight basis. Effects of dietary SeMet on survival, swimming activity, growth, whole-body proximate composition, tissue Se concentrations, and histopathology were determined. Sturgeon survival among treatment groups did not differ significantly with a mean survival rate of 99+/-0.43% across all groups. A significant decrease (p<0.05) in swimming activity and growth rate was observed in sturgeon fed at or above 41.7 microg Se/g diet. Dietary SeMet concentrations were negatively correlated with whole-body protein and lipid content, but positively correlated with ash and moisture content. Selenium accumulated in the kidney, muscle, liver, gill, and plasma tissues in a dose-dependent manner. Histopathological alterations in the liver and kidney were observed in sturgeon fed above 20.5 microg Se/g diet. The threshold dietary Se toxicity concentration for white sturgeon was estimated to lie between 10 and 20 microg Se/g diet based on the histopathological alterations in the kidney. Research examining the consequences of elevated dietary Se concentrations on more sensitive life stages and the interactive effects of Se with other chemical or physical stressors are needed in order to determine if dietary threshold should be lowered to minimize the potential impacts of Se on white sturgeon in the San Francisco Bay-Delta.

  10. The potential toxicity of copper nanoparticles and copper sulphate on juvenile Epinephelus coioides.

    PubMed

    Wang, Tao; Long, Xiaohua; Cheng, Yongzhou; Liu, Zhaopu; Yan, Shaohua

    2014-07-01

    Copper nanoparticles (Cu-NPs) were widely used in various industrial and commercial applications. In this study the effects of Cu-NPs and soluble Cu were investigated on juvenile Epinephelus coioides. The fish were exposed in triplicate to control, 20 or 100μgCuL(-1) as either copper sulphate (CuSO4) or Cu-NPs in a semi-static aqueous culture for 25 days. The growth parameters were significantly lower at 100μgCuL(-1) as CuSO4 or Cu-NPs treatment compared to control. Time-dependent Cu accumulation in all tissues increased with increasing the Cu dose. The percentage of total Cu found in remaining tissues (head, bones, fins, etc.) decreased more in the CuSO4 than Cu-NPs treatment after 25 days, but increased in all other tissues (especially in liver). Compared with the control, either Cu-NPs or CuSO4 induced higher malonaldehyde concentration in tissues by overwhelming total superoxide dismutase activity, total glutathione concentration and Na(+)/K(+)-ATPase activity, but the opposite results were recorded for the brain. With increasing the CuSO4 or Cu-NPs dose, apoptosis was exacerbated in the liver and gills, more so by CuSO4 than Cu-NPs. Overall, these findings showed that Cu-NPs had the toxic effects similar to dissolved Cu; hence, Cu-NPs need to be included in the assessment of toxicological impacts in the aquatic environment.

  11. Profiling animal toxicants by automatically mining public bioassay data: a big data approach for computational toxicology.

    PubMed

    Zhang, Jun; Hsieh, Jui-Hua; Zhu, Hao

    2014-01-01

    In vitro bioassays have been developed and are currently being evaluated as potential alternatives to traditional animal toxicity models. Already, the progress of high throughput screening techniques has resulted in an enormous amount of publicly available bioassay data having been generated for a large collection of compounds. When a compound is tested using a collection of various bioassays, all the testing results can be considered as providing a unique bio-profile for this compound, which records the responses induced when the compound interacts with different cellular systems or biological targets. Profiling compounds of environmental or pharmaceutical interest using useful toxicity bioassay data is a promising method to study complex animal toxicity. In this study, we developed an automatic virtual profiling tool to evaluate potential animal toxicants. First, we automatically acquired all PubChem bioassay data for a set of 4,841 compounds with publicly available rat acute toxicity results. Next, we developed a scoring system to evaluate the relevance between these extracted bioassays and animal acute toxicity. Finally, the top ranked bioassays were selected to profile the compounds of interest. The resulting response profiles proved to be useful to prioritize untested compounds for their animal toxicity potentials and form a potential in vitro toxicity testing panel. The protocol developed in this study could be combined with structure-activity approaches and used to explore additional publicly available bioassay datasets for modeling a broader range of animal toxicities.

  12. The Effect of Toxic Cyanobacteria on Human and Animal Health

    EPA Science Inventory

    The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

  13. The Effect of Toxic Cyanobacteria on Human and Animal Health

    EPA Science Inventory

    The study of environmental health typically focuses on human populations. However, companion animals, livestock and wildlife also experience adverse health effects from environmental pollutants. Animals may experience direct exposure to pollutants unlike people in most ambient ex...

  14. Social Interactions of Juvenile Brown Boobies at Sea as Observed with Animal-Borne Video Cameras

    PubMed Central

    Yoda, Ken; Murakoshi, Miku; Tsutsui, Kota; Kohno, Hiroyoshi

    2011-01-01

    While social interactions play a crucial role on the development of young individuals, those of highly mobile juvenile birds in inaccessible environments are difficult to observe. In this study, we deployed miniaturised video recorders on juvenile brown boobies Sula leucogaster, which had been hand-fed beginning a few days after hatching, to examine how social interactions between tagged juveniles and other birds affected their flight and foraging behaviour. Juveniles flew longer with congeners, especially with adult birds, than solitarily. In addition, approximately 40% of foraging occurred close to aggregations of congeners and other species. Young seabirds voluntarily followed other birds, which may directly enhance their foraging success and improve foraging and flying skills during their developmental stage, or both. PMID:21573196

  15. Combined effects of cadmium and salinity on juvenile Takifugu obscurus: cadmium moderates salinity tolerance; salinity decreases the toxicity of cadmium

    PubMed Central

    Wang, Jun; Zhu, Xuexia; Huang, Xin; Gu, Lei; Chen, Yafen; Yang, Zhou

    2016-01-01

    Obscure puffer Takifugu obscurus, a species of anadromous fish, experiences several salinity changes in its lifetime. Cadmium (Cd) is a toxic heavy metal that can potentially induce oxidative stress in fish. The present study aimed to detect the combined effects of Cd (0, 5, 10, 20 and 50 mg L−1) and salinity (0, 15 and 30 ppt) on juvenile T. obscurus. Results showed the juveniles could survive well under different salinities; however, with Cd exposure, the survival rates significantly decreased at 0 and 30 ppt. At 15 ppt, tolerance to Cd increased. Cd exposure clearly induced oxidative stress, and the responses among different tissues were qualitatively similar. Salinity acted as a protective factor which could reduce the reactive oxygen species and malondialdehyde levels. In addition, salinity could enhance the antioxidant defense system, including superoxide dismutase, catalase and glutathione. Na+/K+–ATPase activity significantly decreased under Cd exposure in gill, kidney and intestine. These findings indicated that Cd could moderate the adaptability of juvenile T. obscurus to high salinity and low salinity played a protective role upon Cd exposure. Thus, the role of salinity should be considered when evaluating the effect of heavy metals on anadromous and estuarine fishes. PMID:27487764

  16. Toxicity of cadmium and lead to juvenile red swamp crayfish, Procambarus clarkii, and effects on fecundity of adults

    SciTech Connect

    Naqvi, S.M.; Howell, R.D. )

    1993-08-01

    Heavy metals such as Cd and Pb may affect aquatic organisms adversely if they are sublethally exposed for a long time. Acute toxicities of a number of heavy metals to different species of crayfish have been reported by several investigators. However, the chronic toxicities of different heavy metals have not been reported as frequently. P. clarkii is of considerable commercial importance to the economy of Louisiana, which produces 98% of the total harvest of the US, worth approximately 143 million dollars annually. This prompted us to use this crayfish for: (1) determining the 96-hr LC[sub 50] values for Cd and Pb using juvenile P. clarkii and (2) assessing the chronic effects of Cd and Pb on the fecundity of adults and hatching success of metal-exposed eggs. 12 refs., 4 tabs.

  17. A Roadmap for the Development of Alternative (Non-Animal) Methods for Systemic Toxicity Testing

    EPA Science Inventory

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new prod...

  18. Approaches to extrapolating animal toxicity data on organic solvents to public health

    EPA Science Inventory

    Developing predictive relationships between exposure and toxicity in humans is difficult because 1) available data are usually derived from experimental animals whose sensitivity to the chemical relative to humans is unknown; 2) the specific neurotoxic endpoints measured in labor...

  19. A Roadmap for the Development of Alternative (Non-Animal) Methods for Systemic Toxicity Testing

    EPA Science Inventory

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new prod...

  20. Approaches to extrapolating animal toxicity data on organic solvents to public health

    EPA Science Inventory

    Developing predictive relationships between exposure and toxicity in humans is difficult because 1) available data are usually derived from experimental animals whose sensitivity to the chemical relative to humans is unknown; 2) the specific neurotoxic endpoints measured in labor...

  1. Assessment of Acute Toxicity of Hexachloroethane in Laboratory Animals

    DTIC Science & Technology

    1978-01-09

    camphoraceous odor, readily sublimes without meltinq and is solubl,: in alcohol. benzene, chloroform, ether and oil: insoluble in water. It is used as a solvent...in explosives, as ý camphor suostitute in celluloid, and as a rubber vulcanizing accelerator.’ It is used in veterinary practice as an anthelminthic...moderately toxic orally, produced reversible eye irritation and little or no skin irritation. Although it sublimes at room temperature

  2. Definitive evaluation of Wheeler Reservoir sedments toxicity using juvenile freshwater mussels (Andodonta imbecillis Say)

    SciTech Connect

    Wade, D.C.

    1992-10-01

    Reservoir sediments near the Decatur, Alabama, industrial waterfront were screened for acute (9-day) toxicity to 8-day old freshwater mussels In 1990. only two locations, designated as stations Alpha (TRM 303.4L, Dry Branch Embayment) and Delta (TRM 301.lL), were found to be toxic to mussels. Toxicity correlated strongly with unionized ammonia measured daily In porewater samples during the study. A definitive study was conducted in 1991 to determine persistence of the toxicity observed In 1990 at the two locations and to determine levels (magnitude) of toxicity and the role of sediment ammonia and/or other sediment contaminants. The 1991 TVA study, reported herein, found reoccurring (persistent) toxicity at both locations. Porewater was toxic at concentrations of 100, 50, and 25 percent. Toxicity was not observed in samples diluted to 12.5 percent.

  3. Poisoning by toxic animals in China--18 autopsy case studies and a comprehensive literature review.

    PubMed

    Chen, Long; Huang, Guang-zhao

    2013-10-10

    Although exposure to animal venom and poison, such as snakebites, bee stings, and contact, with toads, is a common problem, reported deaths are rare. The present report discusses 18 fatal cases in China. Causes of death were grouped into 6 categories, including 1 case of tetrodotoxin poisoning, 1 case of gallbladder poisoning, 3 cases of snake venom toxicity, 4 cases of melittin toxicity, 4 cases of cantharidin poisoning and 5 cases of venenum bufonis poisoning. The epidemiology of each venom-induced death, the mechanism of exposure to venom, and the target organs and tissues affected by these toxic animals were here systematically reviewed. Such details are important to even suspected cases of venom damage. The associated problems related to forensic medicine, such as manner of death and possible attribution to the toxic effects of various animals, are also discussed herein.

  4. Testing retinal toxicity of drugs in animal models using electrophysiological and morphological techniques.

    PubMed

    Perlman, Ido

    2009-02-01

    Drugs are frequently tested for retinal toxicity in animal models in order to address applied and basic research questions. When a retinal toxicity study is designed, the researcher needs to consider several factors depending on his/her research questions. Among the factors that need to be addressed before a toxicity study is conducted are: the animal species to be used, choice of experimental (functional and/or morphological) techniques, procedure of testing, period of follow-up, and modes of data analysis. This review is a summary of 20 years' experience of studying retinal toxicity of different drugs in rabbits and rats. The use of the electroretinogram and the visual evoked potential for assessment of outer and inner retinal function, respectively, is described as well as the use of morphological techniques (histology, histochemistry, and immunocytochemistry). The advantages and limitations of functional and morphological techniques are discussed with specific examples from my experience. Recommendations for future drug toxicity studies are summarized.

  5. Nitrate toxicity to aquatic animals: a review with new data for freshwater invertebrates.

    PubMed

    Camargo, Julio A; Alonso, Alvaro; Salamanca, Annabella

    2005-03-01

    Published data on nitrate (NO3-) toxicity to freshwater and marine animals are reviewed. New data on nitrate toxicity to the freshwater invertebrates Eulimnogammarus toletanus, Echinogammarus echinosetosus and Hydropsyche exocellata are also presented. The main toxic action of nitrate is due to the conversion of oxygen-carrying pigments to forms that are incapable of carrying oxygen. Nitrate toxicity to aquatic animals increases with increasing nitrate concentrations and exposure times. In contrast, nitrate toxicity may decrease with increasing body size, water salinity, and environmental adaptation. Freshwater animals appear to be more sensitive to nitrate than marine animals. A nitrate concentration of 10 mg NO3-N/l (USA federal maximum level for drinking water) can adversely affect, at least during long-term exposures, freshwater invertebrates (E. toletanus, E. echinosetosus, Cheumatopsyche pettiti, Hydropsyche occidentalis), fishes (Oncorhynchus mykiss, Oncorhynchus tshawytscha, Salmo clarki), and amphibians (Pseudacris triseriata, Rana pipiens, Rana temporaria, Bufo bufo). Safe levels below this nitrate concentration are recommended to protect sensitive freshwater animals from nitrate pollution. Furthermore, a maximum level of 2 mg NO3-N/l would be appropriate for protecting the most sensitive freshwater species. In the case of marine animals, a maximum level of 20 mg NO3-N/l may in general be acceptable. However, early developmental stages of some marine invertebrates, that are well adapted to low nitrate concentrations, may be so susceptible to nitrate as sensitive freshwater invertebrates.

  6. Effects of Calcium and Magnesium Ions on Acute Copper Toxicity to Glochidia and Early Juveniles of the Chinese Pond Mussel Anodonta woodiana.

    PubMed

    Liu, Hongbo; Chen, Xiubao; Su, Yanping; Kang, Ik Joon; Qiu, Xuchun; Shimasaki, Yohei; Oshima, Yuji; Yang, Jian

    2016-10-01

    We evaluated the effects of calcium (Ca(2+)) and magnesium (Mg(2+)) ions on copper (Cu) toxicity to glochidia and newly-transformed juvenile mussels (age 1-2 days) of the Chinese pond mussel (Anodonta woodiana). Acute Cu toxicity tests were performed with glochidia for 24 h and juveniles for 96 h with measured Ca(2+) concentrations of 1.1, 14, 26, 51, and 99 mg L(-1), or measured Mg(2+) concentrations of 2.6, 11, 21, and 39 mg L(-1). The Ca(2+) and Mg(2+) cations provided no statistically significant protection against Cu toxicity to glochidia or juveniles. The 24-h EC50 value for glochidia was 82 μg L(-1) Cu, and contrastly, 96-h EC50 value for newly-transformed juvenile mussels was as low as 12 μg L(-1) Cu, implying that the juveniles of A. woodiana are more vulnerable to Cu contamination at concentrations close to currently-accepted levels.

  7. Alterations of valve closing behavior in juvenile Catarina scallops (Argopecten ventricosus Sowerby, 1842) exposed to toxic metals.

    PubMed

    Sobrino-Figueroa, A; Cáceres-Martínez, C

    2009-11-01

    We conducted an evaluation of alterations produced in the valve closing speed of juvenile Argopecten ventricosus (Catarina scallop) exposed to the metals cadmium, chromium and lead, because of the connection of this response to the state of health of the mollusk. Bioassays were conducted with 50 juveniles (length 3 +/- 0.5 cm) exposed to 0.02, 0.1, 0.2 mg Cd l(-1); 0.1, 0.5, 1.0 mg Cr l(-1); 0.04, 0.2, 0.4 mg Pb l(-1) and 0.8 and 1.6 mg Cd + Cr + Pb l(-1) for 480 h. The average valve closing speed at the end of the experiment was under 1 s in the control group, from 2 to 3.6 s in the bioassays with cadmium, from 1.4 to 3.4 s with chromium, from 3 to 12 s with lead, and from 12 to 15 s with the metal mixtures. It was found that there are significant differences between the values recorded in assays with metals and the control (P < 0.05). The retardation of valve closing in the organisms exposed to toxic substances is probably caused by damage to the sensory cilia located on the edge of the mantle.

  8. Sublethal and acute toxicity of the ethylene glycol butyl ether ester formulation of triclopyr to juvenile coho salmon (Oncorhynchus kisutch).

    PubMed

    Johansen, J A; Geen, G H

    1990-01-01

    The toxicity of Garlon4, the ethylene glycol butyl ether ester formulation of the herbicide tryclopyr, to juvenile coho salmon (Oncorhynchus kisutch) was investigated at several lethal and sublethal concentrations. Fish behavior, random activity and oxygen uptake were monitored. Coho salmon exhibited three distinct responses related to concentration and duration of exposure: (1) at concentrations greater than 0.56 mg/L fish were initially lethargic, then regressed to a highly distressed condition characterized by elevated oxygen uptake and finally death, (2) at 0.32-0.43 mg/L fish were lethargic throughout the exposure period with reduced oxygen uptake, and (3) at concentrations less than or equal to 0.10 mg/L fish were hypersensitive to stimuli, exhibiting elevated activity and oxygen uptake levels during photoperiod transitions. Whole body residue analysis showed that uptake of the ester and subsequent hydrolysis to the acid form in the fish was rapid, with significant accumulation of the acid in the tissues. This suggests that some threshold tissue concentrations were associated with the observed results. For juvenile coho salmon the 96-hr LC50 of Garlon4 was 0.84 mg/L.

  9. Periphyton photosynthesis as an indicator of effluent toxicity: Relationship to effects on animal test species

    SciTech Connect

    Lewis, M.A.

    1992-01-01

    The use of freshwater and marine plants in effluent toxicity evaluations is uncommon despite the presence of test methods and recommendations for their use. It has been assumed that aquatic plants are less sensitive than animal test species and consequently, results from toxicity tests with invertebrates and fish have been used often as a surrogate data base. The study evaluated the ability of these animal toxicity tests to provide safe concentrations for in-stream periphyton. The toxicity of several samples of a treated municipal effluent were determined during a five-month period by monitoring short-term changes in periphyton photosynthesis (carbon-14 uptake) and by observing the effects on young production and survival of cultured daphnids and the fathead minnow. The effect levels from the various tests were compared. The effluent was seldom acutely toxic to Daphnia magna and the fathead minnow (Pimephales promelas) but it was consistently acutely and chronically toxic to Ceriodaphnia dubia. Chronic effect levels ranged between 17 and 71% effluent. Significant inhibition and stimulation of periphyton photosynthesis occurred at concentrations of 6 to 39% effluent. Periphyton photosynthesis was a more sensitive effect parameter than animal survival and in some cases than Ceriodaphnia reproductive performance. The results indicate that effluent toxicity tests conducted routinely with daphnids and fish may not be sufficient to predict effects on indigenous flora in receiving waters.

  10. Variable toxicity of silver nanoparticles to Daphnia magna: effects of algal particles and animal nutrition.

    PubMed

    Conine, Andrea L; Frost, Paul C

    2017-01-01

    Aquatic environments vary widely in aspects other than their physicochemical properties that could alter the toxicity of novel contaminants. One factor that could affect chemical toxicity to aquatic consumers is their nutritional environment as it can strongly affect their physiology and life history. Nutrition has the potential to alter an organism's response to the toxin or how the toxin interacts with the consumer through its food. Here we determined how growth and survival responses of Daphnia to an emerging contaminant, silver nanoparticles (AgNPs), are affected by the presence of food and its stoichiometric food quality. We used a series of survival tests, each slightly modified, to determine whether variable toxicity in different nutritional environments resulted from algal sequestration of AgNPs in a nontoxic form or from changes to the nutritional status of the test animals. We found that the presence of algae, of good or poor quality, reduced the toxicity of AgNPs on animal growth and survival. However, the decrease in AgNP toxicity was greater for animals consuming P-rich compared to P-poor food. We found evidence that this effect of food quality was due to greater algal uptake of AgNPs by P-rich than by P-stressed algae. However, we also found animal nutrition, in the absence of algal AgNP binding, could affect toxicity with P-nourished animals surviving slightly better when exposed to AgNPs compared to their P-stressed counterparts. Our results show an important role for algal particles and their P content in determining the toxicity of AgNPs in natural waters primarily due to their binding and uptake abilities and, less so, to their effects on animal nutrition.

  11. Alterations in juvenile flatfish gill epithelia induced by sediment-bound toxicants: A comparative in situ and ex situ study.

    PubMed

    Martins, Carla; Alves de Matos, António P; Costa, Maria H; Costa, Pedro M

    2015-12-01

    Juvenile Solea senegalensis were exposed in the laboratory (ex situ) and field (in situ) to different sediments of a moderately impacted estuary (the Sado, Portugal) for 28 days. A qualitative histopathological screening yielded scant lesions to gills, albeit alterations such as epithelial hyperplasia being evident and more frequent in fish exposed ex situ. Fully quantitative traits, namely chloride and goblet cell count and size revealed differences between the two bioassay approaches, with ex situ experiments likely enhancing bioavailability of toxicants. Chloride cells endured autolytic processes that could, at least in part, relate to contamination by mixed metals and polycyclic aromatic hydrocarbons (PAHs). Goblet cells did not reveal changes in the chemistry of mucous. Still, their number and size was reduced in fish exposed ex situ to the sediments most contaminated by PAHs, with evidence for adaptation. Also, copper histochemistry revealed the potential role of mucocytes in the regulation of metals.

  12. Assessing potential toxicity of chloride-affected groundwater discharging to an urban stream using juvenile freshwater mussels (Lampsilis siliquoidea).

    PubMed

    Roy, James W; McInnis, Rodney; Bickerton, Greg; Gillis, Patricia L

    2015-11-01

    Groundwater contaminants, such as chloride from road salt, pose a threat to aquatic ecosystems when and where they discharge to surface waters. Here we study the application of a laboratory toxicity bioassay to field-collected samples from contaminated groundwater discharging to an urban stream. The objectives were to assess the potential toxicity of the discharging groundwater, while also exploring the suitability of such standard tests to site groundwater. Juvenile freshwater mussels were chosen as a groundwater-appropriate (endobenthic) test organism. Groundwater was sampled from 6 sites at approximate depths of 0, 10, and 50 cm below the sediment. Concentrations of chloride and several metals were above aquatic life guidelines in some samples. Exposure (96-h) to site groundwater resulted in survival of 90-100% and 80-100% for the 0-cm and deeper samples, respectively, indicating that groundwater may pose a toxicological threat to freshwater mussels. Several samples with high chloride had a survival rate of 80%, but generally there was poor correlation between survival and individual contaminants. Parallel juvenile mussel exposures using reconstituted water and NaCl predicted survival in the natural groundwater below 50% based on chloride concentrations. This indicates some protective ability of groundwater, possibly associated with water hardness. Finally, some technical issues with performing bioassays with groundwater were noted. First, aeration of previously anoxic groundwater samples caused marked changes in water quality (especially metal concentrations). Second, calcite crystals formed on the mussel shells in samples with elevated chloride and water hardness, though with no apparent negative effects. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  13. Reproduction and juvenile animal toxicology studies in the rat with a new allergy vaccine adjuvanted with monophosphoryl lipid A (MPL(®)) for the treatment of grass pollen allergy.

    PubMed

    Baldrick, Paul; Hewings, Simon; Skinner, Murray

    2011-11-01

    Pollinex(®) Quattro Grass has been developed for the prevention or relief of allergic symptoms caused by pollen in both adults and children. Reproduction and juvenile animal toxicology studies have been performed. Subcutaneous injection on Day 14 prior to pairing and on Days 6 and 13 of gestation to pregnant rats at 2000SU/0.5 mL elicited no signs of maternal or embryo-foetal toxicity. Mating, fertility, fecundity and pup parameters were all unaffected by treatment. Once-weekly subcutaneous administration at ascending doses of 300, 800, 2000 and 2000SU/0.5 mL followed by a 4 week non-dose period to juvenile rats from 3 weeks of age showed no signs of obvious toxicity. As in a previously performed adult animal toxicology study with the vaccine, not unexpected, but relatively minor, immuno-stimulatory effects were seen in this study along with injection site reaction which can largely be attributed to the presence of tyrosine in the formulation.

  14. Mutagenicity and toxicity of carcinogenic and other hydrazine derivatives: correlation between toxic potency in animals and toxic potency in Salmonella typhimurium TA1538.

    PubMed

    Malca-Mor, L; Stark, A A

    1982-10-01

    Eleven hydrazine derivatives and an aromatic amine were examined for mutagenicity and toxicity to Salmonella typhimurium. Phenylhydrazine, 2-nitrophenylhydrazine, 4-nitrophenylhydrazine, 2,4-dinitrophenylhydrazine, p-tolylhydrazine, and 4-nitroaniline were found to be frameshift mutagens (strain TA1538). Benzylhydrazine, m-hydroxybenzylhydrazine, p-hydrazinobenzoic acid, L-tyrosine hydrazide, p-aminobenzoyl hydrazide, and isoniazid were not mutagenic. All chemicals were toxic to strain TA1538. A qualitative correlation was found between the pK of the compounds and their mutagenicity. Relative toxicities of hydrazines to bacteria were found to be closely correlated with the relative toxicities of the same compounds in animals. Described herein is a methodology for the rapid prescreening of chemicals which may be used as drugs for those with a high benefit/risk ratio.

  15. Toxicity of agricultural subsurface drainwater from the San Joaquin Valley, California to juvenile chinook salmon and striped bass

    USGS Publications Warehouse

    Saiki, Michael K.; Jennings, Mark R.; Wiedmeyer, Raymond H.

    1992-01-01

    Juvenile chinook salmon Oncorhynchus tshawytscha (40-50 mm total length, TL) and striped bass Morone saxatilis (30-40 mm TL) were exposed to serial dilutions (100, 50, 25, and 12.5%) of agricultural subsurface drainwater (WWD), reconstituted drainwater (RWWD), and reconstituted seawater (IO). Agricultural subsurface drainwater contained naturally elevated concentrations of major ions (such as sodium and sulfate) and trace elements (especially boron and selenium), RWWD contained concentrations of major ions that mimicked those in WWD but trace elements were not elevated, and IO contained concentrations of total dissolved salt that were similar to those in WWD and RWWD but chloride replaced sulfate as the dominant anion. After 28 d of static exposure, over 75% of the chinook salmon in 100% WWD had died, whereas none had died in other dilutions and water types. Growth of chinook salmon in WWD and RWWD, but not in IO, exhibited dilution responses. All striped bass died in 100% WWD within 23 d, whereas 19 of 20 striped bass had died in 100% RWWD after 28 d. In contrast, none died in 100% IO. Growth of striped bass was impaired only in WWD. Fish in WWD accumulated as much as 200 μg/g (dry-weight basis) of boron, whereas fish in control water accumulated less than 3.1 μg/g. Although potentially toxic concentrations of selenium occurred in WWD (geometric means, 158-218 μg/L), chinook salmon and striped bass exposed to this water type accumulated 5.7 μg Se/g or less. These findings indicate that WWD was toxic to chinook salmon and striped bass. Judging from available data, the toxicity of WWD was due primarily to high concentrations of major ions present in atypical ratios, to high concentrations of sulfate, or to both. High concentrations of boron and selenium also may have contributed to the toxicity of WWD, but their effects were not clearly delineated.

  16. Evaluation of acute copper toxicity to juvenile freshwater mussels (fatmucket, lampsilis siliquoidea) in natural and reconstituted waters

    USGS Publications Warehouse

    Wang, N.; Mebane, C.A.; Kunz, J.L.; Ingersoll, C.G.; May, T.W.; Arnold, W.R.; Santore, R.C.; Augspurger, T.; Dwyer, F.J.; Barniiart, M.C.

    2009-01-01

    The influence of dissolved organic carbon (DOC) and water composition on the toxicity of copper to juvenile freshwater mussels (fatmucket, Lampsilis siliquoidea) were evaluated in natural and reconstituted waters. Acute 96-h copper toxicity tests were conducted at four nominal DOC concentrations (0, 2.5, 5, and 10 mg/L as carbon [C]) in dilutions of natural waters and in American Society for Testing and Materials (ASTM) reconstituted hard water. Toxicity tests also were conducted in ASTM soft, moderately hard, hard, and very hard reconstituted waters (nominal hardness 45-300 mg/L as CaCO3). Three natural surface waters (9.5-11 mg/L DOC) were diluted to obtain a series of DOC concentrations with diluted well water, and an extract of natural organic matter and commercial humic acid was mixed with ASTM hard water to prepare a series of DOC concentrations for toxicity testing. Median effective concentrations (EC50s) for dissolved copper varied >40-fold (9.9 to >396 ??g Cu/L) over all 21 treatments in various DOC waters. Within a particular type of DOC water, EC50s increased 5- to 12-fold across DOC concentrations of 0.3 to up to 11 mg C/L. However, EC50s increased by only a factor of 1.4 (21 30 ??g Cu/L) in the four ASTM waters with wide range of water hardness (52-300 mg CaCO 3/L). Predictions from the biotic ligand model (BLM) for copper explained nearly 90% of the variability in EC50s. Nearly 70% of BLM-normalized EC50s for fatmucket tested in natural waters were below the final acute value used to derive the U.S. Environmental Protection Agency acute water quality criterion for copper, indicating that the criterion might not be protective of fatmucket and perhaps other mussel species. ?? 2009 SETAC.

  17. Toxicity and bioaccumulation of waterborne and dietary selenium in juvenile bluegill (Lepomis macrochirus)

    USGS Publications Warehouse

    Cleveland, Laverne; Little, Edward E.; Buckler, Denny R.; Wiedmeyer, Raymond H.

    1993-01-01

    Juvenile bluegill (Lepomis macrochirus) were exposed to waterborne selenium as a 6:1 mixture of selenate to selenite (as Se) for 60 d and to dietary seleno-l-methionine for 90 d. Measured concentrations of total selenium in the waterborne exposure ranged from 0.16 to 2.8 mg/l, and concentrations of seleno-l-methionine in the test diet ranged from 2.3 to 25.0 mg/kg wet weight. Mortality, body weight, condition factor, swimming and feeding behavior, aggression, and selenium tissue residues were monitored during the tests. Increased mortality at measured concentrations of 0.64 mg Se/l and greater was the primary adverse effect of waterborne selenium on the juvenile bluegill. Bluegill exposed to 2.8 mg/l of waterborne Se for 30 d exhibited a significant reduction in condition factor (K), whereas dietary exposure of bluegill to 25 mg Se/kg for 30 d and 13 mg Se/kg or greater for 90 d elicited significant reductions in K. Mortality and swimming activity of bluegill were not affected in the dietary exposure. Net accumulation of Se from both water and diet was directly related to exposure concentration. Bioconcentration factors ranged from 5 to 7 for bluegill exposed to waterborne Se and from 0.5 to 1.0 for fish exposed to dietary Se. Results of these laboratory tests indicate that survival of bluegill may be impaired in natural waters with elevated Se concentrations.

  18. Assessment of the sublethal toxicity of organochlorine pesticide endosulfan in juvenile common carp (Cyprinus carpio).

    PubMed

    Salvo, Lígia M; Bainy, Afonso C D; Ventura, Eliana C; Marques, Maria R F; Silva, José Roberto M C; Klemz, Cláudio; Silva de Assis, Helena C

    2012-01-01

    This study is aimed at evaluating the sublethal effects of endosulfan (EDS) in juvenile common carp (Cyprinus carpio). For this purpose, fish were exposed for 15 days to the technical EDS (95% pure) diluted in dimethyl sulfoxide (DMSO) 0.1% of the total volume in water solution in a semi-static system at sublethal concentration (1 μg/L). Subsequently, the liver somatic index (LSI) and factor condition (K) were determined. The total cytocrome P450 (CYP), CYP1A isoform, and the ethoxyresorufin-O-deethylase (EROD) activity were determined from the hepatic microsomal fraction as well as the activity of the oxidative stress enzyme system such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GP(X)), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH). Among the parameters assessed, EDS at the sublethal concentration in subchronic exposure caused significant changes in liver somatic indices as well as induction of the phase I biotransformation system and oxidative stress in juvenile common carp (Cyprinus carpio). Thus, it is seen that the use of biochemical biomarkers of environmental contamination in this study proved to be an extremely important tool for detecting the adverse effects of xenobiotics in the aquatic environment, even at low concentration.

  19. Racial tropism of a highly toxic clone of Actinobacillus actinomycetemcomitans associated with juvenile periodontitis.

    PubMed Central

    Haubek, D; Dirienzo, J M; Tinoco, E M; Westergaard, J; López, N J; Chung, C P; Poulsen, K; Kilian, M

    1997-01-01

    Actinobacillus actinomycetemcomitans strains with enhanced levels of production of leukotoxin are characterized by a 530-bp deletion from the promoter region of the leukotoxin gene operon. Previous isolates with this deletion constituted a single clone belonging to serotype b, although they displayed minor differences among each other. We have analyzed the geographic dissemination of this clone by examining 326 A. actinomycetemcomitans isolates from healthy and periodontally diseased individuals as well as from patients with different types of extraoral infections originating from countries worldwide. A total of 38 isolates, all belonging to the same clone, showed the 530-bp deletion. Comparison of a 440-bp sequence from the promoter region of the leukotoxin gene operon from 10 of these strains revealed complete identity, which indicates that the deletion originates from a single mutational event. This particular clone was exclusively associated with localized juvenile periodontitis (LJP). In at least 12 of 28 families from which the clone was isolated, more than one family member had LJP. Notably, all the subjects carrying this clone had a genetic affiliation with the African population. These observations suggest that juvenile periodontitis in some adolescents with an African origin is associated with a disseminating clone of A. actinomycetemcomitans. PMID:9399490

  20. Prevention and treatment of Nitrite toxicity in juvenile steelhead trout (Salmo gairdneri)

    USGS Publications Warehouse

    Wedemeyer, Gary A.; Yasutake, W.T.

    1978-01-01

    The efficacy of mineral salts, pH, and tetramethylthianine (methylene blue) treatment in reducing the acute toxicity of nitrite to fingerling steelhead trout (Salmo gairdneri) was determined using a static bioassay system at 10 °C. The acute toxicity (96-h LC50) was reduced by a factor of about 24 for 5-g steelhead and 13 for 10-g fish when the total water hardness was increased from 25 to 300 mg/L (as CaCO3). NaCl or CaCl2 additions (0–200 mg/L) reduced toxicity by a factor of up to 3 for NaCl and 50 for CaCl2. Increasing the pH from 6.0 to 8.0 decreased toxicity by a factor of about 8 for the smaller and 3 for the larger fish. Methylene blue at 0.1 or 1.0 mg/L was effective in decreasing acute toxicity. For alleviating methemoglobinemia, removing the fish to freshwater for 48 h was about as effective as 1.0 mg/L methylene blue. Chronic exposure in soft water to 0.03 mg/L NO2-N for 6 mo caused no significant growth reduction, gill histological changes, hematological dyscrasias, or impaired ability of the smolts to adapt to 30‰ seawater and grow for an additional 2 mo. Key words: nitrite, toxicity, fish, methylene blue, pH, salts, acute toxicity, chronic toxicity

  1. Freshwater toxicity testing using rehydrated Philodina sp. (Rotifera) as test animals.

    PubMed

    Snell, Terry W; Johnston, Rachel K; Matthews, Amelia B

    2017-10-01

    Rotifers have become widely used in aquatic toxicology as a rapid screening test for toxicity. The commercial availability of diapausing embryos (cysts) have facilitated their popularity because test animals can be obtained without having to master the details of culturing. Other rotifer species have life stages capable of surviving desiccation and also could be used in non-culture systems for toxicity assessment. In this article, we describe a system for toxicity testing in freshwater based on rehydrating desiccated bdelloid rotifers in the genus Philodina. These animals can remain in this anhydrobiotic state for more than one year and then rehydrate within hours to provide animals for toxicity tests. We describe three endpoints: a 1.5 h ingestion test, a 24 h mortality test, and a five day reproductive test. The latter test requires feeding and a method using a dried commercial product is explained. Using desiccated rotifers and dried food in toxicity tests make this system especially attractive because of its flexibility and low threshold of biological expertise required to execute the tests. The use of the Philodina toxicity test is illustrated with four metals: copper, lead, mercury and cadmium. Reproduction generally was the most sensitive endpoint, with EC50s of 0.33, 0.44, 0.60, and 0.12 mg/L, respectively. Ingestion was a close second with EC50s of 0.13, 1.64, 0.64, and 6.26 mg/L, respectively. © 2017 Wiley Periodicals, Inc.

  2. Screening toxicity evaluation of Wheeler Reservoir sediments using juvenile freshwater mussels (Anodonta imbecillis say) exposed to sediment interstitial water

    SciTech Connect

    Wade, D.C.

    1990-12-01

    Reservoir sediments (porewater) near several wastewater outfalls at Decatur, Alabama, were screened for acute (9-day) toxicity to 8-day old freshwater mussels. Sampling locations corresponded to four of five sites previously surveyed by the Alabama Wildlife Federation and Alabama mussel divers. A site located on the opposite (north) overbank where mussels are abundant was chosen as the study control. Reference sediments from an outdoor channel at TVA's Aquatic Research Laboratory (ARL) with flow-through Wheeler Reservoir water and from a downstream (Kentucky) reservoir were included in the study for comparative purposes. Toxicity was observed at two of the Decatur sites, and in the ARL channel. Sediments from the other two Decatur sites, the north overbank (control), and Kentucky Reservoir were not toxic to the test animals. Toxicity at station Alpha and from the ARL channel was correlated with un-ionized ammonia present in porewater during the test. Toxicity at station Delta was above the level explained by the regression model examined for ammonia. The site at Decatur having the greatest toxicity and ammonia concentration (Alpha) was located in the Dry Branch Embayment. Elevated ammonia in sediment collected from ARL was attributed to natural events. 13 refs., 4 figs., 6 tabs.

  3. Dissociation in the effects of stress and D1 receptors activation on basolateral amygdalar LTP in juvenile and adult animals.

    PubMed

    Schayek, Rachel; Maroun, Mouna

    2017-02-01

    Post-weaning or juvenility is a critical developmental stage during which neural structures as the medial prefrontal cortex (mPFC) and amygdala and the neurotransmitter systems undergo major reorganization and thus are susceptible to the effects of environmental factors. Interactions between the mPFC and the amygdala are critical for fear regulation. Changes in plasticity in the projections from the mPFC to the basolateral amygdala (BLA) were previously shown following stress and fear. In the present study, we examined possible differences between adult and PW animals in the (1) effects of exposure to stress on BLA- LTP and (2) the possible dependency of mPFC-BLA LTP on N-methyl-d-aspartate (NMDA) and Dopamine (D) receptors activation. The results show that similarly to the adults, the mPFC- BLA pathway in the PW animals is not amenable to the induction of LTP. However, in contrast to adult animals, exposure to stress in PW animals did not result in enhanced BLA-LTP. Interestingly, only under activation of the D1 receptors, PW animals expressed LTP in the BLA. In both groups of age, the NMDA partial agonist d-cycloserine (DCS) did not result in any change in the levels of potentiation. Our results confirm differences between the PW and the adult animal and show that stress and the activation of Dopamine are associated with different effects; which may have potential implications for the treatment of anxiety and stress disorders across development. Copyright © 2016. Published by Elsevier Ltd.

  4. Superoxide dismutase activity in juvenile Litopenaeus vannamei and Nodipecten subnodosus exposed to the toxic dinoflagellate Prorocentrum lima.

    PubMed

    Campa-Córdova, Angel I; Núñez-Vázquez, Erick J; Luna-González, Antonio; Romero-Geraldo, María J; Ascencio, Felipe

    2009-04-01

    The toxic effect of the dinoflagellate Prorocentrum lima on juvenile American whiteleg shrimp Litopenaeus vannamei and giant lion-paw scallop Nodipecten subnodosus was evaluated. Organisms were exposed to three densities (500, 2000, or 5000 cells mL(-1)), superoxide dismutase activity and soluble protein in the hepatopancreas and muscle were determined at 1, 6, 24 and 48 h after challenge. Shrimp exposed at 5000 cells mL(-1) significantly increased SOD activity in the hepatopancreas at 1 h post-challenge, whereas enzymatic activity in muscle significantly increased at 24 h at all densities. Scallops exposed to 500 and 2000 cells mL(-1) showed significant SOD activity increase in hepatopancreas at 24 and 12 h, respectively. Mortality at 48 h was 100% in scallops exposed to 5000 cells mL(-1). Shrimp showed higher levels of SOD activity than scallops. Soluble protein content in the shrimp hepatopancreas was significantly higher at densities of 500 and 2000 cells mL(-1) at 6 and 1 h, respectively. Soluble protein content in the scallop hepatopancreas was higher than control values at 1 h after challenge. In this study, 500 cells mL(-1) was enough to trigger SOD activity in two benthic species exposed to the toxic dinoflagellate P. lima.

  5. Toxicity of a glufosinate- and several glyphosate-based herbicides to juvenile amphibians from the Southern High Plains, USA.

    PubMed

    Dinehart, Simon K; Smith, Loren M; McMurry, Scott T; Anderson, Todd A; Smith, Philip N; Haukos, David A

    2009-01-15

    Pesticide toxicity is often proposed as a contributing factor to the world-wide decline of amphibian populations. We assessed acute toxicity (48 h) of a glufosinate-based herbicide (Ignite 280 SL) and several glyphosate-based herbicide formulations (Roundup WeatherMAX, Roundup Weed and Grass Killer Super Concentrate, Roundup Weed and Grass Killer Ready-To-Use Plus on two species of amphibians housed on soil or moist paper towels. Survival of juvenile Great Plains toads (Bufo cognatus) and New Mexico spadefoots (Spea multiplicata) was reduced by exposure to Roundup Weed and Grass Killer Ready-To-Use Plus on both substrates. Great Plains toad survival was also reduced by exposure to Roundup Weed and Grass Killer Super Concentrate on paper towels. New Mexico spadefoot and Great Plains toad survival was not affected by exposure to the two agricultural herbicides (Roundup WeatherMAX and Ignite 280 SL) on either substrate, suggesting that these herbicides likely do not pose an immediate risk to these species under field conditions.

  6. Toxicity of ozonated animal manure to the house fly, Musca domestica.

    PubMed

    Masten, S J; Kim-Yang, H; Walker, E D; Roman, H; Yokoyama, M T

    2001-01-01

    Swine manure slurries were ozonated at a dosage of 1 g/L and tested for their toxicity to the house fly (Musca domestica). The observed toxicity of ozonated swine manure was consistent and independent of origin of the swine manure. A dose (dilution) response curve was performed. A 50% dilution in the ozonated swine manure slurry resulted in 90% reduction in toxicity. Neither the synthetic nor ozonated synthetic swine manure, both of which contained higher concentrations of formaldehyde and three other unidentified carbonyl compounds than the ozonated swine manure, were toxic to the flies. Ozonated swine manure slurry was centrifuged and passed through a 0.45-microm filter. The liquid phase was as toxic as the unfiltered slurry; as such, the toxicant appears to be present in liquid phase. Neither ammonia, hydrogen sulfide, formaldehyde, nor other simple aldehydes appeared to be the toxic agent. The toxic agent appears to be a polar chemical compound and is concentrated in the urine. Several possible compounds have been identified. The toxicity of untreated and ozonated manure slurries from different livestock was compared. Six animal manure slurries (beef and dairy cattle, horse, poultry, sheep, and swine) were ozonated (dosage of 1 g/L) and tested for toxicity to the house fly. Ozonated dairy cattle manure slurry showed 78% mortality after 72 h, whereas ozonated swine manure slurry achieved a 100% mortality rate in 48 h. Neither the unozonated dairy nor swine manure slurries, nor any of the other raw or ozonated manure slurries, were toxic to the flies.

  7. Acute toxicity of cadmium, copper, zinc, ammonia, 3,3 prime -dichlorobenzidine, 2,6-dichloro-4-nitroaniline, methylene chloride, and 2,4,6-trichlorophenol to juvenile grass shrimp and killifish

    SciTech Connect

    Burton, D.T.; Fisher, D.J. )

    1990-05-01

    The acute toxicity of several compounds was investigated while performing a toxicity evaluation of a complex chemical effluent. The tests were conducted for one or more of the following reasons: (1) data were not available for the chemical; (2) data were not available for the species; or (3) data were not available for the juvenile life stage of the species. Forty-eight hour acute toxicity tests were run on juvenile grass shrimp (Palaemonetes pugio) and juvenile killifish (Fundulus heteroclitus) exposed to the following compounds: cadmium, copper, zinc, ammonia, 3,3{prime}-dichlorobenzidine, 2,6-dichloro-4-nitroaniline, methylene chloride (dichloromethane) and 2,4,6-trichlorophenol.

  8. Are quantum dots toxic? Exploring the discrepancy between cell culture and animal studies.

    PubMed

    Tsoi, Kim M; Dai, Qin; Alman, Benjamin A; Chan, Warren C W

    2013-03-19

    Despite significant interest in developing quantum dots (QDs) for biomedical applications, many researchers are convinced that QDs will never be used for treating patients because of their potential toxicity. The perception that QDs are toxic is rooted in two assumptions. Cadmium-containing QDs can kill cells in culture. Many researchers then assume that because QDs are toxic to cells, they must be toxic to humans. In addition, many researchers classify QDs as a homogeneous group of materials. Therefore, if CdSe QDs are harmful, they extrapolate this result to all QDs. Though unsubstantiated, these assumptions continue to drive QD research. When dosing is physiologically appropriate, QD toxicity has not been demonstrated in animal models. In addition, QDs are not uniform: each design is a unique combination of physicochemical properties that influence biological activity and toxicity. In this Account, we summarize key findings from in vitro and in vivo studies, explore the causes of the discrepancy in QD toxicological data, and provide our view of the future direction of the field. In vitro and in vivo QD studies have advanced our knowledge of cellular transport kinetics, mechanisms of QD toxicity, and biodistribution following animal injection. Cell culture experiments have shown that QDs undergo design-dependent intracellular localization and they can cause cytotoxicity by releasing free cadmium into solution and by generating free radical species. In animal experiments, QDs preferentially enter the liver and spleen following intravascular injection, undergo minimal excretion if larger than 6 nm, and appear to be safe to the animal. In vitro and in vivo studies show an apparent discrepancy with regard to toxicity. Dosing provides one explanation for these findings. Under culture conditions, a cell experiences a constant QD dose, but the in vivo QD concentration can vary, and the organ-specific dose may not be high enough to induce detectable toxicity. Because QDs

  9. A review of reproductive and developmental toxicity of silver nanoparticles in laboratory animals.

    PubMed

    Ema, Makoto; Okuda, Hirokazu; Gamo, Masashi; Honda, Kazumasa

    2017-01-01

    We summarized significant effects reported in the literature on the reproductive and developmental toxicity of silver nanoparticles (AgNPs) in laboratory animals. AgNPs showed testicular/sperm toxicity in males and ovarian and embryonic toxicity in females. Maternal injection of AgNPs delayed physical development and impaired cognitive behavior in offspring. Ag was accumulated in the testes after administration of AgNPs. AgNPs were identified in the visceral yolk sac after administration during early gestation in mice. Radiolabeled AgNPs were detected in placenta, breast milk, and pre- and postnatal offspring after injection during late gestation in rats. Ag in the ionic form, and possibly also particles, was suggested to be bioavailable. Although this review provides initial information on the potential reproductive and developmental toxicity of AgNPs, data is still very limited. Further studies using state-of-the-art methodologies and the relevant routes and doses for human exposure are required.

  10. Toxicity of dispersant application: Biomarkers responses in gills of juvenile golden grey mullet (Liza aurata).

    PubMed

    Milinkovitch, Thomas; Godefroy, Joachim; Théron, Michaël; Thomas-Guyon, Hélène

    2011-10-01

    Dispersant use in nearshore areas is likely to increase the exposure of aquatic organisms to petroleum. To measure the toxicity of this controversial response technique, golden grey mullets (Liza aurata) were exposed to mechanically dispersed oil, chemically dispersed oil, dispersant alone in seawater, water-soluble fraction of oil and to seawater as a control treatment. Several biomarkers were assessed in the gills (enzymatic antioxidant activities, glutathione content, lipid peroxidation) and in the gallbladder (polycylic aromatic hydrocarbons metabolites). The significant differences between chemically dispersed oil and water soluble fraction of oil highlight the environmental risk to disperse an oil slick when containment and recovery can be conducted. The lack of significance between chemically and mechanically dispersed oil suggests that dispersant application is no more toxic than the natural dispersion of the oil slick. The results of this study are of interest in order to establish dispersant use policies in nearshore areas.

  11. Interactive neurobehavioral toxicity of diazinon, malathion, and ethoprop to juvenile coho salmon.

    PubMed

    Laetz, Cathy A; Baldwin, David H; Hebert, Vincent; Stark, John D; Scholz, Nathaniel L

    2013-03-19

    In western North America, mixtures of current use pesticides have been widely detected in streams and other aquatic habitats for threatened and endangered Pacific salmon and steelhead (Oncorhynchus sp.). These include organophosphate insecticides that inhibit acetylcholinesterase (AChE) enzyme activity in the salmon nervous system, thereby disrupting swimming and feeding behaviors. Several organophosphates have been shown to interact as mixtures to produce synergistic AChE inhibition at concentrations near or above the upper range of surface water detections in freshwater systems. To evaluate potential synergism at lower concentrations (near or below 1 part per billion), juvenile coho (Oncorhynchus kisutch) were exposed to a range of mixtures of diazinon-malathion and ethoprop-malathion below a cumulative 0.05 of the predicted EC50 for AChE inhibition, as determined from single chemical concentration-response curves. Brain enzyme inhibition was concentration-dependent, with a 90% reduction and a significant decrease in spontaneous swimming speed at the highest binary mixture concentrations evaluated (diazinon-malathion at 2.6 and 1.1 μg/L, respectively; ethoprop-malathion at 2.8 and 1.2 μg/L, respectively). Brain enzyme activity gradually recovered over six weeks. Our findings extend earlier observations of organophosphate synergism in salmon and reveal an unusually steep concentration-response relationship across a mere 2-fold increase in mixture concentration.

  12. Juvenile freshwater mussel (Bivalvia: unionidae) responses to acute toxicity testing with copper

    SciTech Connect

    Jacobson, P.J.; Cherry, D.S.; Neves, R.J. ); Farris, J.L. )

    1993-05-01

    The sensitivities of newly metamorphosed juveniles of Villosa iris and Anodonta grandis to copper were determined using 24-h static bioassays. Two methods of assessing postexposure response were compared: direct visual examination and the use of vital staining with neutral red. Both species responded to copper exposures, exhibiting valve closure at concentrations as low as 24 [mu]g Cu per liter for Villosa iris and 17 [mu]g Cu per liter for Anodonta grandis. EC50 values of 27 [mu]g Cu per liter (Villosa iris) and 33 [mu]g Cu per liter (Anodonta grandis) were calculated on the basis of the valve closure response. Use of vital staining with neutral red provided an EC50 of 29 [mu]g Cu per liter for Villosa iris. The amber coloration of Anodonta grandis valves prevented determination of an EC50 using the vital staining. LC50 values of 83 [mu]g Cu per liter (Villosa iris) and 44 [mu]g Cu per liter (Anodonta grandis) were calculated from the results of vital staining. Neutral red was found to be effective in assessing postexposure mortality and sublethal responses after acute exposures to copper.

  13. Nebivolol Ameliorates Cardiac NLRP3 Inflammasome Activation in a Juvenile-Adolescent Animal Model of Diet-Induced Obesity.

    PubMed

    Xie, Qihai; Wei, Tong; Huang, Chenglin; Liu, Penghao; Sun, Mengwei; Shen, Weili; Gao, Pingjin

    2016-09-30

    NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d). Treatment with nebivolol prevented HFD-induced obesity associated excess cardiac lipid accumulation as well as myocardial mitochondrial dysfunction. Nebivolol attenuated pro-inflammatory cytokines secretion and NLRP3 inflammasome activation in myocardium of obese rats. In parallel, nebivolol treatment of obese animals increased cardiac β3-AR expression, reversing the reduction of endothelial nitric oxide synthase (eNOS). In vitro, nebivolol treatment of palmitate-incubated H9C2 cells suppressed autophagy, restored mitochondrial biogenesis, leading to decreased mitochondrial reactive oxygen species (mtROS) generation, and suppressed NLRP3 inflammasome activation. Meanwhile the presence of shRNA against β3-AR or against eNOS deteriorated the protective effects of nebivolol. These data suggest the beneficial effect of nebivolol on myocardial lipotoxicity contributing to inhibiting NLRP3 inflammasome activation possibly via improved mitochondrial dysfunction.

  14. Nebivolol Ameliorates Cardiac NLRP3 Inflammasome Activation in a Juvenile-Adolescent Animal Model of Diet-Induced Obesity

    PubMed Central

    Xie, Qihai; Wei, Tong; Huang, Chenglin; Liu, Penghao; Sun, Mengwei; Shen, Weili; Gao, Pingjin

    2016-01-01

    NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d). Treatment with nebivolol prevented HFD-induced obesity associated excess cardiac lipid accumulation as well as myocardial mitochondrial dysfunction. Nebivolol attenuated pro-inflammatory cytokines secretion and NLRP3 inflammasome activation in myocardium of obese rats. In parallel, nebivolol treatment of obese animals increased cardiac β3-AR expression, reversing the reduction of endothelial nitric oxide synthase (eNOS). In vitro, nebivolol treatment of palmitate-incubated H9C2 cells suppressed autophagy, restored mitochondrial biogenesis, leading to decreased mitochondrial reactive oxygen species (mtROS) generation, and suppressed NLRP3 inflammasome activation. Meanwhile the presence of shRNA against β3-AR or against eNOS deteriorated the protective effects of nebivolol. These data suggest the beneficial effect of nebivolol on myocardial lipotoxicity contributing to inhibiting NLRP3 inflammasome activation possibly via improved mitochondrial dysfunction. PMID:27686325

  15. Toxicity testing: the search for an in vitro alternative to animal testing.

    PubMed

    May, J E; Xu, J; Morse, H R; Avent, N D; Donaldson, C

    2009-01-01

    Prior to introduction to the clinic, pharmaceuticals must undergo rigorous toxicity testing to ensure their safety. Traditionally, this has been achieved using in vivo animal models. However, besides ethical reasons, there is a continual drive to reduce the number of animals used for this purpose due to concerns such as the lack of concordance seen between animal models and toxic effects in humans. Adequate testing to ensure any toxic metabolites are detected can be further complicated if the agent is administered in a prodrug form, requiring a source of cytochrome P450 enzymes for metabolism. A number of sources of metabolic enzymes have been utilised in in vitro models, including cell lines, primary human tissue and liver extracts such as S9. This review examines current and new in vitro models for toxicity testing, including a new model developed within the authors' laboratory utilising HepG2 liver spheroids within a co-culture system to examine the effects of chemotherapeutic agents on other cell types.

  16. Chronic toxicity of verapamil on juvenile rainbow trout (Oncorhynchus mykiss): effects on morphological indices, hematological parameters and antioxidant responses.

    PubMed

    Li, Zhi-Hua; Velisek, Josef; Zlabek, Vladimir; Grabic, Roman; Machova, Jana; Kolarova, Jitka; Li, Ping; Randak, Tomas

    2011-01-30

    In this study, the toxic effects of verapamil (VRP) were studied on juvenile rainbow trout, Oncorhynchus mykiss, by chronic semi-static bioassay. Fish were exposed to sublethal concentrations of VRP (0.5, 27 and 270 μg/L) for 0, 21 and 42 d. Multiple biomarkers were measured, including morphological indices, hematological parameters and antioxidant responses of different tissues (brain, gill, liver, muscle and intestine). Based on the results, there was no significant change in all parameters measured in fish exposed to VRP at environmental related concentration, but VRP-induced stress in fish exposed to higher concentrations reflected the significant changes of physiological and biochemical responses. Through principal component analysis and integrated biomarker response assessment, effects induced by VRP-stress in each test group were distinguished. Additionally, all parameters measured in this study displayed various dependent patterns to VRP concentrations and exposure time using two-way ANOVA statistic analysis. In short, the multiple responses in fish indicated that VRP induced physiological stress and could be used as potential biomarkers for monitoring residual VRP in aquatic environment; but molecular and genetic mechanisms of these physiological responses in fish are not clear and need to be further studied. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    PubMed

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  18. Toxic effects in juvenile sea cucumber Apostichopus japonicas (Selenka) exposure to benzo[a]pyrene.

    PubMed

    Li, Chao; Zhou, Shun; Ren, Yichao; Jiang, Senhao; Xia, Bin; Dong, Xiaoyu

    2016-12-01

    To understand the physiological response of sea cucumber, Apostichopus japonicas, were exposed to different concentration of benzo[a]pyrene (B[a]P), and the growth, survival, antioxidant enzyme (SOD and T-AOC) activities were tested. Meanwhile, the quantitative real-time PCR technology was utilized to quantize the expression of immune related genes (i.e. innate immune genes, HSP genes and anti-oxidative genes). In our result, the SOD activity and T-AOC activity were induced at lower level of B[a]P (0.03 μg/L), however, a reduction of SOD activity and T-AOC activity were observed at relatively high B[a]P concentration (3 and 9 μg/L) for A. japonicas. Furthermore, the distinct expression patterns of selected immune-related genes were detected among different concentrations, and a general trend of down-regulation was observed at higher concentration. Especially, lysozyme almost showed the highest down-regulation at all concentrations, followed by NOS. Collectively, the growth, survival and expression signatures of immune related genes reflected an overall suppression of innate immunity in sea cucumber following exposure. Future functional studies should be carried out to characterize the detailed roles of immune genes and their related responses under B[a]P toxicity. Additionally, better understanding of the molecular indicators governing the healthy status under environmental toxicity would facilitate a healthy and sustainable culture program.

  19. A review of toxicity studies of single-walled carbon nanotubes in laboratory animals.

    PubMed

    Ema, Makoto; Gamo, Masashi; Honda, Kazumasa

    2016-02-01

    We summarized the findings of in vivo toxicity studies of single-walled carbon nanotubes (SWCNTs) in laboratory animals. The large majority addressed the pulmonary toxicity of SWCNTs in rodents. Inhalation, pharyngeal aspiration, and intratracheal instillation studies revealed that SWCNTs caused acute and chronic inflammation, granuloma formation, collagen deposition, fibrosis, and genotoxic effects in the lungs. Pulmonary toxicity of well-dispersed SWCNTs was more potent than less dispersed ones. Airway exposure to SWCNTs also induced cardiovascular diseases in mice. Oxidative stress was caused by the administration of SWCNTs. Injected SWCNTs were distributed throughout most of the organs including the brain, mainly retained in the lungs, liver, and spleen, and eliminated through the kidney and bile duct. Orally administered SWCNTs are suggested to be absorbed from the gastrointestinal tract to the blood circulation in mice and rats. Although no definitive study on the carcinogenicity of SWCNTs is available at present, evidence of carcinogenicity has not been reported in toxicity studies cited in this review. Overall, the available data provides initial information on SWCNT toxicity. To further clarify their toxicity and risk assessment, studies should be conducted using well-characterized SWCNTs, standard protocols, and the relevant route and doses of human exposure.

  20. Evaluation of the toxic effect of peracetic acid on grass carp (Ctenopharyngodon idella) juveniles.

    PubMed

    Chupani, Latifeh; Stara, Alzbeta; Velisek, Josef; Zuskova, Eliska

    2014-01-01

    The aim of present study was to evaluate the effect of peracetic acid (PAA) on haematotological and biochemical indices, antioxidant status, micronucleus induction and histopathological alterations of liver and gill in grass carp. Grass carp (Ctenopharyngodon idella) juveniles were exposed to therapeutic concentrations (1, and 3 mg x l(-1)) of PAA for a period of 10 days. Selected haematotological indices--the erythrocyte count (RBC), haematocrit (PCV), haemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and leukocyte count (WBC), and biochemical indices--glucose (Glu), total protein (TP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), and lactate dehydrogenase (LDH) were evaluated in plasma. Activity of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR), as well as levels of thiobarbituric acid reactive substances (TBARS) were assessed in gill and liver. Micronucleus frequency in peripheral erythrocytes was counted in control and experimental fish. Histological examinations of gill and liver were performed. No significant differences were found in haematological parameters measured. Statistically significant (p < 0.05) alterations in the activities of AST, CK and LDH were found in treated fish compared to control groups. Fish exposed to 1 mg x l(-1) of PAA showed significantly lower (p < 0.05) SOD activity in liver and gill while catalase activity indicated a significant decrease (p < 0.05) only in gill tissue. Other significant changes were observed in GR activity in gill in both PAA exposed groups, while GR activity in liver remained unchanged. There was no significant difference in the count of micronuclei between control and exposed fish. Haemorrhage, fusion of primary lamellae, degeneration of secondary lamellae, some clubbing on primary and secondary lamellae tips, and lifting of epithelial cells were found in

  1. Is Boric Acid Toxic to Reproduction in Humans? Assessment of the Animal Reproductive Toxicity Data and Epidemiological Study Results.

    PubMed

    Duydu, Yalçın; Başaran, Nurşen; Ustündağ, Aylin; Aydın, Sevtap; Undeğer, Ulkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Brita Schulze; Golka, Klaus; Bolt, Hermann Maximilian

    2016-01-01

    Boric acid and sodium borates are classified as toxic to reproduction in the CLP Regulation under "Category 1B" with the hazard statement of "H360FD". This classification is based on the reprotoxic effects of boric acid and sodium borates in animal experiments at high doses. However, boron mediated reprotoxic effects have not been proven in epidemiological studies so far. The epidemiological study performed in Bandırma boric acid production plant is the most comprehensive published study in this field with 204 voluntarily participated male workers. Sperm quality parameters (sperm morphology, concentration and motility parameters), FSH, LH and testosterone levels were determined in all participated employees as the reproductive toxicity biomarkers of males. However, boron mediated unfavorable effects on reproduction in male workers have not been determined even in the workers under very high daily boron exposure (0.21 mg B/kg-bw/day) conditions. The NOAEL for rat reproductive toxicity is equivalent to a blood boron level of 2020 ng/g. This level is higher than the mean blood boron concentration (223.89 ± 69.49 ng/g) of the high exposure group workers in Bandırma boric acid production plant (Turkey) by a factor of 9. Accordingly, classifying boric acid and sodium borates under "Category 1B" as "presumed reproductive human toxicant in the CLP regulation seems scientifically not reasonable. The results of the epidemiological studies (including the study performed in China) support for a down-classification of boric acid from the category 1B, H360FD to category 2, H361d, (suspected of damaging the unborn child).

  2. Sirtuin1 Regulates the Stem Cell Therapeutic Effects on Regenerative Capability for Treating Severe Heart Failure in a Juvenile Animal Model.

    PubMed

    Ozawa, Hideto; Miyagawa, Shigeru; Fukushima, Satsuki; Itoh, Emiko; Harada, Akima; Saito, Atsuhiro; Ueno, Takayoshi; Toda, Koichi; Kuratani, Toru; Sawa, Yoshiki

    2016-09-01

    This study hypothesized that autologous cell transplantation therapy could have greater therapeutic efficacy in juvenile patients than in adult patients, related to differences in sirtuin1 (SIRT1) expression in transplanted cells. A model of heart failure was established in mini-pigs by using coronary artery occlusion. Stem cell cultures were established from juvenile and adult mini-pigs. The cells were prepared as cell sheets and transplanted into corresponding adult or juvenile mini-pigs, and the therapeutic effects were examined in vivo and in vitro. Next, SIRT1 knockdown cells were established using small interfering RNAs for SIRT1, and the therapeutic effects of the cells were examined in vitro and in vivo in Lewis rat models of heart failure. Cardiac function showed significantly more improvement in juvenile than in adult pigs. Histologic analysis revealed significant reduction of myocardial fibrosis and hypertrophic response in juvenile pigs. In vitro analysis demonstrated that doubling time was significantly shorter, the ratio of Ki67-positive cells was significantly greater, and the expression of SIRT1, hypoxia-induced factor-1α, hepatocyte growth factor, and stromal cell-derived factor-1 was significantly upregulated in juvenile cells. SIRT1 knockdown cells showed decreased proliferation and cytokine release potential compared with wild-type cells. Transplantation of SIRT1 knockdown stem cell sheets showed lesser improvement of cardiac function after severe heart failure in Lewis rats than in controls. Sirtuin1 expression in transplanted cells enhances the skeletal stem cell sheet therapeutic effects for treating severe heart failure in a juvenile animal model. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Fish meal in animal feed and human exposure to persistent bioaccumulative and toxic substances.

    PubMed

    Dórea, José G

    2006-11-01

    Persistent and bioaccumulative toxic substances (PBTSs) that end up in fish are health hazards and the object of fish-consumption advisories. Some of these substances are present as extraneous contaminants, e.g., man-made lipophilic pollutants such as organohalogen pollutants, and others such as monomethyl mercury can be considered naturally occurring. Omnivores (e.g., poultry and swine) and especially ruminants that are fed contaminated fish meal can pass monomethyl mercury and organohalogen pollutants to eggs, meat, and dairy products. Differences in fish meal PBTS profiles and farm animal (e.g., poultry, swine, cattle, and farmed fish) physiology modulate PBTSs in animal products. Fish-consumption advisories issued to protect human health do not extend to fish by-products fed to farmed animals. Animals (especially farmed fish) that are fed fish meal can bioconcentrate monomethyl mercury in protein matrices, and organohalogen pollutants can be passed on in the fat components of derived foods. Policies to decrease exposure to monomethyl mercury and organohalogen pollutants must consider farming practices that use fish by-products. A risk assessment of toxic contaminants in fish meal may indicate that food safety objectives must consider the human health impact of foods derived from animals fed contaminated meal.

  4. Animal models to assess the toxicity, immunogenicity and effectiveness of candidate influenza vaccines.

    PubMed

    Eichelberger, Maryna C; Green, Martin D

    2011-09-01

    Every year, > 100 million doses of licensed influenza vaccine are administered worldwide, with relatively few serious adverse events reported. Initiatives to manufacture influenza vaccines on different platforms have come about to ensure timely production of strain-specific as well as universal vaccines. To prevent adverse events that may be associated with these new vaccines, it is important to evaluate the toxicity of new formulations in animal models. This review outlines preclinical studies that evaluate safety, immunogenicity and effectiveness of novel products to support further development and clinical trials. This has been done through a review of the latest literature describing vaccines under development. The objective of preclinical safety tests is to demonstrate the absence of toxic contaminants and adventitious agents. Additional tests that characterize vaccine content more completely, or demonstrate the absence of exacerbated disease following virus challenge in vaccinated animals, may provide additional data to ensure the safety of new vaccine strategies.

  5. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    NASA Astrophysics Data System (ADS)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  6. Consensus report on the future of animal-free systemic toxicity testing.

    PubMed

    Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna-Maria; Schwarz, Michael; Stephens, Martin; Taalman, Rob; Knudsen, Thomas B; McKim, James; Harris, Georgina; Pamies, David; Hartung, Thomas

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Century in 2007. It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity and allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics) (Fig. 1). CAAT-Europe assembled experts from Europe, America and Asia to design a scientific roadmap for future risk assessment approaches and the outcome was then further discussed and refined in two consensus meetings with over 200 stakeholders. The key recommendations include: focusing on improving existing methods rather than favoring de novo design; combining hazard testing with toxicokinetics predictions; developing integrated test strategies; incorporating new high content endpoints to classical assays; evolving test validation procedures; promoting collaboration and data-sharing of different industrial sectors; integrating new disciplines, such as systems biology and high throughput screening; and involving regulators early on in the test development process. A focus on data quality, combined with increased attention to the scientific background of a test method, will be important drivers. Information from each test system should be mapped along adverse outcome pathways. Finally, quantitative information on all factors and key events will be fed into systems biology models that allow a probabilistic risk assessment with flexible

  7. Acute and chronic nitrite toxicity in juvenile pike-perch (Sander lucioperca) and its compensation by chloride.

    PubMed

    Wuertz, S; Schulze, S G E; Eberhardt, U; Schulz, C; Schroeder, J P

    2013-05-01

    Pike-perch Sander lucioperca is currently considered as one of the most promising candidates for production in freshwater recirculation aquaculture systems (RAS). Here, due to the lack of studies on nitrite (NO(2)(-)) toxicity in pike-perch, a flow-through exposure at 0, 0.44, 0.88, 1.75, 3.5, 7, 14 and 28 mg/L NO(2)(-)-N was carried out to determine the acute and chronic toxicity over a period of 32 days. In juvenile pike-perch, 120 h LC(50) was 6.1mg/L NO(2)(-)-N and at ≥14 mg/L NO(2)(-)-N all fish had died within 24 h. Chronic exposure revealed a significant build up of NO(2)(-) in the plasma as well as in the muscles at ≥0.44 mg/L NO(2)(-)-N peaking in fish exposed to the highest concentration of 3.5 mg/L NO(2)(-)-N after 32 days. Still, due to high individual variation methemoglobin (MetHb) was only significantly increased (p<0.01) at 3.5 mg/L NO(2)(-)-N. No adverse effects on red blood cells (RBC) and hematocrit were observed in any of the treatments. In a second experiment, compensation of NO(2)(-) toxicity at increasing chloride concentrations (40 (freshwater), 65, 90, 140, 240, 440 mg/L Cl(-)) was observed at a constant exposure of 10 mg/L NO(2)(-)-N for 42 days. At ≥240 mg/L Cl(-), NO(2)(-) build-up in blood plasma and muscle was completely inhibited. At lower Cl(-) concentrations (≤140 mg/L), NO(2)(-) was significantly increased in plasma, but only insignificantly elevated in muscle due to high individual variation. MetHb was increased significantly difference only at 40 mg/L Cl(-) (freshwater control) compared to the control. Again, high individual variations were observed. As a conclusion, S. lucioperca is moderately sensitive towards NO(2)(-) and acceptable levels in RAS should hence not exceed 1.75 mg/L NO(2)(-)-N to avoid MetHb formation. However, based on the 120 h LC(50) and a factor of 0.01 according to Sprague (1971), a NO(2)(-) concentration of ≤0.061 mg/L NO(2)(-)-N is considered as "safe." Thereby, no NO(2)(-) should accumulate in

  8. Maintaining tissue selenium species distribution as a potential defense mechanism against methylmercury toxicity in juvenile white sturgeon (Acipenser transmontanus).

    PubMed

    Huang, Susie Shih-Yin; Hung, Silas S O; Chan, Hing Man

    2014-11-01

    Selenium (Se) has been shown to antagonize mercury (Hg) toxicity. We have previously demonstrated that orally intubated selenomethionine (SeMet) and methylmercury (MeHg) reduced tissue Se accumulation, as well as blood and kidney Hg concentrations in juvenile white sturgeon (Acipenser transmontanus). However, the form of Se accumulated is not known. In this study, three organoseleniums: selenocysteine (Sec), Se-methyl-selenocysteine (MSeCys), and SeMet and two inorganic Se species: selenate and selenite were determined and quantified in the blood at different post-intubation periods (12, 24, 48h) and in the muscle, liver, and kidneys at 48h in white sturgeon orally intubated with a single dose of control (carrier), SeMet (500μg Se/kg body weight; BW), MeHg (850μg Hg/kg BW), and both (Se+Hg; at 500μg Se/kg and 850μg Hg/kg BW). When only SeMet was intubated, the accumulative/unmodified pathway took precedent in the blood, white muscle, liver, and kidneys. In the presence of MeHg, however, active metabolic transformation and de novo synthesis of biologically active Se forms are seen in the liver and kidneys, as indicated by a gradual increase in blood Sec:SeMet ratios and Se metabolites. In the white muscle, mobilization of endogenous Se storage by MeHg is supported by the absence of tissue SeMet and detectable levels of blood SeMet. In contrast, co-intubation with SeMet increased muscle SeMet. The high levels of unknown Se metabolites and detectable levels of selenite in the kidney reflect its role as the major excretory organ for Se. Selenium metabolism is highly regulated in the kidneys, as Se speciation was not affected by MeHg or by its co-intubation with SeMet. In the Se+Hg group, the proportion of SeMet in the liver has decreased to nearly 1/8th of that of the SeMet only group, resulting in a more similar selenocompound distribution profile to that of the MeHg only group. This is likely due to the increased need for Se metabolites necessary for Me

  9. Statistical studies of animal response data from USF toxicity screening test method

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Machado, A. M.

    1978-01-01

    Statistical examination of animal response data obtained using Procedure B of the USF toxicity screening test method indicates that the data deviate only slightly from a normal or Gaussian distribution. This slight departure from normality is not expected to invalidate conclusions based on theoretical statistics. Comparison of times to staggering, convulsions, collapse, and death as endpoints shows that time to death appears to be the most reliable endpoint because it offers the lowest probability of missed observations and premature judgements.

  10. Statistical studies of animal response data from USF toxicity screening test method

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Machado, A. M.

    1978-01-01

    Statistical examination of animal response data obtained using Procedure B of the USF toxicity screening test method indicates that the data deviate only slightly from a normal or Gaussian distribution. This slight departure from normality is not expected to invalidate conclusions based on theoretical statistics. Comparison of times to staggering, convulsions, collapse, and death as endpoints shows that time to death appears to be the most reliable endpoint because it offers the lowest probability of missed observations and premature judgements.

  11. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review.

    PubMed

    Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F; Huo, Li-Jun

    2017-01-01

    In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

  12. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

    PubMed Central

    Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F.; Huo, Li-Jun

    2017-01-01

    In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations. PMID:28928662

  13. Acute toxicity and sublethal effects of fipronil on detoxification enzymes in juvenile zebrafish (Danio rerio).

    PubMed

    Wu, Haihua; Gao, Cuie; Guo, Yaping; Zhang, Yuping; Zhang, Jianzhen; Ma, Enbo

    2014-10-01

    The acute toxicity of fipronil and its sublethal effects on detoxification enzymes (carboxylesterases (CarEs), glutathione S-transferases (GSTs), and 7-ethoxycoumarin O-deethylase (ECOD)) in zebrafish (Danio rerio) were investigated. The results indicated that the 24-h LC50 of fipronil for zebrafish was 220.4 μg/L (95% CI: 173.7-272.4 μg/L). Sublethal concentrations of fipronil did not cause significant changes in CarEs activities. In the liver and muscle tissues, GST activities at the tested concentrations did not significantly differ from those in the control. In the brain and gill tissues, GST activities at a concentration of 4 μg/L were significantly lower than those at a concentration of 2 μg/L. The results suggest that CarEs and GSTs were not suitable biomarkers for fipronil effects in D. rerio. A significant induction in the ECOD activities in the brain, gill, liver, and muscle tissues was observed compared with the control. Moreover, the dose-dependent responses of the ECOD activity were observed after treatment with sublethal concentrations of fipronil in the range of 2-20 μg/L. The results suggested that ECOD could be a suitable biomarker of fipronil effects in D. rerio. Copyright © 2014. Published by Elsevier Inc.

  14. Ammonia toxicity induces glutamine accumulation, oxidative stress and immunosuppression in juvenile yellow catfish Pelteobagrus fulvidraco.

    PubMed

    Li, Ming; Gong, Shiyan; Li, Qing; Yuan, Lixia; Meng, Fanxing; Wang, Rixin

    2016-01-01

    A study was carried to test the response of yellow catfish for 28 days under two ammonia concentrations. Weight gain of fish exposure to high and low ammonia abruptly increased at day 3. There were no significant changes in fish physiological indexes and immune responses at different times during 28-day exposure to low ammonia. Fish physiological indexes and immune responses in the treatment of high ammonia were lower than those of fish in the treatment of low ammonia. When fish were exposed to high ammonia, the ammonia concentration in the brain increased by 19-fold on day 1. By comparison, liver ammonia concentration reached its highest level much earlier at hour 12. In spite of a significant increase in brain and liver glutamine concentration, there was no significant change in glutamate level throughout the 28-day period. The total superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase (GR) activities in the brain gradually decreased from hour 0 to day 28. Liver SOD, GPX and GR activities reached the highest levels at hour 12, and then gradually decreased. Thiobarbituric acid reactive substance brain and liver content gradually increased throughout the 28-day period. Lysozyme, acid phosphatase and alkaline phosphatase activities in the liver reached exceptionally low levels after day 14. This study indicated that glutamine accumulation in the brain was not the major cause of ammonia poisoning, the toxic reactive oxygen species is not fully counter acted by the antioxidant enzymes and immunosuppression is a process of gradual accumulation of immunosuppressive factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Comparative ovarian microarray analysis of juvenile hormone-responsive genes in water flea Daphnia magna: potential targets for toxicity.

    PubMed

    Toyota, Kenji; Williams, Timothy D; Sato, Tomomi; Tatarazako, Norihisa; Iguchi, Taisen

    2017-03-01

    The freshwater zooplankton Daphnia magna has been extensively employed in chemical toxicity tests such as OECD Test Guidelines 202 and 211. Previously, it has been demonstrated that the treatment of juvenile hormones (JHs) or their analogues to female daphnids can induce male offspring production. Based on this finding, a rapid screening method for detection of chemicals with JH-activity was recently developed using adult D. magna. This screening system determines whether a chemical has JH-activity by investigating the male offspring inducibility. Although this is an efficient high-throughput short-term screening system, much remains to be discovered about JH-responsive pathways in the ovary, and whether different JH-activators act via the same mechanism. JH-responsive genes in the ovary including developing oocytes are still largely undescribed. Here, we conducted comparative microarray analyses using ovaries from Daphnia magna treated with fenoxycarb (Fx; artificial JH agonist) or methyl farnesoate (MF; a putative innate JH in daphnids) to elucidate responses to JH agonists in the ovary, including developing oocytes, at a JH-sensitive period for male sex determination. We demonstrate that induction of hemoglobin genes is a well-conserved response to JH even in the ovary, and a potential adverse effect of JH agonist is suppression of vitellogenin gene expression, that might cause reduction of offspring number. This is the first report demonstrating different transcriptomics profiles from MF and an artificial JH agonist in D. magna ovary, improving understanding the tissue-specific mode-of-action of JH. Copyright © 2016 John Wiley & Sons, Ltd.

  16. In vitro cytotoxicity testing of 30 reference chemicals to predict acute human and animal toxicity

    SciTech Connect

    Barile, F.A.; Arjun, S.; Borges, L. )

    1991-03-11

    This study was conducted in cooperation with the Scandinavian Society of Cell Toxicology, as part of the Multicenter Evaluation for In Vitro Cytotoxicity (MEIC), and was designed to develop an in vitro model for predicting acute human and animal toxicity. The technique relies on the ability of cultured transformed rat lung epithelial cells (L2) to incorporate radiolabled amino acids into newly synthesized proteins in the absence or presence of increasing doses of the test chemical, during a 24-hr incubation. IC50 values were extrapolated from the dose-response curves after linear regression analysis. Human toxic blood concentrations estimated from rodent LD50 values suggest that our experimental IC50's are in close correlation with the former. Validation of the data by the MEIC committee shows that our IC50 values predicted human lethal dosage as efficient as rodent LD50's. It is anticipated that this and related procedures may supplement or replace currently used animal protocols for predicting human toxicity.

  17. Does the presence of microplastics influence the acute toxicity of chromium(VI) to early juveniles of the common goby (Pomatoschistus microps)? A study with juveniles from two wild estuarine populations.

    PubMed

    Luís, Luís G; Ferreira, Pedro; Fonte, Elsa; Oliveira, Miguel; Guilhermino, Lúcia

    2015-07-01

    Toxicological interactions between microplastics (MP) and other environmental contaminants are of grave concern. Here, the potential influence of MP in the short-term toxicity of chromium to early juveniles of Pomatoschistus microps was investigated. Three null hypotheses were tested: (1) exposure to Cr(VI) concentrations in the low ppm range does not induce toxic effects on juveniles; (2) the presence of microplastics in the water does not influence the acute toxicity of Cr(VI) to juveniles; (3) the environmental conditions of the natural habitat where fish developed do not influence their sensitivity to Cr(VI)-induced acute stress. Fish were collected in the estuaries of Minho (M-est) and Lima (L-est) Rivers (NW Iberian Peninsula) that have several abiotic differences, including in the water and sediment concentrations of various environmental contaminants. After acclimatization to laboratory conditions, two 96h acute bioassays were carried out with juveniles from both estuaries to: (i) investigate the effects of Cr(VI) alone; (ii) investigate the effects of Cr(VI) in the presence of MP (polyethylene spheres 1-5μm ∅). Cr(VI) alone induced mortality (96h-LC50s: 14.4-30.5mg/l) and significantly decreased fish predatory performance (≤74%). Thus, in the range of concentrations tested (5.6-28.4mg/l) Cr(VI) was found to be toxic to P. microps early juveniles, therefore, we rejected hypothesis 1. Under simultaneous exposure to Cr(VI) and MP, a significant decrease of the predatory performance (≤67%) and a significant inhibition of AChE activity (≤31%) were found. AChE inhibition was not observed in the test with Cr(VI) alone and MP alone caused an AChE inhibition ≤21%. Mixture treatments containing Cr(VI) concentration ≥3.9mg/l significantly increased LPO levels in L-est fish, an effect that was not observed under Cr(VI) or MP single exposures. Thus, toxicological interactions between Cr(VI) and MP occurred, therefore, we rejected hypothesis 2. In the

  18. Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?

    PubMed Central

    Munday, Rex

    2013-01-01

    Okadaic acid (OA) and its derivatives, which are produced by dinoflagellates of the genera Prorocentrum and Dinophysis, are responsible for diarrhetic shellfish poisoning in humans. In laboratory animals, these toxins cause epithelial damage and fluid accumulation in the gastrointestinal tract, and at high doses, they cause death. These substances have also been shown to be tumour promoters, and when injected into the brains of rodents, OA induces neuronal damage reminiscent of that seen in Alzheimer’s disease. OA and certain of its derivatives are potent inhibitors of protein phosphatases, which play many roles in cellular metabolism. In 1990, it was suggested that inhibition of these enzymes was responsible for the diarrhetic effect of these toxins. It is now repeatedly stated in the literature that protein phosphatase inhibition is not only responsible for the intestinal effects of OA and derivatives, but also for their acute toxic effects, their tumour promoting activity and their neuronal toxicity. In the present review, the evidence for the involvement of protein phosphatase inhibition in the induction of the toxic effects of OA and its derivatives is examined, with the conclusion that the mechanism of toxicity of these substances requires re-evaluation. PMID:23381142

  19. Predicting human drug toxicity and safety via animal tests: can any one species predict drug toxicity in any other, and do monkeys help?

    PubMed

    Bailey, Jarrod; Thew, Michelle; Balls, Michael

    2015-12-01

    Animals are still widely used in drug development and safety tests, despite evidence for their lack of predictive value. In this regard, we recently showed, by producing Likelihood Ratios (LRs) for an extensive data set of over 3,000 drugs with both animal and human data, that the absence of toxicity in animals provides little or virtually no evidential weight that adverse drug reactions will also be absent in humans. While our analyses suggest that the presence of toxicity in one species may sometimes add evidential weight for risk of toxicity in another, the LRs are extremely inconsistent, varying substantially for different classes of drugs. Here, we present further data from analyses of other species pairs, including non-human primates (NHPs), which support our previous conclusions, and also show in particular that test results inferring an absence of toxicity in one species provide no evidential weight with regard to toxicity in any other species, even when data from NHPs and humans are compared. Our results for species including humans, NHPs, dogs, mice, rabbits, and rats, have major implications for the value of animal tests in predicting human toxicity, and demand that human-focused alternative methods are adopted in their place as a matter of urgency.

  20. Using Online Tool (iPrior) for Modeling ToxCast™ Assays Towards Prioritization of Animal Toxicity Testing.

    PubMed

    Abdelaziz, Ahmed; Sushko, Yurii; Novotarskyi, Sergii; Körner, Robert; Brandmaier, Stefan; Tetko, Igor V

    2015-01-01

    The use of long-term animal studies for human and environmental toxicity estimation is more discouraged than ever before. Alternative models for toxicity prediction, including QSAR studies, are gaining more ground. A recent approach is to combine in vitro chemical profiling and in silico chemical descriptors with the knowledge about toxicity pathways to derive a unique signature for toxicity endpoints. In this study we investigate the ToxCast™ Phase I data regarding their ability to predict long-term animal toxicity. We investigated thousands of models constructed in an effort to predict 61 toxicity endpoints using multiple descriptor packages and hundreds of in vitro assays. We investigated the use of in vitro assays and biochemical pathways on model performance. We identified 10 toxicity endpoints where biologically derived descriptors from in vitro assays or pathway perturbations improved the model prediction ability. In vivo toxicity endpoints proved generally challenging to model. Few models were possible to readily model with a balanced accuracy (BA) above 0.7. We also constructed in silico models to predict the outcome of 144 in vitro assays. This showed better statistical metrics with 79 out of 144 assays having median balanced accuracy above 0.7. This suggests that the in vitro datasets have a better modelability than in vivo animal toxicities for the given datasets. Moreover, we published an online platform (http://iprior.ochem.eu) that automates large-scale model building and analysis.

  1. Male reproductive toxicity of lead in animals and humans. ASCLEPIOS Study Group

    PubMed Central

    Apostoli, P.; Kiss, P.; Porru, S.; Bonde, J. P.; Vanhoorne, M.

    1998-01-01

    OBJECTIVE: To critically review the literature on male reproductive toxicity of lead in animals and humans. METHODS: A systematic literature search identified a total of 32 experimental studies in animals and 22 epidemiological studies, one case report on humans and five review articles or documents. The studies were evaluated by paying attention mainly to sample size, study design, exposure, and dose characterisation, analytical method standardisation, and quality assurance. RESULTS: Several studies on rats and other rodents indicated that blood lead concentrations > 30-40 micrograms/dl were associated with impairment of spermatogenesis and reduced concentrations of androgens. However, other animal studies, mainly about histopathological, spermatozoal, and hormonal end points, indicated that certain species and strains were quite resistant to the reproductive toxicity of lead and that different testicular lead concentrations could account for these differences. The human studies focused mainly on semen quality, endocrine function, and birth rates in occupationally exposed subjects, and showed that exposure to concentrations of inorganic lead > 40 micrograms/dl in blood impaired male reproductive function by reducing sperm count, volume, and density, or changing sperm motility and morphology. No relevant effects were detected on endocrine profile. CONCLUSION: Several factors make it difficult to extrapolate the animal data to the human situation. The difficulties are mainly due to differences between species in reproductive end points and to the level of exposure. Concentrations of blood lead > 40 micrograms/dl seemed to be associated with a decrease in sperm count, volume, motility, and morphological alterations and a possible modest effect on endocrine profile. Dose-response relation, in particular at a threshold level, is poorly understood, and site, mode, or mechanism of action are unknown. Also, the effects were not always the same or associated in the same on

  2. Juvenile angiofibroma

    MedlinePlus

    Nasal tumor; Angiofibroma - juvenile; Benign nasal tumor; Juvenile nasal angiofibroma; JNA ... Juvenile angiofibroma is not very common. It is most often found in adolescent boys. The tumor contains ...

  3. Body-on-a-chip systems for animal-free toxicity testing.

    PubMed

    Mahler, Gretchen J; Esch, Mandy B; Stokol, Tracy; Hickman, James J; Shuler, Michael L

    2016-10-01

    Body-on-a-chip systems replicate the size relationships of organs, blood distribution and blood flow, in accordance with human physiology. When operated with tissues derived from human cell sources, these systems are capable of simulating human metabolism, including the conversion of a prodrug to its effective metabolite, as well as its subsequent therapeutic actions and toxic side-effects. The system also permits the measurement of human tissue electrical and mechanical reactions, which provide a measure of functional response. Since these devices can be operated with human tissue samples or with in vitro tissues derived from induced pluripotent stem cells (iPS), they can play a significant role in determining the success of new pharmaceuticals, without resorting to the use of animals. By providing a platform for testing in the context of human metabolism, as opposed to animal models, the systems have the potential to eliminate the use of animals in preclinical trials. This article will review progress made and work achieved as a direct result of the 2015 Lush Science Prize in support of animal-free testing. 2016 FRAME.

  4. Aspergillus fumigatus toxicity and gliotoxin levels in feedstuff for domestic animals and pets in Argentina.

    PubMed

    Pena, G A; Pereyra, C M; Armando, M R; Chiacchiera, S M; Magnoli, C E; Orlando, J L; Dalcero, A M; Rosa, C A R; Cavaglieri, L R

    2010-01-01

    To evaluate gliotoxin production by Aspergillus fumigatus strains isolated from feedstuff intended for domestic animals and pets, and to determine the amount of gliotoxin in these substrates. A total of 150 feedstuff samples were collected. They were composed of 30 samples each of five different feed types (pigs, poultry, cattle, horse and pets). Aspergillus fumigatus gliotoxin production ability and gliotoxin presence in feedstuff was determined by HPLC. Aspergillus fumigatus strains were isolated from all of the tested samples. Strains from cattle, horses and pet food were able to produce gliotoxin. Corn silage samples intended for cattle did not show gliotoxin contamination. All the other tested samples had gliotoxin levels ranging from 29 to 209 microg g(-1). Horse and poultry feed samples had the greatest contamination frequency. Feed samples contaminated with gliotoxin are potentially toxic to animals. The presence of gliotoxin could affect animal productivity and health. Moreover, there are risks of contamination to farm workers handling improperly stored animal feed. Aspergillus fumigatus strains isolated from different sources should be investigated to determine prevention and control strategies.

  5. Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysis.

    PubMed

    Fettiplace, Michael R; McCabe, Daniel J

    2017-08-01

    The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models. We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran's Q for heterogeneity and I(2) to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger's test to assess for publication bias in studies. Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1-0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models. Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid.

  6. Effect of indigenous animals on chronic end points in freshwater sediment toxicity tests

    SciTech Connect

    Reynoldson, T.B.; Day, K.E.; Clarke, C.; Milani, D. )

    1994-06-01

    Sediment toxicity tests were conducted using three species of benthic invertebrates, Chironomus riparius, Hyalella azteca, and Hexagenia limbata, with various densities of the oligochaete worm Tubifex tubifex. It was shown that indigenous animals, simulated by the presence of Tubifex tubifex, did not affect survival of the test species (P [>=] 0.05) but did reduce growth in all three test species and in two species at the lowest tested densities, equivalent to 1,460 worms per square meter. At densities of Tubifex tubifex equivalent to 20,000 m[sup [minus]2], the growth of Chironomus riparius was reduced by >90%, Hyalella azteca by >60%, and Hexagenia limbata by almost 50%. The densities of oligochaetes are equivalent to those found in many contaminated sites. Therefore, it is concluded that the presence of indigenous organisms can confound the interpretation of toxicity test results, based on chronic end points. It is recommended that removal of organisms by considered before toxicity tests are conducted with freshwater sediments from sites with large populations of benthic invertebrates, especially oligochaete worms.

  7. Analgesic, antipyretic, anti-inflammatory and toxic effects of andrographolide derivatives in experimental animals.

    PubMed

    Suebsasana, Supawadee; Pongnaratorn, Panicha; Sattayasai, Jintana; Arkaravichien, Tarinee; Tiamkao, Siriporn; Aromdee, Chantana

    2009-09-01

    Andrographolide (1) and 14-deoxy-11,12-didehydroandrographolide (2) are active constituents of Andrographis paniculata (Burm. f.), family Acanthaceae. A. paniculata extracts are reported to have antiviral, antipyretic, immunostimulant and anticancer activities. In this study, 1 and its 14-acetyl- (4) and 3,19-isopropylidenyl- (3) derivatives, as well as 2 and its 3,19-dipalmitoyl-derivative (5), were intraperitoneally tested for their analgesic, antipyretic, anti-inflammatory and acute toxicity effects in animal models. Analgesic effects were tested in mice using hot plate and writhing tests to distinguish the central and peripheral effects, respectively. The results showed that, at 4 mg/kg, all tested substances have significant analgesic effects, and the highest potency was seen with 3, 4 and 5. Increasing the dose of 3 and 5 to 8 mg/kg did not increase the analgesic effect. In the writhing test, 3 and 5, but not 1, showed significant results. In a baker's yeast-induced fever model, 3 and 5 significantly reduced rats' rectal temperature (p < 0.05). In a carrageenan-induced inflammation model, 1, 3 and 5 significantly reduced rats' paw volume. Doses of 3 and 5 up to 100 mg/kg did not show any serious toxic effects. From this study, 3 and 5 are the most interesting derivatives, showing much greater potency than their parent compounds. These could be further developed as analgesic, antipyretic and anti-inflammatory agents, without any serious toxicity.

  8. Aquatic toxicity of four veterinary drugs commonly applied in fish farming and animal husbandry.

    PubMed

    Kołodziejska, Marta; Maszkowska, Joanna; Białk-Bielińska, Anna; Steudte, Stephanie; Kumirska, Jolanta; Stepnowski, Piotr; Stolte, Stefan

    2013-08-01

    Doramectin (DOR), metronidazole (MET), florfenicol (FLO), and oxytetracycline (OXT) are among the most widely used veterinary drugs in animal husbandry or in aquaculture. Contamination of the environment by these pharmaceuticals has given cause for concern in recent years. Even though their toxicity has been thoroughly analyzed, knowledge of their ecotoxicity is still limited. We investigated their aquatic toxicity using tests with marine bacteria (Vibrio fischeri), green algae (Scenedesmus vacuolatus), duckweed (Lemna minor) and crustaceans (Daphnia magna). All the ecotoxicological tests were supported by chemical analyses to confirm the exposure concentrations of the pharmaceuticals used in the toxicity experiments, since deviations from the nominal concentration can result in underestimation of biological effects. It was found that OXT and FLO have a stronger adverse effect on duckweed (EC50=3.26 and 2.96mgL(-1) respectively) and green algae (EC50=40.4 and 18.0mgL(-1)) than on bacteria (EC50=108 and 29.4mgL(-1)) and crustaceans (EC50=114 and 337mgL(-1)), whereas MET did not exhibit any adverse effect in the tested concentration range. For DOR a very low EC50 of 6.37×10(-5)mgL(-1) towards D. magna was determined, which is five orders of magnitude lower than values known for the toxic reference compound K2Cr2O7. Our data show the strong influence of certain veterinary drugs on aquatic organisms and contribute to a sound assessment of the environmental hazards posed by commonly used pharmaceuticals.

  9. A new mechanism of macrophyte mitigation: how submerged plants reduce malathion's acute toxicity to aquatic animals.

    PubMed

    Brogan, William R; Relyea, Rick A

    2014-08-01

    A growing body of evidence suggests that aquatic plants can mitigate the toxicity of insecticides to sensitive aquatic animals. The current paradigm is that this ability is driven primarily by insecticide sorption to plant tissues, especially for hydrophobic compounds. However, recent work shows that submerged plants can strongly mitigate the toxicity of the relatively hydrophilic insecticide malathion, despite the fact that this compound exhibits a slow sorption rate to plants. To examine this disparity, we tested the hypothesis that the mitigating effect of submerged plants on malathion's toxicity is driven primarily by the increased water pH from plant photosynthesis causing the hydrolysis of malathion, rather than by sorption. To do this, we compared zooplankton (Daphnia magna) survival across five environmentally relevant malathion concentrations (0, 1, 4, 6, or 36 μg L(-1)) in test containers where we chemically manipulated water pH in the absence of plants or added the submerged plant (Elodea canadensis) but manipulated plant photosynthetic activity via shading or no shading. We discovered that malathion was equally lethal to Daphnia at all concentrations tested when photosynthetically inactive (i.e. shaded) plants were present (pH at time of dosing=7.8) or when pH was chemically decreased (pH=7.7). In contrast, when photosynthetically active (i.e. unshaded) plants were present (pH=9.8) or when pH was chemically increased (pH=9.5), the effects of 4 and 6 μg L(-1) of malathion on Daphnia were mitigated strongly and to an equal degree. These results demonstrate that the mitigating effect of submerged plants on malathion's toxicity can be explained entirely by a mechanism of photosynthesizing plants causing an increase in water pH, resulting in rapid malathion hydrolysis. Our findings suggest that current ecotoxicological models and phytoremediation strategies may be overlooking a critical mechanism for mitigating pesticides. Copyright © 2014 Elsevier Ltd

  10. Invited review: Efficacy, metabolism, and toxic responses to chlorate salts in food and laboratory animals.

    PubMed

    Smith, D J; Oliver, C E; Taylor, J B; Anderson, R C

    2012-11-01

    For over 100 yr, scientists have explored uses of sodium chlorate in agricultural applications. Sodium chlorate is a strong oxidizer, and thus can be very hazardous when not handled accordingly. Nevertheless, late 19th century agriculturists and scientists attempted to exploit the chemical properties of sodium chlorate as an herbicide and food preservative. It is the herbicidal utility that led to subsequent use of sodium chlorate in the agricultural industry since then. However, in 2000, USDA-ARS scientists proposed a new and targeted use of sodium chlorate against enterobacteria in food animal production. Specifically, when orally dosed in to cattle (Bos taurus), swine (Sus scrofa), broilers (Gallus gallus), turkeys (Meleagris gallopavo), and sheep (Ovis aries), chlorate reduced the fecal shedding of common enteropathogens of the Enterobacteriaceae family. Subsequent to this discovery, the efficacy of chlorate salts has been demonstrated in numerous production classes within species. Doses of sodium chlorate as low as 30 mg/kg BW, but typically 50 to 150 mg/kg BW, have been used to demonstrate efficacy against pathogens. Single or short-duration (<3 d) exposures to oral chlorate at concentrations < 150 mg/kg BW have not produced acute toxicity or clinical signs (labored breathing, methemoglobinemia) in food animals. In all species studied to date, the major biotransformation product of chlorate is chloride ion; chlorite is not present in tissues or excreta of chlorate dosed animals. Chlorate is rapidly eliminated in ruminants and nonruminants, primarily in urine; likewise, residual chlorate in tissues depletes rapidly. Application of any new chemical entity to food animal production carries with it a responsibility to understand adverse reactions that intended and nonintended exposures may have in target and (or) nontarget animals and an understanding of the pathways of elimination that occur after exposure. Therefore, the purpose of this review is to summarize

  11. Usefulness of sediment toxicity tests with estuarine plants and animals to indicate municipal and industrial effluent impact

    SciTech Connect

    Lewis, M.A.; Weber, D.E.

    1994-12-31

    The environmental impact of municipal and industrial effluents has been predicted from results from single species toxicity tests. The goal of these tests is to ensure that water quality criteria and the designated use of the waterbody is not impacted. Recently, the focus of some effluent toxicity evaluation has centered on determining the effluent impact on the sediment in the receiving water. This study evaluated the toxicities of several sediment samples collected above and below six outfalls to the Pensacola Bay system. Toxicities were determined using three macrophytic plants and four animal species. The sediments, with few exceptions, exhibited a low level of toxicity. The mysid shrimp was more sensitive than Ampelisca, Leptocheirus and the sheepshead minnow. The sensitivities of the plants, Echinochloa crusgalli, Scirpus robustus and Sesbania macrocarpa, were comparable to those of the animal species. The toxicity of time sediment, when compared to that of the effluent, determined using standard single species of plants and animals was less. Overall, the sediment toxicity tests were useful in providing insight on the impact of effluents. However, the application and usefulness of this assessment tool is highly dependent upon a variety of factors, including the geomorphological characteristics of the receiving waters.

  12. Effects of amiodarone on the pharmacokinetics and toxicity of digoxin in laboratory animals.

    PubMed

    Staneva-Stoytcheva, D; Kristeva, E

    1992-04-01

    Some pharmacokinetic interactions between digoxin and amiodarone were studied in experiments on rabbits. An increase of digoxin serum levels was established in amiodarone-treated rabbits (amiodarone 30 mg/kg s.c. for five days alone or together with digoxin). The calculated elimination half-life (t 1/2) and the area under the curve (AUC) of digoxin were increased and the digoxin clearance was decreased, being most pronounced in animals receiving amiodarone-digoxin combination for five days. There were no changes either in digoxin toxicity in amiodarone-treated guinea pigs or in serum levels of T4, T3 and TTH. The possible mechanisms of digoxin-amiodarone interactions are discussed.

  13. Effects of amiodarone on the pharmacokinetics and toxicity of digoxin in laboratory animals.

    PubMed

    Staneva-Stoytcheva, D; Kristeva, E

    1991-01-01

    Some pharmacokinetic interactions between digoxin and amiodarone were studied in experiments on rabbits. An increase of digoxin serum levels was established in amiodarone-treated rabbits (amiodarone 30 mg/kg s. c. for five days administered alone or together with digoxin). The calculated elimination half-life(t1/2) and the area under the curve (AUC) of digoxin were increased and the digoxin clearance was decreased, being most pronounced in animals receiving a combination of amiodarone and digoxin for five days. Changes were observed neither in the digoxin toxicity in amiodarone-treated guinea-pigs nor in the serum levels of T4, T3 and TTH. The possible mechanisms of the digoxin-amiodarone interactions are discussed.

  14. Toxicity and residue studies in dairy animals with firemaster FF-1 (polybrominated biphenyls).

    PubMed

    Robl, M G; Jenkins, D H; Wingender, R J; Gordon, D E

    1978-04-01

    Two studies (one in Holstein calves and one in Holstein cows) were conducted to determine potential toxicity and residue levels following oral ingestion of polybrominated biphenyls (PBB). The material was FireMaster FF-1. Administration was by gelatin capsules. Doses in calves were 0.1, 1.0, 10, or 100 mg/kg body weight, while doses in cows were equivalent to 0.01, 0.1, 1.0, or 10 ppm in the diet. The calves were sacrificed after 2, 4, 6, or 12 weeks. The cows were fed 158 or 228 days, and were then in a recovery period for 182 or 112 days. In the calf study, signs of toxicity were observed only in animals fed 100 mg/kg-day. Administration of 10 mg/kg-day or less for up to 12 weeks caused no overt signs of toxicity. Histologic studies were conducted upon selected organs and tissues taken at time of sacrifice. The only treatment-induced lesions among animals fed 0.1 mg/kg-day were minimal lesions in the kidney and skin in the one calf fed at this level for 12 weeks. Treatment-induced lesions were present in the kidneys, skin, and/or liver from some animals fed levels of 1.0 mg/kg-day and above. The relative severity of these lesions was related to the level and length of exposure. Treatment-associated changes were observed in the testes of all males in this study. The hypospermatogenesis observed was consistent with the age of the animals due to prepuberal development of the testes. No clinical signs of toxicity or histologic changes attributed to PBB were observed in the cows. Two cows were pregnant at the initiation of the study and give birth to normal, healthy calves during the study. These calves grew normally and appeared healthy when sacrificed at about 6 months of age. Residue levels were quantitated as the hexabromobiphenyl isomer (BP-6) which is the major isomer present in the PBB mixture. Tissue residue levels in calves increased with dose and duration of administration of PBB with highest levels being found in the fat. At 100 mg/kg the levels in fat were

  15. Selective cytoprotective effect of histamine on doxorubicin-induced hepatic and cardiac toxicity in animal models

    PubMed Central

    Lamas, DJMartinel; Nicoud, MB; Sterle, HA; Carabajal, E; Tesan, F; Perazzo, JC; Cremaschi, GA; Rivera, ES; Medina, VA

    2015-01-01

    The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5 mg/kg for rats and 1 mg/kg for mice, daily subcutaneous injection starting 24 h before treatment with Dox), Dox (2 mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox-induced cardiac and hepatic toxicity, and encourage the translation to clinical practice. PMID:27551485

  16. Targeting ATM ameliorates mutant Huntingtin toxicity in cell and animal models of Huntington's disease.

    PubMed

    Lu, Xiao-Hong; Mattis, Virginia B; Wang, Nan; Al-Ramahi, Ismael; van den Berg, Nick; Fratantoni, Silvina A; Waldvogel, Henry; Greiner, Erin; Osmand, Alex; Elzein, Karla; Xiao, Jingbo; Dijkstra, Sipke; de Pril, Remko; Vinters, Harry V; Faull, Richard; Signer, Ethan; Kwak, Seung; Marugan, Juan J; Botas, Juan; Fischer, David F; Svendsen, Clive N; Munoz-Sanjuan, Ignacio; Yang, X William

    2014-12-24

    Age-related neurodegenerative disorders including Alzheimer's disease and Huntington's disease (HD) consistently show elevated DNA damage, but the relevant molecular pathways in disease pathogenesis remain unclear. One attractive gene is that encoding the ataxia-telangiectasia mutated (ATM) protein, a kinase involved in the DNA damage response, apoptosis, and cellular homeostasis. Loss-of-function mutations in both alleles of ATM cause ataxia-telangiectasia in children, but heterozygous mutation carriers are disease-free. Persistently elevated ATM signaling has been demonstrated in Alzheimer's disease and in mouse models of other neurodegenerative diseases. We show that ATM signaling was consistently elevated in cells derived from HD mice and in brain tissue from HD mice and patients. ATM knockdown protected from toxicities induced by mutant Huntingtin (mHTT) fragments in mammalian cells and in transgenic Drosophila models. By crossing the murine Atm heterozygous null allele onto BACHD mice expressing full-length human mHTT, we show that genetic reduction of Atm gene dosage by one copy ameliorated multiple behavioral deficits and partially improved neuropathology. Small-molecule ATM inhibitors reduced mHTT-induced death of rat striatal neurons and induced pluripotent stem cells derived from HD patients. Our study provides converging genetic and pharmacological evidence that reduction of ATM signaling could ameliorate mHTT toxicity in cellular and animal models of HD, suggesting that ATM may be a useful therapeutic target for HD. Copyright © 2014, American Association for the Advancement of Science.

  17. Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and antioxidants activity in vitro.

    PubMed

    Mattei, R; Dias, R F; Espínola, E B; Carlini, E A; Barros, S B

    1998-03-01

    The effects on toxic and behavioral levels of guarana (Paullinia cupana) were assessed in rats and mice subsequent to acute and chronic administrations and were compared to those produced by Ginseng (Panax ginseng). Experimental parameters included tests for antioxidant capacity in vitro and measured in vivo, toxicological screening, progress in weight, motor activity, death rate, and histopathological examination of the viscera. Guarana showed an antioxidant effect because, even at low concentrations (1.2 microg/ml), it inhibited the process of lipid peroxidation. In high doses of 1000-2000 mg/kg (i.p. and p.o.) it did not induce significant alterations in parameters for toxicological screening. No effects on motor activity were observed, neither did guarana alter the hypnotic effect of pentobarbital. Ginseng (250-1000 mg/kg i.p.), however, elicited reductions in motor activity, eyelid ptosis and bristling fur. Consumption of liquids containing guarana or ginseng and progress in weight of the animals remained at levels similar to the controls, even after prolonged administration. The percentage mortality was equivalent in control and in treated groups. The absence of toxicity of guarana was also demonstrated by histopathological examination, with no alteration being detected in heart, lungs, stomach, small and large intestine, liver, pancreas, kidneys, bladder and spleen.

  18. Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals

    PubMed Central

    Jarockyte, Greta; Daugelaite, Egle; Stasys, Marius; Statkute, Urte; Poderys, Vilius; Tseng, Ting-Chen; Hsu, Shan-Hui; Karabanovas, Vitalijus; Rotomskis, Ricardas

    2016-01-01

    The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe3O4) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3–24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining. PMID:27548152

  19. The role of in vitro methods as alternatives to animals in toxicity testing.

    PubMed

    Anadón, Arturo; Martínez, María Aranzazu; Castellano, Victor; Martínez-Larrañaga, María Rosa

    2014-01-01

    It is accepted that animal testing should be reduced, refined or replaced as far as it is practicably possible. There are also a wide variety of in vitro models, which are used as screening studies and mechanistic investigations. The ability of an in vitro assay to be reliable, biomedically, is essential in pharmaceutical development. Furthermore, it is necessary that cells used in in vitro testing mimic the phenotype of cells within the human target tissue. The focus of this review article is to identify the key points of in vitro assays. In doing so, the authors take into account the chemical agents that are assessed and the integrated in vitro testing strategies. There is a transfer of toxicological data from primary in vivo animal studies to in vitro assays. The key element for designing an integrated in vitro testing strategy is summarized as follows: exposure modeling of chemical agents for in vitro testing; data gathering, sharing and read-across for testing a class of chemical; a battery of tests to assemble a broad spectrum of data on different mechanisms of action to predict toxic effects; and applicability of the test and the integrated in vitro testing strategies and flexibility to adjust the integrated in vitro testing strategies to test substance. While these methods will be invaluable if effective, more studies must be done to ensure reliability and suitability of these tests for humans.

  20. Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

    PubMed Central

    2012-01-01

    Background Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. Methods/Design The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Results Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic

  1. Reproducibility of toxicity test data as a function of mouse strain, animal lot, and operator. [for bisphenol A polycarbonate

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Furst, A.

    1978-01-01

    The toxicity screening test method developed at the University of San Francisco was evaluated for reproducibility. The variables addressed were strain of mouse, lot of animals, and operator. There was a significant difference in response between Swiss Webster mice and ICR mice, with the latter exhibiting greater resistance. These two strains of mice are not interchangeable in this procedure. Variation between individual animals was significant and unavoidable. In view of this variation, between-lot and between-operator variations appear to have no practical significance. The significant variation between individual animals stresses the need for average values based on at least four animals, and preferably values based on at least two experiments and eight animals. Efforts to compare materials should be based on the evaluation of relatively simple responses using substantial numbers of animals, rather than on elaborate evaluation of single animals

  2. Reproducibility of toxicity test data as a function of mouse strain, animal lot, and operator. [for bisphenol A polycarbonate

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Furst, A.

    1978-01-01

    The toxicity screening test method developed at the University of San Francisco was evaluated for reproducibility. The variables addressed were strain of mouse, lot of animals, and operator. There was a significant difference in response between Swiss Webster mice and ICR mice, with the latter exhibiting greater resistance. These two strains of mice are not interchangeable in this procedure. Variation between individual animals was significant and unavoidable. In view of this variation, between-lot and between-operator variations appear to have no practical significance. The significant variation between individual animals stresses the need for average values based on at least four animals, and preferably values based on at least two experiments and eight animals. Efforts to compare materials should be based on the evaluation of relatively simple responses using substantial numbers of animals, rather than on elaborate evaluation of single animals

  3. A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report*.

    PubMed

    Basketter, David A; Clewell, Harvey; Kimber, Ian; Rossi, Annamaria; Blaauboer, Bas; Burrier, Robert; Daneshian, Mardas; Eskes, Chantra; Goldberg, Alan; Hasiwa, Nina; Hoffmann, Sebastian; Jaworska, Joanna; Knudsen, Thomas B; Landsiedel, Robert; Leist, Marcel; Locke, Paul; Maxwell, Gavin; McKim, James; McVey, Emily A; Ouédraogo, Gladys; Patlewicz, Grace; Pelkonen, Olavi; Roggen, Erwin; Rovida, Costanza; Ruhdel, Irmela; Schwarz, Michael; Schepky, Andreas; Schoeters, Greet; Skinner, Nigel; Trentz, Kerstin; Turner, Marian; Vanparys, Philippe; Yager, James; Zurlo, Joanne; Hartung, Thomas

    2012-01-01

    Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science.

  4. Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans

    EPA Pesticide Factsheets

    Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans (Presented by James McKim, Ph.D., DABT, Founder and Chief Science Officer, CeeTox) (5/25/2012)

  5. Juvenile Arthritis

    MedlinePlus

    ... A Patient / Caregiver Diseases & Conditions Juvenile Arthritis Juvenile Arthritis Fast Facts Arthritis in children is treatable. It ... as fevers or rash. What is juvenile idiopathic arthritis? Several types of arthritis, all involving chronic (long- ...

  6. Estimation of bisphenol A-Human toxicity by 3D cell culture arrays, high throughput alternatives to animal tests.

    PubMed

    Lee, Dong Woo; Oh, Woo-Yeon; Yi, Sang Hyun; Ku, Bosung; Lee, Moo-Yeal; Cho, Yoon Hee; Yang, Mihi

    2016-09-30

    Bisphenol A (BPA) has been widely used for manufacturing polycarbonate plastics and epoxy resins and has been extensively tested in animals to predict human toxicity. In order to reduce the use of animals for toxicity assessment and provide further accurate information on BPA toxicity in humans, we encapsulated Hep3B human hepatoma cells in alginate and cultured them in three dimensions (3D) on a micropillar chip coupled to a panel of metabolic enzymes on a microwell chip. As a result, we were able to assess the toxicity of BPA under various metabolic enzyme conditions using a high-throughput and micro assay; sample volumes were nearly 2,000 times less than that required for a 96-well plate. We applied a total of 28 different enzymes to each chip, including 10 cytochrome P450s (CYP450s), 10 UDP-glycosyltransferases (UGTs), 3 sulfotransferases (SULTs), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase 2 (ALDH2). Phase I enzyme mixtures, phase II enzyme mixtures, and a combination of phase I and phase II enzymes were also applied to the chip. BPA toxicity was higher in samples containing CYP2E1 than controls, which contained no enzymes (IC50, 184±16μM and 270±25.8μM, respectively, p<0.01). However, BPA-induced toxicity was alleviated in the presence of ADH (IC50, 337±17.9μM), ALDH2 (335±13.9μM), and SULT1E1 (318±17.7μM) (p<0.05). CYP2E1-mediated cytotoxicity was confirmed by quantifying unmetabolized BPA using HPLC/FD. Therefore, we suggest the present micropillar/microwell chip platform as an effective alternative to animal testing for estimating BPA toxicity via human metabolic systems.

  7. Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals.

    PubMed

    Majeed, Muhammed; Bani, Sarang; Natarajan, Sankaran; Pandey, Anjali; S, Naveed

    2017-01-01

    3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed.

  8. Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals

    PubMed Central

    Majeed, Muhammed; Bani, Sarang; Natarajan, Sankaran; Pandey, Anjali; S, Naveed

    2017-01-01

    3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed. PMID:28257483

  9. An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.

    PubMed

    Marin, Veronica; Rosso, Natalia; Dal Ben, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, Silvia

    2016-01-01

    Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.

  10. An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

    PubMed Central

    Marin, Veronica; Rosso, Natalia; Dal Ben, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, Silvia

    2016-01-01

    Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches. PMID:27391242

  11. Feasibility and precision of cerebral blood flow and cerebrovascular reactivity MRI measurements using a computer-controlled gas delivery system in an anesthetised juvenile animal model.

    PubMed

    Winter, Jeff D; Fierstra, Jorn; Dorner, Stephanie; Fisher, Joseph A; St Lawrence, Keith S; Kassner, Andrea

    2010-11-01

    To demonstrate the feasibility and repeatability of cerebrovascular reactivity (CVR) imaging using a controlled CO(2) challenge in mechanically ventilated juvenile pigs. Precise end-tidal partial pressure CO(2) (PETCO(2)) control was achieved via a computer-controlled model-driven prospective end-tidal targeting (MPET) system integrated with mechanical ventilation using a custom-built secondary breathing circuit. Test-retest blood-oxygen level dependent (BOLD) CVR images were collected in nine juvenile pigs by quantifying the BOLD response to iso-oxic square-wave PETCO(2) changes. For comparison, test-retest baseline arterial spin labeling (ASL) cerebral blood flow (CBF) images were collected. Repeatability was quantified using the intra-class correlation coefficient (ICC) and coefficient of variation (CV). The repeatability of the PETCO(2) (CV < 2%) step changes resulted in BOLD CVR ICC > 0.94 and CV < 6% for cortical brain regions, which was similar to ASL CBF repeatability (ICC > 0.96 and CV < 4%). This study demonstrates the feasibility and precision of CVR imaging with an MPET CO(2) challenge in mechanically ventilated subjects using an animal model. Translation of this method into clinical imaging protocols may enable CVR imaging in young children with cerebrovascular disease who require general anesthesia. © 2010 Wiley-Liss, Inc.

  12. Toxicity thresholds for juvenile freshwater mussels Echyridella menziesii and crayfish Paranephrops planifrons, after acute or chronic exposure to Microcystis sp.

    PubMed

    Clearwater, S J; Wood, S A; Phillips, N R; Parkyn, S M; Van Ginkel, R; Thompson, K J

    2014-05-01

    Survival of juvenile freshwater mussels (Echyridella menziesii (Gray, 1843) formerly known as Hyridella menziesi) and crayfish (Paranephrops planifrons, White, 1842) decreased after four days exposure to microcystin-containing cell-free extracts (MCFE) of Microcystis sp. at concentrations typical of severe cyanobacterial blooms. Crayfish survival was 100, 80, and 50% in microcystin concentrations of 1339, 2426, and 11146 μg L(-1) respectively, and shade- and shelter-seeking behavior was negatively affected when concentrations were ≥2426 μg L(-1) . Mussel survival decreased to 92% and reburial rates decreased to 16% after exposure for 96 h to MCFE containing microcystins at concentrations of 5300 μg L(-1) . Crayfish survival was 100% when fed freeze-dried Microcystis sp. incorporated into an artificial diet (6-100 μg microcystin kg(-1) ww) at dietary doses from 0.03 to 0.55 μg g(-1) body weight d(-1) for 27 days. Specific growth rate was significantly lower in crayfish fed ≥0.15 μg g(-1) body weight day(-1) compared with controls, but not compared with a diet incorporating nontoxic cyanobacteria. Microcystins accumulated preferentially in crayfish hepatopancreas and mussel digesta as MCFE or dietary concentrations increased. These laboratory data indicate that, assuming dissolved oxygen concentrations remain adequate, and no simultaneous exposure to live Microcystis sp. cells, cell-free microcystins will only be a significant stressor to juvenile crayfish and mussels in severe Microcystis sp. blooms. In contrast, crayfish were negatively affected by relatively low concentrations of microcystins in artificial diets compared with those measured locally in benthic cyanobacterial mats.

  13. The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans.

    PubMed

    VanDuyn, Natalia; Nass, Richard

    2014-03-01

    Parkinson's disease (PD) is the most prevalent neurodegenerative motor disorder worldwide, and results in the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta. Gene-environment interactions are believed to play a significant role in the vast majority of PD cases, yet the toxicants and the associated genes involved in the neuropathology are largely ill-defined. Recent epidemiological and biochemical evidence suggests that methylmercury (MeHg) may be an environmental toxicant that contributes to the development of PD. Here, we report that a gene coding for the putative multidrug resistance protein MRP-7 in Caenorhabditis elegans modulates whole animal and DA neuron sensitivity to MeHg. In this study, we demonstrate that genetic knockdown of MRP-7 results in a twofold increase in Hg levels and a dramatic increase in stress response proteins associated with the endoplasmic reticulum, golgi apparatus, and mitochondria, as well as an increase in MeHg-associated animal death. Chronic exposure to low concentrations of MeHg induces MRP-7 gene expression, while exposures in MRP-7 genetic knockdown animals results in a loss of DA neuron integrity without affecting whole animal viability. Furthermore, transgenic animals expressing a fluorescent reporter behind the endogenous MRP-7 promoter indicate that the transporter is expressed in DA neurons. These studies show for the first time that a multidrug resistance protein is expressed in DA neurons, and its expression inhibits MeHg-associated DA neuron pathology.

  14. Assessment of diurnal systemic dose of agrochemicals in regulatory toxicity testing--an integrated approach without additional animal use.

    PubMed

    Saghir, Shakil A; Bartels, Michael J; Rick, David L; McCoy, Alene T; Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Sue Marty, M; Terry, Claire; Bailey, Jason P; Billington, Richard; Bus, James S

    2012-07-01

    Integrated toxicokinetics (TK) data provide information on the rate, extent and duration of systemic exposure across doses, species, strains, gender, and life stages within a toxicology program. While routine for pharmaceuticals, TK assessments of non-pharmaceuticals are still relatively rare, and have never before been included in a full range of guideline studies for a new agrochemical. In order to better understand the relationship between diurnal systemic dose (AUC(24h)) and toxicity of agrochemicals, TK analyses in the study animals is now included in all short- (excluding acute), medium- and long-term guideline mammalian toxicity studies including reproduction/developmental tests. This paper describes a detailed procedure for the implementation of TK in short-, medium- and long-term regulatory toxicity studies, without the use of satellite animals, conducted on three agrochemicals (X11422208, 2,4-D and X574175). In these studies, kinetically-derived maximum doses (KMD) from short-term studies instead of, or along with, maximum tolerated doses (MTD) were used for the selection of the high dose in subsequent longer-term studies. In addition to leveraging TK data to guide dose level selection, the integrated program was also used to select the most appropriate method of oral administration (i.e., gavage versus dietary) of test materials for rat and rabbit developmental toxicity studies. The integrated TK data obtained across toxicity studies (without the use of additional/satellite animals) provided data critical to understanding differences in response across doses, species, strains, sexes, and life stages. Such data should also be useful in mode of action studies and to improve human risk assessments. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Toxic effects on bioaccumulation and hematological parameters of juvenile rockfish Sebastes schlegelii exposed to dietary lead (Pb) and ascorbic acid.

    PubMed

    Kim, Jun-Hwan; Kang, Ju-Chan

    2017-02-20

    Juvenile rockfish, Sebastes schlegelii (mean length 11.3 ± 1.2 cm, and mean weight 32.5 ± 4.1 g) were exposed for four weeks to dietary lead (Pb(2+)) at 0, 120, and 240 mg/L and ascorbic acid (AsA) at 100, 200, and 400 mg/L. The exposure concentrations and duration of significant Pb-induced accumulations in specific tissues of S. schlegelii were assessed. High levels of ascorbic acid significantly attenuated accumulations following exposure to dietary Pb. Dietary Pb exposure caused a significant increase in blood Pb concentrations, whereas red blood cell (RBC) count, hematocrit, and hemoglobin were significantly decreased. Notable changes were also observed in plasma calcium, magnesium, glucose, cholesterol, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvate transaminase (GPT). The growth performance of S. schlegelii was significantly decreased. High doses AsA supplemention were effective in attenuating the changes brought about by dietary Pb exposure.

  16. The toxic effects on the stress and immune responses in juvenile rockfish, Sebastes schlegelii exposed to hexavalent chromium.

    PubMed

    Kim, Jun-Hwan; Kang, Ju-Chan

    2016-04-01

    Juvenile Sebastes schlegelii (mean length 13.7±1.7cm, and mean weight 55.6±4.8g) were exposed for 4 weeks with the different levels of dietary chromium (Cr(6+)) concentration (0, 30, 60, 120 and 200mg/L). The plasma cortisol and heat shock protein 70 was evaluated as stress indicators. Plasma cortisol was significantly increased in response to the dietary chromium exposure over 120mg/kg at 2 and 4 weeks. Heat shock protein 70 was also notably increased over 120mg/kg at 2 weeks and over 60mg/kg at 4 weeks. In the immune response, immunoglobulin M was considerably increased in the concentration of 240mg/kg at 2 weeks and over 120mg/kg at 4 weeks. Lysozyme activity was considerably induced by the dietary hexavalent chromium exposure. A significant increase in plasma lysozyme activity was observed at 240mg/kg after 2 weeks and over 60mg/kg after 4 weeks, kidney lysozyme was also increased over 120mg/kg at 2 and 4 weeks. The results demonstrate that dietary Cr exposure can induce a significant stress and immune stimulation.

  17. Minocycline treatment suppresses juvenile development and growth by attenuating insulin/TOR signaling in Drosophila animal model

    PubMed Central

    Yun, Hyun Myoung; Noh, Sujin; Hyun, Seogang

    2017-01-01

    Minocycline is a broad spectrum, semi-synthetic tetracycline analog that is used to treat bacterial infection. Recently, this drug has been receiving increasing attention for its non-antibiotic properties, including anti-inflammatory, tumor suppressive, and neuroprotective effects. Drosophila is a useful model organism for studying human metabolism and disease. In this study, we investigated the effects of minocycline on juvenile development and growth in Drosophila. Feeding minocycline to Drosophila larvae suppresses larval body growth and delays the timing of pupation in a dose-dependent manner. We found that the drug treatment decreased the activated form of Akt and S6K in peripheral tissues, which suggested that the insulin/target of rapamycin (TOR) signaling had been attenuated. Specifically enhancing TOR activity in the prothoracic gland (PG), the ecdysone-generating organ, attenuated the drug-induced developmental delay, which is consistent with the critical role of PG’s TOR signaling in determining pupation time. Our results reveal previously unrecognized effects of minocycline and offer a new potential therapeutic opportunity for various pathological conditions associated with insulin/TOR signaling. PMID:28317899

  18. Eisai hyperbilirubinemic rat (EHBR) as an animal model affording high drug-exposure in toxicity studies on organic anions.

    PubMed

    Naba, Hiroyasu; Kuwayama, Chitose; Kakinuma, Chihaya; Ohnishi, Shuhei; Ogihara, Takuo

    2004-10-01

    The Eisai hyperbilirubinemic rat (EHBR) should be a useful animal model for studies on the toxicity of organic anions which are substrates of multidrug resistance-associated protein 2 (Mrp2), since the systemic exposure to these compounds is expected to be increased in EHBR. In this study, we tested the value of EHBR for this purpose, using pravastatin (PV) and methotrexate (MTX) as model compounds. In the case of a single oral dose of PV (200 mg/kg), C(max) in plasma was 4.0-fold higher and AUC(0-infinity) was 3.6-fold larger than those of normal Sprague-Dawley rats (SDR), respectively. When multiple doses of PV were given to EHBR without co-administration of any other compound, drug-induced skeletal muscle toxicity (myopathy/rhabdomyolysis) and increased creatine phosphokinase (CPK) level were observed, whereas a control experiment using SDR did not show any toxic change. When a single dose of MTX (0.6 mg/kg) was given to EHBR orally, C(max) was 1.7-fold higher and AUC(0-infinity) was 1.6-fold larger than those of SDR, respectively. When multiple doses of MTX were given to EHBR, the changes in bone marrow, spleen and intestines were more severe than those in SDR. These findings support the view that EHBR would be a valuable animal model for toxicity studies on organic anion compounds which are substrates of Mrp2.

  19. Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches: a workshop report.

    PubMed

    van der Laan, Jan Willem; Chapin, Robert E; Haenen, Bert; Jacobs, Abigail C; Piersma, Aldert

    2012-06-01

    Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives. The reproductive cycle is complex and not all mechanisms of development can be mimicked in vitro. Therefore, efforts are underway to characterize the available alternative tests with regard to the mechanism of action they include. One alternative test is the mouse embryonic stem cell test (EST), which has been studied since the late 1990s. It is a genuine 3R "alternative" assay as it is essentially animal-free. A meeting was held to review the state-of-the-art of various in vitro models for prediction of developmental toxicity. Although the predictivity of individual assays is improving, a battery of several assays is likely to have even higher predictivity, which is necessary for regulatory acceptance. The workshop concluded that an important first step is a thorough survey of the existing rat and rabbit studies, to fully characterize the frequency of responses and the types of effects seen. At the same time, it is important to continue the optimization of in vitro assays. As more experience accumulates, the optimal conditions, assay structure, and applicability of the alternative assays are expected to emerge. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. A review of toxicity studies on graphene-based nanomaterials in laboratory animals.

    PubMed

    Ema, Makoto; Gamo, Masashi; Honda, Kazumasa

    2017-04-01

    We summarized the findings of toxicity studies on graphene-based nanomaterials (GNMs) in laboratory mammals. The inhalation of graphene (GP) and graphene oxide (GO) induced only minimal pulmonary toxicity. Bolus airway exposure to GP and GO caused acute and subacute pulmonary inflammation. Large-sized GO (L-GO) was more toxic than small-sized GO (S-GO). Intratracheally administered GP passed through the air-blood barrier into the blood and intravenous GO distributed mainly in the lungs, liver, and spleen. S-GO and L-GO mainly accumulated in the liver and lungs, respectively. Limited information showed the potential behavioral, reproductive, and developmental toxicity and genotoxicity of GNMs. There are indications that oxidative stress and inflammation may be involved in the toxicity of GNMs. The surface reactivity, size, and dispersion status of GNMs play an important role in the induction of toxicity and biodistribution of GNMs. Although this review paper provides initial information on the potential toxicity of GNMs, data are still very limited, especially when taking into account the many different types of GNMs and their potential modifications. To fill the data gap, further studies should be performed using laboratory mammals exposed using the route and dose anticipated for human exposure scenarios.

  1. The effluent toxicity assessment toolbox international perspective on tools and concepts and opportunities for animal alternatives

    EPA Science Inventory

    Effluent testing has been utilized in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only relatively recently that toxicity-based effluent assessments and subsequent dischar...

  2. Differences in alarm calls of juvenile and adult European ground squirrels (Spermophilus citellus): Findings on permanently marked animals from a semi-natural enclosure.

    PubMed

    Schneiderov, Irena; Schnitzerov, Petra; Uhlikov, Jitka; Brandl, Pavel; Zouhar, Jan; Matejů, Jan

    2015-11-01

    The European ground squirrel (Spermophilus citellus) emits alarm calls that warn conspecifics of potential danger. Although it has been observed that inexperienced juveniles of this species emit alarm calls that sound similar to those of adults, studies focusing on juvenile alarm calls are lacking. We analyzed the acoustic structure of alarm calls emitted by six permanently marked European ground squirrels living in a semi-natural enclosure when they were juveniles and after 1 year as adults. We found that the acoustic structure of the juvenile alarm calls was significantly different from those of adults and that the alarm calls underwent nearly the same changes in all studied individuals. All juveniles emitted alarm calls consisting of one element with almost constant frequency, but their alarm calls included a second frequency-modulated element after their first hibernation as adults. Our data show that the duration of the first element is significantly shorter in adults than in juveniles. Additionally, the frequency of the first element is significantly higher in adults than in juveniles. Similar to previous findings in other Palearctic ground squirrel species, our data are inconsistent with the assumption that juvenile mammals emit vocalizations with higher fundamental frequencies than adults. However, our results do not support the previously suggested hypothesis that juvenile ground squirrels conceal information regarding their age in their alarm calls because we found significant differences in alarm calls of juveniles and adults. © 2015 Wiley Periodicals, Inc.

  3. [Health effects of solar cell component material. Toxicity of indium compounds to laboratory animals determined by intratracheal instillations].

    PubMed

    Tanaka, Akiyo; Hirata, Miyuki

    2013-01-01

    Owing to the increasing interest being paid to the issue of the global environment, the production of solar cells has increased rapidly in recent years. Copper indium gallium diselenide (CIGS) is a new efficient thin film used in some types of solar cell. Indium is a constitutive element of CIGS thin-film solar cells. It was thought that indium compounds were not harmful until the beginning of the 1990s because there was little information regarding the adverse health effects on humans or animals arising from exposure to indium compounds. After the mid-1990s, data became available indicating that indium compounds can be toxic to animals. In animal studies, it has been clearly demonstrated that indium compounds cause pulmonary toxicity and that the dissolution of indium compounds in the lungs is considerably slow, as shown by repeated intratracheal instillations in experimental animals. Thus, it is necessary to pay much greater attention to human exposure to indium compounds, and precautions against possible exposure to indium compounds are paramount with regard to health management.

  4. Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules.

    PubMed

    Nobre, Lígia S; Jeremias, Hélia; Romão, Carlos C; Saraiva, Lígia M

    2016-01-28

    Transition metal carbonyl complexes used as CO-releasing molecules (CORMs) for biological and therapeutic applications may exhibit interesting antimicrobial activity. However, understanding the chemical traits and mechanisms of action that rule this activity is required to establish a rationale for the development of CORMs into useful antibiotics. In this work the bactericidal activity, the toxicity to eukaryotic cells, and the ability of CORMs to deliver CO to bacterial and eukaryotic cells were analysed for a set of seven CORMs that differ in the transition metal, ancillary ligands and the CO release profile. Most of these CORMs exhibited bactericidal properties that decrease in the following order: CORM-2 > CORM-3 > ALF062 > ALF850 > ALF186 > ALF153 > [Fe(SBPy3)(CO)](BF4)2. A similar yet not entirely coincident decreasing order was found for their induction of intracellular reactive oxygen species (ROS) in E. coli. In contrast, studies in model animal cells showed that for any given CORM, the level of intracellular ROS generated was negligible when compared with that measured inside bacteria. Importantly, these CORMs were in general not toxic to eukaryotic cells, namely murine macrophages, kidney LLC-PK1 epithelial cells, and liver cell line HepG2. CORM-2 and CORM-3 delivered CO to the intracellular space of both E. coli and the two types of tested eukaryotic cells, yet toxicity was only elicited in the case of E. coli. CO delivered by ALF186 into the intercellular space did not enter E. coli cells and the compound was not toxic to either bacteria or to eukaryotic cells. The Fe(ii) carbonyl complex [Fe(SBPy3)(CO)](2+) had the reverse, undesirable toxicity profile, being unexpectedly toxic to eukaryotic cells and non-toxic to E. coli. ALF153, the most stable complex in the whole set, was essentially devoid of toxicity or ROS induction ability in all cells. These results suggest that CORMs have a relevant therapeutic potential as antimicrobial drugs since (i) they

  5. Evaluation of the threat of marine CO2 leakage-associated acidification on the toxicity of sediment metals to juvenile bivalves.

    PubMed

    Basallote, M Dolores; Rodríguez-Romero, Araceli; De Orte, Manoela R; Del Valls, T Ángel; Riba, Inmaculada

    2015-09-01

    The effects of the acidification associated with CO2 leakage from sub-seabed geological storage was studied by the evaluation of the short-term effects of CO2-induced acidification on juveniles of the bivalve Ruditapes philippinarum. Laboratory scale experiments were performed using a CO2-bubbling system designed to conduct ecotoxicological assays. The organisms were exposed for 10 days to elutriates of sediments collected in different littoral areas that were subjected to various pH treatments (pH 7.1, 6.6, 6.1). The acute pH-associated effects on the bivalves were observed, and the dissolved metals in the elutriates were measured. The median toxic effect pH was calculated, which ranged from 6.33 to 6.45. The amount of dissolved Zn in the sediment elutriates increased in parallel with the pH reductions and was correlated with the proton concentrations. The pH, the pCO2 and the dissolved metal concentrations (Zn and Fe) were linked with the mortality of the exposed bivalves. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Evaluation of some in vitro tests to reduce and replace the sub-acute animal toxicity studies.

    PubMed

    Chhabra, Rajendra S; Ress, Nancy B; Harbell, John W; Curren, Rodger D

    2004-06-01

    The toxicologic and carcinogenic potential of chemicals is usually determined through a sequence of acute, sub-acute (14-day), sub-chronic (90-day) and chronic (two-year) studies in rats and mice of both sexes. The US National Toxicology Program (NTP) does not conduct acute toxicity studies. Dose levels for 14-day toxicity studies are typically estimated from information in the literature, if available. The toxicology information obtained from 14-day studies is used in the selection of doses for 90-day studies. The protocol for 14-day studies consists of five doses and control groups and five animals per group of each sex and species, resulting in the use of 120 animals per study. At present, in addition to refining the current testing protocols, the NTP is evaluating the potential for in vitro test methods to partially or completely avoid the need for 14-day toxicity studies, especially for chemicals where the dermal route of exposure is used. The in vitro assays used were the EpiDerm bioassay to estimate dermal irritation, the neutral red uptake (NRU) bioassay to estimate systemic toxicity and the primary rat hepatocyte cytotoxicity (PRHC) assay to estimate hepatotoxicity. The purpose of using these assays was to assess their potential for predicting relative in vivo toxicity and to support dose selection decisions for 90-day studies. In general, based on these limited number of studies, the EpiDerm and NRU tests were predictive of the responses observed in in vivo studies. However, a larger comparative database is needed to derive definitive conclusions regarding the value of in vitro tests in the prediction of in vivo effects.

  7. Size-Dependent Toxicity Differences of Intratracheally Instilled Manganese Oxide Nanoparticles: Conclusions of a Subacute Animal Experiment.

    PubMed

    Máté, Zsuzsanna; Horváth, Edina; Kozma, Gábor; Simon, Tímea; Kónya, Zoltán; Paulik, Edit; Papp, András; Szabó, Andrea

    2016-05-01

    Incomplete information on toxicological differences of micro- and nanometer-sized particles raised concerns about the effects of the latter on health and environment. Besides chemical composition, size and surface-to-volume ratio of nanoparticles (NPs) can affect toxicity. To investigate size-dependent toxicity differences, we used particles made of dioxide of the neurotoxic heavy metal manganese (Mn), typically found in inhaled metal fumes, in three size ranges (size A, 9.14 ± 1.98 nm; size B, 42.36 ± 8.06 nm; size C, 118.31 ± 25.37 nm). For modeling the most frequent route of exposure to Mn, NPs were given to rats for 6 weeks by intratracheal instillation. Of each NP size, 3 or 6 mg/kg body weight was given while control animals were vehicle treated. Neurotoxicity was assessed by measuring spontaneous locomotor activity in an open field and by recording spontaneous and evoked electrical activity from the somatosensory cortical area. Mn content of brain, lung, and blood, measured by ICP-MS, were correlated to the observed functional alterations to see the relationship between Mn load and toxic effects. Body weight gain and organ weights were measured as general toxicological indices. The toxicity of size A and size B NPs proved to be stronger compared to size C NPs, seen most clearly in decreased body weight gain and altered spontaneous cortical activity, which were also well correlated to the internal Mn dose. Our results showed strong effect of size on NP toxicity, thus, beyond inappropriateness of toxicity data of micrometer-sized particles in evaluation of NP exposure, differentiation within the nano range may be necessary.

  8. Resistance to toxic plants: The right animal in the right pasture at the right time

    USDA-ARS?s Scientific Manuscript database

    Neurotoxic poisonous plants negatively impact livestock on many western rangelands, which results in annual economic losses of millions of dollars from animal deaths, increased management and treatment costs, and if animals are deferred from grazing, the underutilization of otherwise highly nutritio...

  9. Animator

    ERIC Educational Resources Information Center

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  10. Animator

    ERIC Educational Resources Information Center

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  11. Hazard evaluation of soil contaminants with aquatic animals and plant toxicity tests

    SciTech Connect

    Ramanathan, A.; Burks, S.L.

    1996-12-31

    Deleterious effects upon the biota should be one of the principal characteristics used to perform the initial assessment of contamination and the acceptable level of clean-up at hazardous waste sites. Acute toxicity tests are probably the best means for conducting rapid preliminary assessment of distribution and extent of toxic conditions at a site. On the other hand acute toxicity tests may not be adequate indicators of potential effects at critical life stages or responses to longer term exposure to contaminants. Chronic toxicity tests are generally more sensitive than acute tests, and can be used to predict {open_quotes}no effect{close_quotes} or {open_quotes}safe{close_quotes} levels of contamination. In addition, chronic tests provide a better index of field population responses and more closely mimic actual exposure in the field. Partial chronic tests such as the 7 d Ceriodaphnia sp. survival and reproduction test and 7 d fathead minnow survival and growth test are widely used to predict effects upon critical stages in the life cycle of chemical and mixtures. The overall objective of this project was to evaluate the potential hazard of contaminants at an abandoned oil refinery upon aquatic ecosystems within the vicinity. A battery of acute and partial chronic toxicity tests were used to evaluate potential effects of contaminated soil and leachates of soil upon rice seed germination and root growth, Ceriodaphnia acute survival, fathead minnow acute survival, Microtox acute response, 7 d Ceriodaphnia survival and reproduction, and 7 d fathead minnow survival and growth. The specific tests used to accomplish the overall objective included; (1) To estimate phytotoxicity of the soil at the selected contaminated areas within the refinery, (2) to determine potential for leaching at the selected contaminated areas within the refinery, and (3) to assess the relative toxicity of each of the six contaminated areas in the refinery. 13 refs., 3 tabs.

  12. Comparison of aqueous levels of inflammatory mediators between toxic anterior segment syndrome and endotoxin-induced uveitis animal models.

    PubMed

    Eom, Youngsub; Lee, Dong Yeol; Kang, Bo-Ram; Heo, Jeong-Hwa; Shin, Kyung-Ho; Kim, Hyo Myung; Song, Jong Suk

    2014-08-21

    To compare clinical findings and the aqueous levels of inflammatory mediators between toxic anterior segment syndrome (TASS) and endotoxin-induced uveitis (EIU) animal models and to evaluate the efficacy of systemic steroid pretreatment in both animal models. Rats were used in this study. Ortho-phthalaldehyde solution was injected into the anterior chamber to produce TASS (n=30), and lipopolysaccharide was injected into one hind footpad to produce EIU (n=30). Clinical findings were evaluated under slit-lamp examination, and the aqueous levels of prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) were measured 24 hours after these procedures. Twelve of the rats in each animal model were pretreated with intraperitoneal injection of dexamethasone for 4 days before the development of TASS and EIU. Corneal haze scores were significantly higher for TASS than EIU, but clinical scores for anterior uveitis were not different between the two animal models. Although aqueous levels of PGE2 were markedly increased in both animal models, PGE2 levels were significantly higher for TASS than for EIU. However, an increase in aqueous levels of TNF-α was observed only in EIU. Dexamethasone pretreatment reduced the corneal haze score and clinical score for anterior uveitis in both animal models and inhibited the increase in aqueous levels of PGE2 and TNF-α. Prostaglandin E2 and TNF-α in aqueous humor seem to be regulated differently in animal models of TASS and EIU. However, dexamethasone pretreatment improved the clinical findings and inhibited the increases in PGE2 and TNF-α in both animal models. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  13. Larvicidal activity of the water extract of Moringa oleifera seeds against Aedes aegypti and its toxicity upon laboratory animals.

    PubMed

    Ferreira, Paulo M P; Carvalho, Ana F U; Farias, Davi F; Cariolano, Nara G; Melo, Vânia M M; Queiroz, Maria G R; Martins, Alice M C; Machado-Neto, Joaquim G

    2009-06-01

    In this work, biological effects of the water extract of Moringa oleifera seeds (WEMOS) were assessed on eggs and 3rd instar larvae of Aedes aegypti and on its toxicity upon laboratory animals (Daphnia magna, mice and rats). Crude WEMOS showed a LC50 value of 1260microg/mL, causing 99.2 +/- 2.9% larvae mortality within 24 h at 5200microg/mL, though this larvicidal activity has been lost completely at 80 masculineC/10 min. WEMOS did not demonstrate capacity to prevent egg hatching. After extensive dialyses of the crude WEMOS into watersoluble dialyzable (DF) and nondyalizable (NDF) fractions, only DF maintained its efficacy to kill larvae. Acute toxicity evaluations on daphnids (EC50 of 188.7microg/mL) and mice (LD50 of 446.5 mg/kg body weight) pointed out to low toxicity. Despite the thymus hypertrophy, WEMOS revealed to be harmless in orally and subacutelytreated rats. In conclusion, WEMOS has thermostable bioactive compounds against Ae. aegypti larvae with apparent molecular mass lower than 12 kDa and moderately toxic potential.

  14. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop (presentation)

    EPA Science Inventory

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicit...

  15. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop

    EPA Science Inventory

    Since the 1940’s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that ...

  16. Acrylamide: Inhibition of formation in processed food and mitigation of toxicity in cells, animals, and humans

    USDA-ARS?s Scientific Manuscript database

    Potentially toxic acrylamide is largely derived from the heat-unducing reactions between the amino group of the amino acid asparagine and carbonyl groups of glucose and fructose in plant derived foods including cereals, coffees, almonds, and potatoes. This review surveys and consolidates the followi...

  17. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop (presentation)

    EPA Science Inventory

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicit...

  18. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop

    EPA Science Inventory

    Since the 1940’s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that ...

  19. Magnetic resonance for evaluation of toxic encephalopathies: implications from animal experiments.

    PubMed

    Igisu, Hideki; Kinoshita, Yoshimasa

    2007-03-01

    Examinations of brain of rats intoxicated with hexachlorophene or acrylamide with ultrahigh-field (4.7 T) proton magnetic resonance (MR) showed alterations consistent with clinical pictures in humans and morphological findings in experimental animals. On the other hand, conventional biochemical analyses have revealed that ethylene oxide, methyl bromide, and acrylamide inhibit creatine kinase (CK; an enzyme catalyzing the reaction: ATP+creatine<-->ADP+phosphocreatine) activities in the brain of animals. Thus, 31P MR combined with magnetization transfer may be utilized to monitor living humans (or animals) intoxicated with these chemicals by determining CK activities in the target organ.

  20. Ending the use of animals in toxicity testing and risk evaluation.

    PubMed

    Rowan, Andrew N

    2015-10-01

    This article discusses the use of animals for the safety testing of chemicals, including pharmaceuticals, household products, pesticides, and industrial chemicals. It reviews changes in safety testing technology and what those changes mean from the perspective of industrial innovation, public policy and public health, economics, and ethics. It concludes that the continuing use of animals for chemical safety testing should end within the decade as cheaper, quicker, and more predictive technologies are developed and applied.

  1. Farm Animal Models of Organic Dust Exposure and Toxicity: Insights and Implications for Respiratory Health

    PubMed Central

    McClendon, Chakia J.; Gerald, Carresse L.; Waterman, Jenora T.

    2016-01-01

    Purpose of review Modern food animal production is a major contributor to the global economy, owing to advanced intensive indoor production facilities aimed at increasing market readiness and profit. Consequences of these advances are accumulation of dusts, gases and microbial products that diminish air quality within production facilities. Chronic inhalation exposure contributes to onset and exacerbation of respiratory symptoms and diseases in animals and workers. This article reviews literature regarding constituents of farm animal production facility dusts; animal responses to production building and organic dust exposure, and the effect of chronic inhalation exposure on pulmonary oxidative stress and inflammation. Recent findings –Porcine models of production facility and organic dust exposures reveal striking similarities to observations of human cells, tissues and clinical data. Oxidative stress plays a key role in mediating respiratory diseases in animals and humans, and enhancement of antioxidant levels through nutritional supplements can improve respiratory health. Summary – Pigs are well adapted to the exposures common to swine production buildings and thus serve as excellent models for facility workers. Insight for understanding mechanisms governing organic dust associated respiratory diseases may come from parallel comparisons between farmers and the animals they raise. PMID:25636160

  2. Multiple mitigation mechanisms: Effects of submerged plants on the toxicity of nine insecticides to aquatic animals.

    PubMed

    Brogan, William R; Relyea, Rick A

    2017-01-01

    Understanding the processes that regulate contaminant impacts in nature is an increasingly important challenge. For insecticides in surface waters, the ability of aquatic plants to sorb, or bind, hydrophobic compounds has been identified as a primary mechanism by which toxicity can be mitigated (i.e. the sorption-based model). However, recent research shows that submerged plants can also rapidly mitigate the toxicity of the less hydrophobic insecticide malathion via alkaline hydrolysis (i.e. the hydrolysis-based model) driven by increased water pH resulting from photosynthesis. However, it is still unknown how generalizable these mitigation mechanisms are across the wide variety of insecticides applied today, and whether any general rules can be ascertained about which types of chemicals may be mitigated by each mechanism. We quantified the degree to which the submerged plant Elodea canadensis mitigated acute (48-h) toxicity to Daphnia magna using nine commonly applied insecticides spanning three chemical classes (carbamates: aldicarb, carbaryl, carbofuran; organophosphates: malathion, diazinon, chlorpyrifos; pyrethroids: permethrin, bifenthrin, lambda-cyhalothrin). We found that insecticides possessing either high octanol-water partition coefficients (log Kow) values (i.e. pyrethroids) or high susceptibility to alkaline hydrolysis (i.e. carbamates and malathion) were all mitigated to some degree by E. canadensis, while the plant had no effect on insecticides possessing intermediate log Kow values and low susceptibility to hydrolysis (i.e. chlorpyrifos and diazinon). Our results provide the first general insights into which types of insecticides are likely to be mitigated by different mechanisms based on known chemical properties. We suggest that current models and mitigation strategies would be improved by the consideration of both mitigation models.

  3. Fungicidal activity of AKWATON and in vitro assessment of its toxic effects on animal cells.

    PubMed

    Oulé, Mathias Kégnon; Staines, Kenton; Lightly, Tasia; Roberts, Loren; Traoré, Yannick Léandre; Dickman, Michael; Bernier, Anne-Marie; Diop, Lamine

    2015-01-01

    Acquired superficial fungal infections are among the most common infections. It is necessary to create new effective and non-toxic disinfectants. AKWATON is a new disinfectant of the polymeric guanidine family. Its fungicidal activity against Trichophyton mentagrophytes and its in vitro toxicity assessment were determined in this study. The MIC, minimum fungicidal concentration (MFC) and time required for its fungicidal activity at the MFC were evaluated using the official methods of analysis of the Association of Official Analytical Chemists, with modifications as recommended by the Canadian General Standards Board. The toxic effects of AKWATON and of four commercial disinfectants were evaluated on rat pancreatic (C2C12) and muscle (RnM5F) cells, using the trypan blue and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] methods. The MIC, MFC and time required for the fungicidal activity of AKWATON at the MFC were 0.025 % (w/v), 0.045 % (w/v) and 2.5 min, respectively. Cell cultures and the different tests carried out showed that the AKWATON-based disinfectant killed fewer cells than the commercial disinfectants, sparing 80 % of C2C12 cells and 65 % of RnM5F cells, whilst some of the well-known disinfectants currently on the market killed 85-100 % of cells. This study demonstrates that AKWATON has great potential as an odourless, colourless, non-corrosive and safe disinfectant for use in hospitals, the agriculture industry, farming and household facilities.

  4. Proposal for a tiered approach to developmental toxicity testing for veterinary pharmaceutical products for food-producing animals.

    PubMed

    Hurtt, M E; Cappon, G D; Browning, A

    2003-05-01

    In order to establish the safety of veterinary drug residues in human food, a number of toxicological evaluations are required, including the assessment of potential risks to development. In the light of the use of developmental toxicity testing for risk characterization, we evaluated whether conducting these tests in more than one species was redundant. Review of the published Summary Reports of recommendations of the EU Committee for Veterinary Medicinal Products supplemented with data from the Joint FAO/WHO Expert Committee on Food Additives (JECFA) reports on veterinary drug residues in food identified 120 compounds, of which 105 had teratogenicity information in more than one species. The analysis of these compounds, representing a variety of chemical and pharmacological classes, provided justification for consideration of the use of a tiered approach for developmental toxicity evaluation of veterinary drugs for food-producing animals. The tiered approach begins with developmental toxicity testing in a rodent species, preferably the rat. If teratogenicity is observed, no testing in a second species would be required, except under specific circumstances where the ADI is determined based on the NOEL from this study. If a negative or an equivocal result for teratogenicity were observed in the rodent, then a developmental test in a second species, preferably the rabbit, would be conducted. The tiered approach provides thorough hazard identification, based on the use of a second species for compounds negative for teratogenicity in the rodent, and maintains maximum public protection based on the extremely low potential for human exposure to these compounds, while making a genuine attempt to limit unnecessary animal testing.

  5. Acrylamide: inhibition of formation in processed food and mitigation of toxicity in cells, animals, and humans.

    PubMed

    Friedman, Mendel

    2015-06-01

    Potentially toxic acrylamide is largely derived from the heat-inducing reactions between the amino group of the amino acid asparagine and carbonyl groups of glucose and fructose in plant-derived foods including cereals, coffees, almonds, olives, potatoes, and sweet potatoes. This review surveys and consolidates the following dietary aspects of acrylamide: distribution in food, exposure and consumption by diverse populations, reduction of the content in different food categories, and mitigation of adverse in vivo effects. Methods to reduce acrylamide levels include selecting commercial food with a low acrylamide content, selecting cereal and potato varieties with low levels of asparagine and reducing sugars, selecting processing conditions that minimize acrylamide formation, adding food-compatible compounds and plant extracts to food formulations before processing that inhibit acrylamide formation during processing of cereal products, coffees, teas, olives, almonds, and potato products, and reducing multiorgan toxicity (antifertility, carcinogenicity, neurotoxicity, teratogenicity). The herein described observations and recommendations are of scientific interest for food chemistry, pharmacology, and toxicology, but also have the potential to benefit nutrition, food safety, and human health.

  6. Modulation of radiation-induced organs toxicity by cremophor-el in experimental animals.

    PubMed

    Ramadan, L A; Shouman, S A; Sayed-Ahmed, M M; El-Habit, O H

    2001-02-01

    Pharmacological and cytogenetic evaluations of the protective effects of polyethoxylated castor oil cremophor-EL (cremophor) against hepato, renal and bone marrow toxicity induced by gamma irradiation in normal rats were carried out. A single dose of irradiation (6 Gy) caused hepatic and renal damage manifested biochemically as an elevation in levels of serum alanine and aspartate aminotransferase as well as an increase in blood urea. Cremophor administration at a dose level of 50 microl kg-1 intravenously 1 day before exposure to irradiation (6 Gy) protected the liver and kidney as indicated by the recovery of levels of hepatic aminotransferase, urea and lipid profiles to normal values. Gamma irradiation of male rats caused a decrease in reduced glutathione and an increase in the oxidized form in rat-liver homogenate. A highly significant increase in the incidence of micronucleated normochromatic erythrocytes and micronucleated polychromatic erythrocytes was observed after irradiation exposure. The induced genotoxicity in the bone marrow cells was corrected by pretreatment with cremophor. The findings of this study suggest that cremophor pretreatment can potentially be used clinically to prevent irradiation-induced hepato, renal and bone marrow toxicity without interference with its cytotoxic activity.

  7. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity.

    PubMed

    Wei, Kai; Li, Wei; Gao, Shan; Ji, Bin; Zang, Yating; Su, Bo; Wang, Kaile; Yao, Maosheng; Zhang, Jue; Wang, Jinglin

    2016-01-05

    Ricin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant, and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns, and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney, and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment.

  8. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity

    PubMed Central

    Wei, Kai; Li, Wei; Gao, Shan; Ji, Bin; Zang, Yating; Su, Bo; Wang, Kaile; Yao, Maosheng; Zhang, Jue; Wang, Jinglin

    2016-01-01

    Ricin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant, and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns, and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney, and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment. PMID:26728251

  9. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity

    NASA Astrophysics Data System (ADS)

    Wei, Kai; Li, Wei; Gao, Shan; Ji, Bin; Zang, Yating; Su, Bo; Wang, Kaile; Yao, Maosheng; Zhang, Jue; Wang, Jinglin

    2016-01-01

    Ricin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant, and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns, and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney, and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment.

  10. Using early life stages of marine animals to screen the toxicity of priority hazardous and noxious substances.

    PubMed

    Cunha, Isabel; Torres, Tiago; Oliveira, Helena; Martins, Rosário; McGowan, Thomas; Sheahan, David; Santos, Miguel Machado

    2017-04-01

    This study provides toxicity values for early life stages (ELS) of two phylogenetically distinct marine animal taxa, the sea urchin (Paracentrotus lividus), a deuterostome invertebrate, and the turbot (Scophthalmus maximus), a vertebrate (teleost), when challenged by six hazardous and noxious substances (HNS): aniline, butyl acrylate, m-cresol, cyclohexylbenzene, hexane and trichloroethylene. The aim of the study was to provide preliminary information on toxic effects of representative and relevant priority HNS to assess the risk posed by spills to marine habitats and therefore improve preparedness and the response at the operational level. Selection criteria to include each compound in the study were (1) inclusion in the HASREP (2005) list; (2) presence on the priority list established by Neuparth et al. (2011); (3) paucity of toxicological data (TOXnet and ECOTOX) for marine organisms; (4) behaviour in the water according to the categories defined by the European Behaviour classification system (GESAMP 2002), by selecting compounds with different behaviours in water; and (5) physicochemical and toxicological properties, where available, in order to anticipate the most toxic compounds. Aniline and m-cresol were the most toxic compounds with no observed apical effect concentration (NOAEC) values for sea urchin ranging between 0.01 and 0.1 mg/L, followed by butyl acrylate and cyclohexylbenzene with NOAECs ranging between 0.1 and 1.0 mg/L and trichloroethylene with NOAEC values that were in the range between 1 and 10 mg/L, reflecting their behaviour in water, mostly vapour pressure, but also solubility and log Kow. Hexane was toxic only for turbot embryos, due to its neurotoxic effects, and not for sea urchin larvae, at concentrations in the range between 1 and 10 mg/L. The concentrations tested were of the same order of magnitude for both species, and it was observed that sea urchin embryos (length of the longest arm) are more sensitive than turbot eggs larvae

  11. Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity.

    PubMed

    Shaw, C A; Tomljenovic, L

    2013-07-01

    We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer's and has been linked to this disease and to the Guamanian variant, ALS-PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome.

  12. Toxicity of molybdenum and its trace analysis in animal tissues and plants.

    PubMed

    Abbasi, S A

    1981-01-01

    A sensitive, selective, rapid and reproducible method is presented for the analysis of submicrogram levels of molybdenum in animal tissues (Liver) and plants. The method is based on solvent extraction of Molybdenum (VI) using isoamyl alcohol solution of N-o-tolyl-o-methoxy-benzohydroxamic acid at pH 1.5-2.5, and subsequent spectrophotometric determination of the yellow extract at 350 nm.

  13. Liposomal butamben gel formulations: toxicity assays and topical anesthesia in an animal model.

    PubMed

    Cereda, Cintia Maria Saia; Guilherme, Viviane Aparecida; Alkschbirs, Melissa Inger; de Brito Junior, Rui Barbosa; Tofoli, Giovana Radomille; Franz-Montan, Michelle; de Araujo, Daniele Ribeiro; de Paula, Eneida

    2017-03-01

    The aim of this study was to evaluate the in vitro cytotoxicity and the in vivo analgesic effect and local toxicity of the local anesthetic butamben (BTB) encapsulated in conventional or elastic liposomes incorporated in gel formulations. The results showed that both gel formulations of liposomal BTB reduced the cytotoxicity (p < 0.001; one-way ANOVA/Tukey's test) and increased the topical analgesic effect (p < 0.05; one-way ANOVA/Tukey's test) of butamben, compared to plain BTB gel. The gel formulations presented good rheological properties, and stability assays detected no differences in physicochemical stability up to 30 d after preparation. Moreover, histological assessment revealed no morphological changes in rat skin after application of any of the gel formulations tested.

  14. Improved dispersion method of multi-wall carbon nanotube for inhalation toxicity studies of experimental animals.

    PubMed

    Taquahashi, Yuhji; Ogawa, Yukio; Takagi, Atsuya; Tsuji, Masaki; Morita, Koichi; Kanno, Jun

    2013-01-01

    A multi-wall carbon nanotube (MWCNT) product Mitsui MWNT-7 is a mixture of dispersed single fibers and their agglomerates/aggregates. In rodents, installation of such mixture induces inflammatory lesions triggered predominantly by the aggregates/agglomerates at the level of terminal bronchiole of the lungs. In human, however, pulmonary toxicity induced by dispersed single fibers that reached the lung alveoli is most important to assess. Therefore, a method to generate aerosol predominantly consisting of dispersed single fibers without changing their length and width is needed for inhalation studies. Here, we report a method (designated as Taquann method) to effectively remove the aggregate/agglomerates and enrich the well-dispersed singler fibers in dry state without dispersant and without changing the length and width distribution of the single fibers. This method is base on two major concept; liquid-phase fine filtration and critical point drying to avoid re-aggregation by surface tension. MWNT-7 was suspended in Tert-butyl alcohol, freeze-and-thawed, filtered by a vibrating 25 µm mesh Metallic Sieve, snap-frozen by liquid nitrogen, and vacuum-sublimated (an alternative method to carbon dioxide critical point drying). A newly designed direct injection system generated well-dispersed aerosol in an inhalation chamber. The lung of mice exposed to the aerosol contained single fibers with a length distribution similar to the original and the Taquann-treated sample. Taquann method utilizes inexpensive materials and equipments mostly found in common biological laboratories, and prepares dry powder ready to make well-dispersed aerosol. This method and the chamber with direct injection system would facilitate the inhalation toxicity studies more relevant to human exposure.

  15. Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

    SciTech Connect

    Tonk, Elisa C.M.; Verhoef, Aart; Gremmer, Eric R.; Loveren, Henk van; Piersma, Aldert H.

    2012-04-01

    The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 at doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the

  16. Acute toxicity of sodium nitrate, potassium nitrate, and potassium chloride and their effects on the hemolymph composition and gill structure of early juvenile blue swimmer crabs(Portunus pelagicus Linnaeus, 1758) (Decapoda, Brachyura, Portunidae).

    PubMed

    Romano, Nicholas; Zeng, Chaoshu

    2007-09-01

    Various nutrients, including K+ and NO3-, are increasingly being discharged into aquatic systems via anthropogenic sources, which may impact marine organisms. The present study was conducted on blue swimmer crab (Portunus pelagicus) early juveniles to determine the acute toxicity of NaNO3, KNO3, and KCl; if a toxicity interaction exists between K+ and NO3-; the hemolymph Na+, K+, and Ca2+ changes; and the gill histopathological alterations following exposure to elevated NaNO3, KNO3, and KCl levels. A total of 20 replicate crabs were exposed to each of the five NaNO3, KNO3, and KCl concentrations for 96 h. After 96 h, the surviving crabs were sampled for hemolymph Na+, K+, and Ca2+ levels and fixed for histological examination of the anterior gills. The 96-h median lethal concentration of NaNO3-N, KNO3-N, KNO3-K, and KCl-K was 3,452, 112, 312, and 356 mg/L, respectively, for early P. pelagicus juveniles. The toxicity of NaNO3-N was significantly less (p < 0.01) than that of KNO3-N. Furthermore, at the same K+ levels, KNO3-K was significantly (p < 0.05) more toxic than KCl-K, indicating a toxicity interaction between K+ and NO3-. Following exposure to elevated KNO3 and KCl levels, the crabs had significantly higher (p < 0.01) hemolymph K+ levels compared to the control. Conversely, following exposure to elevated NaNO3 concentrations, the crabs had significantly higher (p < 0.01) hemolymph Na+ levels but significantly lower (p < 0.01) hemolymph K+ levels. Despite the markedly different hemolymph ionic changes following NaNO3 and KNO3/KCl exposure, the histopathological changes to the anterior gill lamellae of the crabs appeared to be similar, including lamellae swelling, epithelial thickening, pillar cell disruption, necrosis, and distortion.

  17. Toxic effects of two sources of dietborne cadmium on the juvenile cobia, Rachycentron canadum L. and tissue-specific accumulation of related minerals.

    PubMed

    Liu, Kang; Chi, Shuyan; Liu, Hongyu; Dong, Xiaohui; Yang, Qihui; Zhang, Shuang; Tan, Beiping

    2015-08-01

    In the present study, juvenile cobia, Rachycentron canadum L. were fed diets contaminated by two different sources of cadmium: squid viscera meal (SVM-Cd, organic form) and cadmium chloride (CdCl2-Cd, inorganic form). The Cd concentrations in fish diet were approximate 3.0, 5.0 and 10.0mg Cd kg(-1) for both inorganic and organic forms. In the control diet (0.312mg Cd kg(-1) diet, Cd mainly come from fish meal), no cadmium was added. The experiment lasted for 16 weeks and a statistically significant inverse relationship was observed between specific growth rate (SGR) and the concentration of dietary Cd. The SGR of cobia fed a diet with SVM-Cd increased at the lowest doses and decreased with the increasing level of dietary SVM. Fish fed diet contaminated SVM-Cd had significantly higher SGR than those fed diets contaminated CdCl2-Cd among the high Cd level diets treatments. The dietary Cd levels also significantly affected the survival rate of the fish. Among the hematological characteristics and plasma constituents, glutamic-pyruvic transaminase activities and alkaline phosphatase activities in serum and liver increased and hepatic superoxide dismutase activity decreased with the increasing dietary Cd levels. The cobia fed diet contaminated by high level of CdCl2-Cd had significantly higher ALP activity than cobia fed diet contaminated by high level of SVM-Cd. The results from these studies indicate no differences in toxicity response to dietborne SVM-Cd and CdCl2-Cd at a low level of Cd. However, at a higher level, cobia was more sensitive to dietborne CdCl2-Cd than SVM-Cd. Based on quadratic regression of SGR, The Cd concentrations was 3.617mg kg(-1) in the optimal diet, Cd source was SVM (126mg Cd kg(-1) in SVM) which stimulate the growth of cobia and the added level was determined to be 26.7g kg(-1) diet in the present study. Cd accumulations in the kidney of cobia fed both types of Cd were higher than other tissues, and the order of Cd accumulation in tissues

  18. Temperature rise and microplastics interact with the toxicity of the antibiotic cefalexin to juveniles of the common goby (Pomatoschistus microps): Post-exposure predatory behaviour, acetylcholinesterase activity and lipid peroxidation.

    PubMed

    Fonte, Elsa; Ferreira, Pedro; Guilhermino, Lúcia

    2016-11-01

    The goal of this study was to investigate the toxicity of cefalexin to Pomatoschistus microps juveniles in relation to the presence of microplastics in the water and temperature rise. After acclimatization, groups of wild juveniles were exposed for 96h to artificial salt water (control), microplastics alone (0.184mg/l), cefalexin alone (1.3-10mg/l) and in mixture with microplastics (cefalexin: 1.3-10mg/l; microplastics: 0.184mg/l) at 20 and 25°C. Effect criteria were mortality, post-exposure predatory performance (PEPP), acetylcholinesterase activity (AChE) and lipid peroxidation levels (LPO). At 20°C, concentrations of cefalexin alone≥5mg/l significantly reduced PEPP (up to 56%; 96h-EC50=8.4mg/l), indicating toxicity of the antibiotic to juveniles after short-term exposure to water concentrations in the low ppm range. At 20°C, fish exposed to microplastics alone did not have significant differences in any of the parameters tested relative to the control group but tended to have an inhibition of the PEPP (23%) and AChE (21%); at 25°C, microplastics alone caused mortality (33%) and PEPP inhibition (28%). Thus, microplastics are toxic to P. microps juveniles. At 20°C, under simultaneous exposure to cefalexin and microplastics, the PEPP was significantly reduced (at cefalexin concentrations≥1.25mg/l). Moreover, at 25°C, the toxicity curves of cefalexin (PEPP based), alone and in mixture with microplastics, were significantly different (p<0.05; 96h-EC50 of 3.8 and 5.2mg/l, respectively), and the integrated data analysis indicated significant interactions between the two substances for all biomarkers. Thus, the presence of microplastics in the water influenced the toxicity of cefalexin. The rise of water temperature (from 20°C to 25°C), increased the microplastics-induced mortality (from 8 to 33%), and the inhibitory effects of cefalexin on the PEPP (up to 70%). Significant differences (p<0.05) between the toxicity curves of cefalexin alone at distinct

  19. Xenopus laevis is a potential alternative model animal species to study reproductive toxicity of phytoestrogens.

    PubMed

    Cong, Lin; Qin, Zhan-Fen; Jing, Xiang-Ning; Yang, Lei; Zhou, Jing-Ming; Xu, Xiao-Bai

    2006-05-10

    This study investigated effects of phytoestrogen quercetin on the gonadal development in Xenopus laevis. X. laevis at Nieuwkoop and Faber stage 46/47 were exposed to 50, 100 and 200 microg/L quercetin till 1 month postmetamorphosis. Gonads from frogs at 1 and 3 months postmetamorphosis were examined in gross morphology and histology. The highest dose of quercetin as well as estradiol (E2) significantly increased the percentages of phenotypic females. Exposure to quercetin at all doses induced abnormal testes with certain ovarian characteristics to some degree in gross morphology, including ovotestes. The abnormality rate exceeded 10% in each quercetin treatment. Histologic examination revealed that some abnormal testes exhibited intersexuality with testicular structure and ovarian structure or oocytes interspersed in testicular structure at 1 month postmetamorphosis. At 3 months postmetamorphosis, testicular abnormalities were more obvious, such as necrosis or apoptosis of spermatogonia, occurrence of developed or undeveloped oocytes, delay of the development of seminiferous tubes without or less late stage spermatocytes. The results have shown that quercetin cannot only feminize but also impair testicular development of X. laevis, i.e. X. laevis is sensitive to phytoestrogen. It is suggested that X. laevis might be an alternative model species to study reproductive toxicity of phytoestrogens.

  20. Juvenile Arthritis

    MedlinePlus

    Juvenile arthritis (JA) is arthritis that happens in children. It causes joint swelling, pain, stiffness, and loss of motion. It can affect any joint, but ... of JA that children get is juvenile idiopathic arthritis. There are several other forms of arthritis affecting ...

  1. Acute toxic effects of single dose dacarbazine: hematological and histological changes in an animal model.

    PubMed

    Milijašević, B; Stefanović, D; Lalić-Popović, M; Tomić, Z; Kolarović, J; Lalošević, D; Mikov, M

    2014-11-01

    Treatment of advanced soft tissue sarcoma usually includes dacarbazine (DTIC), an alkylating agent that methylates DNA and is active during all phases of the cell cycle. Common side effects of DTIC include nausea, vomiting, impaired liver and kidney function, myelosuppression, and pneumonia. There are no accounts, however, of histological and hematological changes caused by DTIC. We investigated acute hematological and morphological changes in different organs and in tumors that were caused by a single dose of DTIC. Adult Syrian golden hamsters were inoculated with a suspension of tumorigenic baby hamster kidney (BHK) cells by subcutaneous injection. On day 14 after inoculation, doses of 1.4, 1.6, 1.8 or 2.0 g/m(2) DTIC were injected intraperitoneally into the hamsters. Hamsters in the control group were injected with physiological saline in the same way. Seven days after drug or saline injection the animals were sacrificed and samples of blood, heart, kidney, liver, lungs, spleen, small intestine and tumor were excised, processed and analyzed. Mitoses were counted using an ocular extension with engraved frame. Anemia, thrombocytopenia and leukocytosis were found in the control group of hamsters with fibrosarcoma, whereas animals with fibrosarcoma treated with DTIC developed anemia, thrombocytopenia and leukopenia. Severe pneumonia and moderate hepatitis were detected in all DTIC treated groups. Effects of DTIC on tumor cells included rounding and enlargement of nuclei and rarefaction of chromatin. The number of mitoses was reduced with increasing doses of DTIC. Hepatitis, myelosuppression, pneumonia, and dose-related inhibition of tumor cell proliferation were observed after a single dose of DTIC.

  2. The development of response surface pathway design to reduce animal numbers in toxicity studies

    PubMed Central

    2014-01-01

    Background This study describes the development of Response Surface Pathway (RSP) design, assesses its performance and effectiveness in estimating LD50, and compares RSP with Up and Down Procedures (UDPs) and Random Walk (RW) design. Methods A basic 4-level RSP design was used on 36 male ICR mice given intraperitoneal doses of Yessotoxin. Simulations were performed to optimise the design. A k-adjustment factor was introduced to ensure coverage of the dose window and calculate the dose steps. Instead of using equal numbers of mice on all levels, the number of mice was increased at each design level. Additionally, the binomial outcome variable was changed to multinomial. The performance of the RSP designs and a comparison of UDPs and RW were assessed by simulations. The optimised 4-level RSP design was used on 24 female NMRI mice given Azaspiracid-1 intraperitoneally. Results The in vivo experiment with basic 4-level RSP design estimated the LD50 of Yessotoxin to be 463 μg/kgBW (95% CI: 383–535). By inclusion of the k-adjustment factor with equal or increasing numbers of mice on increasing dose levels, the estimate changed to 481 μg/kgBW (95% CI: 362–566) and 447 μg/kgBW (95% CI: 378–504 μg/kgBW), respectively. The optimised 4-level RSP estimated the LD50 to be 473 μg/kgBW (95% CI: 442–517). A similar increase in power was demonstrated using the optimised RSP design on real Azaspiracid-1 data. The simulations showed that the inclusion of the k-adjustment factor, reduction in sample size by increasing the number of mice on higher design levels and incorporation of a multinomial outcome gave estimates of the LD50 that were as good as those with the basic RSP design. Furthermore, optimised RSP design performed on just three levels reduced the number of animals from 36 to 15 without loss of information, when compared with the 4-level designs. Simulated comparison of the RSP design with UDPs and RW design demonstrated the superiority of RSP. Conclusion

  3. Approaches to extrapolating animal toxicity data on organic solvents to public health.

    PubMed

    Bushnell, Philip J; Boyes, William K; Shafer, Timothy J; Bale, Ambuja S; Benignus, Vernon A

    2007-03-01

    Synthesizing information about the acute neurotoxicity of organic solvents into predictive relationships between exposure and effect in humans is difficult because (1) data are usually derived from experimental animals whose sensitivity to the chemical relative to humans is unknown; (2) the specific endpoints measured in laboratory animals seldom translate into effects of concern in humans; and (3) the mode of action of the chemical is rarely understood. We sought to develop approaches to estimate the hazard and cost of exposure to organic solvents, focusing on the acute behavioral effects of toluene in rats and humans. Available published data include studies of shock avoidance behavior in rats and choice reaction time in humans. A meta-analysis of these data suggested that a 10% change in rat avoidance behavior occurs at a blood concentration of toluene 25 times higher than the concentration at which a 10% change in human choice reaction time occurs. In contrast, our in vitro studies of nicotinic acetylcholine receptors indicated that human and rat receptors do not differ in sensitivity to toluene. Analysis of other dose-response relationships for visual and cognitive functions in rats suggests that the apparent difference between rats and humans may be driven by the specific endpoints measured in the two species rather than by inherent differences in sensitivity to toluene. We also explored the hypothesis that dose-equivalence relationships may be used to compare the societal costs of two chemicals. For example, ethanol-induced changes in choice reaction time, for which societal costs are estimatable, may be used as a benchmark effect for estimating the monetary benefits of controlling exposure to organic solvents. This dose-equivalence method is applicable for solvents because this set of data fulfills three important assumptions about equivalence relationships based on a single effect: (1) a common dose metric (concentration of the chemical in the brain); (2

  4. The development of response surface pathway design to reduce animal numbers in toxicity studies.

    PubMed

    Dewi, Sagita; Aune, Tore; Bunæs, John A Aasen; Smith, Adrian J; Larsen, Stig

    2014-03-25

    This study describes the development of Response Surface Pathway (RSP) design, assesses its performance and effectiveness in estimating LD50, and compares RSP with Up and Down Procedures (UDPs) and Random Walk (RW) design. A basic 4-level RSP design was used on 36 male ICR mice given intraperitoneal doses of Yessotoxin. Simulations were performed to optimise the design. A k-adjustment factor was introduced to ensure coverage of the dose window and calculate the dose steps. Instead of using equal numbers of mice on all levels, the number of mice was increased at each design level. Additionally, the binomial outcome variable was changed to multinomial. The performance of the RSP designs and a comparison of UDPs and RW were assessed by simulations. The optimised 4-level RSP design was used on 24 female NMRI mice given Azaspiracid-1 intraperitoneally. The in vivo experiment with basic 4-level RSP design estimated the LD50 of Yessotoxin to be 463 μg/kgBW (95% CI: 383-535). By inclusion of the k-adjustment factor with equal or increasing numbers of mice on increasing dose levels, the estimate changed to 481 μg/kgBW (95% CI: 362-566) and 447 μg/kgBW (95% CI: 378-504 μg/kgBW), respectively. The optimised 4-level RSP estimated the LD50 to be 473 μg/kgBW (95% CI: 442-517). A similar increase in power was demonstrated using the optimised RSP design on real Azaspiracid-1 data. The simulations showed that the inclusion of the k-adjustment factor, reduction in sample size by increasing the number of mice on higher design levels and incorporation of a multinomial outcome gave estimates of the LD50 that were as good as those with the basic RSP design. Furthermore, optimised RSP design performed on just three levels reduced the number of animals from 36 to 15 without loss of information, when compared with the 4-level designs. Simulated comparison of the RSP design with UDPs and RW design demonstrated the superiority of RSP. Optimised RSP design reduces the number of animals

  5. Toxic effect of single treatment with bromantane on neurological status of experimental animals.

    PubMed

    Iezhitsa, I N; Spasov, A A; Bugaeva, L I; Morozov, I S

    2002-04-01

    Neurotoxicological profile of actoprotector bromantane was studied on rats using S. Irwin's protocol of multi-test observation. The drug in doses of 30-300 mg/kg stimulated and in doses of 600-9,600 mg/kg suppressed behavioral activity. Spontaneous motor activity increased after single treatment with bromantane in doses of 30-300 mg/kg, did not change after treatment in doses of 600 mg/kg, and was inhibited after treatment in doses above 600 mg/kg. In doses of 300-600 mg/kg the drug reduced pain sensitivity threshold and in doses above 600 mg/kg elevated the pain threshold and tactile sensitivity and reaction to knock. Bromantane induced mydriasis in all studied doses; in doses above 10 g/kg the preparation induced blepharoptosis. In doses above 5 g/kg bromantane slightly increased respiration rate and depth (Kussmaul-like respiration). In some animals bromantane in high doses induced regurgitation, diarrhea, and polyuria. Rectal temperature decreased by 0.5-1 degrees C after virtually all doses. Behavioral effects of bromantane in doses of 30 and 600 mg/kg were associated with stimulation of the central dopamine and suppression of muscarinic and nicotinic cholinergic structures, n-cholinolytic effects of bromantane was more pronounced at a dose of 30 mg/kg than at a dose of 600 mg/kg.

  6. The interaction of genetics and environmental toxicants in amyotrophic lateral sclerosis: results from animal models.

    PubMed

    Sher, Roger B

    2017-06-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in the progressive death of motor neurons, leading to paralysis and eventual death. There is presently no cure for ALS, and only two drugs are available, neither of which provide significant extension of life. The wide variation in onset and progression of the disease, both in sporadic and even in strongly penetrant monogenic familial forms of ALS, indicate that in addition to background genetic variation impacting the disease process, environmental exposures are likely contributors. Epidemiological evidence worldwide implicates exposures to bacterial toxins, heavy metals, pesticides, and trauma as probable environmental factors. Here, we review current advances in gene-environment interactions in ALS animal models. We report our recent discoveries in a zebrafish model of ALS in relation to exposure to the cyanobacterial toxin BMAA, and discuss several results from mouse models that show interactions with exposure to mercury and statin drugs, both leading to acceleration of the disease process. The increasing research into this combinatorial gene-environment process is just starting, but shows early promise to uncover the underlying biochemical pathways that instigate the initial motor neuron defects and lead to their rapidly progressive dysfunction.

  7. The use of freshwater and saltwater animals to distinguish between the toxic effects of salinity and contaminants in irrigation drain water

    USGS Publications Warehouse

    Ingersoll, Christopher G.; Dwyer, F.J.; Burch, S.A.; Nelson, M.K.; Buckler, D.R.; Hunn, J.B.

    1992-01-01

    Irrigation drain waters entering Stillwater Wildlife Management Area (SWMA) in south-western Nevada contain elevated levels of salinity and several inorganic contaminants (As, B, Cu, Li, Mo, and Sr). Mortalities of fish and waterfowl at the management area are believed to be associated with the poor water quality of the drains. The objective of the present study was to use fresh-water and saltwater animals to distinguish between the toxic effects of salinity and contaminants in effluent samples collected from irrigation drain waters. Static acute effluent tests were conducted with water collected from four sites at SWMA. Animals acclimated or cultured in fresh water (fathead minnows, Pimephales promelas; amphipods, Hyalella azteca; cladocerans, Daphnia magna) and salt water (striped bass, Morone saxatilis; amphipods, Hyalella azteca; and cladocerans, Daphnia magna) were used to separate toxic effects of salinity from the effects of inorganic contaminants in the drain water. One drain water (TJ drain, salinity 19 parts per thousand (grams per liter), osmolality 503 mmol/kg, hardness 3,780 mg/L as CaCO3) was toxic only to freshwater animals and saltwater cultured daphnids; water from a receiving pond (Pintail Bay, salinity 23 g/L, osmolality 542 mmol/kg, hardness 830 mg/L as CaCO3) was toxic to both freshwater and saltwater animals. Acute tests conducted with reconstituted waters representative of the Pintail Bay sample indicated that atypical ion ratios were toxic to striped bass and amphipods, even without the addition of inorganic contaminants. However, the addition of inorganic contaminants representative of the Pintail Bay sample increased the toxicity of this reconstituted water. These findings indicate that the toxicity of the TJ drain sample was related mainly to elevated salinity and that the toxicity of the Pintail Bay sample was a function of inorganic contamination and atypical ion ratios in combination with elevated salinity.

  8. Carbonyl emission and toxicity profile of diesel blends with an animal-fat biodiesel and a tire pyrolysis liquid fuel.

    PubMed

    Ballesteros, R; Guillén-Flores, J; Martínez, J D

    2014-02-01

    In this paper, two diesel fuels, an animal-fat biodiesel and two diesel blends with the animal-fat biodiesel (50vol.%) and with a tire pyrolysis liquid (TPL) fuel (5vol.%) have been tested in a 4-cylinder, 4-stroke, turbocharged, intercooled, 2.0L Nissan diesel automotive engine (model M1D) with common-rail injection system and diesel oxidation catalyst (DOC). Carbonyl emissions have been analyzed both before and after DOC and specific reactivity of carbonyl profile has been calculated. Carbonyl sampling was carried out by means of a heated line, trapping the gas in 2,4-DNPH cartridges. The eluted content was then analyzed in an HPLC system, with UV-VIS detection. Results showed, on the one hand, an increase in carbonyl emissions with the biodiesel fraction in the fuel. On the other hand, the addition of TPL to diesel also increased carbonyl emissions. These trends were occasionally different if the emissions were studied after the DOC, as it seems to be selectivity during the oxidation process. The specific reactivity was also studied, finding a decrease with the oxygen content within the fuel molecule, although the equivalent ozone emissions slightly increased with the oxygen content. Finally, the emissions toxicity was also studied, comparing them to different parameters defined by different organizations. Depending on the point of study, emissions were above or below the established limits, although acrolein exceeded them as it has the least permissive values.

  9. Juvenile Firesetting.

    PubMed

    Peters, Brittany; Freeman, Bradley

    2016-01-01

    Juvenile firesetting is a significant cause of morbidity and mortality in the United States. Male gender, substance use, history of maltreatment, interest in fire, and psychiatric illness are commonly reported risk factors. Interventions that have been shown to be effective in juveniles who set fires include cognitive behavior therapy and educational interventions, whereas satiation has not been shown to be an effective intervention. Forensic assessments can assist the legal community in adjudicating youth with effective interventions. Future studies should focus on consistent assessment and outcome measures to create more evidence for directing evaluation and treatment of juvenile firesetters.

  10. SEASONAL VARIATION IN PLASMA SEX STEROID CONCENTRATION IN JUVENILE ALLIGATORS

    EPA Science Inventory

    Seasonal variation in plasma sex steroid concentrations is common in mature vertebrates, and is occasionally seen in juvenile animals. In this study, we examine the seasonal pattern of sex hormone concentration in juvenile American alligators (Alligator mississippiensis) and make...

  11. SEASONAL VARIATION IN PLASMA SEX STEROID CONCENTRATION IN JUVENILE ALLIGATORS

    EPA Science Inventory

    Seasonal variation in plasma sex steroid concentrations is common in mature vertebrates, and is occasionally seen in juvenile animals. In this study, we examine the seasonal pattern of sex hormone concentration in juvenile American alligators (Alligator mississippiensis) and make...

  12. Evaluation of plant and animal protein sources as partial or total replacement of fish meal in diets for juvenile Nile tilapia

    USDA-ARS?s Scientific Manuscript database

    A feeding trial was conducted in a closed system with Nile tilapia (Oreochromis niloticus) juveniles (mean weight, 2.84 g) to examine the effects of total replacement of fish meal (FM), with and without supplementation of DL-methionine (Met) and L-lysine (Lys), by plant protein sources. Fish were f...

  13. Dermatomyositis (Juvenile)

    MedlinePlus

    ... of children with JDM may have a more chronic course that is less responsive to therapy. Juvenile ... disease and arthritis. Since the myopathies can be chronic diseases, it is important for patients to have ...

  14. Juvenile Prostitution.

    ERIC Educational Resources Information Center

    Csapo, Marg

    1986-01-01

    Recent research and Canadian government committee reports concerning juvenile prostitution are reviewed. Proposals are made in the realms of law and social policy; and existing programs are described. (DB)

  15. Cellulose/soy protein isolate composite membranes: evaluations of in vitro cytocompatibility with Schwann cells and in vivo toxicity to animals.

    PubMed

    Luo, Lihua; Gong, Wenrong; Zhou, Yi; Yang, Lin; Li, Daokun; Huselstein, Celine; Wang, Xiong; He, Xiaohua; Li, Yinping; Chen, Yun

    2015-01-01

    To evaluate the in vitro cytocompatibility of cellulose/soy protein isolate composite membranes (CSM) with Schwann cells and in vivo toxicity to animals. A series of cellulose/soy protein isolate composite membranes (CSM) were prepared by blending, solution casting and coagulation process. The cytocompatibility of the CSM to Schwann cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and by direct cells culture of Schwann cells on the surfaces of the CSM, respectively. The in vivo toxicity of the CSM to animals were also evaluated by acute toxicity testing, skin sensitization testing, pyrogen testing and intracutaneous stimulation testing, respectively, according to the ISO 10993 standard. The MTT assay showed that the cell viability of Schwann cells cultured in extracts from the CSM was higher than that from the neat cellulose membrane without containing SPI component. The direct cells culture indicated that the Schwann cells could attach and grow well on the surface of the CSM and the incorporation of SPI into cellulose contributed to improvement of cell adhesion and proliferation. The evaluations of in vivo biological safety suggested that the CSM showed no acute toxicity, no skin sensitization and no intracutaneous stimulation to the experimental animals. The CSM had in vitro cytocompatibility with Schwann cells and biological safety to animals, suggesting potential for the applications as nerve conduit for the repair of nerve defect.

  16. Experiments on the efficacy and toxicity of locoregional chemotherapy of liver tumors with 5-fluoro-2'-deoxyuridine (FUDR) and 5-fluorouracil (5-FU) in an animal model.

    PubMed

    Bartkowski, R; Berger, M R; Aguiar, J L; Henne, T H; Dörsam, J; Geelhaar, G H; Schlag, P; Herfarth, C

    1986-01-01

    For the investigation of locoregional chemotherapy of liver neoplasms we developed a standardized animal model in the rat. Continuous infusion therapy or repeated bolus injections of FUDR or 5-FU were given via the hepatic artery, the portal vein or the vena cava in tumor-bearing animals. The efficacy of the treatment was determined by measuring the tumor volume 3 weeks after tumor cell implantation. For the evaluation of the local and systemic toxicity serum GOT, GPT, and total bilirubin were determined. DNA single strand breaks were assessed in isolated liver and bone marrow cells. Inhibition of colony formation of bone marrow stem cells was determined by CFU-C and CFU-S bioassay. A significant reduction of tumor growth was observed only after continuous infusion of FUDR via the hepatic artery. Systemic toxicity was lowest in this group for both compounds while the local liver toxicity was only slightly elevated.

  17. Efficacy and Safety/Toxicity Study of Recombinant Vaccinia Virus JX-594 in Two Immunocompetent Animal Models of Glioma

    PubMed Central

    Lun, XueQing; Chan, Jennifer; Zhou, Hongyuan; Sun, Beichen; Kelly, John JP; Stechishin, Owen Owen; Bell, John C; Parato, Kelley; Hu, Kang; Vaillant, Dominique; Wang, Jiahu; Liu, Ta-Chiang; Breitbach, Caroline; Kirn, David; Senger, Donna L; Forsyth, Peter A

    2010-01-01

    The purpose of this study was to investigate the oncolytic potential of the recombinant, granulocyte macrophage colony-stimulating factor (GM-CSF)-expressing vaccinia virus (VV) JX-594 in experimental malignant glioma (MGs) in vitro and in immunocompetent rodent models. We have found that JX-594 killed all MG cell lines tested in vitro. Intratumoral (i.t.) administration of JX-594 significantly inhibited tumor growth and prolonged survival in rats-bearing RG2 intracranial (i.c.) tumors and mice-bearing GL261 brain tumors. Combination therapy with JX-594 and rapamycin significantly increased viral replication and further prolonged survival in both immunocompetent i.c. MG models with several animals considered “cured” (three out of seven rats >120 days, terminated experiment). JX-594 infected and killed brain tumor-initiating cells (BTICs) from patient samples grown ex vivo, and did so more efficiently than other oncolytic viruses MYXV, Reovirus type-3, and VSVΔM51. Additional safety/toxicity studies in nontumor-bearing rodents treated with a supratherapeutic dose of JX-594 demonstrated GM-CSF-dependent inflammation and necrosis. These results suggest that i.c. administered JX-594 triggers a predictable GM-CSF-mediated inflammation in murine models. Before proceeding to clinical trials, JX-594 should be evaluated in the brains of nonhuman primates and optimized for the viral doses, delivery routes as well as the combination agents (e.g., mTOR inhibitors). PMID:20808290

  18. Efficacy and safety/toxicity study of recombinant vaccinia virus JX-594 in two immunocompetent animal models of glioma.

    PubMed

    Lun, XueQing; Chan, Jennifer; Zhou, Hongyuan; Sun, Beichen; Kelly, John J P; Stechishin, Owen Owen; Bell, John C; Parato, Kelley; Hu, Kang; Vaillant, Dominique; Wang, Jiahu; Liu, Ta-Chiang; Breitbach, Caroline; Kirn, David; Senger, Donna L; Forsyth, Peter A

    2010-11-01

    The purpose of this study was to investigate the oncolytic potential of the recombinant, granulocyte macrophage colony-stimulating factor (GM-CSF)-expressing vaccinia virus (VV) JX-594 in experimental malignant glioma (MGs) in vitro and in immunocompetent rodent models. We have found that JX-594 killed all MG cell lines tested in vitro. Intratumoral (i.t.) administration of JX-594 significantly inhibited tumor growth and prolonged survival in rats-bearing RG2 intracranial (i.c.) tumors and mice-bearing GL261 brain tumors. Combination therapy with JX-594 and rapamycin significantly increased viral replication and further prolonged survival in both immunocompetent i.c. MG models with several animals considered "cured" (three out of seven rats >120 days, terminated experiment). JX-594 infected and killed brain tumor-initiating cells (BTICs) from patient samples grown ex vivo, and did so more efficiently than other oncolytic viruses MYXV, Reovirus type-3, and VSV(ΔM51). Additional safety/toxicity studies in nontumor-bearing rodents treated with a supratherapeutic dose of JX-594 demonstrated GM-CSF-dependent inflammation and necrosis. These results suggest that i.c. administered JX-594 triggers a predictable GM-CSF-mediated inflammation in murine models. Before proceeding to clinical trials, JX-594 should be evaluated in the brains of nonhuman primates and optimized for the viral doses, delivery routes as well as the combination agents (e.g., mTOR inhibitors).

  19. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

  20. Acute toxicity of resmethrin, malathion and methoprene to larval and juvenile American lobsters (Homarus amemcanus) and analysis of pesticide levels in surface waters after Scourge™, Anvil™ and Altsoid™ application

    USGS Publications Warehouse

    Zulkosky, Ann M.; Ruggieri, Joseph P.; Terracciano, Stephen A.; Brownawell, Bruce J.; McElroy, Anne E.

    2005-01-01

    Acute toxicity and immune response, combined with temperature stress effects, were evaluated in larval and juvenile American lobsters (Homarus americanus) exposed to malathion, resmethrin and methoprene. These pesticides were used to control West Nile virus in New York in 1999, the same year the American lobster population collapsed in western Long Island Sound (LIS). Whereas the suite of pesticides used for mosquito control changed in subsequent years, a field study was also conducted to determine pesticide concentrations in surface waters on Long Island and in LIS after operational applications. The commercial formulations used in 2002 and 2003—Scourge, Anvil and Altosid—contain the active ingredients resmethrin, sumithrin and methoprene, respectively. Concentrations of the synergist piperonyl butoxide (PBO) were also measured as a proxy for pesticide exposure. Acute mortality in Stage I-II larval lobsters demonstrated that they are extremely sensitive to continuous resmethrin exposure. Resmethrin LC50s for larval lobsters determined under flow-through conditions varied from 0.26–0.95 μg L−1 in 48- and 96-h experiments at 16°C, respectively. Increased temperature (24°C) did not significantly alter resmethrin toxicity. Malathion and methoprene were less toxic than resmethrin. The 48-h LC50 for malathion was 3.7 μg L−1 and methoprene showed no toxicity at the highest (10 μg L−1) concentration tested. Phenoloxidase activity was used as a measure of immune response for juvenile lobsters exposed to sublethal pesticide concentrations. In continuous exposures to sublethal doses of resmethrin (0.03 μg L−1) or malathion (1 μg L−1) for 7 d at 16 or 22°C, temperature had a significant effect on phenoloxidase activity (P ≤ 0.006) whereas pesticide exposure did not (P = 0.880). The analytical methods developed using high performance liquid chromatography coupled to time-of-flight mass spectroscopy (LC-TOF-MS) provided high sensitivity with mass

  1. Amelioration of Acute Mercury Toxicity by a Novel, Non-Toxic Lipid Soluble Chelator N,N'bis-(2-mercaptoethyl)isophthalamide: Effect on Animal Survival, Health, Mercury Excretion and Organ Accumulation.

    PubMed

    Clarke, David; Buchanan, Roger; Gupta, Niladri; Haley, Boyd

    2012-01-01

    The toxic effects of mercury are known to be complex with specific enzyme inhibitions and subsequent oxidative stress adding to the damaging effects. There are likely other factors involved, such as the development of impaired metal ion homeostasis and depletion of thiol and selenium based metabolites such as cysteine and selenium. Much of the toxicity of mercury occurs at the intracellular level via binding of Hg(2+) to thiol groups in specific proteins. Therefore, amelioration of mercury toxicity by the use of chelation would likely be enhanced by the use of a chelator that could cross the cell membrane and the blood brain barrier. It would be most favorable if this compound was of low toxicity, had appropriate pharmacokinetics, bound and rendered mercury cation non-toxic and had antioxidant properties. Herein we report on such a chelator, N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI), and, using an animal model, show that it prevented the toxic effects associated with acute exposure induced by injected mercury chloride.

  2. Lung toxicity in mice of airborne particulate matter from a modern layer hen facility containing Proposition 2-compliant animal caging.

    PubMed

    Franzi, Lisa M; Linderholm, Angela L; Rabowsky, Michelle; Last, Jerold A

    2017-03-01

    Proposition 2, which requires that egg-laying hens be confined only in ways that allow these animals to lie down, stand up, fully extend their limbs and turn around freely, was passed by the voters of California in 2008. These new housing requirements were introduced in the USA and European Union without considering the potential impact of changes in layer hen housing on the health of poultry workers in the new facilities. Particles were collected from ambient air inside a large layer hen complex featuring separate barns with conventional battery caging, enriched caging, or 'free range' (aviary) housing during winter, spring, and summer seasons over one year. Toxicity of the particles was evaluated by analysis of inflammatory cell influx into lung lavage fluid after intratracheal instillation into mice. Capacity of the particles to elicit oxidative stress was evaluated using a macrophage cell line engineered with a reporter gene sensitive to nuclear factor κB activation. We observed similar pro-inflammatory and pro-oxidant effects of the particles collected from different types of barns and over different seasons, suggesting that standard industrial hygiene techniques for evaluating respirable particles in ambient air can adequately monitor worker risk. Based on particle concentrations found in ambient air in the barns, we can rank the facilities for worker exposure to particles as conventional caging (now banned) approximately equal to enriched caging (permitted under Proposition 2). Aviary housing is associated with increased exposure of workers to particulate matter and, therefore, to greater risk of allergic reactions and/or decreased respiratory function.

  3. Juvenile Spondyloarthritis

    PubMed Central

    Gmuca, Sabrina; Weiss, Pamela F.

    2015-01-01

    Purpose of review To provide a comprehensive update of the pathogenesis, diagnostic imaging, treatments, and disease activity measurements of juvenile spondyloarthritis (JSpA). Recent findings Genetic and microbiome studies have provided new information regarding possible pathogenesis of JSpA. Recent work suggests that children with JSpA have decreased thresholds for pain in comparison to healthy children. Additionally, pain on physical examination and abnormalities on ultrasound of the entheses are not well correlated. Treatment guidelines for juvenile arthritis, including JSpA, were published by the American College of Rheumatology and are based on active joint count and presence of sacroiliitis. Recent studies have established the efficacy of tumor necrosis factor inhibitors in the symptomatic treatment of axial disease, though their efficacy for halting progression of structural damage is less clear. Newly developed disease activity measures for JSpA include the Juvenile Arthritis Disease Activity Score and the JSpA Disease Activity index. In comparison to other categories of juvenile arthritis, children with JSpA are less likely to attain and sustain inactive disease. Summary Further microbiome and genetic research may help elucidate JSpA pathogenesis. More randomized therapeutic trials are needed and the advent of new composite disease activity measurement tools will hopefully allow for the design of these greatly needed trials. PMID:26002028

  4. Interim report on the genetic and animal toxicity testing of SRC-I products, intermediates, and waste materials. Appendix D. Acute animal studies reports

    SciTech Connect

    Drozdowicz, B.Z.; Kelly, C.M.

    1983-09-01

    Appendix D is a collection of 25 individual reports on the toxicity of SRC-I products, intermediates and residues to rabbits, rats and guinea pigs with acute oral, dermal and inhalation exposure. It includes also eye and dermal irritation tests in rabbits and guinea pigs and dermal sensitization studies in albino guinea pigs. (LTN)

  5. Application of a novel integrated toxicity testing strategy incorporating "3R" principles of animal research to evaluate the safety of a new agrochemical sulfoxaflor.

    PubMed

    Terry, Claire; Rasoulpour, Reza J; Saghir, Shakil; Marty, Sue; Gollapudi, B Bhaskar; Billington, Richard

    2014-05-01

    Plant protection products (PPPs) and the active substance(s) contained within them are rigorously and comprehensively tested prior to registration to ensure that human health is not impacted by their use. In recent years, there has been a widespread drive to have more relevant testing strategies (e.g., ILSI/HESI-ACSA and new EU Directives), which also take account of animal welfare, including the 3R (replacement, refinement, and reduction) principles. The toxicity potential of one such new active substance, sulfoxaflor, a sulfoximine insecticide (CAS #946578-00-3), was evaluated utilizing innovative testing strategies comprising: (1) an integrated testing scheme to optimize information obtained from as few animals as possible (i.e., 3R principles) through modifications of standard protocols, such as enhanced palatability study design, to include molecular endpoints, additional neurotoxicity and immunotoxicity parameters in a subchronic toxicity study, and combining multiple test guidelines into one study protocol; (2) generation of toxicokinetic data across dose levels, sexes, study durations, species, strains and life stages, without using satellite animals, which was a first for PPP development, and (3) addition of prospective mode of action (MoA) endpoints within repeat dose toxicity studies as well as proactive inclusion of specific MoA studies as an integral part of the development program. These novel approaches to generate key data early in the safety evaluation program facilitated informed decision-making on the need for additional studies and contributed to a more relevant human health risk assessment. This supplement also contains papers which describe in more detail the approach taken to establish the MoA and human relevance framework related to toxicities elicited by sulfoxaflor in the mammalian toxicology studies: developmental toxicity in rats mediated via the fetal muscle nicotinic acetylcholine receptor (nAChR) ( Ellis-Hutchings et al. 2014 ); liver

  6. Juvenile Justice in Milwaukee

    ERIC Educational Resources Information Center

    Williams, Gary L.; Greer, Lanetta

    2010-01-01

    Historically, there have been several attempts made to address issues surrounding juvenile delinquency. The Wisconsin Legislature outlines the objectives of the juvenile justice system in the Juvenile Justice Code in s. 939.01, ?to promote a juvenile justice system capable of dealing with the problem of juvenile delinquency, a system which will…

  7. Necrotizing fasciitis in captive juvenile Crocodylus porosus caused by Streptococcus agalactiae: an outbreak and review of the animal and human literature.

    PubMed

    Bishop, E J; Shilton, C; Benedict, S; Kong, F; Gilbert, G L; Gal, D; Godoy, D; Spratt, B G; Currie, B J

    2007-11-01

    We observed an outbreak of necrotizing fasciitis associated with Streptococcus agalactiae infection in a group of juvenile saltwater crocodiles (Crocodylus porosus). We undertook screening of crocodiles and the environment to clarify the source of the outbreak and evaluated the isolates cultured from post-mortem specimens with molecular methods to assess clonality and the presence of known group B streptococcal virulence determinants. The isolates were indistinguishable by pulsed-field gel electrophoresis. They were a typical serotype Ia strain with the Calpha-like protein gene, epsilon (or alp1), the mobile genetic elements IS381 ISSag1 and ISSag2, and belonged to multi-locus sequence type (ST) 23. All of these characteristics suggest they were probably of human origin. We review the medical and veterinary literature relating to S. agalactiae necrotizing fasciitis, epidemiology and virulence determinants.

  8. Juvenile xanthogranuloma.

    PubMed

    Singh, R; Ghazali, W

    1992-05-01

    Juvenile xanthogranuloma is a benign cutaneous growth presenting as papules or nodules. It is characterized by an intradermal collection of lipid-laden macrophages and varying degrees of fibroblastic proliferation. We have recently observed two patients with xanthogranulomas: one was found to have a papular type and the second patient had multiple nodular growths. We present these cases, which should be considered in the differential diagnosis of skin nodules.

  9. PROFILE OF TOXIC RESPONSE TO SEDIMENTS USING WHOLE-ANIMAL AND IN VITRO SUBMITOCHONDRIAL PARTICLE (SMP) ASSAYS

    EPA Science Inventory

    A rapid bioassy for monitoring acute toxicity of wastewater, ground water, and soil and sediment extracts using submitochondrial particles (SMP) has been developed. The assay utilizes the mitochondrial electron transfer enzyme complex present in all eukaryotic cells. Prior develo...

  10. PROFILE OF TOXIC RESPONSE TO SEDIMENTS USING WHOLE-ANIMAL AND IN VITRO SUBMITOCHONDRIAL PARTICLE (SMP) ASSAYS

    EPA Science Inventory

    A rapid bioassy for monitoring acute toxicity of wastewater, ground water, and soil and sediment extracts using submitochondrial particles (SMP) has been developed. The assay utilizes the mitochondrial electron transfer enzyme complex present in all eukaryotic cells. Prior develo...

  11. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... for You Healthy School Lunch Planner Juvenile Idiopathic Arthritis (JIA) KidsHealth > For Teens > Juvenile Idiopathic Arthritis (JIA) ... people under age 17. What Is Juvenile Idiopathic Arthritis? Arthritis doesn't affect young people as much ...

  12. Juvenile rheumatoid arthritis

    MedlinePlus

    ... joints. This form of JIA may turn into rheumatoid arthritis. It may involve five or more large and ... no known prevention for JIA. Alternative Names Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ...

  13. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Juvenile Idiopathic Arthritis (JIA) KidsHealth > For Teens > Juvenile Idiopathic ... can affect people under age 17. What Is Juvenile Idiopathic Arthritis? Arthritis doesn't affect young people ...

  14. Profile of toxic response to sediments using whole-animal and in vitro submitochondrial particle (SMP) assays

    SciTech Connect

    Bettermann, A.D.; Dorofi, J.C.; Lazorchak, J.M.

    1996-03-01

    A rapid bioassay for monitoring acute toxicity of wastewater, ground water, and soil and sediment extracts using submitochondrial particles (SMP) has been developed. The assay utilizes the mitochondrial electron transfer enzyme complex, present in all eukaryotic cells. Prior developmental work with pure chemicals chosen from the US Environmental Protection Agency`s (EPA) priority pollutant list documented order-of-magnitude predictability between the bioassay response and whole-organism tests (e.g., fathead minnow). Recent work has adapted the assay for analysis of uncharacterized environmental samples, including stormwater runoff, landfill leachate, and soil and sediment extracts. A feasibility study was performed to determine whether the SMP assay could detect toxicity in samples previously assessed for toxicity to amphipods. Acute toxicity tests using Hyalella azteca were performed on 30 sediment samples from Colorado`s Arkansas River, Eagle River, and Chalk Creek watersheds, all of which have been directly or indirectly affected by heavy metal mine tailings and drainage. In parallel, two SMP assay protocols designed to differentiate between modes of toxicity were performed on elutriate samples from 23 of the above sites. The results from analysis of the sediments differed widely in the nature and degree of test responses. Significant correlation was found between the responses of the SMP electron transfer protocol and the whole-organisms assay, and between the responses of the SMP electron transfer protocol and levels of zinc and sulfur, as determined by inductively coupled plasma spectroscopy.

  15. Juvenile dermatomyositis: treatment with intravenous gammaglobulin.

    PubMed

    Collet, E; Dalac, S; Maerens, B; Courtois, J M; Izac, M; Lambert, D

    1994-02-01

    High-dose intravenous gammaglobulin (IVGG) has proved to be effective in the treatment of a number of immune disorders. We report two patients with juvenile dermatomyositis (DM) who improved with IVGG therapy. These patients had become refractory to corticosteroids and had developed unacceptable steroid toxicity. We suggest that IVGG can be useful in the treatment of juvenile DM, by reducing steroid requirements, and replacing immunosuppressive drugs.

  16. Routes and modes of administration of resorcinol and their relationship to potential manifestations of thyroid gland toxicity in animals and man.

    PubMed

    Welsch, Frank

    2008-01-01

    Medical case reports published in the 20th century over the course of several decades show that resorcinol caused reversible adverse effects on the human thyroid gland (TG) manifested as hypothyroidism. Affected patients had ulcerating leg varicosities and underwent prolonged treatment with ointments containing high concentrations of resorcinol. In animal studies resorcinol failed to induce TG toxicity, unless pharmacokinetic/toxicokinetic (PK/TK) conditions were manipulated (e.g., injection of resorcinol in oil or application in a slow release formulation). A recently completed two-generation reproductive toxicity study in rats did not detect any adverse effects on either reproductive or TG end points (Welsch, Nemec, and Lawrence, 2008, Int. J. Toxicol. 37, this issue). Resorcinol intake via drinking water up to the palatability limit had resulted in average daily intakes (mg/kg) of 233 in F0 and F1 males and 304 (premating/gestation) or 660 (lactation) in females. Free resorcinol in blood plasma was barely detectable in a few parental animals, indicating rapid metabolism. This short review communication offers a perspective on compromised human skin barrier function as a likely cause of drastic increases in resorcinol absorption. In conjunction with multiple daily applications over many months to hyperemic, inflamed, and lesioned human skin much higher absorption was likely responsible for the reported human TG toxicity.

  17. Fighting Juvenile Gun Violence. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Sheppard, David; Grant, Heath; Rowe, Wendy; Jacobs, Nancy

    This bulletin describes the Office of Juvenile Justice and Delinquency Prevention's efforts to fight juvenile gun violence. The Office awarded four community demonstration grants to implement "Partnerships To Reduce Juvenile Gun Violence." Partnership goals include increasing the effectiveness of existing strategies by enhancing and…

  18. Acute toxicity of a commercial glyphosate formulation on European sea bass juveniles (Dicentrarchus labrax L.): gene expressions of heme oxygenase-1 (ho-1), acetylcholinesterase (AChE) and aromatases (cyp19a and cyp19b).

    PubMed

    Prevot-D'Alvise, N; Richard, S; Coupé, S; Bunet, R; Grillasca, J P

    2013-12-31

    Acute toxicity of Roundup, a commercial glyphosate--based herbicide, was evaluated in a teleost marine fish, the European sea bass, after 96 h of exposure. The LC50 96-h value of Roundup was 529 mg/L. Juveniles (Dicentrarchus labrax L.) were exposed to a sublethal concentration (35% of the LC50, i.e. 193 mg/L) of Roundup for 96-h. The study of heme oxygenase-1 (ho-1) gene expression was performed in four tissues (liver, gills, brain and gonads) and highlighted the disruption of antioxidant defence system. Results showed that ho-1 mRNA levels in liver and gills significantly decreased (p<0.001 and p<0.01 respectively) in fish exposed to 193 mg/L of Roundup, whereas in brain and gonads, ho-1 mRNA level was not altered. The analysis of acetylcholinesterase expression was used to evaluate the overall neurotoxicity of the herbicide and aromatase genes to assess the alteration of the endocrine system. Results showed that AChE and cyp19b gene transcriptions significantly increased (p<0.01) in brain of sea bass, whereas aromatase gene expression (cyp19a) in gonads was not significantly altered. Our results showed complex tissue-specific transcriptional responses after 96 h of exposure to a sublethal concentration. All these disruptions confirmed the deleterious effects of this glyphosate-based herbicide in a marine species.

  19. The effect of soil composition and hydration on the bioavailability and toxicity of cadmium to hibernating juvenile American toads (Bufo americanus)

    USGS Publications Warehouse

    James, Stacy M.; Little, Edward E.; Semlitsch, Raymond D.

    2004-01-01

    The soil ecotoxicology literature has focused primarily on a few major taxa, to the neglect of other fossorial organisms such as amphibians. We selected cadmium (Cd) and the American toad (Bufo americanus) as a model contaminant and biological species to assess the impact of soil contamination on amphibian hibernation survival and post-hibernation condition. Soil sand composition (50, 70, 90%) and hydration (100, 150% water holding capacity (WHC)) were manipulated in addition to Cd concentration (0, 56, 165, 483 μg/g) to determine whether these soil properties affect toxicity. Soil Cd concentration significantly reduced survival and locomotor performance, and was correlated negatively with percent mass loss and positively with whole body Cd concentration. Higher sand content resulted in less mass loss and greater Cd uptake. Toads that were hibernated in 50% sand hydrated to 100% WHC had higher survival, less mass loss, and better sprint performance than those hibernated in 50% sand, 150% WHC. This study demonstrates that concentrations of Cd found in soil at highly contaminated sites can be bioaccumulated by hibernating amphibians and may reduce fitness. Differences in microhabitat use may cause species to vary in their exposure and susceptibility to soil contamination. The toxicity of Cd to amphibians could be greater in natural systems where there are multiple stressors and fluctuations in environmental variables.

  20. Predicting chronic copper and nickel reproductive toxicity to Daphnia pulex-pulicaria from whole-animal metabolic profiles.

    PubMed

    Taylor, Nadine S; Kirwan, Jennifer A; Johnson, Craig; Yan, Norman D; Viant, Mark R; Gunn, John M; McGeer, James C

    2016-05-01

    The emergence of omics approaches in environmental research has enhanced our understanding of the mechanisms underlying toxicity; however, extrapolation from molecular effects to whole-organism and population level outcomes remains a considerable challenge. Using environmentally relevant, sublethal, concentrations of two metals (Cu and Ni), both singly and in binary mixtures, we integrated data from traditional chronic, partial life-cycle toxicity testing and metabolomics to generate a statistical model that was predictive of reproductive impairment in a Daphnia pulex-pulicaria hybrid that was isolated from an historically metal-stressed lake. Furthermore, we determined that the metabolic profiles of organisms exposed in a separate acute assay were also predictive of impaired reproduction following metal exposure. Thus we were able to directly associate molecular profiles to a key population response - reproduction, a key step towards improving environmental risk assessment and management.

  1. Juvenile Justice & Youth Violence.

    ERIC Educational Resources Information Center

    Howell, James C.

    Youth violence and the juvenile justice system in the United States are explored. Part 1 takes stock of the situation. The first chapter discusses the origins and evaluation of the juvenile justice system, and the second considers the contributions of the Federal Juvenile Justice and Delinquency Prevention Act to the existing juvenile justice…

  2. Juvenile Justice & Youth Violence.

    ERIC Educational Resources Information Center

    Howell, James C.

    Youth violence and the juvenile justice system in the United States are explored. Part 1 takes stock of the situation. The first chapter discusses the origins and evaluation of the juvenile justice system, and the second considers the contributions of the Federal Juvenile Justice and Delinquency Prevention Act to the existing juvenile justice…

  3. Treating Juvenile Crime.

    ERIC Educational Resources Information Center

    Gelber, Seymour

    1983-01-01

    Although juvenile crime rates have not changed significantly in the last five years, the juvenile courts' ability to handle crime has deteriorated. To treat the problem of juvenile crime effectively requires intervention at the earliest sign of delinquency and an assessment of the juvenile courts and school system. (AM)

  4. Intravenous injection of unfunctionalized carbon-based nanomaterials confirms the minimal toxicity observed in aqueous and dietary exposures in juvenile rainbow trout (Oncorhynchus mykiss).

    PubMed

    Boyle, David; Sutton, Paul A; Handy, Richard D; Henry, Theodore B

    2017-09-20

    Numerous ecotoxicology studies of carbon-based nanomaterials (CNMs) have been conducted in fishes; however, different approaches have been used to make CNM dispersions and dose tanks for aqueous exposures, and to prepare food containing CNMs for dietary studies. This diversity of experimental methods has led to conflicting results and difficulties in comparing studies. The objective of the present study was to evaluate intravenous injection of unfunctionalized CNMs in rainbow trout (Oncorhynchus mykiss), as a means of delivering a known internal dose, on tissue biochemistry and histopathological lesions; then, subsequently, to compare the results with our previous work on aqueous and dietary exposures of rainbow trout to CNMs. Rainbow trout were injected in the caudal vein with corn oil dispersions of 200 μg (approximately 1 μg g(-1)) of either the fullerene C60, single-walled carbon nanotubes (SWCNTs), or amorphous carbon black. After 96 h, injected fish were euthanized and tissue samples collected for biochemistry and histology. Histological examination of the kidney of fish injected intravenously indicated the presence of black material consistent with the injected carbon treatments. However, there were no additional lesions associated with CNM exposure compared to controls. There were also no significant changes in haematology, or ionoregulatory disturbance in blood plasma among the intravenously injected fish. Significant elevation in lipid peroxidation (thiobarbituric acid reactive substances TBARS) was detected only in kidney and spleen of fish injected with SWCNTs, but not the other carbon treatments. The elevated TBARS following injection contrasted with CNMs delivered via aqueous or dietary routes in our previous studies, suggesting that the latter exposure routes may not lead to absorption and toxicity in the internal tissues. Comparison of the effects of injected CNMs with aqueous and dietary CNMs exposures indicates that these materials are of

  5. The nutritive value of grasspea (Lathyrus sativus) and allied species, their toxicity to animals and the role of malnutrition in neurolathyrism.

    PubMed

    Enneking, Dirk

    2011-03-01

    The safe use of grasspea (Lathyrus sativus) and allied species (L. cicera, L. clymenum and L. ochrus) requires a better understanding of the factors that are involved in the development of neurolathyrism. A suitable animal model is needed. The nutritional quality, seed chemical composition, the role of malnutrition, synergistic action of antinutritional factors, the toxicity of both seed and forage to animals, metabolism and tissue distribution of the toxic amino acid beta-N-oxalyl-alpha,beta-L-diaminopropionic acid (ODAP) in mammals are reviewed. Malnutrition is not necessary for the development of neurolathyrism, however, the supply of sulfur amino acids by Lathyrus spp. is limited by the combined action of several antinutritional factors and the low inherent levels in the seeds. Metabolism or excretion of ODAP and clearance from the central nervous system appear to function well under normal circumstances, while species differences exist. Interruptions to these processes and excessive concurrent demands for reduced sulfur amino acids are likely to be conducive to the onset of neurotoxicity.

  6. Determination of Toxic Activities in Bothrops spp. Snake Venoms Using Animal-Free Approaches: Correlation Between In Vitro Versus In Vivo Assays.

    PubMed

    de Souza, Letícia Lopes; Stransky, Stephanie; Guerra-Duarte, Clara; Flor-Sá, Ana; Schneider, Francisco Santos; Kalapothakis, Evanguedes; Chávez-Olórtegui, Carlos

    2015-10-01

    The main purpose of this study is to investigate the in vitro toxic effects of 5 Bothrops spp. snake venoms, which are part of the antigenic mixture used for the production of Brazilian antivenom, and evaluate their correlation with the in vivo toxic activities of Bothrops spp. venoms. The correlation analysis could be helpful for the replacement of living animals experimentation for in vitro bioassay. Cytotoxicity, L-amino acid oxidase (LAAO), proteolitic (serine and metalloproteinase), hyaluronidase (Hyal), and phospholipase A2 (PLA2) activities were estimated and the correlation coefficient was determined for each activity in relation to lethality, edema, hemorrhage and necrosis induced in live animals by B. jararaca, B. alternatus, B. jararacussu, B. neuwiedi, and B. moojeni venoms. The lethal activity in mice was highly related to Hyal activity (r = 0.94, p < .05), edema related to PLA2 activity (r = 0.94, p < .05), whereas the necrotizing activity showed high correlation with LAAO activity (r = 0.83, p < .05). A very significant correlation between in vitro cytotoxicity and LAAO activities was also observed (r = 0.97, p < .05).

  7. Disrupting Self-Assembly and Toxicity of Amyloidogenic Protein Oligomers by “Molecular Tweezers” - from the Test Tube to Animal Models

    PubMed Central

    Attar, Aida; Bitan, Gal

    2014-01-01

    Despite decades of research, therapy for diseases caused by abnormal protein folding and aggregation (amyloidoses) is limited to treatment of symptoms and provides only temporary and moderate relief to sufferers. The failure in developing successful disease-modifying drugs for amyloidoses stems from the nature of the targets for such drugs – primarily oligomers of amyloidogenic proteins, which are distinct from traditional targets, such as enzymes or receptors. The oligomers are metastable, do not have well-defined structures, and exist in dynamically changing mixtures. Therefore, inhibiting the formation and toxicity of these oligomers likely will require out-of-the-box thinking and novel strategies. We review here the development of a strategy based on targeting the combination of hydrophobic and electrostatic interactions that are key to the assembly and toxicity of amyloidogenic proteins using lysine (K)-specific “molecular tweezers” (MTs). Our discussion includes a survey of the literature demonstrating the important role of K residues in the assembly and toxicity of amyloidogenic proteins and the development of a lead MT derivative called CLR01, from an inhibitor of protein aggregation in vitro to a drug candidate showing effective amelioration of disease symptoms in animal models of Alzheimer’s and Parkinson’s diseases. PMID:23859557

  8. OVERVIEW: USING MODE OF ACTION AND LIFE STAGE INFORMATION TO EVALUATE THE HUMAN RELEVANCE OF ANIMAL TOXICITY DATA.

    EPA Science Inventory

    A manuscript summarizes a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans. A complete mode of action human relevance analysis - as distinct from mode of action (MOA) analysis alone - depends on robust info...

  9. OVERVIEW: USING MODE OF ACTION AND LIFE STAGE INFORMATION TO EVALUATE THE HUMAN RELEVANCE OF ANIMAL TOXICITY DATA.

    EPA Science Inventory

    A manuscript summarizes a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans. A complete mode of action human relevance analysis - as distinct from mode of action (MOA) analysis alone - depends on robust info...

  10. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

    SciTech Connect

    Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J. )

    1990-10-15

    Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy.

  11. Strategic Focus on 3R Principles Reveals Major Reductions in the Use of Animals in Pharmaceutical Toxicity Testing

    PubMed Central

    Törnqvist, Elin; Annas, Anita; Granath, Britta; Jalkesten, Elisabeth; Cotgreave, Ian; Öberg, Mattias

    2014-01-01

    The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. Substantial reduction in animal use was achieved by different strategies, including improved study design, method development and project coordination. Major animal savings were shown in both regulatory and investigative safety studies. If a similar (i.e. 53%) reduction had been achieved simultaneously within the twelve largest pharmaceutical companies, the equivalent reduction world-wide would be about 150,000 rats annually. The results point at the importance of a strong 3R culture, with scientific engagement, collaboration and a responsive management being vital components. A strong commitment in leadership for the 3R is recommended to be translated into cross-department and inter-profession involvement in projects for innovation, validation and implementation. Synergies between all the three Rs are observed and conclude that in silico-, in vitro- and in vivo-methods all hold the potential for applying the reduction R and should be consequently coordinated at a strategic level. PMID:25054864

  12. Strategic focus on 3R principles reveals major reductions in the use of animals in pharmaceutical toxicity testing.

    PubMed

    Törnqvist, Elin; Annas, Anita; Granath, Britta; Jalkesten, Elisabeth; Cotgreave, Ian; Öberg, Mattias

    2014-01-01

    The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. Substantial reduction in animal use was achieved by different strategies, including improved study design, method development and project coordination. Major animal savings were shown in both regulatory and investigative safety studies. If a similar (i.e. 53%) reduction had been achieved simultaneously within the twelve largest pharmaceutical companies, the equivalent reduction world-wide would be about 150,000 rats annually. The results point at the importance of a strong 3R culture, with scientific engagement, collaboration and a responsive management being vital components. A strong commitment in leadership for the 3R is recommended to be translated into cross-department and inter-profession involvement in projects for innovation, validation and implementation. Synergies between all the three Rs are observed and conclude that in silico-, in vitro- and in vivo-methods all hold the potential for applying the reduction R and should be consequently coordinated at a strategic level.

  13. Repeated recall and PKMζ maintain fear memories in juvenile rats.

    PubMed

    Oliver, Chicora F; Kabitzke, Patricia; Serrano, Peter; Egan, Laura J; Barr, Gordon A; Shair, Harry N; Wiedenmayer, Christoph

    2016-12-01

    We examined the neural substrates of fear memory formation and maintenance when repeated recall was used to prevent forgetting in young animals. In contrast to adult rats, juveniles failed to show contextual fear responses at 4 d post-fear conditioning. Reconsolidation sessions 3 and 6 d after conditioning restored contextual fear responses in juveniles 7 d after initial training. In juveniles that received reconsolidation sessions, protein kinase M zeta (PKMζ) increased in the amygdala, but not in the hippocampus. These data suggest that repeated reminders and increased PKMζ maintain fear responses in juvenile animals that otherwise would not exhibit this behavior.

  14. Subchronic toxicity and anti-HSV-1 activity in experimental animal of dolabelladienetriol from the seaweed, Dictyota pfaffii.

    PubMed

    Garrido, Valéria; Barros, Caroline; Melchiades, Vanessa A; Fonseca, Rainomar Raimundo; Pinheiro, Sergio; Ocampo, Patrícia; Teixeira, Valéria L; Cavalcanti, Diana N; Giongo, Viveca; Ratcliffe, Norman A; Teixeira, Gerlinde; Paixão, Izabel Christina N P

    2017-03-08

    This study examined in rats the subchronic toxicity and anti- HSV-1activity after oral administration of dolabelladienetriol (D1), a diterpene isolated from the seaweed Dictyota pfaffii. In subchronic toxicity (SCT) tests, female rats received D1 by gavage 15 mg/kg/day (n = 5) for 50 days, and general behavior, death, hematological, biochemical and histological changes in the liver, kidney, stomach, and duodenum were determined. For the anti-HSV-1 activity, female mice were infected and treated orally with a dose of 20 mg/kg (n = 5) twice a day with D1 and any lesions in the skin were then recorded for 18 days. Dolabelladienetriol in SCT did not significantly change behavior, body weight, hematological or biochemical profiles. The liver and kidneys, however, showed some alterations in rats treated with D1, similar to those in rats treated with ACV, while the other tissues had no significant changes. The anti-HSV-1 activity of D1 had a similar efficacy to the ACV drug control in mice. Our results showed that D1 has potential commercial development as a new HSV-1drug.

  15. Evidence for neurotoxicity associated with amoxicillin in juvenile rats.

    PubMed

    Atli, O; Demir-Ozkay, U; Ilgin, S; Aydin, T H; Akbulut, E N; Sener, E

    2016-08-01

    Amoxicillin (AMX) is one of the most commonly prescribed antibiotics for children, and childhood is the period to have the highest risk for toxicity cases including drug-induced adverse reactions. Some neurological adverse effects (anxiety, hyperactivity, confusion, convulsions, and behavioral changes) have been reported related to AMX treatment. In the present study, we aimed to determine the neurotoxic effects of AMX administration at clinically relevant doses in female juvenile rats. AMX was administered in single oral daily doses of 25 and 50 mg/kg for 14 days. According to our results, while AMX administration caused a significant increase in the immobility time of animals, swimming time of these animals significantly decreased. AMX administration significantly reduced the onset of pentylenetetrazole-induced convulsions. The serotonin levels of brain tissues in the AMX-administered groups were decreased significantly, which is thought to be related to depression. The glutamate levels in brain tissues increased significantly in AMX-administered groups, which is thought to be related to convulsion. Otherwise, superoxide dismutase and catalase activities were significantly decreased in brain tissues of AMX-administered groups. In conclusion, AMX administration triggered depression and shortened the time of the appearance of first seizure in juvenile rats. Also, altered brain neurotransmitter levels and increased oxidative stress observed in our study were thought to be the possible underlying mechanisms of AMX-induced neurotoxicity.

  16. A comparative study of plant and animal mitochondria exposed to paraquat reveals that hydrogen peroxide is not related to the observed toxicity.

    PubMed

    Peixoto, Francisco; Vicente, Joaquim; Madeira, Vítor M C

    2004-12-01

    Rat liver mitochondria are much more susceptible to protein oxidation induced by paraquat than plant mitochondria. The unsaturated index and the peroxidizability index are higher in rat than in potato tuber. The levels of superoxide dismutase and glutathione reductase are concurrent with the different sensitivities to paraquat, with higher activities in plant mitochondria. However, glutathione peroxidase and catalase activities are higher in rat mitochondria. Paraquat (10 mM) inhibited all the enzymatic activities; excluding catalase all the other activities were inhibited to a similar degree. The differential sensitivities of plant and animal mitochondria to paraquat correlate with fatty acid composition of mitochondrial lipids and a similar correlation was also established for some antioxidant enzymes. At the mitochondrial level, H(2)O(2) is not a major factor of paraquat toxicity since rat liver mitochondria which exhibit higher activities of glutathione peroxidase and catalase are however more susceptible to paraquat.

  17. Toxicity of a Novel Herbomineral Preparation Las01 on Human Cancer Cell Lines and Its Safety Profile in Humans and Animals

    PubMed Central

    Sheikh, Saba; Srivastava, Ashok; Tripathi, Rajesh; Tripathi, Shalini; Trivedi, V. P.; Saxena, R. C.

    2012-01-01

    Polyhedral formulations based on Rasayana therapy described in Charaka Samhita showed remarkable improvement in quality of life of various cancer patients who have been found to be refractory or poor responders to modern chemotherapy and radiation treatment. One of the most recent novel herbomineral preparation, Las01 prepared absolutely as per the instruction given in the ancient Ayurvedic literature has been found to be effective as a potent anticancer drug in the human cell lines, the MCF-7 and Hela cancer cell lines. This novel preparation of Las01 is also found to be devoid of toxicity both in animals as well as in human subjects, which is the main drawback of chemotherapeutic agents used in modern system of medicine. Our results warrant multicentric clinical trials on a large scale which seems to be a future promising drug to cure incurables cancer patients. PMID:22969832

  18. The Role of Oxidative Stress in Methamphetamine-induced Toxicity and Sources of Variation in the Design of Animal Studies.

    PubMed

    McDonnell-Dowling, Kate; Kelly, John P

    2017-01-01

    The prevalence of methamphetamine (MA) use has increased in recent years. In order to assess how this drug produces its effects, both clinical and preclinical studies have recently begun to focus on oxidative stress as an important biochemical mechanism in mediating these effects. The purpose of this review is to illustrate the variation in the design of preclinical studies investigating MA exposure on oxidative stress parameters in animal models. The experimental variables investigated and summarised include MA drug treatment, measurements of oxidative stress and antioxidant treatments that ameliorate the harmful effects of MA. These preclinical studies differ greatly in their experimental design with respect to the dose of MA (ranging between 0.25 and 20 mg/kg), the dosing regime (acute, binge or chronic), the time of measurement of oxidative stress (0.5 h to 2 wks after last MA administration), the antioxidant system targeted and finally the use of antioxidants including the route of administration (i.p. or p.o.), the frequency of exposure and the time of exposure (preventative or therapeutic). The findings in this paper suggest that there is a large diversity among these studies and so the interpretation of these results is challenging. For this reason, the development of guidelines and how best to assess oxidative stress in animal models may be beneficial. The use of these simple recommendations mean that results will be more comparable between laboratories and that future results generated will give us a greater understanding of the contribution of this important biochemical mechanism and its implications for the clinical scenario.

  19. Juvenile Delinquency: An Introduction

    ERIC Educational Resources Information Center

    Smith, Carolyn A.

    2008-01-01

    Juvenile Delinquency is a term which is often inaccurately used. This article clarifies definitions, looks at prevalence, and explores the relationship between juvenile delinquency and mental health. Throughout, differences between males and females are explored. (Contains 1 table.)

  20. Juvenile Delinquency: An Introduction

    ERIC Educational Resources Information Center

    Smith, Carolyn A.

    2008-01-01

    Juvenile Delinquency is a term which is often inaccurately used. This article clarifies definitions, looks at prevalence, and explores the relationship between juvenile delinquency and mental health. Throughout, differences between males and females are explored. (Contains 1 table.)

  1. Local Tumor Control and Normal Tissue Toxicity of Pulsed Low-Dose Rate Radiotherapy for Recurrent Lung Cancer: An In Vivo Animal Study.

    PubMed

    Zhang, Peng; Wang, Bin; Chen, Xiaoming; Cvetkovic, Dusica; Chen, Lili; Lang, Jinyi; Ma, C-M

    2015-01-01

    This study investigates (1) local tumor control and (2) normal tissue toxicity of pulsed low-dose rate radiotherapy (PLDR) for recurrent lung cancer. For study 1, nude mice were implanted with A549 tumors and divided into the following 3 groups: (1) control (n = 10), (2) conventional radiotherapy (RT; n = 10), and (3) PLDR (n = 10). Tumor-bearing mice received 2 Gy daily dose for 2 consecutive days. Weekly magnetic resonance imaging was used for tumor growth monitoring. For study 2, 20 mice received 8 Gy total body irradiation either continuously (n = 10) or 40 × 0.2 Gy pulses with 3-minute intervals (n = 10). For study 1, both conventional RT and PLDR significantly inhibited the growth of A549 xenografts compared with the control group (>35% difference in the mean tumor volume; P < .05). The PLDR results were slightly better than conventional RT (8% difference in the mean tumor volume; P > .05). For study 2, the average weight was 20.94 ± 1.68 g and 25.69 ± 1.27 g and the survival time was 8 days and 12 days for mice treated with conventional RT and PLDR (P < .05), respectively. This study showed that PLDR could control A549 tumors as effectively as conventional RT, and PLDR induced much less normal tissue toxicity than conventional RT. Thus, PLDR would be a good modality for recurrent lung cancers. This article reports our results of an in vivo animal investigation of PLDR for the treatment of recurrent cancers, which may not be eligible for treatment because of the dose limitations on nearby healthy organs that have been irradiated in previous treatments. This was the first in vivo study to quantify the tumor control and normal tissue toxicities of PLDR using mice with implanted tumors, and our findings provided evidence to support the clinical trials that employ PLDR treatment techniques.

  2. A review of implications of antiquality and toxic components in unconventional feedstuffs advocated for use in intensive animal production in Nigeria.

    PubMed

    Aregheore, E M

    1998-02-01

    There are a number of unconventional feed resources in Nigeria. Most are rich sources of plant protein. Since protein is the most expensive and limiting nutrient in tropical livestock nutrition, these unconventional feed resources may fill a gap in protein deficiency. However, most contain antiquality and toxic components which make them unsafe as protein and carbohydrate sources in livestock nutrition. The presence of saponins, lectins, tannins, trypsin inhibitors, cyanogenic glucoside and others in African locust bean meal (Parkia filicoidea Welw), avocado seed meal (Persea americana), bambara groundnut meal (Voandzeia subterranea), cocoa by-product meal (Theobroma coca), coffee pulp meal (Coffee arabica), mango seed kernel meal (Mangifera indica), rubber seed meal (Hevea brasiliensis), sesame seed (Sesamum indicum L) and shear-butter cake (Vitellaria paradoxa, G) are not uncommon and make rations prepared with them unpalatable and unacceptable to animals. They also interfere with nutrient bioavailability and utilization. Drying, soaking, leaching and fermentation are simple means of detoxifying these feed sources to reduce the presence of antiquality and toxic components.

  3. Biosynthesis of silver nanoparticles using dried fruit extract of Ficus carica - Screening for its anticancer activity and toxicity in animal models.

    PubMed

    Jacob, S Justin Packia; Prasad, V L Siva; Sivasankar, S; Muralidharan, P

    2017-04-01

    There is an increasing commercial demand for various nanoparticles due to their extensive applicability in various areas such as electronics, catalysis, chemistry, energy and medicine. Metallic nanoparticles are traditionally synthesized by wet chemical techniques, where the chemicals used are quite often toxic and flammable. Fig has been a typical fruit component of the health-promoting Mediterranean diet for a very long time. In the present study, we describe a cost effective and eco-friendly technique for green synthesis of silver nanoparticles from 1 mM AgNO3 solution through the extract of dried fig (Ficus carica L.) fruit as reducing as well as capping agent. Nanoparticles were characterized using UV absorption spectroscopy and SEM. The sizes of the spherical silver particles were found to be in the range of 54-89 nm. The biologically synthesized nanoparticles also exhibited a significant cytotoxic effect on MCF7cell lines and further animal acute toxicity results state that the above AgNPs are toxicologically safe by oral administration.

  4. Studies on the effect of 4-methylpyrazole on methanol poisoning using the monkey as an animal model: with particular reference to the ocular toxicity.

    PubMed

    Blomstrand, R; Ingemansson, S O

    1984-07-01

    Young cynomolgus monkeys (Macaca fascicularis) were chosen as a model to investigate the ocular toxicity in animals poisoned with methanol and treated with 4-methylpyrazole (4-MP). The metabolism of methanol in the monkey was investigated after administration of 4-MP. Plasma levels of methanol, formic acid, 4-MP and 4-hydroxy-MP (4-OH-MP) were determined. After intramuscular injection, 4-MP was rapidly absorbed and depressed the elimination rate of methanol as well as the accumulation of formate in the blood. The results show the same great individual variations in monkeys as in humans regarding the susceptibility to methanol poisoning. Administration of a single dose of 5 g/kg induces a serious intoxication in most monkeys, causing death to some of them. Two monkeys receiving a single dose of 6 g/kg of methanol developed a serious initial inebriation and were treated with 4-MP. These monkeys survived and showed no signs of toxicity on ocular examinations which included ophtalmoscopy and electroretinogram (ERG) recordings.

  5. Juvenile Arrests, 2000. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    This bulletin examines the national and state juvenile arrest rate in 2000 using data reported annually by local law enforcement agencies nationwide to the FBI's Uniform Crime Reporting program. Results indicate that the murder rate in 2000 was the lowest since 1965; juvenile arrests for violence in 2000 were the lowest since 1988; few juveniles…

  6. Juvenile Arrests, 2007. Juvenile Justice Bulletin

    ERIC Educational Resources Information Center

    Puzzanchera, Charles

    2009-01-01

    This Bulletin summarizes 2007 juvenile crime and arrest data reported by local law enforcement agencies across the country and cited in the FBI report, "Crime in the United States 2007." The Bulletin describes the extent and nature of juvenile crime that comes to the attention of the justice system. It serves as a baseline for comparison for…

  7. Juvenile Arrests, 1998. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    This report provides a summary and analysis of national and state juvenile arrest data in the United States. In 1998, law enforcement agencies made an estimated 2.6 million arrests of persons under age 18. Federal Bureau of Investigations statistics indicate that juveniles account for 18% of all arrests, and 17% of all violent crime arrests in…

  8. Juvenile Arrests, 1999. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    This bulletin presents a summary and analysis of national and state juvenile arrest data for 1999. Data come from the FBI's annual "Crime in the United States" report, which offers the estimated number of crimes reported to law enforcement agencies. The 1999 murder rate was the lowest since 1966. Of the nearly 1,800 juveniles murdered in…

  9. Juvenile Arrests 1996. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    In 1996, law enforcement agencies in the United States made an estimated 2.9 million arrests of persons under the age of 18. According to Federal Bureau of Investigation (FBI) figures, juveniles accounted for 19% of all arrests and 19% of all violent crime in 1996. The substantial growth in juvenile crime that began in the late 1980s peaked in…

  10. Juvenile Justice Glossary.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Provides a list of terms pertaining to the juvenile justice system, such as appeal and due process, that are used throughout this edition of "Update on Law-Related Education," in particular, with the teaching strategies "The Case of Gerry Gault" (SO 532 196) "Today's Juvenile Court" (SO 532 197), and "Using the Juvenile Justice Poster" (SO 532…

  11. Concepts Shaping Juvenile Justice

    ERIC Educational Resources Information Center

    White, Rob

    2008-01-01

    Rob White's paper explores ways in which community building can be integrated into the practices of juvenile justice work. He provides a model of what can be called "restorative social justice", one that builds upon the juvenile conferencing model by attempting to fuse social justice concerns with progressive juvenile justice practices.

  12. Toxicity bioassays: Water pollution effects on aquatic animals and plants. June 1986-February 1990 (A bibliography from the Selected Water Resources Abstracts data base). Report for June 1986-February 1990

    SciTech Connect

    Not Available

    1990-03-01

    This bibliography contains citations concerning toxicity-bioassay studies of water-pollution effects on reproduction, growth, and mortality of aquatic animals and plants. Industrial and agricultural water pollutants such as metals, chemicals, pesticides, and herbicides are evaluated and tested. Standard fishes and algal assays are used to determine effects of potential toxicants. (This updated bibliography contains 145 citations, 51 of which are new entries to the previous edition.)

  13. The classification of motor neuron defects in the zebrafish embryo toxicity test (ZFET) as an animal alternative approach to assess developmental neurotoxicity.

    PubMed

    Muth-Köhne, Elke; Wichmann, Arne; Delov, Vera; Fenske, Martina

    2012-07-01

    Rodents are widely used to test the developmental neurotoxicity potential of chemical substances. The regulatory test procedures are elaborate and the requirement of numerous animals is ethically disputable. Therefore, non-animal alternatives are highly desirable, but appropriate test systems that meet regulatory demands are not yet available. Hence, we have developed a new developmental neurotoxicity assay based on specific whole-mount immunostainings of primary and secondary motor neurons (using the monoclonal antibodies znp1 and zn8) in zebrafish embryos. By classifying the motor neuron defects, we evaluated the severity of the neurotoxic damage to individual primary and secondary motor neurons caused by chemical exposure and determined the corresponding effect concentration values (EC₅₀). In a proof-of-principle study, we investigated the effects of three model compounds thiocyclam, cartap and disulfiram, which show some neurotoxicity-indicating effects in vertebrates, and the positive controls ethanol and nicotine and the negative controls 3,4-dichloroaniline (3,4-DCA) and triclosan. As a quantitative measure of the neurotoxic potential of the test compounds, we calculated the ratios of the EC₅₀ values for motor neuron defects and the cumulative malformations, as determined in a zebrafish embryo toxicity test (zFET). Based on this index, disulfiram was classified as the most potent and thiocyclam as the least potent developmental neurotoxin. The index also confirmed the control compounds as positive and negative neurotoxicants. Our findings demonstrate that this index can be used to reliably distinguish between neurotoxic and non-neurotoxic chemicals and provide a sound estimate for the neurodevelopmental hazard potential of a chemical. The demonstrated method can be a feasible approach to reduce the number of animals used in developmental neurotoxicity evaluation procedures.

  14. Juvenile polyposis syndrome.

    PubMed

    Brosens, Lodewijk Aa; Langeveld, Danielle; van Hattem, W Arnout; Giardiello, Francis M; Offerhaus, G Johan A

    2011-11-28

    Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes. Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis. In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway. It has been suggested that cancer in juvenile polyposis may develop through the so-called "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma. Recognition of this rare disorder is important for patients and their families with regard to treatment, follow-up and screening of at risk individuals. Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome. In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome.

  15. Juvenile polyposis syndrome

    PubMed Central

    Brosens, Lodewijk AA; Langeveld, Danielle; van Hattem, W Arnout; Giardiello, Francis M; Offerhaus, G Johan A

    2011-01-01

    Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes. Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis. In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway. It has been suggested that cancer in juvenile polyposis may develop through the so-called “landscaper mechanism” where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma. Recognition of this rare disorder is important for patients and their families with regard to treatment, follow-up and screening of at risk individuals. Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome. In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome. PMID:22171123

  16. Successful euthanasia of a juvenile fin whale.

    PubMed Central

    Daoust, P Y; Ortenburger, A I

    2001-01-01

    A stranded juvenile fin whale was successfully euthanized with an intravenous injection of sedative and cardioplegic drugs. Veterinarians may face a number of serious difficulties if called to perform this task, and advance preparation is required for successful euthanasia of these animals. Images Figure 1. PMID:11272456

  17. Interim report on the genetic and animal toxicity testing of SRC-I products, intermediates, and waste materials. Appendix G. Sample history and documentation

    SciTech Connect

    Drozdowicz, B.Z.; Kelly, C.M.

    1983-09-01

    This document traces the history of the samples used in the genetic and animal toxicity testing of SRC products, process intermediates, and waste materials. It begins with a brief summary (Table G-1, page G.1.2), which indicates the source, further processing, storage, and transmittals of all sample materials used in the testing. This summary is followed by more detailed descriptions of the various stages in the handling of sample materials, which in turn refer to various letters, work orders, and memos that document the history of these materials. A large number of materials originating from several sources are involved in this testing. Almost all of thes materials received further processing to prepare samples that are more representative of products, process intermediates, and waste materials expected to be produced by the SRC-I Demonstration Plant. ICRC believes that all the samples were produced, handled, and prepared in such a way as to render them fully representative of the SRC-I process as it would be practiced at the SRC-I Demonstration Plant.

  18. Site-specific chemical modification with polyethylene glycol of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) improves antitumor activity and reduces animal toxicity and immunogenicity

    PubMed Central

    Tsutsumi, Yasuo; Onda, Masanori; Nagata, Satoshi; Lee, Byungkook; Kreitman, Robert J.; Pastan, Ira

    2000-01-01

    Chemical modification of proteins with polyethylene glycol (PEGylation) can increase plasma half-lives, stability, and therapeutic potency. To make a PEGylated recombinant immunotoxin with improved therapeutic properties, we prepared a mutant of anti-Tac(Fv)-PE38 (LMB-2), a recombinant immunotoxin composed of a single-chain Fv fragment of the anti-human Tac monoclonal antibody to the IL-2 receptor α subunit fused to a 38-kDa fragment of Pseudomonas exotoxin. For site-specific PEGylation of LMB-2, one cysteine residue was introduced into the peptide connector (ASGCGPE) between the Fv and the toxin. This mutant LMB-2 (cys1-LMB-2), which retained full cytotoxic activity, was then site-specifically conjugated with 5 or 20 kDa of polyethylene glycol-maleimide. When compared with unmodified LMB-2, both PEGylated immunotoxins showed similar cytotoxic activities in vitro but superior stability at 37°C in mouse serum, a 5- to 8-fold increase in plasma half-lives in mice, and a 3- to 4-fold increase in antitumor activity. This was accompanied by a substantial decrease in animal toxicity and immunogenicity. Site-specific PEGylation of recombinant immunotoxins may increase their therapeutic potency in humans. PMID:10890891

  19. Comparison of the localization of tetrodotoxin between wild pufferfish Takifugu rubripes juveniles and hatchery-reared juveniles with tetrodotoxin administration.

    PubMed

    Okita, Kogen; Takatani, Tomohiro; Nakayasu, Junichi; Yamazaki, Hideki; Sakiyama, Kazutaka; Ikeda, Koichi; Arakawa, Osamu; Sakakura, Yoshitaka

    2013-09-01

    To reveal the accumulation profile of tetrodotoxin (TTX) in pufferfish Takifugu rubripes juveniles, we compared the localization of TTX in various tissues among wild juveniles and hatchery-reared juveniles with or without TTX administration using immunohistochemical technique with anti-TTX monoclonal antibody. Immuno-positive reaction was observed in hepatic tissue, basal cell of skin and olfactory, olfactory epithelium, optic nerve and brain (optic tectum, cerebellum, medulla oblongata) of wild juveniles (body length: BL, 4.7-9.4 cm). TTX was detected in the same tissues as wild juveniles and epithelial cell layer of intestine of hatchery-reared juveniles (BL, 5.0-5.3 cm) to which TTX was orally administrated. No positive reaction was observed from the tissues of hatchery-reared juveniles without TTX administration. These results suggest that orally administrated TTX to the non-toxic cultured juveniles is accumulated in the same manner of wild juveniles. In addition, our study revealed that pufferfish accumulates TTX in the central nervous system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Selective Toxicity of Persian Gulf Sea Cucumber (Holothuria parva) and Sponge (Haliclona oculata) Methanolic Extracts on Liver Mitochondria Isolated from an Animal Model of Hepatocellular Carcinoma

    PubMed Central

    Seydi, Enayatollah; Motallebi, Abbasali; Dastbaz, Maryam; Dehghan, Sahar; Salimi, Ahmad; Nazemi, Melika; Pourahmad, Jalal

    2015-01-01

    Background: Natural products isolated from marine environments are well known for their pharmacodynamic potential in diverse disease treatments, such as for cancer or inflammatory conditions. Sea cucumbers are marine animals of the phylum Echinoderm and the class Holothuroidea, with leathery skin and gelatinous bodies. Sponges are important components of Persian Gulf animal communities, and the marine sponges of the genus Haliclona have been known to display broad-spectrum biological activity. Many studies have shown that sea cucumbers and sponges contain antioxidants and anti-cancer compounds. Objectives: This study was designed to determine the selective toxicity of Persian Gulf sea cucumber (Holothuria parva) and sponge (Haliclona oculata) methanolic extracts on liver mitochondria isolated from an animal model of hepatocellular carcinoma, as part of a national project that hopes to identify novel potential anticancer candidates among Iranian Persian Gulf flora and fauna. Materials and Methods: To induce hepatocarcinogenesis, rats were given diethylnitrosamine (DEN) injections (200 mg/kg i.p. by a single dose), and then the cancer was promoted with 2-acetylaminofluorene (2-AAF) (0.02 w/w) for two weeks. Histopathological evaluations were performed, and levels of liver injury markers and a specific liver cancer marker (alpha-fetoprotein), were determined for confirmation of hepatocellular carcinoma induction. Finally, mitochondria were isolated from cancerous and non-cancerous hepatocytes. Results: Our results showed that H. parva methanolic extracts (250, 500, and 1000 µg/mL) and H. oculata methanolic extracts (200, 400, and 800 µg/mL) increased reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP), mitochondrial swelling, and cytochrome c release in the mitochondria obtained from cancerous hepatocytes, but not in mitochondria obtained from non-cancerous liver hepatocytes. These extracts also induced caspase-3 activation, which is

  1. Juvenile myoclonic epilepsy.

    PubMed

    Buchanan, N

    1995-08-01

    Juvenile myoclonic epilepsy is a relatively common, though under diagnosed, form of epilepsy that commences in adolescence. The distinguishing symptoms, diagnosis and medical management are discussed.

  2. Binge ethanol in adulthood exacerbates negative outcomes following juvenile traumatic brain injury.

    PubMed

    Karelina, Kate; Gaier, Kristopher R; Prabhu, Maya; Wenger, Vanessa; Corrigan, Timothy E D; Weil, Zachary M

    2017-02-01

    Traumatic brain injuries (TBI) are a major public health problem with enormous costs in terms of health care dollars, lost productivity, and reduced quality of life. Alcohol is bidirectionally linked to TBI as many TBI patients are intoxicated at the time of their injury and we recently reported that, in accordance with human epidemiological data, animals injured during juvenile development self-administered significantly more alcohol as adults than did sham injured mice. There are also clinical data that drinking after TBI significantly reduces the efficacy of rehabilitation and leads to poorer long-term outcomes. In order to determine whether juvenile traumatic brain injury also increased the vulnerability of the brain to the toxic effects of high dose alcohol, mice were injured at 21days of age and then seven weeks later treated daily with binge-like levels of alcohol 5g/kg (by oral gavage) for ten days. Binge-like alcohol produced a greater degree of neuronal damage and neuroinflammation in mice that sustained a TBI. Further, mice that sustained a juvenile TBI exhibited mild learning and memory impairments in adulthood following binge alcohol and express a significant increase in hippocampal ectopic localization of newborn neurons. Taken together, these data provide strong evidence that a mild brain injury occurring early in life renders the brain highly vulnerable to the consequences of binge-like alcohol consumption.

  3. Feasibility of repeated testing for learning ability in juvenile primates for pediatric safety assessment.

    PubMed

    Rose, C; Luetjens, C M; Grote-Wessels, S; Weinbauer, G F

    2015-11-01

    Assessment of learning ability in nonhuman primate (NHP) models is sometimes requested by regulatory authorities. The double choice object discrimination task using a Wisconsin General Testing Apparatus (WGTA) approach is typically being applied. In this study, the WGTA approach was performed on 66 juvenile cynomolgus monkeys aged 8-9 months in the predose phase of juvenile toxicity assessment. In addition, reversal learning data of seven control animals/gender were obtained for the weeks 25 and 52 of dosing. Gender differences in the number of days required to pass the habituation, learning or reversal learning phases were statistically comparable, males and females may be combined for statistical analysis. At first instance, the habituation phase was passed on average after 6.4 days, and the learning test on average after 8.6 days with improvement to 2.0-2.6 days for habituation and 6.4-6.7 days for learning in weeks 52. Power analysis (α = 0.05, one-sided t-test) revealed a sample size of 8 and 41 to predict a 50% and 20% difference, respectively. In conclusion, examination for learning ability, but not for memory ability (during repeated testing) is feasible in juvenile NHPs using the WGTA approach. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Renewing Juvenile Justice

    ERIC Educational Resources Information Center

    Macallair, Daniel; Males, Mike; Enty, Dinky Manek; Vinakor, Natasha

    2011-01-01

    The Center on Juvenile and Criminal Justice (CJCJ) was commissioned by Sierra Health Foundation to critically examine California's juvenile justice system and consider the potential role of foundations in promoting systemic reform. The information gathered by CJCJ researchers for this report suggests that foundations can perform a key leadership…

  5. Juvenile Confinement in Context

    ERIC Educational Resources Information Center

    Mendel, Richard A.

    2012-01-01

    For more than a century, the predominant strategy for the treatment and punishment of serious and sometimes not-so-serious juvenile offenders in the United States has been placement into large juvenile corrections institutions, alternatively known as training schools, reformatories, or youth corrections centers. America's heavy reliance on…

  6. Juvenile Delinquency Intervention.

    ERIC Educational Resources Information Center

    Lipsey, Mark W.

    1988-01-01

    Three meta-analyses by C. J. Garrett (1984, 1985), P. Kaufman (1985), and W. S. Davidson and others (1984) of juvenile delinquency interventions are summarized. This systematic literature review indicates that interventions to reduce juvenile delinquency may have small, but meaningful, impacts. Promising avenues for future research are suggested.…

  7. Juvenile generalized pustular psoriasis.

    PubMed

    Xiao, Ting; Li, Bo; He, Chun-Di; Chen, Hong-Duo

    2007-08-01

    Generalized pustular psoriasis (GPP) is an erythrodermic, generalized form of pustular psoriasis. GPP is rare in children. The present study describes a case of juvenile GPP and reviews 12 juvenile GPP inpatients treated at our hospital in the period 1978-2005.

  8. Juvenile Rights. Second Edition.

    ERIC Educational Resources Information Center

    Eaneman, Paulette S.; And Others

    These classroom materials are part of the Project Benchmark series designed to teach secondary students about our legal concepts and systems. This unit focuses on juvenile rights and responsibilities under the law. The materials outline juvenile rights and responsibilities in the areas of parental control, education, free expression, search and…

  9. Distinguishing juvenile homicide from violent juvenile offending.

    PubMed

    DiCataldo, Frank; Everett, Meghan

    2008-04-01

    Juvenile homicide is a social problem that has remained a central focus within juvenile justice research in recent years. The term juvenile murderer describes a legal category, but it is purported to have significant scientific meaning. Research has attempted to conceptualize adolescent murderers as a clinical category that can be reliably distinguished from their nonhomicidal counterparts. This study examined 33 adolescents adjudicated delinquent or awaiting trial for murder and 38 adolescents who committed violent, nonhomicidal offenses to determine whether the two groups differed significantly on family history, early development, delinquency history, mental health, and weapon possession variables. The nonhomicide group proved more problematic on many of these measures. Two key factors did distinguish the homicide group: These adolescents endorsed the greater availability of guns and substance abuse at the time of their commitment offenses. The significance of this finding is discussed, and the implications for risk management and policy are reviewed.

  10. Workshop summary: phosgene-induced pulmonary toxicity revisited: appraisal of early and late markers of pulmonary injury from animal models with emphasis on human significance.

    PubMed

    Pauluhn, J; Carson, A; Costa, D L; Gordon, T; Kodavanti, U; Last, J A; Matthay, M A; Pinkerton, K E; Sciuto, A M

    2007-08-01

    pulmonary threshold dose. Exposure concentrations high enough to elicit an increased acute extravasation of plasma constituents into the alveolus may also be associated with surfactant dysfunction, intra-alveolar accumulation of fibrin and collagen, and increased recruitment and activation of inflammatory cells. Although the exact mechanisms of toxicity have not yet been completely elucidated, consensus was reached that the acute pulmonary toxicity of phosgene gas is consistent with a simple, irritant mode of action at the site of its initial deposition/retention. The acute concentration x time mortality relationship of phosgene gas in rats is extremely steep, which is typical for a local, directly acting pulmonary irritant gas. Due to the high lipophilicity of phosgene gas, it efficiently penetrates the lower respiratory tract. Indeed, more recent published evidence from animals or humans has not revealed appreciable irritant responses in central and upper airways, unless exposure was to almost lethal concentrations. The comparison of acute inhalation studies in rats and dogs with focus on changes in BAL fluid constituents demonstrates that dogs are approximately three to four times less susceptible to phosgene than rats under methodologically similar conditions. There are data to suggest that the dog may be useful particularly for the study of mechanisms associated with the acute extravasation of plasma constituents because of its size and general morphology and physiology of the lung as well as its oronasal breathing patterns. However, the study of the long-term sequelae of acute effects is experimentally markedly more demanding in dogs as compared to rats, precluding the dog model to be applied on a routine base. The striking similarity of threshold concentrations from single exposure (increased protein in BAL fluid) and repeated-exposure 3-mo inhalation studies (increased pulmonary collagen deposition) in rats supports the notion that chronic changes depend on acute

  11. Safety assessment of DHA-rich microalgae from Schizochytrium sp. Part V: target animal safety/toxicity study in growing swine.

    PubMed

    Abril, Ruben; Garrett, Jack; Zeller, Samuel G; Sander, Wayne J; Mast, Richard W

    2003-02-01

    The purpose of this study was to determine the potential toxicity of docosahexaenoic acid (DHA)-rich microalgae (DRM) from Schizochytrium sp., administered in the diet of growing swine. DRM was administered in the diet to groups of castrated male growing pigs (mixed commercial breeds, Landrace & Large White) reared from early weaned (weighing approximately 20 lbs) to approximately 250-270 lbs. Over the course of the 120 day study, animals were fed ad libitum four DRM treatment diets, each designed to optimize weight gain over the growing cycle, and a control diet. DRM was incorporated into the diet of the first treatment group at a level delivering 2.680 kg DRM per pig over the course of 120 days (a constant, whole-life exposure) equating to 598 g DHA per pig. DRM was incorporated into finisher diets only (administered over the last 42 days of the growing cycle) to treatment groups 2, 3, and 4 delivering 1.169, 3.391, and 5.746 kg DRM per pig (261, 756, and 1281 g DHA per pig). These levels represent approximately 1, 3, and 5 times the anticipated commercial dose and were delivered in a feeding strategy designed to mimic commercial use. Vitamin E was added to all diet groups to provide supplementary dietary antioxidant given the high content of polyunsaturated fat in DRM. There were no statistically significant treatment-related effects in clinical observations, body weights, food consumption, mortality, hematologic values, gross necropsy findings, organ weights or histopathology. The only DRM treatment-related changes were higher weight gain and feed conversion efficiency, anticipated results based on the increased fat content in the experimental DRM treatments. This study demonstrates that administration of DRM (at up to five times the anticipated commercial dose) did not produce any treatment-related adverse effects in commercial strains of swine. Copyright 2003 Elsevier Science (USA)

  12. Differential Expression of Sclerostin In Adult and Juvenile Mouse Calvaria

    PubMed Central

    Kwan, Matthew D.; Quarto, Natalina; Gupta, Deepak M.; Slater, Bethany; Wan, Derrick C.; Longaker, Michael T.

    2010-01-01

    Background An understanding of the molecular mechanisms controlling bone formation is central to skeletal tissue engineering efforts. The observation that immature animals are able to heal calvarial defects while adult animals are not has proven to be a useful tool for examining these mechanisms. Thus, we compared expression of sclerostin, a bone inhibitor, between the calvaria of juvenile and adult mice. Methods Parietal bone was harvested from juvenile (6 day old, n=20) and adult (60 day old, n=20) mice. Sclerostin transcript and protein levels were compared between the parietal bone of juvenile and adult mice using polymerase chain reaction (PCR), Western blotting, and immunohistochemistry (IHC). Finally, osteoblasts from the parietal bone of juvenile and adult mice were harvested and cultured under osteogenic differentiation conditions with and without recombinant sclerostin (200ng/ml). Terminal osteogenic differentiation was assessed at 21 days with Alizarin red staining. Results PCR, Western blot analysis, and IHC all confirmed greater expression of sclerostin in the parietal bone of adult mice when compared to that of juvenile mice. Osteoblasts, whether from juvenile or adult parietal bones, demonstrated reduced capacity for osteogenic differentiation when exposed to recombinant sclerostin. Conclusion Given sclerostin’s role in inhibiting bone formation, our findings suggest that differences in expression levels of sclerostin may play a role in the differential regenerative capacity of calvaria from juvenile and adult animals. These findings suggest it as a potential target to abrogate in future tissue engineering studies. PMID:21285764

  13. Gold nephropathy in juvenile rheumatoid arthritis.

    PubMed

    Husserl, F E; Shuler, S E

    1979-01-01

    A 2-year-old girl was treated with gold salts for juvenile rheumatoid arthritis. Treatment had to be discontinued when persistent proteinuria was detected. As this case report indicates, close monitoring of the urine is mandatory during treatment with gold salts to detect early signs of toxicity: hematuria followed by casts and then proteinuria as therapy is continued. Histologic examination with electron microscopy will help to differentiate the different forms of gold toxicity. When the findings are consistent with gold-induced renal involvement, therapy should be discontinued. The gold nephropathy usually resolves in time, with no permanent renal damage.

  14. Juvenile Justice in California, 1983.

    ERIC Educational Resources Information Center

    California State Dept. of Justice, Sacramento. Bureau of Criminal Statistics and Special Services.

    This publication provides an overview of the processing of juvenile delinquency cases through the California juvenile justice system; provides information to aid administrators, planners, and researchers in the administration of juvenile justice; and maintains baseline data for further studies of the system. Information on juvenile arrests and…

  15. Toxicity bioassays: Water pollution effects on aquatic animals and plants. (Latest citations from the Selected Water Resources Abstracts database). Published Search

    SciTech Connect

    Not Available

    1993-11-01

    The bibliography contains citations concerning toxicity bioassay studies of water pollution effects on reproduction, growth, and mortality of aquatic fauna and flora. Industrial and agricultural water pollutants such as heavy metals, chemicals, pesticides, and herbicides are evaluated and tested. Standard fish and algal assays are used to determine effects of potential toxicants. (Contains 250 citations and includes a subject term index and title list.)

  16. Toxicity bioassays: Water-pollution effects on aquatic animals and plants. (Latest citations from the Selected Water Resources Abstracts data base). Published Search

    SciTech Connect

    Not Available

    1992-08-01

    The bibliography contains citations concerning toxicity bioassay studies of water pollution effects on reproduction, growth, and mortality of aquatic fauna and flora. Industrial and agricultural water pollutants such as heavy metals, chemicals, pesticides, and herbicides are evaluated and tested. Standard fish and algal assays are used to determine effects of potential toxicants. (Contains 250 citations and includes a subject term index and title list.)

  17. Toxicity of imidacloprid to the terrestrial isopod Porcellio scaber (Isopoda, Crustacea).

    PubMed

    Drobne, Damjana; Blazic, Mateja; Van Gestel, Cornelis A M; Leser, Vladka; Zidar, Primoz; Jemec, Anita; Trebse, Polonca

    2008-04-01

    Imidacloprid is a neonicotinoid insecticide with neurotoxic action that, as a possible alternative for commonly used organophosphorus pesticides, has gained registration in about 120 countries for use in over 140 agricultural crops. Only few data are available on its toxicity for soil invertebrates. We therefore assessed the effects of imidacloprid on survival, weight gain, feeding rate, total protein content, glutathione S-transferase activity (GST), and digestive gland epithelial thickness in juveniles and adults of the terrestrial isopod Porcellio scaber. After two weeks of feeding on imidacloprid-dosed food, weight gain (NOEC 5 microg/g dry food) and feeding rate (NOEC 10 microg/g) in juveniles, and feeding rate (NOEC<10 microg/g) and digestive gland epithelial thickness (NOEC<10 microg/g) in adults were most affected. In juveniles induction of GST activity and increase of total protein content per wet animal weight was detected at 5 microg/g dry food, whereas in adults a reduction of GST was observed at 25 microg/g (NOEC 10 microg/g). An estimate of actual intake rates suggests that imidacloprid affects isopods at similar exposure concentrations as insects. The toxicity of imidacloprid was similar to that of the organophosphorus pesticide diazinon, tested earlier using the same methods [Stanek, K., Drobne, D., Trebse, P., 2006. Linkage of biomarkers along levels of biological complexity in juvenile and adult diazinon fed terrestrial isopod (Porcellio scaber, Isopoda, Crustacea). Chemosphere 64, 1745-1752]. At actual environmental concentrations, diazinon poses a higher risk to P. scaber. Due to its increasing use in crop protection and higher persistence in soil, imidacloprid might however, be potentially more dangerous after long-term application. We conclude that toxicity testing with P. scaber provides relevant, repeatable, reproducible and comparable toxicity data that is useful for the risk assessment of pesticides in the terrestrial environment.

  18. Juvenile Sex Offenders.

    PubMed

    Ryan, Eileen P; Otonichar, Joseph M

    2016-07-01

    Sexual offending by juveniles accounts for a sizable percentage of sexual offenses, especially against young children. In this article, recent research on female juvenile sex offenders (JSOs), risk factors for offending in juveniles, treatment, and the ways in which these youth may differ from general delinquents will be reviewed. Most JSOs do not go on to develop paraphilic disorders or to commit sex offenses during adulthood, and as a group, they are more similar to nonsexual offending juvenile delinquents than to adult sex offenders. Recent research has elucidated some differences between youth who commit sex offenses and general delinquents in the areas of atypical sexual interests, the use of pornography, and early sexual victimization during childhood.

  19. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... rule out other conditions or infections, such as Lyme disease , that may cause similar symptoms or occur along ... ESR) Bones, Muscles, and Joints Evaluate Your Child's Lyme Disease Risk Word! Arthritis Arthritis Lupus Juvenile Idiopathic Arthritis ( ...

  20. Do benthic sediment characteristics explain the distribution of juveniles of the deposit-feeding sea cucumber Australostichopus mollis?

    NASA Astrophysics Data System (ADS)

    Slater, Matthew J.; Jeffs, Andrew G.

    2010-10-01

    Despite the economic importance of many deposit-feeding sea cucumbers, the ecology of their juveniles is poorly understood and factors influencing juvenile habitat selection remain largely unexplained. We investigated the importance of the characteristics of the available sediment in determining the highly localised distribution of juveniles of the deposit-feeding Australasian sea cucumber Australostichopus mollis. Wild-caught juveniles were displaced to non-juvenile habitats with surface sediments characterised by lower total organic content (TOM) and nitrogen content, higher chlorophyll- a content and coarser grain size profiles compared to juvenile sites. The growth of displaced individual animals was monitored over 9 months and compared to control animals caged in the juvenile habitats. Displaced juvenile sea cucumbers had high survival rates that did not differ significantly from juvenile habitats. Displaced juveniles exhibited significantly higher specific growth rate (SGR) than those at juvenile sites ( p < 0.001), although the growth of individuals was highly variable within individual cages and among sites. The lower TOM and nitrogen content, and coarser grain size profiles at non-juvenile sites did not result in reductions in juvenile survival or growth. Higher microphytobenthic activity may have resulted in the higher growth rates observed at shallow non-juvenile sites. The SGR of juveniles over the first 6 months of the experiment ranged between 0.45% d - 1 and 0.74% d - 1 for all sites. This was followed by marked growth limitation between 6 and 9 months either as a result of increasing juvenile biomass in cages or seasonal growth limitation. A subsequent reduction in juvenile density resulted in markedly increased growth over the following 3 month period. Juvenile A. mollis show an ability to exploit a variety of benthic sediment food sources, indicating that their highly localised distribution is not due to differences in the food quality of

  1. Juvenile crime and criminal justice: resolving border disputes.

    PubMed

    Fagan, Jeffrey

    2008-01-01

    Rising juvenile crime rates during the 1970s and 1980s spurred state legislatures across the country to exclude or transfer a significant share of offenders under the age of eighteen to the jurisdiction of the criminal court, essentially redrawing the boundary between the juvenile and adult justice systems. Jeffrey Fagan examines the legal architecture of the new boundary-drawing regime and how effective it has been in reducing crime. The juvenile court, Fagan emphasizes, has always had the power to transfer juveniles to the criminal court. Transfer decisions were made individually by judges who weighed the competing interests of public safety and the possibility of rehabilitating young offenders. This authority has now been usurped by legislators and prosecutors. The recent changes in state law have moved large numbers of juveniles into the adult system. As many as 25 percent of all juvenile offenders younger than eighteen, says Fagan, are now prosecuted in adult court. Many live in states where the age boundary between juvenile and criminal court has been lowered to sixteen or seventeen. The key policy question is: do these new transfer laws reduce crime? In examining the research evidence, Fagan finds that rates of juvenile offending are not lower in states where it is relatively more common to try adolescents as adults. Likewise, juveniles who have been tried as adults are no less likely to re-offend than their counterparts who have been tried as juveniles. Treating juveniles as adult criminals, Fagan concludes, is not effective as a means of crime control. Fagan argues that the proliferation of transfer regimes over the past several decades calls into question the very rationale for a juvenile court. Transferring adolescent offenders to the criminal court exposes them to harsh and sometimes toxic forms of punishment that have the perverse effect of increasing criminal activity. The accumulating evidence on transfer, the recent decrease in serious juvenile

  2. Sex differences in play behavior in juvenile tufted capuchin monkeys (Cebus apella)

    PubMed Central

    Paukner, Annika; Suomi, Stephen J.

    2008-01-01

    According to the motor training hypothesis, play behavior in juvenile primates improves motor skills that are required in later adult life. Sex differences in juvenile play behavior can therefore be expected when adult animals assume distinct sexually dimorphic roles. Tufted capuchin monkeys show sexually dimorphic levels of physical antagonism in both inter- and intragroup encounters. Accordingly, it can be predicted that juvenile capuchins also show sex differences in social play behavior. To test this hypothesis, the play behavior of nine juvenile and two infant capuchins was examined. As predicted, juvenile males showed significantly higher levels of social play (wrestle, chase) than juvenile females, but no differences were found in nonsocial play (arboreal, object). Levels of infant play behavior were comparable to that of juveniles. These results lend support to the motor training hypothesis and highlight the need for more detailed investigations of individual differences in play behavior. PMID:18668302

  3. Vocational Teachers' Role in Serving Juvenile Offenders.

    ERIC Educational Resources Information Center

    Meers, Gary D.

    1983-01-01

    Educators need to understand the juvenile justice system to understand what juvenile offenders go through while completing their sentences. This article reviews cases and juvenile charge classifications, and presents a model for alternative sentencing options for juveniles. (JOW)

  4. Expression of cytochromes p450 in fetal, infant, and juvenile liver of cynomolgus macaques.

    PubMed

    Ise, Ryota; Kondo, Satoshi; Kato, Hiroto; Imai, Noritaka; Akiyama, Hideo; Iwasaki, Kazuhide; Yamazaki, Hiroshi; Uno, Yasuhiro

    2011-01-01

    Preclinical data of fetal, infant, and juvenile animals are important for the prediction of drug toxicity in fetuses and children. However, expression of drug-metabolizing enzymes, including cytochromes P450 (CYPs), have not been fully investigated in fetal, infant, or juvenile liver of the cynomolgus macaque, an animal species important for preclinical studies. In this study, hepatic expression of 20 cynomolgus macaque CYPs (mfCYPs) in the CYP1-4 subfamilies that are relevant to drug metabolism was measured in fetuses, infants, and juveniles using DNA microarrays. Expression of most mfCYPs, including those moderately or abundantly expressed in postnatal livers such as mfCYP2A23, mfCYP2A24, mfCYP2B6, mfCYP2C9, mfCYP2C19, mfCYP2C76, mfCYP2D17, mfCYP2E1 mfCYP3A4, and mfCYP3A5, was much less abundant in fetal livers, but increased substantially after birth. In contrast, expression of mfCYP2C8 in fetal livers was not substantially different from postnatal livers. Since human CYP3A7 is expressed more abundantly in fetal livers than in adult livers, mfCYP3A7, an ortholog of human CYP3A7, was analyzed by quantitative polymerase chain reaction. Expression of mfCYP3A7 in fetal livers was much lower than that in postnatal livers, and greatly increased after birth, unlike the expression of human CYP3A7. These results indicate that expression of most mfCYPs examined was low in fetal livers, but increased greatly in postnatal livers, with a few exceptions such as mfCYP2C8.

  5. Seasonal effects of leached mirex on selected estuarine animals.

    PubMed

    Tagatz, M E; Borthwick, P W; Forester, J

    1975-01-01

    Four 28-day seasonal experiments were conducted using selected estuarine animals in outdoor tanks that received continuous flow of mirex-laden water. Mirex (dodecachlorooctahydro-1,3,4-metheno-2H-cyclobuta [cd] pentalene) leached from fire ant bait (0.3% mirex) by fresh water and then mixed with salt water was toxic to blue crabs (Callinectes sapidus), pink shrimp (Penaeus duorarum), and grass shrimp (Palaemonetes pugio) but not to sheepshead minnows (Cyprinodon variegatus), at concentrations less than 0.53 mug/L in water. The amount of leaching was greatest in summer and least in spring. Greatest mortality occurred in summer at the highest water temperature and concentration of mirex; least mortality occurred in spring at the next to the lowest temperature and at the lowest concentration. Earliest deaths of blue crabs occurred after six days of exposure and shrimps after two days. Small juvenile crabs were more sensitive to leached mirex than were large juveniles. Mirex did not appear to affect growth or frequency of molting in crabs. All exposed animals concentrated mirex. Among animals that survived for 28 days, sheepshead minnows concentrated mirex 40,800X above the concentration in the water, blue crabs 2,300X, pink shrimp 10,000X, and grass shrimp 10,800X. Sand substrata contained mirex up to 770X that in the water. Most control and exposed animals in samples examined histologically had normal tissues, but alteration in gills of some exposed fish and natural pathogens in some exposed and control crabs and shrimp were observed. The experiments demonstrated that mirex can be leached from bait by fresh water, concentrated by estuarine organisms, and can be toxic to crabs and shrimps.

  6. Evaluation of the physiology of Medaka as a model animal for standardized toxicity tests of chemicals by using mRNA expression profiling.

    PubMed

    Iwahashi, Hitoshi; Kishi, Katsuyuki; Kitagawa, Emiko; Suzuki, Katsunori; Hayashi, Yasuyuki

    2009-05-15

    The fish acute toxicity test in the Organisation for Economic CoOperation and Development "OECD Guidelines for Testing of Chemicals" is an essential test for environmental toxicity. Here, we have tried to evaluate the physiology of medaka during these test procedures by using genomics. Genomics technology can provide genome-wide expression profiles of mRNA, and these profiles correspond to the physiology of organisms. Thus, a comparison of mRNA expression profiles gives information on the reproducibility of experimental conditions. Expression profiles of mRNA were measured for medakas maintained within the allowable range of the test conditions and also under extreme conditions beyond the guideline limits. We confirmed the high physiological reproducibility of medaka kept in the recommended conditions of the fish acute toxicity test in the "OECD Guidelines for Testing of Chemicals" from the expression profiles obtained under all experimental conditions, except for the types of feeding.

  7. Magnetic resonance imaging assessment of the ventricular system in the brains of adult and juvenile beagle dogs treated with posaconazole IV Solution.

    PubMed

    Hines, C D G; Song, X; Kuruvilla, S; Farris, G; Markgraf, C G

    2015-01-01

    Noxafil® (posaconazole; POS) is a potent, selective triazole antifungal approved for use in adults as an oral suspension, oral tablet and intravenous (IV) Solution. In support of pediatric administration of POS IV Solution to childrenjuvenile pre-weaning Beagle dogs was conducted, which showed enlarged lateral ventricles in the brain at the conclusion of a 6 week dosing period. To evaluate the impact of this finding on older age dogs, which would support administration to children>two years of age, two studies were undertaken using magnetic resonance imaging (MRI) to monitor brain ventricle size longitudinally during three months administration of POS IV in adult and juvenile dogs. Necropsy was performed on all animals at the end of the studies. From the baseline MRI images, great variability in ventricle size was noted in both the adult and juvenile dogs; these images were used to distribute differently sized ventricles between treatment and vehicle groups as to not skew group means during the course of the study. POS IV Solution had no effect on ventricle volume at any timepoint during dosing in either the adult or the juvenile dogs. Further, no gross or histomorphologic differences between groups were observed in either study. Compared to juvenile dogs, MRI analysis showed that adult dogs had larger ventricles, lower variability in all ventricle volumes, and a greater rate of increase in total ventricle volume. Information on growth and development of brains is one of the few areas in which more detailed information is available about humans than about the standard laboratory animals used to model disease and predict toxicities. The use of MRI helped elucidate large natural variabilities in the dog brain, which could have altered the interpretation of this de-risking study, and provided a valuable noninvasive means to monitor the brain ventricles longitudinally. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Toxic Hazards Research Unit

    NASA Technical Reports Server (NTRS)

    Macewen, J. D.; Vernot, E. H.

    1971-01-01

    The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1970 through May 1971 reviewed. Modification of the animal exposure facilities primarily for improved human safety but also for experimental integrity and continuity are discussed. Acute toxicity experiments were conducted on hydrogen fluoride (HF), hydrogen chloride (HCl), nitrogen dioxide (NO2), and hydrogen cyanide (HCN) both singly and in combination with carbon dioxide (CO). Additional acute toxicity experiments were conducted on oxygen difluoride (OF2) and chlorine pentafluoride (ClF5). Subacute toxicity studies were conducted on methylisobutylketone and dichloromethane (methylene dichloride). The interim results of further chronic toxicity experiments on monomethylhydrazine (MMH) are also described.

  9. Juvenile Incarceration and Health.

    PubMed

    Barnert, Elizabeth S; Perry, Raymond; Morris, Robert E

    2016-03-01

    Addressing the health status and needs of incarcerated youth represents an issue at the nexus of juvenile justice reform and health care reform. Incarcerated youth face disproportionately higher morbidity and higher mortality compared to the general adolescent population. Dental health, reproductive health, and mental health needs are particularly high, likely as a result of lower access to care, engagement in high-risk behaviors, and underlying health disparities. Violence exposure and injury also contribute to the health disparities seen in this population. Further, juvenile incarceration itself is an important determinant of health. Juvenile incarceration likely correlates with worse health and social functioning across the life course. Correctional health care facilities allow time for providers to address the unmet physical and mental health needs seen in this population. Yet substantial challenges to care delivery in detention facilities exist and quality of care in detention facilities varies widely. Community-based pediatricians can serve a vital role in ensuring continuity of care in the postdetention period and linking youth to services that can potentially prevent juvenile offending. Pediatricians who succeed in understanding and addressing the underlying social contexts of their patients' lives can have tremendous impact in improving the life trajectories of these vulnerable youth. Opportunities exist in clinical care, research, medical education, policy, and advocacy for pediatricians to lead change and improve the health status of youth involved in the juvenile justice system.

  10. Preventive immunization of aged and juvenile non-human primates to beta-amyloid

    PubMed Central

    2012-01-01

    animals. Conclusions Our results indicate that preventive Aβ immunization is a safe therapeutic approach lacking adverse CNS immune system activation or other serious side-effects in both aged and juvenile NHP cohorts. A significant shift in the composition of soluble oligomers towards smaller species might facilitate removal of toxic Aβ species from the brain. PMID:22554253

  11. Modulation of brain steroidogenesis by affecting transcriptional changes of steroidogenic acute regulatory (StAR) protein and cholesterol side chain cleavage (P450scc) in juvenile Atlantic salmon (Salmo salar) is a novel aspect of nonylphenol toxicity.

    PubMed

    Arukwe, Augustine

    2005-12-15

    Gene expression patterns for key brain steroidogenic (StAR, P450scc, CYP11beta) and xenobiotic- and steroid-metabolizing enzymes (CYP1A1 and CYP3A) have been investigated in waterborne nonylphenol (5, 15, and 50 microg/ L) treated juvenile Atlantic salmon (Salmo salar), in addition to carrier vehicle (ethanol) exposed fish, sampled at different time intervals (0, 3, and 7 days) after exposure. Gene expression patterns were studied using the quantitative polymerase chain reaction (real-time PCR). Treatment of juvenile salmon with nonylphenol caused significant induction of steroidogenic acute regulatory (StAR) protein mRNA at day 7 postexposure in the group receiving 15 microg of nonylphenol/L. P450scc was first induced in the group treated with 5 microg of nonylphenol/L at day 7; thereafter, an apparent nonylphenol-concentration-dependent decrease in P450scc mRNA was observed. CYP11beta mRNA was significantly induced at day 3 after exposure to 5 betag of nonylphenol/L; thereafter, CYP11beta mRNA levels were inhibited below control levels in the 15 and 50 microg of nonylphenol/L groups at day 3. At day 7, significant induction of CYP11beta mRNA was observed only in the group exposed to 15 microg of nonylphenol/L. For CYP1A1 mRNA, apparent nonylphenol-concentration-dependent decreases were observed at day 7 postexposure. CYP3A mRNA was significantly induced by all nonylphenol exposure concentrations at day 7. When exposed groups were compared, CYP3A transcript was significantly induced between 5 and 15 microg of nonylphenol/ L, and decreased between 15 and 50 microg of nonylphenol/ L. The ethanol control showed a significant reduction of CYP3A mRNA at day 3 postexposure. The present study has demonstrated variations in three key steroidogenic proteins and xenobiotic- and steroid-metabolizing CYP isoenzyme gene transcripts in the brain of nonylphenol-exposed juvenile salmon. Therefore, the present study represents a novel aspect of neuroendocrine effects of

  12. Blocking Aβ seeding-mediated aggregation and toxicity in an animal model of Alzheimer's Disease: A novel therapeutic strategy for neurodegeneration

    PubMed Central

    Eleuteri, Simona; Di Giovanni, Saviana; Rockenstein, Edward; Mante, Mike; Adame, Antony; Trejo, Margarita; Wrasidlo, Wolf; Wu, Fang; Fraering, Patrick C.; Masliah, Eliezer; Lashuel, Hilal A.

    2014-01-01

    Aβ accumulation plays a central role in the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that process of Aβ nucleated polymerization is essential for Aβ fibril formation, pathology spreading and toxicity. Therefore, targeting this process represent an effective therapeutic strategy to slow or block disease progression. To discover compounds that might interfere with the Aβ seeding capacity, toxicity and pathology spreading, we screened a focused library of FDA-approved drugs in vitro using a seeding polymerization assay and identified small molecule inhibitors that specifically interfered with Aβ seeding-mediated fibril growth and toxicity. Mitoxantrone, bithionol and hexachlorophene were found to be the strongest inhibitors of fibril growth and protected primary cortical neuronal cultures against Aβ-induced toxicity. Next, we assessed the effects of these three inhibitors in vivo in the mThy1-APPtg mouse model of AD (8-month-old mice). We found that mitoxantrone and bithionol, but not hexachlorophene, stabilized diffuse amyloid plaques, reduced the levels of Aβ42 oligomers and ameliorated synapse loss, neuronal damage and astrogliosis. Together, our findings suggest that targeting fibril growth and Aβ seeding capacity constitutes a viable and effective strategy for protecting against neurodegeneration and disease progression in AD. PMID:25173807

  13. Extending juvenility in grasses

    DOEpatents

    Kaeppler, Shawn; de Leon Gatti, Natalia; Foerster, Jillian

    2017-04-11

    The present invention relates to compositions and methods for modulating the juvenile to adult developmental growth transition in plants, such as grasses (e.g. maize). In particular, the invention provides methods for enhancing agronomic properties in plants by modulating expression of GRMZM2G362718, GRMZM2G096016, or homologs thereof. Modulation of expression of one or more additional genes which affect juvenile to adult developmental growth transition such as Glossy15 or Cg1, in conjunction with such modulation of expression is also contemplated. Nucleic acid constructs for down-regulation of GRMZM2G362718 and/or GRMZM2G096016 are also contemplated, as are transgenic plants and products produced there from, that demonstrate altered, such as extended juvenile growth, and display associated phenotypes such as enhanced yield, improved digestibility, and increased disease resistance. Plants described herein may be used, for example, as improved forage or feed crops or in biofuel production.

  14. Juvenile Sex Offenders.

    PubMed

    Ryan, Eileen P

    2016-01-01

    Public policy has tended to treat juvenile sex offenders (JSOs) as adult sex offenders in waiting, despite research that contradicts this notion. Although as a group, JSOs are more similar to general delinquents than to adult sex offenders, atypical sexual interests and sexual victimization during childhood may be a pathway for sexual offending that differentiates some JSOs from their nonsexually delinquent peers. Developmental considerations must be considered in risk assessment evaluations of these youth. This article reviews theories of sexual offending in youth, risk factors for juvenile offending and reoffending, psychopathology in JSOs, risk assessment, and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Potential impacts of blooms of the toxic dinoflagellate Karenia brevis on the growth, survival and juvenile recruitment of the non-native green mussel Perna viridis in southeastern United States.

    PubMed

    McFarland, Katherine; Jean, Fred; Thébault, Julien; Volety, Aswani K

    2016-01-01

    Red tide blooms formed by Karenia brevis are frequent along the Gulf coast of Florida and it is unclear what tolerance the green mussel Perna viridis, a recently introduced species to coastal waters, has toward these events. Established populations of P. viridis were monitored along the coastal waters of Estero Bay, Florida before, during and following two consecutive red tide blooms to assess the potential effects on growth, survival and juvenile recruitment. Upon onset of the bloom, growth rates fell from 6 to 10 mm month(-1) (March 2011-November 2011) to less than 3 mm month(-1). In the succeeding years, K. brevis blooms were present, and average growth of individually tagged mussels remained below 3 mm month(-1). During growth monitoring the use of calcein as an internal marker was tested with positive staining results and no observed effect on growth or survival. In March 2012, following the first red tide bloom, a population-wide mortality event was observed. Following this event, increased mortality rates were observed with peaks during onset of the bloom in the fall of 2012 and 2013. Juvenile recruitment was also limited during years in which blooms persisted into the spring spawning period suggesting gamete and/or larval sensitivity to K. brevis. Although it cannot be conclusively determined that the cause of reduced growth and survival is due to red tide events, the parallels observed suggest that K. brevis is a factor in the observed changes in population structure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Toxicity Reference Database

    EPA Pesticide Factsheets

    The Toxicity Reference Database (ToxRefDB) contains approximately 30 years and $2 billion worth of animal studies. ToxRefDB allows scientists and the interested public to search and download thousands of animal toxicity testing results for hundreds of chemicals that were previously found only in paper documents. Currently, there are 474 chemicals in ToxRefDB, primarily the data rich pesticide active ingredients, but the number will continue to expand.

  17. Animal Testing

    NASA Astrophysics Data System (ADS)

    Moretto, Johnny; Chauffert, Bruno; Bouyer, Florence

    The development of a new anticancer drug is a long, complex and multistep process which is supervised by regulatory authorities from the different countries all around the world [1]. Application of a new drug for admission to the market is supported by preclinical and clinical data, both including the determination of pharmacodynamics, toxicity, antitumour activity, therapeutic index, etc. As preclinical studies are associated with high cost, optimization of animal experiments is crucial for the overall development of a new anticancer agent. Moreover, in vivo efficacy studies remain a determinant panel for advancement of agents to human trials and thus, require cautious design and interpretation from experimental and ethical point of views.

  18. Combinatorial QSAR Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Quantitative Structure-Activity Relationship (QSAR) toxicity models have become popular tools for identifying potential toxic compounds and prioritizing candidates for animal toxicity tests. However, few QSAR studies have successfully modeled large, diverse mammalian toxicity end...

  19. Combinatorial QSAR Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Quantitative Structure-Activity Relationship (QSAR) toxicity models have become popular tools for identifying potential toxic compounds and prioritizing candidates for animal toxicity tests. However, few QSAR studies have successfully modeled large, diverse mammalian toxicity end...

  20. Toxicity of the cyanobacterium Cylindrospermopsis raciborskii to Daphnia magna.

    PubMed

    Nogueira, Isabel C G; Saker, Martin L; Pflugmacher, Stephan; Wiegand, Claudia; Vasconcelos, Vítor M

    2004-10-01

    The effect of two strains of Cylindrospermopsis raciborskii on the survivorship, somatic growth, and detoxification processes of juvenile Daphnia magna were investigated. Both strains of C. raciborskii (and also Ankistrodesmus falcatus, used as the control) were given to newborn D. magna at equivalent biovolumes. The survival curves for D. magna subjected to the two C. raciborskii treatments differed from those of the starved and fed treatments. After 48 h of exposure, the percentage of D. magna surviving after exposure to Cylin-A (a cylindrospermopsin-producing strain isolated from Australia) and Cylin-P (a non-cylindrospermopsin-producing strain isolated from Portugal) was 10.00% and 93.33%, respectively. The strain that produces cylindrospermopsin caused the greatest toxic effect in juvenile D. magna. Statistically significant differences in D. magna body size between the four treatments (Cylin-A, Cylin-P, A. falcatus, and starved) were detected after 48 h of exposure. The juvenile D. magna that received the two C. raciborskii treatments showed an increase in size (relative to their size at T(0)) of 2.54% and 38.14%, respectively. These values were statistically significantly different than those of the A. falcatus-fed control (55.54%) and the starved control (11.47%). In both C. raciborskii treatments there was a tendency for increased GST enzyme activities after 24 h of exposure. Cylindrospermopsin was detected (HPLC-MS/MS) in D. magna tissues after 24 and 48 h (0.025 and 0.02 ng animal(-)1, respectively). The results of this study indicate that C. raciborskii can affect the fitness and growth potential of juvenile D. magna. Copyright 2004 Wiley Periodicals, Inc.

  1. Toxic megacolon

    MedlinePlus

    ... disease - toxic megacolon; Crohn disease - toxic megacolon; Ulcerative colitis - toxic megacolon ... people with an inflamed colon due to: Ulcerative colitis , or Crohn disease that is not well controlled ...

  2. Effect of water pH on the toxicity of 2,4,5-trichlorophenol to four species of freshwater animals

    SciTech Connect

    Brooke, L.T.; Markee, T.; Vande Venter, F.; Spehar, R.; Erickson, R.

    1994-12-31

    2,4,5-Trichlorophenol (TCP) is a weak acid with a pH of approximately 7.2 which is expected to have a significant effect upon its toxicity. Lumbriculus variegatus, Oncorhynchus mykiss, Pimephales promelas, and Hyalella azteca were exposed to TCP in 96 h flow-through toxicity tests. For the first two species, simultaneous tests were conducted at three pH values (7.0, 7.8, 8.6). The other two species were tested at six pH values conducted in two sets of three simultaneous tests (6.2, 7.4, 8.6 and 6.8, 8.0, 9.2). All species tested showed decreased sensitivity to TCP with increased pH of the water. Over the pH range tested, LC50s for L. variegatus varied by about 5-fold, for P. promelas by 12-fold, for H. azteca by 10-fold, and for O. mykiss by 1.5-fold. The effects of pH on TCP toxicity to P. promelas was also tested in 30 day chronic tests at pH 7.0, 7.8 and 8.6. Survival in these tests was affected by pH similarly to the acute tests. Growth also was less severely affected at higher pH.

  3. Treating the Juvenile Offender

    ERIC Educational Resources Information Center

    Hoge, Robert D., Ed.; Guerra, Nancy G., Ed.; Boxer, Paul, Ed.

    2008-01-01

    This authoritative, highly readable reference and text is grounded in the latest knowledge on how antisocial and criminal behavior develops in youth and how it can effectively be treated. Contributors describe proven ways to reduce juvenile delinquency by targeting specific risk factors and strengthening young people's personal, family, and…

  4. What Is Juvenile Arthritis?

    MedlinePlus

    ... the possible causes of juvenile arthritis. They are studying genetic and environmental factors that they think are involved. They are also trying to improve current treatments and find new medicines that will work better with fewer side effects. Research supported by ...

  5. Juvenile Victimization and Delinquency.

    ERIC Educational Resources Information Center

    Esbensen, Finn-Aage; Huizinga, David

    1991-01-01

    Demographic characteristics of juvenile victims of crime and a potential relationship between victimization and self-reported delinquency are examined for 877 adolescents from a large midwestern city. Lifetime victimization rates (LVRs) are higher for those involved in delinquency, and LVRs rise with age and higher levels of delinquent behavior.…

  6. Treating the Juvenile Offender

    ERIC Educational Resources Information Center

    Hoge, Robert D., Ed.; Guerra, Nancy G., Ed.; Boxer, Paul, Ed.

    2008-01-01

    This authoritative, highly readable reference and text is grounded in the latest knowledge on how antisocial and criminal behavior develops in youth and how it can effectively be treated. Contributors describe proven ways to reduce juvenile delinquency by targeting specific risk factors and strengthening young people's personal, family, and…

  7. Juvenile Battens Disease.

    ERIC Educational Resources Information Center

    Gayton, Romayne

    1987-01-01

    Ten children diagnosed with juvenile Battens disease were tested over a three-year period in general intelligence, memory, listening and speech, motor skills, and general learning. Results showed that the patients followed a predetermined pattern but that the time span for development of memory, communication, and behavior problems varied greatly.…

  8. A Literature Review - Problem Definition Studies on Selected Toxic Chemicals

    DTIC Science & Technology

    1978-06-16

    toxicity . . . . . . . . . 27 3. Acute gastrointestinal and pulmonary toxicity . . . 28 4. Chronic cutaneous toxicity . . . . . . . . .. . 29 5. Other...cancer . . . . . . . 37 d. gastrointestinal toxicity and cancer . . ... 42 e. general mortality . . . . . . . . . . 42 f. other effects... gastrointestinal toxicity . . . . . . . . .. 45 c. pulmonary toxicity and lung cancer . . . - 46 d. carcinogenicity . . . ........ . 49 IV. ANIMAL TOXICITY

  9. Toxic Synovitis

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Toxic Synovitis KidsHealth > For Parents > Toxic Synovitis A A A ... and causes no long-term problems. About Toxic Synovitis Toxic synovitis (also known as transient synovitis ) is ...

  10. Delineating the extent of anterior capsulorhexis with gentian violet using capsulorhexis marker: a preliminary study of efficacy and toxicity in an animal model

    PubMed Central

    Hassaballa, Mohamed Abdel Moneim; Osman, Amr Abd el-Latif

    2011-01-01

    Background: The purpose of this study was to evaluate the efficacy and safety of a new instrument to optimize the size, shape, and centration of anterior capsulorhexis. Methods: The study was divided into two parts. The first part was done in 10 goats’ eyes. A specially designed capsulorhexis marker was used. The lower edge of the instrument was stained by gentian violet and then applied to the anterior capsule to produce a circular mark of 5.5 mm. In five eyes, the gentian violet was applied to the marker using a corneal marking pen; in the remaining five eyes, the gentian violet was applied using a corneal marking pad. In the second part, the toxicity of gentian violet was tested as follows: ten albino rabbits received a gentian violet injection into the anterior chamber in one eye (experimental group) and an equal volume of balanced salt solution in the fellow eye (control group). Five rabbits were sacrificed one day after surgery and the remaining five rabbits after one week. Results: In the first part, there was no difficulty in the introduction or removal of the instrument from all eyes. In the first two eyes, the circular mark was diffuse due to sliding of the marker on the surface of the anterior capsule. In the remaining eight eyes, there was a well-centered, rounded mark which was adequately stained. In the second part, there was no histopathological evidence of corneal toxicity in either group. There was loss of ganglion cells from the neurosensory retina one day after surgery in one eye from the experimental group. At one week, there was no evidence of retinal toxicity in any of the rabbits. Conclusion: This capsulorhexis marker can guide the surgeon to a better centration and proper sizing of anterior capsulorhexis using gentian violet staining. More refinement of the instrument is needed to be able to use it in human eyes. PMID:21750617

  11. Green Biosynthesis, Characterization, In vitro Antidiabetic Activity, and Investigational Acute Toxicity Studies of Some Herbal-mediated Silver Nanoparticles on Animal Models

    PubMed Central

    Shanker, Kalakotla; Mohan, Gottumukkala Krishna; Hussain, Md. Ashwaq; Jayarambabu, Naradala; Pravallika, Poka Lakshmi

    2017-01-01

    Diabetes is a metabolic disorder characterized by hyperglycemia, altered carbohydrate, lipid and protein metabolism. In recent studies, Nanoscience and nanotechnology are blazing fields for researchers; for researchers; of late there has been a prodigious excitement in the field of nanopharmacology to study silver nanoparticle (SNP) synthesis using natural products. Biological methods have been used to synthesize SNPs using medicinally active plants having an antidiabetic role, and this made us to assess the biologically synthesized SNPs from the seed extract of Psoralea corylifolia using 1 mM silver nitrate solution. The synthesized herbal-mediated SNPs (HMSNPs) were subjected to various characterization techniques such as X-ray diffraction analysis (XRD), energy dispersive X-ray (EDX) analysis, transmission electron microscope (TEM), and differential light scattering (DLS), respectively. In the current study the HMSNPs were tested to observe the in vitro antidiabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Huge data from biochemical, cellular, mouse, and chemical inhibitor studies have recognized protein tyrosine phosphatase 1B (PTP1B) as a major negative regulator of insulin signaling. In addition, corroboration suggests that insulin action can be enhanced by the inhibition of PTP1B. Keeping in view of the above fact, the PTP1B assay was done to determine the PTP1 B inhibitory effect of HMSNPs. It can be concluded that medicinal plants can be a good source for the synthe sis of HMSNPs. This study can be used for the development of valuable nanomedicines to treat various ailments, and it also highlights the safety and biocompatibility of SNPs within a biological cell; in vivo parameters need to be considered for further discoveries. SUMMARY In present research, acute oral toxicity studies and in vitro anti diabetic activity of Herbal mediated silver nanoparticles (HMSNPs) has been investigated

  12. Predator-prey role reversals, juvenile experience and adult antipredator behaviour

    PubMed Central

    Choh, Yasuyuki; Ignacio, Maira; Sabelis, Maurice W.; Janssen, Arne

    2012-01-01

    Although biologists routinely label animals as predators and prey, the ecological role of individuals is often far from clear. There are many examples of role reversals in predators and prey, where adult prey attack vulnerable young predators. This implies that juvenile prey that escape from predation and become adult can kill juvenile predators. We show that such an exposure of juvenile prey to adult predators results in behavioural changes later in life: after becoming adult, these prey killed juvenile predators at a faster rate than prey that had not been exposed. The attacks were specifically aimed at predators of the species to which they had been exposed. This suggests that prey recognize the species of predator to which they were exposed during their juvenile stage. Our results show that juvenile experience affects adult behaviour after a role reversal. PMID:23061011

  13. Effect of supplemental taurine on juvenile channel catfish Ictalurus punctatus growth

    USDA-ARS?s Scientific Manuscript database

    Taurine is a beta-amino sulfur amino acid found in most animal tissues. It has many important biological functions in mammals including membrane stabilization, antioxidation, cellular osmoregulation, detoxification, neuromodulation, and brain and eye development. Taurine supplementation in juvenil...

  14. Epigallocatechin-3-gallate and related phenol compounds redirect the amyloidogenic aggregation pathway of ataxin-3 towards non-toxic aggregates and prevent toxicity in neural cells and Caenorhabditis elegans animal model.

    PubMed

    Visentin, Cristina; Pellistri, Francesca; Natalello, Antonino; Vertemara, Jacopo; Bonanomi, Marcella; Gatta, Elena; Penco, Amanda; Relini, Annalisa; De Gioia, Luca; Airoldi, Cristina; Regonesi, Maria E; Tortora, Paolo

    2017-09-01

    The protein ataxin-3 (ATX3) triggers an amyloid-related neurodegenerative disease when its polyglutamine stretch is expanded beyond a critical threshold. We formerly demonstrated that the polyphenol epigallocatechin-3-gallate (EGCG) could redirect amyloid aggregation of a full-length, expanded ATX3 (ATX3-Q55) towards non-toxic, soluble, SDS-resistant aggregates. Here, we have characterized other related phenol compounds, although smaller in size, i.e. (-)-epigallocatechin gallate (EGC), and gallic acid (GA). We analysed the aggregation pattern of ATX3-Q55 and of the N-terminal globular Josephin domain (JD) by assessing the time course of the soluble protein, as well its structural features by FTIR and AFM, in the presence and the absence of the mentioned compounds. All of them redirected the aggregation pattern towards soluble, SDS-resistant aggregates. They also prevented the appearance of ordered side-chain hydrogen bonding in ATX3-Q55, which is the hallmark of polyQ-related amyloids. Molecular docking analyses on the JD highlighted three interacting regions, including the central, aggregation-prone one. All three compounds bound to each of them, although with different patterns. This might account for their capability to prevent amyloidogenesis. Saturation transfer difference NMR experiments also confirmed EGCG and EGC binding to monomeric JD. ATX3-Q55 pre-incubation with any of the three compounds prevented its calcium-influx-mediated cytotoxicity towards neural cells. Finally, all the phenols significantly reduced toxicity in a transgenic Caenorhabditis elegans strain expressing an expanded ATX3. Overall, our results show that the three polyphenols act in a substantially similar manner. GA, however, might be more suitable for antiamyloid treatments due to its simpler structure and higher chemical stability. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on growth and craniofacial proportion

    SciTech Connect

    Schunior, A.; Zengel, A.E.; Mullenix, P.J.; Tarbell, N.J.; Howes, A.; Tassinari, M.S. )

    1990-10-15

    Many long term survivors of childhood acute lymphoblastic leukemia have short stature, as well as craniofacial and dental abnormalities, as side effects of central nervous system prophylactic therapy. An animal model is presented to assess these adverse effects on growth. Cranial irradiation (1000 cGy) with and without prednisolone (18 mg/kg i.p.) and methotrexate (2 mg/kg i.p.) was administered to 17- and 18-day-old Sprague-Dawley male and female rats. Animals were weighed 3 times/week. Final body weight and body length were measured at 150 days of age. Femur length and craniofacial dimensions were measured directly from the bones, using calipers. For all exposed groups there was a permanent suppression of weight gain with no catch-up growth or normal adolescent growth spurt. Body length was reduced for all treated groups, as were the ratios of body weight to body length and cranial length to body length. Animals subjected to cranial irradiation exhibited microcephaly, whereas those who received a combination of radiation and chemotherapy demonstrated altered craniofacial proportions in addition to microcephaly. Changes in growth patterns and skeletal proportions exhibited sexually dimorphic characteristics. The results indicate that cranial irradiation is a major factor in the growth failure in exposed rats, but chemotherapeutic agents contribute significantly to the outcome of growth and craniofacial dimensions.

  16. Transgenic mouse lines expressing rat AH receptor variants - A new animal model for research on AH receptor function and dioxin toxicity mechanisms

    SciTech Connect

    Pohjanvirta, Raimo

    2009-04-15

    Han/Wistar (Kuopio; H/W) rats are exceptionally resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity mainly because of their mutated aryl hydrocarbon receptor (AHR) gene. In H/W rats, altered splicing of the AHR mRNA generates two AHR proteins: deletion (DEL) and insertion (INS) variants, with the INS isoform being predominantly expressed. To gain further insight into their functional properties, cDNAs of these and rat wild-type (rWT) isoform were transferred into C57BL/6J-derived mice by microinjection. The endogenous mouse AHR was eliminated by selective crossing with Ahr-null mice. A single mouse line was obtained for each of the three constructs. The AHR mRNA levels in tissues were generally close to those of C57BL/6 mice in INS and DEL mice and somewhat higher in rWT mice; in testis, however, all 3 constructs exhibited marked overexpression. The transgenic mouse lines were phenotypically normal except for increased testis weight. Induction of drug-metabolizing enzymes by TCDD occurred similarly to that in C57BL/6 mice, but there tended to be a correlation with AHR concentrations, especially in testis. In contrast to C57BL/6 mice, the transgenics did not display any major gender difference in susceptibility to the acute lethality and hepatotoxicity of TCDD; rWT mice were highly sensitive, DEL mice moderately resistant and INS mice highly resistant. Co-expression of mouse AHR and rWT resulted in augmented sensitivity to TCDD and abolished the natural resistance of female C57BL/6 mice, whereas mice co-expressing mouse AHR and INS were resistant. Thus, these transgenic mouse lines provide a novel promising tool for molecular studies on dioxin toxicity and AHR function.

  17. Juvenile offenders assessment.

    PubMed

    Folino, Jorge O; Mayer, Elizabeth L

    2011-09-01

    Evaluation of juveniles is an integral process that includes a broad bio-psycho-social clinical perspective together with the use of auxiliary instruments. The aim of this review is to report relevant issues for this process found in recent publications. Several evidences lead to broadening the assessment process of children and youngsters to include family functioning style. Mental health services allow the evaluation of multiple factors associated with antisocial behavior that may lead to devising preventive actions. In the Juvenile Justice System a wide-ranging evaluation must include the exploration of general personality characteristics and psychopathic traits in particular; attention deficit/hyperactivity disorder; intelligence; substance abuse and conduct disorder must be considered. A number of factors that have an impact on juvenile antisocial behavior have been identified and can be assessed using the appropriate methodology. The exploration of these factors at different developmental stages and in their various manifestations provide guidelines for devising preventive and therapeutic actions as well as for supporting judicial decisions. Though enriching the present state of the art is always a challenge, it is imperative to encourage the governments to utilize this knowledge to improve the care system of children and adolescents.

  18. Juvenile Toxicology: Relevance and Challenges for Toxicologists and Pathologists

    PubMed Central

    Remick, Amera K.; Catlin, Natasha R.; Quist, Erin M.; Steinbach, Thomas J.; Dixon, Darlene

    2015-01-01

    The Society of Toxicologic Pathology (STP) Education Committee and the STP Reproductive Special Interest Group held a North Carolina regional meeting entitled, “Juvenile Toxicology: Relevance and Challenges for Toxicologists and Pathologists” on March 13, 2015, at the National Institute of Environmental Health Sciences/National Toxicology Program in Research Triangle Park, North Carolina. The purpose of this regional meeting was to familiarize attendees with the topic of juvenile toxicity testing and discuss its relevance to clinical pediatric medicine, regulatory perspectives, challenges of appropriate study design confronted by toxicologists, and challenges of histopathologic examination and interpretation of juvenile tissues faced by pathologists. The 1-day meeting was a success with over 60 attendees representing industry, government, research organizations, and academia. PMID:26220944

  19. Enhanced Generalization of Auditory Conditioned Fear in Juvenile Mice

    ERIC Educational Resources Information Center

    Ito, Wataru; Pan, Bing-Xing; Yang, Chao; Thakur, Siddarth; Morozov, Alexei

    2009-01-01

    Increased emotionality is a characteristic of human adolescence, but its animal models are limited. Here we report that generalization of auditory conditioned fear between a conditional stimulus (CS+) and a novel auditory stimulus is stronger in 4-5-wk-old mice (juveniles) than in their 9-10-wk-old counterparts (adults), whereas nonassociative…

  20. Enhanced Generalization of Auditory Conditioned Fear in Juvenile Mice

    ERIC Educational Resources Information Center

    Ito, Wataru; Pan, Bing-Xing; Yang, Chao; Thakur, Siddarth; Morozov, Alexei

    2009-01-01

    Increased emotionality is a characteristic of human adolescence, but its animal models are limited. Here we report that generalization of auditory conditioned fear between a conditional stimulus (CS+) and a novel auditory stimulus is stronger in 4-5-wk-old mice (juveniles) than in their 9-10-wk-old counterparts (adults), whereas nonassociative…

  1. Deferred imitation of object-related actions in human-reared juvenile chimpanzees and orangutans.

    PubMed

    Bering, J M; Bjorklund, D F; Ragan, P

    2000-04-01

    Deferred imitation of object-related actions (e.g., picking up a cloth with a set of tongs) was assessed in 3 enculturated juvenile orangutans (Pongo pygmaeus) and 3 enculturated juvenile chimpanzees (Pan troglodytes). For each task, animals were given 4 min to explore the objects (baseline), followed by a demonstration of the target behavior, and 10 min later, were re-presented the objects (deferred phase). Each animal displayed deferred imitation on at least one trial, with each species demonstrating deferred imitation on approximately half of all possible trials. The findings were interpreted as reflecting cognitive abilities in juvenile great apes that permit deferred imitation under humanlike rearing conditions.

  2. Telepsychiatry in juvenile justice settings.

    PubMed

    Kaliebe, Kristopher E; Heneghan, James; Kim, Thomas J

    2011-01-01

    Telepsychiatry is emerging as a valuable means of providing mental health care in juvenile justice settings. Youth in the juvenile justice system have high levels of psychiatric morbidity. State and local juvenile justice systems frequently struggle to provide specialized psychiatric care, as these systems have limited resources and often operate in remote locations. Case studies in the use of telepsychiatry to provide improved care in juvenile corrections in 4 states are described, along with a review of advantages and disadvantages of telepsychiatry in these settings.

  3. Genetics Home Reference: juvenile idiopathic arthritis

    MedlinePlus

    ... Home Health Conditions juvenile idiopathic arthritis juvenile idiopathic arthritis Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Juvenile idiopathic arthritis refers to a group of conditions involving joint ...

  4. Genetics Home Reference: juvenile primary osteoporosis

    MedlinePlus

    ... Home Health Conditions juvenile primary osteoporosis juvenile primary osteoporosis Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Juvenile primary osteoporosis is a skeletal disorder characterized by thinning of ...

  5. Genetics Home Reference: juvenile myoclonic epilepsy

    MedlinePlus

    ... Home Health Conditions juvenile myoclonic epilepsy juvenile myoclonic epilepsy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Juvenile myoclonic epilepsy is a condition characterized by recurrent seizures (epilepsy). ...

  6. A new mass mortality of juvenile Protoceratops and size-segregated aggregation behaviour in juvenile non-avian dinosaurs.

    PubMed

    Hone, David W E; Farke, Andrew A; Watabe, Mahito; Shigeru, Suzuki; Tsogtbaatar, Khishigjav

    2014-01-01

    Monodominant bonebeds are a relatively common occurrence for non-avian dinosaurs, and have been used to infer associative, and potentially genuinely social, behavior. Previously known assemblages are characterized as either mixed size-classes (juvenile and adult-sized specimens together) or single size-classes of individuals (only juveniles or only adult-sized individuals within the assemblage). In the latter case, it is generally unknown if these kinds of size-segregated aggregations characterize only a particular size stage or represent aggregations that happened at all size stages. Ceratopsians ("horned dinosaurs") are known from both types of assemblages. Here we describe a new specimen of the ceratopsian dinosaur Protoceratops andrewsi, Granger and Gregory 1923 from Mongolia representing an aggregation of four mid-sized juvenile animals. In conjunction with existing specimens of groups of P. andrewsi that includes size-clustered aggregations of young juveniles and adult-sized specimens, this new material provides evidence for some degree of size-clustered aggregation behaviour in Protoceratops throughout ontogeny. This continuity of size-segregated (and presumably age-clustered) aggregation is previously undocumented in non-avian dinosaurs. The juvenile group fills a key gap in the available information on aggregations in younger ceratopsians. Although we support the general hypothesis that many non-avian dinosaurs were gregarious and even social animals, we caution that evidence for sociality has been overstated and advocate a more conservative interpretation of some data of 'sociality' in dinosaurs.

  7. Towards An Advanced Graphene-Based Magnetic Resonance Imaging Contrast Agent: Sub-acute Toxicity and Efficacy Studies in Small Animals

    PubMed Central

    Kanakia, Shruti; Toussaint, Jimmy; Hoang, Dung Minh; Mullick Chowdhury, Sayan; Lee, Stephen; Shroyer, Kenneth R.; Moore, William; Wadghiri, Youssef Z.; Sitharaman, Balaji

    2015-01-01

    Current clinical Gd3+-based T1 magnetic resonance imaging (MRI) contrast agents (CAs) are suboptimal or unsuitable, especially at higher magnetic fields (>1.5 Tesla) for advanced MRI applications such as blood pool, cellular and molecular imaging. Herein, towards the goal of developing a safe and more efficacious high field T1 MRI CA for these applications, we report the sub-acute toxicity and contrast enhancing capabilities of a novel nanoparticle MRI CA comprising of manganese (Mn2+) intercalated graphene nanoparticles functionalized with dextran (hereafter, Mangradex) in rodents. Sub-acute toxicology performed on rats intravenously injected with Mangradex at 1, 50 or 100 mg/kg dosages 3 times per week for three weeks indicated that dosages ≤50 mg/kg could serve as potential diagnostic doses. Whole body 7 Tesla MRI performed on mice injected with Mangradex at a potential diagnostic dose (25 mg/kg or 455 nanomoles Mn2+/kg; ~2 orders of magnitude lower than the paramagnetic ion concentration in a typical clinical dose) showed persistent (up to at least 2 hours) contrast enhancement in the vascular branches (Mn2+ concentration in blood at steady state = 300 ppb, per voxel = 45 femtomoles). The results lay the foundations for further development of Mangradex as a vascular and cellular/ molecular MRI probe. PMID:26625867

  8. Enhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease

    PubMed Central

    Davies, Sian E.; Hallett, Penelope J.; Moens, Thomas; Smith, Gaynor; Mangano, Emily; Kim, Hyoung Tae; Goldberg, Alfred L.; Liu, Ji-Long; Isacson, Ole; Tofaris, George K.

    2014-01-01

    Parkinson's disease is a neurodegenerative disorder, characterized by accumulation and misfolding of α-synuclein. Although the level of α-synuclein in neurons is fundamentally linked to the onset of neurodegeneration, multiple pathways have been implicated in its degradation, and it remains unclear which are the critical ubiquitination enzymes that protect against α-synuclein accumulation in vivo. The ubiquitin ligase Nedd4 targets α-synuclein to the endosomal–lysosomal pathway in cultured cells. Here we asked whether Nedd4-mediated degradation protects against α-synuclein-induced toxicity in the Drosophila and rodent models of Parkinson's disease. We show that overexpression of Nedd4 can rescue the degenerative phenotype from ectopic expression of α-synuclein in the Drosophila eye. Overexpressed Nedd4 in the Drosophila brain prevented the α-synuclein-induced locomotor defect whereas reduction in endogenous Nedd4 by RNAi led to worsening motor function and increased loss of dopaminergic neurons. Accordingly, AAV-mediated expression of wild-type but not the catalytically inactive Nedd4 decreased the α-synuclein-induced dopaminergic cell loss in the rat substantia nigra and reduced α-synuclein accumulation. Collectively, our data in two evolutionarily distant model organisms strongly suggest that Nedd4 is a modifier of α-synuclein pathobiology and thus a potential target for neuroprotective therapies. PMID:24388974

  9. Improving Literacy Skills of Juvenile Detainees. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Hodges, Jane; And Others

    The Office of Juvenile and Delinquency Prevention funded a model designed to improve the literacy level of youth in juvenile detention and correctional facilities. The model specified training language arts teachers and relevant staff and volunteers in direct instruction methods for rapid improvement of students' comprehension, particularly for…

  10. Juvenile Mentoring Program: A Progress Review. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Novotney, Laurence C.; Mertinko, Elizabeth; Lange, James; Baker, Tara Kelley

    The greatest support offered by the Office of Juvenile Justice and Delinquency Prevention for youth mentoring has been through the Juvenile Mentoring Program (JUMP), which provides one-to-one mentoring for youth at risk of delinquency, gang involvement, educational failure, or dropping out of school. Information on JUMP has been collected through…

  11. Juvenile Firesetting: A Research Overview. Juvenile Justice Bulletin

    ERIC Educational Resources Information Center

    Putnam, Charles T.; Kirkpatrick, John T.

    2005-01-01

    In 2002, the National Association of State Fire Marshals (NASFM) began developing applied research initiatives to help professionals curtail juvenile firesetting. The project included a review of the research literature, a conference of researchers and professionals involved in preventing juvenile firesetting, and a final report, upon which this…

  12. Green Biosynthesis, Characterization, In vitro Antidiabetic Activity, and Investigational Acute Toxicity Studies of Some Herbal-mediated Silver Nanoparticles on Animal Models.

    PubMed

    Shanker, Kalakotla; Mohan, Gottumukkala Krishna; Hussain, Md Ashwaq; Jayarambabu, Naradala; Pravallika, Poka Lakshmi

    2017-01-01

    Diabetes is a metabolic disorder characterized by hyperglycemia, altered carbohydrate, lipid and protein metabolism. In recent studies, Nanoscience and nanotechnology are blazing fields for researchers; for researchers; of late there has been a prodigious excitement in the field of nanopharmacology to study silver nanoparticle (SNP) synthesis using natural products. Biological methods have been used to synthesize SNPs using medicinally active plants having an antidiabetic role, and this made us to assess the biologically synthesized SNPs from the seed extract of Psoralea corylifolia using 1 mM silver nitrate solution. The synthesized herbal-mediated SNPs (HMSNPs) were subjected to various characterization techniques such as X-ray diffraction analysis (XRD), energy dispersive X-ray (EDX) analysis, transmission electron microscope (TEM), and differential light scattering (DLS), respectively. In the current study the HMSNPs were tested to observe the in vitro antidiabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Huge data from biochemical, cellular, mouse, and chemical inhibitor studies have recognized protein tyrosine phosphatase 1B (PTP1B) as a major negative regulator of insulin signaling. In addition, corroboration suggests that insulin action can be enhanced by the inhibition of PTP1B. Keeping in view of the above fact, the PTP1B assay was done to determine the PTP1 B inhibitory effect of HMSNPs. It can be concluded that medicinal plants can be a good source for the synthe sis of HMSNPs. This study can be used for the development of valuable nanomedicines to treat various ailments, and it also highlights the safety and biocompatibility of SNPs within a biological cell; in vivo parameters need to be considered for further discoveries.

  13. [Familial juvenile hyperuricemic nephropathy].

    PubMed

    Hummel, Aurélie

    2012-04-01

    Familial juvenile hyperuricemic nephropathy is a rare autosomal dominant disease. It is characterized by abnormal handling of urate responsible for hyperuricaemia often complicated of gouty arthritis. Renal failure is due to tubulointerstitial nephritis. Ultrasonography sometimes finds renal cysts of variable size and number. Renal histology, although not specific, shows interstitial fibrosis, atrophic tubules, sometimes enlarged and with irregular membrane thickening. Renal failure progresses to end stage between 30 and 60 years of age. Allopurinol treatment is recommended at the early stages of the disease, its efficacy on slowing down the progression of the disease is however not proven. There is genetic heterogeneity in familial juvenile hyperuricemic nephropathy. Uromodulin encoding Tamm-Horsfall protein is the only gene to date identified, responsible in less than half of the families. The described mutations most often concern a cystein and are clustering in exon 4. These mutations result in abnormal retention of the protein in endoplasmic reticulum of Henle loop cells and in reduction of its urinary excretion. The pathophysiology of the disease is however still dubious. Indeed, Tamm-Horsfall protein functions are not well known (anti-infectious role, cristallisation inhibition, immunomodulating role). Knock-out mice do not develop renal phenotype but are more prone to E. coli urinary infections. Uromodulin gene mutations have also been described in medullary cystic kidney disease, an autosomal dominant tubulointerstitial nephropathy, considered at first as a distinct disorder. Genetic progress allowed us to consider familial juvenile hyperuricemic nephropathy and medullary cystic kidney disease as the two facets of a same disease, we should call uromodulin associated kidney diseases. At least two other genes have been implicated in similar clinical presentation: TCF2 and the gene encoding renin.

  14. Juvenile Courts- Terms To Know.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Offers a crossword puzzle that focuses on terms learned in this edition of "Update on Law-Related Education." Explains that the letters in the boxes spell the answer to this question: what do juvenile courts try to offer juveniles? Provides the clues and answers to the puzzle. (CMK)

  15. Iatrogenic Effect of Juvenile Justice

    ERIC Educational Resources Information Center

    Gatti, Uberto; Tremblay, Richard E.; Vitaro, Frank

    2009-01-01

    Background: The present study uses data from a community sample of 779 low-SES boys to investigate whether intervention by the juvenile justice system is determined, at least in part, by particular individual, familial and social conditions, and whether intervention by the juvenile courts during adolescence increases involvement in adult crime.…

  16. Juvenile Justice in Rural America.

    ERIC Educational Resources Information Center

    Jankovic, Joanne, Ed.; And Others

    Producing a much-needed organized body of literature about rural juvenile justice, 14 papers (largely from the 1979 National Symposium on Rural Justice) are organized to identify current issues, identify forces causing changes in current systems, review programs responding to rural juvenile justice problems, and provide planning models to aid…

  17. Juvenile Crime. Opposing Viewpoints Series.

    ERIC Educational Resources Information Center

    Sadler, A. E., Ed.

    Books in the Opposing Viewpoints Series present debates about current issues that can be used to teach critical reading and thinking skills. The variety of opinions expressed in this collection of articles and book excerpts explores many aspects of juvenile crime. It is a commonly held view that the number of crimes committed by juveniles is…

  18. Psychopathology in Female Juvenile Offenders

    ERIC Educational Resources Information Center

    Dixon, Angela; Howie, Pauline; Starling, Jean

    2004-01-01

    Background: The aim was to document the spectrum of present and lifetime psychological disorders in female juvenile offenders, and to examine the relations between mental health status and socio-demographic, family and trauma variables. Method: One hundred juvenile offenders were matched with a comparison group of 100 females on age and…

  19. Iatrogenic Effect of Juvenile Justice

    ERIC Educational Resources Information Center

    Gatti, Uberto; Tremblay, Richard E.; Vitaro, Frank

    2009-01-01

    Background: The present study uses data from a community sample of 779 low-SES boys to investigate whether intervention by the juvenile justice system is determined, at least in part, by particular individual, familial and social conditions, and whether intervention by the juvenile courts during adolescence increases involvement in adult crime.…

  20. Suicide Prevention in Juvenile Facilities.

    ERIC Educational Resources Information Center

    Hayes, Lindsay M.

    2000-01-01

    Youth suicide is recognized as a serious public health problem, but suicide within juvenile facilities has not received comparable attention, and the extent and nature of these deaths remain unknown. This article utilizes an example of a young man in a juvenile justice facility who succeeded in committing suicide to illustrate these points.…

  1. Efficacy of phosphodiesterase‐4 inhibitors in juvenile Batten disease (CLN3)

    PubMed Central

    Aldrich, Amy; Bosch, Megan E.; Fallet, Rachel; Odvody, Jessica; Burkovetskaya, Maria; Rama Rao, Kakulavarapu V.; Cooper, Jonathan D.; Drack, Arlene V.

    2016-01-01

    Objective Juvenile neuronal ceroid lipofuscinosis (JNCL), or juvenile Batten disease, is a pediatric lysosomal storage disease caused by autosomal recessive mutations in CLN3, typified by blindness, seizures, progressive cognitive and motor decline, and premature death. Currently, there is no treatment for JNCL that slows disease progression, which highlights the need to explore novel strategies to extend the survival and quality of life of afflicted children. Cyclic adenosine monophosphate (cAMP) is a second messenger with pleiotropic effects, including regulating neuroinflammation and neuronal survival. Here we investigated whether 3 phosphodiesterase‐4 (PDE4) inhibitors (rolipram, roflumilast, and PF‐06266047) could mitigate behavioral deficits and cell‐specific pathology in the Cln3Δex7/8 mouse model of JNCL. Methods In a randomized, blinded study, wild‐type (WT) and Cln3Δex7/8 mice received PDE4 inhibitors daily beginning at 1 or 3 months of age and continuing for 6 to 9 months, with motor deficits assessed by accelerating rotarod testing. The effect of PDE4 inhibitors on cAMP levels, astrocyte and microglial activation (glial fibrillary acidic protein and CD68, respectively), lysosomal pathology (lysosomal‐associated membrane protein 1), and astrocyte glutamate transporter expression (glutamate/aspartate transporter) were also examined in WT and Cln3Δex7/8 animals. Results cAMP levels were significantly reduced in the Cln3Δex7/8 brain, and were restored by PF‐06266047. PDE4 inhibitors significantly improved motor function in Cln3Δex7/8 mice, attenuated glial activation and lysosomal pathology, and restored glutamate transporter expression to levels observed in WT animals, with no evidence of toxicity as revealed by blood chemistry analysis. Interpretation These studies reveal neuroprotective effects for PDE4 inhibitors in Cln3Δex7/8 mice and support their therapeutic potential in JNCL patients. Ann Neurol 2016;80:909–923 PMID:27804148

  2. Mental Illness and Juvenile Offenders

    PubMed Central

    Underwood, Lee A.; Washington, Aryssa

    2016-01-01

    Within the past decade, reliance on the juvenile justice system to meet the needs of juvenile offenders with mental health concerns has increased. Due to this tendency, research has been conducted on the effectiveness of various intervention and treatment programs/approaches with varied success. Recent literature suggests that because of interrelated problems involved for youth in the juvenile justice system with mental health issues, a dynamic system of care that extends beyond mere treatment within the juvenile justice system is the most promising. The authors provide a brief overview of the extent to which delinquency and mental illness co-occur; why treatment for these individuals requires a system of care; intervention models; and the juvenile justice systems role in providing mental health services to delinquent youth. Current and future advancements and implications for practitioners are provided. PMID:26901213

  3. Mental Illness and Juvenile Offenders.

    PubMed

    Underwood, Lee A; Washington, Aryssa

    2016-02-18

    Within the past decade, reliance on the juvenile justice system to meet the needs of juvenile offenders with mental health concerns has increased. Due to this tendency, research has been conducted on the effectiveness of various intervention and treatment programs/approaches with varied success. Recent literature suggests that because of interrelated problems involved for youth in the juvenile justice system with mental health issues, a dynamic system of care that extends beyond mere treatment within the juvenile justice system is the most promising. The authors provide a brief overview of the extent to which delinquency and mental illness co-occur; why treatment for these individuals requires a system of care; intervention models; and the juvenile justice systems role in providing mental health services to delinquent youth. Current and future advancements and implications for practitioners are provided.

  4. Protective role of a methanolic extract of spinach (Spinacia oleracea L.) against Pb toxicity in wheat (Triticum aestivum L.) seedlings: beneficial effects for a plant of a nutraceutical used with animals.

    PubMed

    Lamhamdi, Mostafa; Bakrim, Ahmed; Bouayad, Noureddin; Aarab, Ahmed; Lafont, René

    2013-10-01

    Spinach extracts contain powerful natural antioxidants and have been used to improve the response of animal cells to various stress factors. The aim of the present study was to assess the effects of a methanolic extract of spinach (SE) used at two concentrations (21.7 and 217 ppm) on the growth, certain enzymes and antioxidant systems in wheat seedlings under lead stress. When wheat seedlings were grown for 7 days in a solution containing Pb(NO3)2 (3 mM), germination and growth were impaired, while signs of oxidative stress were observed. SE (217 ppm) pretreatment was able to protect seedlings from Pb toxicity by both reducing Pb uptake and Pb-induced oxidative stress. As a consequence, almost normal germination, elongation, biomass and α-amylase activity were restored by SE (217 ppm) pretreatment of wheat seedlings, in spite of the presence of Pb. Our results support the protective role and the antioxidant effect of SE against Pb. These results show an amazing similarity to the effects of SE in animals, which suggests that providing "nutraceuticals" to plants could improve their "health" status.

  5. Use of neomysis mercedis (crustacea: mysidacea) for estuarine toxicity tests

    SciTech Connect

    Brandt, O.M.; Fujimura, R.W.; Finlayson, B.J. )

    1993-03-01

    The mysid Neomysis mercedis was examined as a test organism for use in acute toxicity tests at intermediate salinities characteristic of estuarine waters. Several sensitive invertebrate species are available for marine assessments (mysids) and freshwater tests (cladocerans), but few are available for estuarine toxicity tests. Observations in the laboratory indicate that Neomysis mercedis can be reared successfully at a temperature of 17[degrees]C, a salinity of 2%, and a population density less than 5/L. Brine shrimp nauplii Artemia salina, algae, and commercial foods were used to sustain mysid cultures. Neomysis mercedis is vivaparous and can complete its life cycle in 3-4 months. Neomysis mercedis is as sensitive as or more sensitive to toxicants than the marine mysid Mysidopsis bahia and the freshwater cladocerans Daphnia magna, Ceriodaphnia dubia, and Simocephalus serrulatus. The mean 96-h LC50 values (concentrations lethal to half the test animals) for N. mercedis, in increasing order, were 0.20 [mu]g/L for thiobencarb, and for malathion, 14 [mu]g/L for carbofuran, 150 [mu]g/L for copper sulfate, 280 [mu]g/L for thiobencarb, and 1,600 [mu]g/L for molinate. Neonates (5 d postrelease) were generally more sensitive than older juveniles. Coefficients of variation (100[center dot]SD/mean) of LC50 values varied from 21 to 35%. 37 refs., 2 figs., 7 tabs.

  6. Multi-scale biomarker evaluation of the toxicity of a commercial azo dye (Disperse Red 1) in an animal model, the freshwater cnidarian Hydra attenuata.

    PubMed

    de Jong, Laetitia; Pech, Nicolas; de Aragão Umbuzeiro, Gisela; Moreau, Xavier

    2016-06-01

    Acute (24 h, 48 h, 72 h) and chronic (7 days) tests have been performed to evaluate the effects of the commercial azo dye Disperse Red 1 (DR1) using various biomarkers in the freshwater invertebrate Hydra attenuata. Morphological changes have been selected to calculate ecotoxicological thresholds for sublethal and lethal DR1 concentrations. A multinomial logistic model showed that the probability of each morphological stage occurrence was function of concentration, time and interaction between both. Results of oxidative balance parameter measurements (72 h and 7 days) suggest that polyps set up defense mechanisms to limit lipid peroxidation caused by DR1. DR1 exposure at hormetic concentrations induces increase of asexual reproductive rates. This result suggests (1) an impact on the fitness-related phenotypical traits and (2) trade-offs between reproduction and maintenance to allow the population to survive harsher conditions. Changes in serotonin immuno-labeling in polyps showing alterations in feeding behavior suggest that chronic DR1 exposure impaired neuronal processes related to ingesting behavior in H. attenuata. This ecotoxicity study sheds light on the possible serotonin function in Hydra model and reports for the first time that serotonin could play a significant role in feeding behavior. This study used a multi-scale biomarker approach investigating biochemical, morphological, reproductive and behavioral endpoints in Hydra attenuata. This organism is proposed for a pertinent animal model to assess ecotoxicological impact of pollutant mixtures in freshwater environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Juvenile 'Perinasal' Angiofibroma.

    PubMed

    Mishra, Anupam; Verma, Veerendra; Mishra, Subhash Chandra

    2017-03-01

    The extranasopharyngeal angiofibroma is a separate clinical entity but those involving infratemporal fossa and cheek resemble juvenile nasopharyngeal angiofibroma (JNA) and hence have been labelled as juvenile perinasal angiofibroma (JPA) in this paper. This paper presents a 7th case of JPA and attempts to review the world literature on JPA, along with a proposal of staging the disease. A 16 year male presented with a painless compressible facial swelling since 7 months without any epistaxis or nasal obstruction. Initially a vascular lesion was suspected but JNA without nasal extension was strongly suspected on imaging. A deep trucut biopsy confirmed the histopathology. The vascular enhancement was significant and the tumour was excised through open approach (Weber Fergusson). JPA that can be regarded as a variant of JNA that fails to extend medially. Imaging demonstrates classical JNA findings with a clear nose/nasopharynx. A deep trucut biopsy under control in inpatient settings may sometimes help. JPA presents most commonly in Stage II where an open facial approach preferably following selective preoperative embolization is indicated. Hence with painless compressible (or non-compressible) cheek swelling suspected to be of a vascular etiology, a high degree of clinical suspicion for JPA needs to maintained in order to prevent a misdiagnosis.

  8. Evaluating the Zebrafish Embryo Toxicity Test for Pesticide ...

    EPA Pesticide Factsheets

    Given the numerous chemicals used in society, it is critical to develop tools for accurate and efficient evaluation of potential risks to human and ecological receptors. Fish embryo acute toxicity tests are 1 tool that has been shown to be highly predictive of standard, more resource-intensive, juvenile fish acute toxicity tests. However, there is also evidence that fish embryos are less sensitive than juvenile fish for certain types of chemicals, including neurotoxicants. The utility of fish embryos for pesticide hazard assessment was investigated by comparing published zebrafish embryo toxicity data from pesticides with median lethal concentration 50% (LC50) data for juveniles of 3 commonly tested fish species: rainbow trout, bluegill sunfish, and sheepshead minnow. A poor, albeit significant, relationship (r2 = 0.28; p < 0.05) was found between zebrafish embryo and juvenile fish toxicity when pesticides were considered as a single group, but a much better relationship (r2 = 0.64; p < 0.05) when pesticide mode of action was factored into an analysis of covariance. This discrepancy is partly explained by the large number of neurotoxic pesticides in the dataset, supporting previous findings that commonly used fish embryo toxicity test endpoints are particularly insensitive to neurotoxicants. These results indicate that it is still premature to replace juvenile fish toxicity tests with embryo-based tests such as the Organisation for Economic Co-op

  9. TOXIC RESPONSES OF THE REPRODUCTIVE SYSTEM

    EPA Science Inventory

    Fish reproduction is arguably one of the most sensitive indicators of exposure to environmental chemicals. Reproductive toxicity can simply be referred to as an alteration in reproductive success. It can occur at several developmental stages (larval, juvenile, and adult) with le...

  10. Toxicity of o,p′-DDE to medaka d-rR strain after a one-time embryonic exposure by in ovo nanoinjection: An early through juvenile life cycle assessment

    USGS Publications Warehouse

    Villalobos, Sergio A.; Papoulias, Diana M.; Pastva, Stephanie D.; Blankenship, Alan L.; Meadows, John C.; Tillitt, Donald E.; Giesy, John P.

    2003-01-01

    The toxicity of o,p′-DDE (1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethylene) was evaluated in embryos of medaka (Oryzias latipes) following a one time exposure via nanoinjection. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of 4 graded doses (0.0005-0.5 ng/egg) of o,p′-DDE in triolein. Embryos were allowed to develop, and fry were reared. Embryonic survival was monitored daily during the first 10 d until hatching and thereafter, on a weekly basis until day 59, at which time the fish were monitored for sexual maturity until day 107. In general, o,p′-DDE caused a dose- and time-dependent mortality. No changes in mortality were observed between the last two time points (day 38 and 59, respectively), and hence a 59 day-LD50 of 346 ng o,p′-DDE/egg was derived from the linear dose-response relationship. Prior to late stage death, only isolated cases of cardiovascular lesions and spinal deformities were observed, but were not dose-dependent. The lowest observable adverse effect level (LOAEL), based on upper 95% CI for regression line=0.0018 mg/kg, and the LOAEL based on exposure doses=0.5 mg/kg. Likewise, the no observable adverse effect level (NOAEL) based on linear extrapolation to 100% survival=0.0000388 mg/kg, while the NOAEL based on exposure doses=0.05 mg/kg. The nanoinjection medaka model has potential in the study of hormonally active compounds in the environment.

  11. Juvenile justice mental health services.

    PubMed

    Thomas, Christopher R; Penn, Joseph V

    2002-10-01

    As the second century of partnership begins, child psychiatry and juvenile justice face continuing challenges in meeting the mental health needs of delinquents. The modern juvenile justice system is marked by a significantly higher volume of cases, with increasingly complicated multiproblem youths and families with comorbid medical, psychiatric, substance abuse disorders, multiple family and psychosocial adversities, and shrinking community resources and alternatives to confinement. The family court is faced with shrinking financial resources to support court-ordered placement and treatment programs in efforts to treat and rehabilitate youths. The recognition of high rates of mental disorders for incarcerated youth has prompted several recommendations for improvement and calls for reform [56,57]. In their 2000 annual report, the Coalition for Juvenile Justice advocated increased access to mental health services that provide a continuum of care tailored to the specific problems of incarcerated youth [58]. The specific recommendations of the report for mental health providers include the need for wraparound services, improved planning and coordination between agencies, and further research. The Department of Justice, Office of Juvenile Justice and Delinquency Prevention has set three priorities in dealing with the mental health needs of delinquents: further research on the prevalence of mental illness among juvenile offenders, development of mental health screening assessment protocols, and improved mental health services [59]. Other programs have called for earlier detection and diversion of troubled youth from juvenile justice to mental health systems [31,56]. Most recently, many juvenile and family courts have developed innovative programs to address specific problems such as truancy or substance use and diversionary or alternative sentencing programs to deal with first-time or nonviolent delinquents. All youths who come in contact with the juvenile justice system

  12. Animal models of hepatotoxicity.

    PubMed

    Bhakuni, Ganesh Singh; Bedi, Onkar; Bariwal, Jitender; Deshmukh, Rahul; Kumar, Puneet

    2016-01-01

    Liver is the largest and important organ in the body, involved in the metabolism of food and drugs. Liver diseases are potentially life threatening for humans. The etiology of liver disorder varied due to different reasons like autoimmune disorder, viral infection, toxic chemical, and due to changing diet style. Liver injury produces pathological changes like increase level of SGOT, SGPT, TB and generation of free radical radicals. A better understanding of primary mechanisms is mandatory for designing of new therapeutic drugs. Therefore, animal models are being developed to mimic human liver diseases. Animal models are being used for several decades to study the pathogenesis of liver disorders and related toxicities. In this review, we revealed various animal models with their merits and demerits. Our main focus is to explore all new and traditional animal models under broad classification like non-invasive, invasive and genetic models which directly or indirectly produce hepatotoxicity.

  13. Maturity-related changes in venom toxicity of the freshwater stingray Potamotrygon leopoldi.

    PubMed

    Kirchhoff, Kim N; Klingelhöfer, Ines; Dahse, Hans-Martin; Morlock, Gertrud; Wilke, Thomas

    2014-12-15

    Aquatic venomous animals such as stingrays represent a largely untapped source for venom-based drug development. However, the major challenge for a potential drug development pipeline is the high inter- and intraspecific variability in toxicity and venom composition. As of today, little is known about maturity-driven changes in these traits in stingrays. The present study investigates the differences in toxicity and venom composition in different maturity stages of the freshwater stingray Potamotrygon leopoldi. This species can be found in the Xingú River basin (Brazil), where it mainly feeds on invertebrates, while being predated by other stingrays or large catfishes. P. leopoldi, as commonly known for stingrays, can cause severe injuries with the venomous dentine spine located at its tails. The toxicity of tissue extracts of juvenile and mature specimens was recorded on a myoblast cell culture bioassay. Venom composition and bioactivity of compounds were analyzed with planar chromatography linked to an Aliivibrio fischeri bioassay. Results revealed a decrease in venom toxicity during maturation, but no changes in venom composition. These findings may indicate that toxicity in mature specimens becomes evolutionary less important, probably due to a decrease in predation pressure.

  14. Miranda Rights: Implications for Juveniles with Disabilities

    ERIC Educational Resources Information Center

    Katsiyannis, Antonis; Barrett, David E.; Losinski, Mickey L.

    2011-01-01

    Juvenile delinquency in the United States has been a persistent concern for decades. Consequently, because more juveniles have been referred to juvenile court and the arrest rate of preteen offenders has increased to almost three times that of older youth, the persistent and often controversial issue of the capacity of juvenile offenders to waive…

  15. Miranda Rights: Implications for Juveniles with Disabilities

    ERIC Educational Resources Information Center

    Katsiyannis, Antonis; Barrett, David E.; Losinski, Mickey L.

    2011-01-01

    Juvenile delinquency in the United States has been a persistent concern for decades. Consequently, because more juveniles have been referred to juvenile court and the arrest rate of preteen offenders has increased to almost three times that of older youth, the persistent and often controversial issue of the capacity of juvenile offenders to waive…

  16. Enuresis, Firesetting, and Cruelty to Animals: Does the Ego Triad Show Predictive Validity?

    ERIC Educational Resources Information Center

    Slavkin, Michael Lawrence

    2001-01-01

    The hypothesis tested in this study was that the presence of enuresis and cruelty to animals in juvenile firesetters would be significantly related to recidivistic firesetting. No relationship was found between firesetting recidivism and enuresis. However, juveniles who were identified as being cruel to animals were more likely to engage in…

  17. Enuresis, Firesetting, and Cruelty to Animals: Does the Ego Triad Show Predictive Validity?

    ERIC Educational Resources Information Center

    Slavkin, Michael Lawrence

    2001-01-01

    The hypothesis tested in this study was that the presence of enuresis and cruelty to animals in juvenile firesetters would be significantly related to recidivistic firesetting. No relationship was found between firesetting recidivism and enuresis. However, juveniles who were identified as being cruel to animals were more likely to engage in…

  18. Juvenile-specific cathepsin proteases in Fasciola spp.: their characteristics and vaccine efficacies.

    PubMed

    Meemon, Krai; Sobhon, Prasert

    2015-08-01

    Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is one of the most neglected tropical zoonotic diseases. One sustainable control strategy against these infections is the employment of vaccines that target proteins essential for parasites' invasion and nutrition acquiring processes. Cathepsin proteases are the most abundantly expressed proteins in Fasciola spp. that have been tested successfully as vaccines against fasciolosis in experimental as well as large animals because of their important roles in digestion of nutrients, invasion, and migration. Specifically, juvenile-specific cathepsin proteases are the more effective vaccines because they could block the invasion and migration of juvenile parasites whose immune evasion mechanism has not yet been fully developed. Moreover, because of high sequence similarity and identity of cathepsins from juveniles with those of adults, the vaccines can attack both the juvenile and adult stages. In this article, the characteristics and vaccine potentials of juvenile-specific cathepsins, i.e., cathepsins L and B, of Fasciola spp. were reviewed.

  19. The use of autologous adult, allogenic juvenile, and combined juvenile-adult cartilage fragments for the repair of chondral defects.

    PubMed

    Bonasia, Davide Edoardo; Martin, James A; Marmotti, Antonio; Kurriger, Gail L; Lehman, Abigail D; Rossi, Roberto; Amendola, Annunziato

    2016-12-01

    The goal of the study was to evaluate the repair of chondral lesions treated with combined autologous adult/allogenic juvenile cartilage fragments, compared with isolated adult and isolated juvenile cartilage fragments. Fifty-eight adult (>16 week old) and five juvenile (<6 week old) New Zealand White female rabbits were used. A large osteochondral defect was created in the center of the femoral trochlea of adult rabbits. The rabbits were divided in four groups: Group 1 = untreated defects (controls); Group 2 = adult cartilage fragments; Group 3 = juvenile cartilage fragments; and Group 4 = adult + juvenile cartilage fragments. Killings were performed at 3 and 6 months. The defects were evaluated with ICRS macroscopic score, modified O'Driscoll score, and Collagen type II immunostaining. At 3 months, Group 4 performed better than Group 1, in terms of modified O'Driscoll score (p = 0.001) and Collagen type II immunostaining (p = 0.015). At 6 months, Group 4 showed higher modified O'Driscoll score (p = 0.003) and Collagen type II immunostaining score (p < 0.001) than Group 1. Histologically, also Group 3 performed better than Group 1 (p = 0.03), and Group 4 performed better than Group 2 (p = 0.004). Mixing adult and juvenile cartilage fragments improved cartilage repair in a rabbit model. In the clinical setting, a new "one-stage" procedure combining the two cartilage sources can be hypothesized, with the advantages of improved chondral repair and large defect coverage, because of the use of an off-the-shelf juvenile allograft. Further studies on larger animals and clinical trials are required to confirm these results.

  20. The cost and benefit of juvenile training on adult perceptual skill.

    PubMed

    Sarro, Emma C; Sanes, Dan H

    2011-04-06

    Sensory experience during development can modify the CNS and alter adult perceptual skills. While this principle draws support from deprivation or chronic stimulus exposure studies, the effect of training is addressed only in adults. Here, we asked whether a brief period of training during development can exert a unique impact on adult perceptual skills. Juvenile gerbils were trained to detect amplitude modulation (AM), a stimulus feature elemental to animal communication sounds. When the performance of these juvenile-trained animals was subsequently assessed in adulthood, it was superior to a control group that received an identical regimen of training as adults. The juvenile-trained animals displayed significantly better AM detection thresholds. This was not observed in an adult group that received only exposure to AM stimuli as juveniles. To determine whether enhanced adult performance was due solely to learning the conditioned avoidance procedure, juveniles were trained on frequency modulation (FM) detection, and subsequently assessed on AM detection as adults. These animals displayed significantly poorer AM detection thresholds than all other groups. Thus, training on a specific auditory task (AM detection) during development provided a benefit to performance on that task in adulthood, whereas an identical training regimen in adulthood did not bring about this enhancement. In contrast, there was a cost, in adulthood, following developmental training on a different task (FM detection). Together, the results demonstrate a period of heightened sensitivity in the developing CNS such that behavioral training in juveniles has a unique impact on adult behavioral capabilities.

  1. Autosomal dominant juvenile recurrent parotitis.

    PubMed Central

    Reid, E; Douglas, F; Crow, Y; Hollman, A; Gibson, J

    1998-01-01

    Juvenile recurrent parotitis is a common cause of inflammatory salivary gland swelling in children. A variety of aetiological factors has been proposed for the condition. Here we present a family where four members had juvenile recurrent parotitis and where two other family members may have had an atypical form of the condition. The segregation pattern in the family is consistent with autosomal dominant inheritance with incomplete penetrance and this suggests that, at least in some cases, genetic factors may be implicated in juvenile recurrent parotitis. PMID:9610807

  2. [JUVENILE DERMATOMYOSITIS AND CALCINOSIS].

    PubMed

    Zhvania, M

    2015-01-01

    Juvenile Dermatomiositis (JD) is autoimmune disease that progresses with time; JD's main differentiated syndromes are rash on the skin, poor function of muscles, and often developing invalidism. If the health practitioners manage to diagnose the JD on an early stage and prescribe the adequate treatment the disease will not progress aggressively. This approach is tangible for practical rheumatology and pediatric. The article aims to present the reasons of the development of the JD and calcinosis. The study based on the description of the patients with JD. There are distinguished the main symptoms of the disease in children: frequent and acute developments of muscles calcinosis, occasionally with diffuse character followed with hypotrophy of the muscles, contractures and invalidism. One of the patient cases that describe the article is the thirteen-year boy with JD indicating repeated sequence of the disease, with diffusive calcinosis, cellulitis followed with secondary infection and impaired vision.

  3. Juvenile nasopharyngeal angiofibroma

    PubMed Central

    Makhasana, Jashika Adil Shroff; Kulkarni, Meena A; Vaze, Suhas; Shroff, Adil Sarosh

    2016-01-01

    Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor arising predominantly in the nasopharynx of adolescent males. It is an aggressive neoplasm and shows a propensity for destructive local spread often extending to the base of the skull and into the cranium. Clinically, however, it is obscure with painless, progressive unilateral nasal obstruction being the common presenting symptom with or without epistaxis and rhinorrhea. Diagnosis of JNA is made by complete history, clinical examination, radiography, nasal endoscopy and by using specialized imaging techniques such as arteriography, computer tomography and magnetic resonance imaging. Histopathology reveals a fibrocellular stroma with spindle cells and haphazard arrangement of collagen interspersed with an irregular vascular pattern. A case report of JNA with rare intra-oral manifestation in a 17-year-old male patient is presented in the article. JNA being an aggressive tumor may recur posttreatment. Thus, early diagnosis, accurate staging, and adequate treatment are essential in the management of this lesion. PMID:27601836

  4. Juvenile idiopathic arthritis.

    PubMed

    Bhatt, Krupa H; Karjodkar, Freny R; Sansare, Kaustubh; Patil, Darshana

    2014-01-01

    Juvenile Idiopathic Arthritis (JIA) is the most chronic musculoskeletal disease of pediatric population. The chronic course of disease has a great impact on oral health. Temporomandibular joint is involved in JIA causing limited mouth opening with progressive open bite, retrognathia, microgenia and bird like appearance. Joints of upper and lower extremities are also involved. Effect on upper limb function leads to difficulty with fine motor movements required for brushing and flossing. This increases incidence of caries and periodontal disease in children. The cause of JIA is still poorly understood and none of the available drugs for JIA can cure the disease. However, prognosis has improved as a result of progress in disease classification and management. The dental practitioner should be familiar with the symptoms and oral manifestations of JIA to help manage as multidisciplinary management is essential.

  5. Juvenile chronic arthritis.

    PubMed

    Southwood, T R; Woo, P

    1995-05-01

    The nomenclature and classification criteria for arthritis in children should be dealt with initially as separate issues, although they are undoubtedly intertwined. The classification criteria should aim to delineate homogeneous patient populations, yet should be flexible enough to incorporate advances in disease knowledge. It should be recognized that arriving at an international consensus for classification criteria will merely provide a set of operational definitions to facilitate research, and not a set of diagnostic criteria. Indeed the only point to obtaining consensus is to begin a process of systematic ongoing review of the criteria. The labels attached to any of these diseases should facilitate accurate communication. In view of the heterogeneous nature of childhood arthritis, consideration should be given to using a broad umbrella term such as juvenile or childhood arthritis only for communicating with the lay public. Medical nomenclature should be formulated to reflect accurately homogeneous subgroups of arthritis, and should not artificially proscribe a relationship between paediatric and adult disease.

  6. [Juvenile idiopathic systemic arthritis].

    PubMed

    Baksiene, Dalia; Kasparaviciene, Jūrate; Zebiene, Migla; Puteliene, Brigita

    2003-01-01

    THE PURPOSE OF THE STUDY was to evaluate the peculiarities of the clinical features, laboratory parameters and tactics of treatment in juvenile idiopatic systematic arthritis. A retrospective data review of 41 children (26 boys and 15 girls) who underwent treatment for systemic arthritis (according to ILAR criteria) in our institution between 1992 and 2002 was performed. The disease started with fever of unknown origin in all cases. In 73% of patients it lasted longer than one month, in 54% fever was with twice daily spikers in the morning and in the evening. The rash during the rise of temperature appeared in 49%, in most cases (70%) there was a maculo-papular rash. Lymphadenopathy and serositis were observed in 32%, hepatomegaly in 29%, and splenomegaly in 24%. Arthritis coincided with the fever in 29% of patients, in majority of cases it was progressing to a severe persistent arthritis after the systematic phase. There was no specific laboratory findings: neutrophilic leucocytosis was found in 73%, anemia - in 80.5%, trombocytosis - in 36.6%, elevated CRP - in 63.4%, dysproteinemia - in 79% of patients. Antinuclear factors were absent in all examined children. For all patients intravenous methylprednisolone pulses have been administered (10-22 mg/kg/infusion). Prednisolone was also continued orally (1-2 mg/kg/day). 24.4% of patients required in addition immunosupressive agents such as methotrexate, azathioprine and cyclophosphamide. Puls-therapy of methylprednisolone is a safe and sufficiently effective method of treatment in most cases of the systematic juvenile arthritis.

  7. Juvenile homosexual homicide.

    PubMed

    Myers, Wade C; Chan, Heng Choon Oliver

    2012-01-01

    Limited information exists on juvenile homosexual homicide (JHH), that is, youths who perpetrate sexual homicides against same-sex victims. Only a handful of cases from the United States and internationally have been described in the literature. This study, the first of its kind, examines the epidemiology, victimology, victim-offender relationship, and weapon-use patterns in JHH offenders using a large U.S. database on homicide spanning three decades. The data for this study were derived from the Federal Bureau of Investigation's Supplementary Homicide Reports (SHRs) for the years 1976 through 2005. A total of 93 cases of JHH were identified. On average, three of these crimes occurred annually in the U.S., and there was a marked decline in its incidence over the study period. Ninety-five percent were male offender-male victim cases and 5% were female offender-female victim cases. JHH offenders were over-represented amongst all juvenile sexual murderers, similar to their adult counterparts. The majority of these boys were aged 16 or 17 and killed adult victims. They were significantly more likely to kill adult victims than other age groups, to be friends or acquaintances of the victims, and to use contact/edged weapons or firearms. Most offenders killed same-race victims, although Black offenders were significantly more likely than White offenders to kill interracially. A case report is provided to illustrate JHH. Further research is needed to promote our understanding of the pathogenesis, etiology, and associated risk factors for this aberrant form of murder by children. Copyright © 2012 John Wiley & Sons, Ltd.

  8. Short communication: Alteration in blood parameters by enrofloxacin in juvenile lesser spotted dogfish (Scyliorhinus canicula, Linnaeus, 1758) after intramuscular injection.

    PubMed

    Zaccaroni, Annalisa; Perez-Lopez, Marcos; de la Casa Resino, Irene; Medri, Gianfranco; Ceneri, Fabrizio; Bertini, Simone; Mordenti, Oliviero; Cortinovis, Luana; Sirri, Rubina; Mandrioli, Luciana

    2017-08-10

    Enrofloxacin (EF) is a veterinary drug for respiratory, gastrointestinal and urinary tract infections. Parenteral administration at doses higher than the manufacturer recommended dosage has induced cartilage lesions in juvenile mammals and poultry. In elasmobranchs EF is commonly used for the treatment of infectious diseases, however only one study has been performed previously to evaluate pharmacokinetics and the potential chondrotoxicity of a fluoroquinolone in adult skates. In present study juvenile lesser spotted dogfish (Scyliorhinus canicula, Linnaeus, 1758) were treated with low (LD, 5mg/kg) and high dose (HD, 10mg/kg) of EF daily via intramuscular injection for 15 consecutive days, as indicated in a recognized treatment. Hematological parameters, oxidative stress and histology of vertebral cartilage were evaluated. No cartilage damage was observed. Hematological parameters evaluation underlined a significant (p=0.035), dose-dependent reduction in red blood cell count and in hematocrit (40% and 6%, respectively). Anyway, the biological significance of this reduction is doubtful, due to limited decrease observed. The evaluation of oxidative stress parameters underlined that glutathione levels, as well as glutathione S-transferase and catalase activities, were significantly increased in HD group animals, with respect to untreated and solvent control groups. Obtained data do not support a toxic effect of EF on dogfish cartilage, while concern arises from hematological and oxidative stress data. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. The impact of a successful anti-myxosporean treatment on the phagocyte functions of juvenile and adult Sparus aurata L.

    PubMed

    Karagouni, E; Athanassopoulou, F; Tsagozis, P; Ralli, E; Moustakareas, T; Lytra, K; Dotsika, E

    2005-01-01

    The aim of the present study was to investigate the impact of a successful anti-myxosporean medication on the innate immune system of fish intensively cultured in the Mediterranean basin. For this purpose, juvenile and adult gilthead seabream (S. aurata L.) naturally infected with Polysporoplasma sparis in the kidney were used in a small-scale field trial. The infected fish were treated orally with the combination of salinomycin and amprolium, two drugs well known for their anti-coccidial effect in other animals. Drug efficacy and safety was evaluated in terms of changes observed in histopathology, mortality and P. sparis intensity and prevalence rate. Phagocytic functions of head-kidney leucocytes were also investigated at the end as well as one month post the medication. Salinomycin with amprolium exhibited a significant reduction in intensity and prevalence rate in both juvenile and adult fish, and no histopathological evidence for toxic side effects was observed. In addition, the successful treatment was closely correlated with a complete restoration of the diminished phagocytic ability and capacity as well as NO, and lysozyme secretion in a time dependent manner. This data suggests that salilomycin with amprolium can be an alternative treatment for myxosporean infections in tropical fish, possibly exhibiting their action through the enhancement of host innate functions.

  10. Toxic proteins in plants.

    PubMed

    Dang, Liuyi; Van Damme, Els J M

    2015-09-01

    Plants have evolved to synthesize a variety of noxious compounds to cope with unfavorable circumstances, among which a large group of toxic proteins that play a critical role in plant defense against predators and microbes. Up to now, a wide range of harmful proteins have been discovered in different plants, including lectins, ribosome-inactivating proteins, protease inhibitors, ureases, arcelins, antimicrobial peptides and pore-forming toxins. To fulfill their role in plant defense, these proteins exhibit various degrees of toxicity towards animals, insects, bacteria or fungi. Numerous studies have been carried out to investigate the toxic effects and mode of action of these plant proteins in order to explore their possible applications. Indeed, because of their biological activities, toxic plant proteins are also considered as potentially useful tools in crop protection and in biomedical applications, such as cancer treatment. Genes encoding toxic plant proteins have been introduced into crop genomes using genetic engineering technology in order to increase the plant's resistance against pathogens and diseases. Despite the availability of ample information on toxic plant proteins, very few publications have attempted to summarize the research progress made during the last decades. This review focuses on the diversity of toxic plant proteins in view of their toxicity as well as their mode of action. Furthermore, an outlook towards the biological role(s) of these proteins and their potential applications is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The changing trade-off between food finding and food stealing in juvenile oystercatchers

    PubMed

    Goss-custard; Cayford; Lea

    1998-03-01

    When juvenile oystercatchers, Haematopus ostralegus, first arrived on the wintering grounds in August and September, they regularly stole mussels, Mytilus edulis, from other, mainly older, oystercatchers. By October, however, juveniles stole far fewer mussels and found almost all their mussels independently for themselves on the mussel bed. Although stealing a mussel was always less profitable than taking a mussel from the mussel bed, a simple rate-maximizing optimality model showed that, in August and September, juveniles increased both their net and gross rates of energy intake by stealing because they were rather inefficient at foraging for themselves. By October, their greater efficiency at finding good quality mussels, combined with the increased resistance of potential victims to kleptoparasitic attacks, resulted in higher intake rates if juveniles stopped stealing mussels and took mussels only from the mussel bed. Copyright 1998 The Association for the Study of Animal Behaviour Copyright 1998 The Association for the Study of Animal Behaviour.

  12. Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats.

    PubMed

    Fuentes, Silvia; Carrasco, Javier; Armario, Antonio; Nadal, Roser

    2014-08-01

    Exposure to stress during childhood and adolescence increases vulnerability to developing several psychopathologies in adulthood and alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis, the prototypical stress system. Rodent models of juvenile stress appear to support this hypothesis because juvenile stress can result in reduced activity/exploration and enhanced anxiety, although results are not always consistent. Moreover, an in-depth characterization of changes in the HPA axis is lacking. In the present study, the long-lasting effects of juvenile stress on adult behavior and HPA function were evaluated in male rats. The juvenile stress consisted of a combination of stressors (cat odor, forced swim and footshock) during postnatal days 23-28. Juvenile stress reduced the maximum amplitude of the adrenocorticotropic hormone (ACTH) levels (reduced peak at lights off), without affecting the circadian corticosterone rhythm, but other aspects of the HPA function (negative glucocorticoid feedback, responsiveness to further stressors and brain gene expression of corticotrophin-releasing hormone and corticosteroid receptors) remained unaltered. The behavioral effects of juvenile stress itself at adulthood were modest (decreased activity in the circular corridor) with no evidence of enhanced anxiety. Imposition of an acute severe stressor (immobilization on boards, IMO) did not increase anxiety in control animals, as evaluated one week later in the elevated-plus maze (EPM), but it potentiated the acoustic startle response (ASR). However, acute IMO did enhance anxiety in the EPM, in juvenile stressed rats, thereby suggesting that juvenile stress sensitizes rats to the effects of additional stressors.

  13. Examining the Effects of External or Internal Radiation Exposure of Juvenile Mice on Late Morbidity after Infection with Influenza A

    PubMed Central

    Misra, Ravi S.; Johnston, Carl J.; Groves, Angela M.; DeDiego, Marta L.; St Martin, Joe; Reed, Christina; Hernady, Eric; Miller, Jen-nie; Love, Tanzy; Finkelstein, Jacob N.; Williams, Jacqueline P.

    2015-01-01

    A number of investigators have suggested that exposure to low-dose radiation may pose a potentially serious health risk. However, the majority of these studies have focused on the short-term rather than long-term effects of exposure to fixed source radiation, and few have examined the effects of internal contamination. Additionally, very few studies have focused on exposure in juveniles, when organs are still developing and could be more sensitive to the toxic effects of radiation. To specifically address whether early-life radiation injury may affect long-term immune competence, we studied 14-day-old juvenile pups that were either 5 Gy total-body irradiated or injected internally with 50 μCi soluble 137Cs, then infected with influenza A virus at 26 weeks after exposure. After influenza infection, all groups demonstrated immediate weight loss. We found that externally irradiated, infected animals failed to recover weight relative to age-matched infected controls, but internally 137Cs contaminated and infected animals had a weight recovery with a similar rate and degree as controls. Externally and internally irradiated mice demonstrated reduced levels of club cell secretory protein (CCSP) message in their lungs after influenza infection. The externally irradiated group did not recover CCSP expression even at the two-week time point after infection. Although the antibody response and viral titers did not appear to be affected by either radiation modality, there was a slight increase in monocyte chemo-attractant protein (MCP)-1 expression in the lungs of externally irradiated animals 14 days after influenza infection, with increased cellular infiltration present. Notably, an increase in the number of regulatory T cells was seen in the mediastinal lymph nodes of irradiated mice relative to uninfected mice. These data confirm the hypothesis that early-life irradiation may have long-term consequences on the immune system, leading to an altered antiviral response. PMID

  14. Examining the Effects of External or Internal Radiation Exposure of Juvenile Mice on Late Morbidity after Infection with Influenza A.

    PubMed

    Misra, Ravi S; Johnston, Carl J; Groves, Angela M; DeDiego, Marta L; St Martin, Joe; Reed, Christina; Hernady, Eric; Miller, Jen-Nie; Love, Tanzy; Finkelstein, Jacob N; Williams, Jacqueline P

    2015-07-01

    A number of investigators have suggested that exposure to low-dose radiation may pose a potentially serious health risk. However, the majority of these studies have focused on the short-term rather than long-term effects of exposure to fixed source radiation, and few have examined the effects of internal contamination. Additionally, very few studies have focused on exposure in juveniles, when organs are still developing and could be more sensitive to the toxic effects of radiation. To specifically address whether early-life radiation injury may affect long-term immune competence, we studied 14-day-old juvenile pups that were either 5 Gy total-body irradiated or injected internally with 50 μCi soluble (137)Cs, then infected with influenza A virus at 26 weeks after exposure. After influenza infection, all groups demonstrated immediate weight loss. We found that externally irradiated, infected animals failed to recover weight relative to age-matched infected controls, but internally (137)Cs contaminated and infected animals had a weight recovery with a similar rate and degree as controls. Externally and internally irradiated mice demonstrated reduced levels of club cell secretory protein (CCSP) message in their lungs after influenza infection. The externally irradiated group did not recover CCSP expression even at the two-week time point after infection. Although the antibody response and viral titers did not appear to be affected by either radiation modality, there was a slight increase in monocyte chemoattractant protein (MCP)-1 expression in the lungs of externally irradiated animals 14 days after influenza infection, with increased cellular infiltration present. Notably, an increase in the number of regulatory T cells was seen in the mediastinal lymph nodes of irradiated mice relative to uninfected mice. These data confirm the hypothesis that early-life irradiation may have long-term consequences on the immune system, leading to an altered antiviral response.

  15. Seasonal variation in plasma sex steroid concentrations in juvenile American alligators.

    PubMed

    Rooney, Andrew A; Crain, D Andrew; Woodward, Allan R; Guillette, Louis J

    2004-01-01

    Seasonal variation in plasma sex steroid concentrations is common in mature vertebrates, and is occasionally seen in juvenile animals. In this study, we examine the seasonal pattern of sex hormone concentration in juvenile American alligators (Alligator mississippiensis) and make a limited comparison of these seasonal patterns on two different lakes in Florida. Male juvenile alligators from a reference lake, Lake Woodruff, displayed temporal patterns in plasma testosterone (T) concentrations that appear to be seasonal. A similar pattern in plasma estradiol-17beta (E(2)) was observed in juvenile females from Lake Woodruff. Males had significantly elevated T concentrations during the spring and late summer, whereas females had elevated E(2) in the spring and late summer and significantly depressed E(2) concentrations during the winter. A limited 4-month survey of animals from contaminated Lake Apopka found a lack of such seasonality. These results suggest that: (1) healthy wild populations of juvenile alligators have a prolonged peripubescent period that is marked by seasonal hormonal cycles, (2) juvenile alligators exposed to environmental contaminants can lack such seasonal cyclicity, and (3) future studies of juvenile alligators should incorporate such seasonality into the experimental design.

  16. The effects of juvenile capsaicin desensitization in rats: behavioral impairments.

    PubMed

    Petrovszki, Zita; Adam, Gábor; Kekesi, Gabriella; Tuboly, Gábor; Morvay, Zita; Nagy, Endre; Benedek, György; Horvath, Gyöngyi

    2014-02-10

    Capsaicin desensitization leads to behavioral changes, some of which are related to schizophrenia, but investigations into these effects have been scarce. The goal of this study was to characterize the consequences of juvenile capsaicin desensitization on different functions: acute and inflammation-induced thermal and mechanical sensitivity, urinary bladder capacity and thermoregulation, and also on the potentially schizophrenia-related impairments in sensory-motor gating, motor activity and cognitive functioning. Male Wistar rats desensitized with increasing doses of subcutaneous capsaicin after weaning were investigated. Heat and mechanical pain sensitivity did not change significantly; however, morphine produced a prolonged decrease in the nociceptive response to inflammation in desensitized animals. Ultrasound examination of the bladder revealed enhanced bladder volume in treated animals. Capsaicin-treated animals had higher body temperature at 22 °C in both dark and light periods, and they also showed prolonged hyperthermia in new environmental circumstances. Warm environment induced a profound impairment of thermoregulation in desensitized animals. The treated animals also showed higher levels of activity during the active phase and at both cool and warm temperatures. The amplitude of the responses to auditory stimuli and prepulse inhibition did not differ between the two groups, but the desensitized animals showed learning impairments in the novel object recognition test. These results suggest that juvenile capsaicin desensitization leads to sustained changes in several functions that may be related to schizophrenia. We propose that capsaicin desensitization, together with other interventions, may lead to an improved chronic animal model of schizophrenia.

  17. Juvenile onset spondyloarthropathies: therapeutic aspects

    PubMed Central

    Burgos-Vargas, R

    2002-01-01

    Juvenile onset spondyloarthropathy (SpA) is a term that refers to a group of human leucocyte antigen (HLA)-B27 associated inflammatory disorders affecting children under the age of 16 years, producing a continuum of clinical symptoms through adulthood. This disease is characterised by enthesopathy and arthropathy affecting the joints of the lower extremities and seronegativity for IgM rheumatoid factor and antinuclear antibodies. Children usually present with undifferentiated SpA and progress to differentiated forms over time. Except for the prevalence of some clinical features at onset, the pathogenic and clinical aspects of juvenile onset SpAs resemble those of the adult disease. Thus application of the same or similar therapeutic measures for both juvenile and adult onset SpAs seems logical. Current treatments for juvenile onset SpA provide symptomatic improvement, but do not alter disease progression. The increased expression of tumour necrosis factor alpha (TNFα) in synovial tissue of patients with adult and juvenile onset SpA and its correlation with infiltration of inflammatory mediators into the synovia suggest a significant pathogenic role of this cytokine. Clinical trials of anti-TNFα antibody (infliximab) therapy in patients with adult onset SpA have demonstrated significant clinical improvement in inflammatory pain, function, disease activity, and quality of life in correlation with histological and immunohistochemical evidence of modulation of synovial inflammatory processes. These promising findings suggest that anti-TNFα therapy may confer similar benefits in patients with juvenile onset SpA. PMID:12381509

  18. Standardization of the juvenile mussel bioassay: Dietary requirements

    SciTech Connect

    Warren, L.W.; Klaine, S.J.

    1995-12-31

    Optimizing a feeding regime is essential for establishing juvenile mussels (Utterbackia imbecillus) as a standard toxicity test organism. Although very little is known about their dietary requirements, these juveniles appear to derive adequate nourishment for survival and growth in batch culture from a diet of the green alga Chlorella vulgaris and Ankistrodesmus falcatus. However, results of previous studies have suggested that mussel diet in culture prior to exposure influences the sensitivity of these organisms to aqueous copper and cadmium exposure. Dietary components included three species of live algae (A. falcatus, C. vulgaris, and Scenedesmus quadricauda) and a suspension of rehydrated, dried Spirulina sp. Less than 24-hr laboratory cultured juveniles were fed all four components or combinations of three algal species daily to determine which mixtures promoted maximal growth. Preliminary data showed growth of control mussels receiving no food was comparable to those organisms fed all four algal species in combination. The greatest increase in shell length of juvenile mussels over 6 days was obtained with the tri-algal combination of A. falcatus, C. vulgaris, and S. quadricauda. The mixture resulting in the least growth included A. falcatus, S. quadricauda, and dried Spirulina sp.

  19. 4-H PetPALS Juvenile Diversion Program Supports At-Risk Youth and Seniors

    ERIC Educational Resources Information Center

    Goble, Connie L.; Miller, Lucinda B.

    2014-01-01

    The 4-H PetPALS Juvenile Diversion Program provides a partnership opportunity with Extension and the juvenile court system to positively impact lives of at-risk youth. At-risk youth are taught by 4-H PetPALS adult volunteer leaders and 4-H PetPALS members to value and respect the human-animal bond, as well as to understand and empathize with…

  20. 4-H PetPALS Juvenile Diversion Program Supports At-Risk Youth and Seniors

    ERIC Educational Resources Information Center

    Goble, Connie L.; Miller, Lucinda B.

    2014-01-01

    The 4-H PetPALS Juvenile Diversion Program provides a partnership opportunity with Extension and the juvenile court system to positively impact lives of at-risk youth. At-risk youth are taught by 4-H PetPALS adult volunteer leaders and 4-H PetPALS members to value and respect the human-animal bond, as well as to understand and empathize with…

  1. One Health and Toxic Cyanobacteria

    EPA Science Inventory

    One Health and toxic cyanobacteria Blooms of toxic freshwater blue-green algae or cyanobacteria (HABs) have been in the news after HABs associated with human and animal health problems have been reported in Florida, California and Utah during 2016. HABs occur in warm, slow moving...

  2. Lead Toxicity

    MedlinePlus

    Agency for Toxic Substances and Disease Registry Case Studies in Environmental Medicine (CSEM) Patient Information Sheet Lead Toxicity What is lead? How are people exposed to lead? • Lead is a soft, blue- ...

  3. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  4. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  5. Digitalis toxicity

    MedlinePlus

    ... including dehydration ) makes digitalis toxicity more likely. Some plants contain chemicals that can cause symptoms similar to digitalis toxicity if they are eaten. These include foxglove, oleander, and lily of the valley.

  6. Variation in animal response to different toxicants

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    The variation in response of different lots of male Swiss albino mice to pyrolysis effluents from surgical cotton and from bisphenol A polycarbonate, and to pure carbon monoxide, is discussed. The variation appeared to be less with the pyrolysis gases from polycarbonate than with pure carbon monoxide.

  7. Variation in animal response to different toxicants

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.

    1977-01-01

    The variation in response of different lots of male Swiss albino mice to pyrolysis effluents from surgical cotton and from bisphenol A polycarbonate, and to pure carbon monoxide, is discussed. The variation appeared to be less with the pyrolysis gases from polycarbonate than with pure carbon monoxide.

  8. Amazing Animals

    ERIC Educational Resources Information Center

    Al-Kuwari, Najat Saad

    2007-01-01

    "Animals" is a three-part lesson plan for young learners with a zoo animal theme. The first lesson is full of activities to describe animals, with Simon Says, guessing games, and learning stations. The second lesson is about desert animals, but other types of animals could be chosen depending on student interest. This lesson teaches…

  9. Managing juvenile Huntington's disease.

    PubMed

    Quarrell, Oliver W J; Nance, Martha A; Nopoulos, Peggy; Paulsen, Jane S; Smith, Jonathan A; Squitieri, Ferdinando

    2013-06-01

    Huntington's disease (HD) is a well-recognized progressive neurodegenerative disorder that follows an autosomal dominant pattern of inheritance. Onset is insidious and can occur at almost any age, but most commonly the diagnosis is made between the ages of 35 and 55 years. Onset ≤20 years of age is classified as juvenile HD (JHD). This age-based definition is arbitrary but remains convenient. There is overlap between the clinical pathological and genetic features seen in JHD and more traditional adult-onset HD. Nonetheless, the frequent predominance of bradykinesia and dystonia early in the course of the illness, more frequent occurrence of epilepsy and myoclonus, more widespread pathology, and larger genetic lesion means that the distinction is still relevant. In addition, the relative rarity of JHD means that the clinician managing the patient is often doing so for the first time. Management is, at best, symptomatic and supportive with few or no evidence-based guidelines. In this article, the authors will review what is known of the condition and present some suggestions based on their experience.

  10. Juvenile mortality in captive lesser kudu (Tragelaphus imberbis) at Basle Zoo and its relation to nutrition and husbandry.

    PubMed

    Besselmann, Dorothea; Schaub, Daniela; Wenker, Christian; Völlm, Jürg; Robert, Nadia; Schelling, Claude; Steinmetz, Hanspeter; Clauss, Marcus

    2008-03-01

    Since 1956, when the Basle Zoo (Switzerland) initiated the breeding of lesser kudu (Tragelaphus imberbis), 43% of the lesser kudu juveniles died before reaching an age of 6 mo. In this study, the objective was to obtain the pathological findings, nutritional history, and family tree information in order to evaluate the influence of husbandry on juvenile mortality in these animals. The main cause of death was white muscle disease (WMD), diagnosed in 14 cases (26%) of the deceased juveniles. Although enclosure size had remained constant and animal accessibility to the public was constantly high, both herd size and juvenile mortality had increased from 1956-2004. The diet consumed by the whole group in 2004 had deficient levels of vitamin E and selenium. The increasing linear trend of the mortality rate since the 1960s was significant, and there was a significant correlation between herd size and overall juvenile mortality. In contrast, there was no correlation between herd size and the occurrence of juvenile mortality associated specifically with WMD. Other investigated factors (sex, inbreeding, and season) had no significant effect on overall mortality up to 6 mo of age or on mortality associated with WMD. These results characterize both a dietary and a husbandry problem, and are supported by a lack of similar juvenile mortality in another facility where the diet was supplemented with vitamin E, animal numbers were kept low, and the enclosure structure offered more retreat options for the animals.

  11. Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway

    SciTech Connect

    Sheng Zhiguo; Cao Xiaojuan; Peng Shuangqing Wang Changyong; Li Qianqian; Wang Yimei; Liu Mifeng

    2008-01-15

    Quinolones (QNs)-induced arthropathy is an important toxic effect in immature animals leading to restriction of their therapeutic use in pediatrics. However, the exact mechanism still remains unclear. Recently, we have demonstrated that ofloxacin, a typical QN, induces apoptosis of alginate microencapsulated juvenile rabbit joint chondrocytes by disturbing the {beta}{sub 1} integrin functions and inactivating the ERK/MAPK signaling pathway. In this study, we extend our initial observations to further elucidate the mechanism(s) of ofloxacin-induced apoptosis by utilizing specific caspase inhibitors. Pretreatment with both caspase-9-specific inhibitor zLEHD-fmk and caspase-8 inhibitor zIETD-fmk attenuated ofloxacin-induced apoptosis and activation of caspase-3 of chondrocyte in a concentration-dependent manner, as determined by fluorescent dye staining, enzyme activity assay and immunoblotting. Furthermore, the activation of caspase-9, -8 and -3 stimulated by ofloxacin was significantly inhibited in the presence of zIETD-fmk while pretreatment with zLEHD-fmk only blocked the activation of caspase-9 and -3. Ofloxacin also stimulated a concentration-dependent translocation of cytochrome c from mitochondria into the cytosol and a decrease of mitochondrial transmembrane potential, which was completely inhibited by zIETD-fmk. In addition, ofloxacin was found to increase the level of Bax, tBid, p53 in a concentration- and time-dependent manner. Taken together, The current results indicate that the caspase-8-dependent mitochondrial pathway is primarily involved in the ofloxacin-induced apoptosis of microencapsulated juvenile rabbit joint chondrocytes.

  12. Endosulfan affects GnRH cells in sexually differentiated juveniles of the perciform Cichlasoma dimerus.

    PubMed

    Piazza, Yanina; Pandolfi, Matías; Da Cuña, Rodrigo; Genovese, Griselda; Lo Nostro, Fabiana

    2015-06-01

    Endosulfan (ES) is an organochlorine pesticide widely used in agriculture despite its high toxicity towards non-target organisms such as fish. It has been demonstrated that ES can cause negative effects on aquatic animals, including disruption of hormonal systems. However, the alterations produced by this pesticide on the reproductive axis of fish prior to sexual maturity, as well as possible modes of action have hardly been studied. This study aimed at assessing the effect of waterborne exposure to the pesticide ES on the reproductive axis during sexual differentiation of juveniles of the South American freshwater cichlid fish Cichlasoma dimerus. No mortality was observed due to ES subchronic exposure (90 days post-fertilization). Exposure to ES did not affect body weight nor morphometric parameters, indicating that larvae nutritional state was not affected. Timing of sexual differentiation, gonadal morphology and sex ratio were likewise not altered by ES. However, ES acted as an endocrine disrupting chemical in this species as the morphometry of gonadotropin-releasing hormones (GnRH) producing cells was altered. Exposure to ES altered nuclear area, cell area and nucleus/cytoplasm ratio of GnRH II neurons, and cell and nuclear area and diameter of GnRH III neurons. Interestingly, in our previous study, exposure before sex differentiation (30 day exposure) caused no alteration to GnRH II and III, and did alter GnRH I and FSH cells. These alterations could lead to changes in circulating hormone levels, especially when fish are exposed for prolonged periods, ultimately impairing reproductive fitness. C. dimerus juveniles can be an interesting biological model to perform toxicological studies with the intent to assess early disruption endpoints in the reproductive axis during development.

  13. Application of a benthic euryhaline amphipod, Corophium sp., as a sediment toxicity testing organism for both freshwater and estuarine systems.

    PubMed

    Hyne, R V; Everett, D A

    1998-01-01

    The use of an as-yet-undescribed euryhaline Corophium sp. amphipod as a sediment toxicity testing organism was assessed. The species was found to be ubiquitous in many tidal areas of the Hawkesbury River catchment. The salinity of habitat sites ranged from 0.1 to 24 ppt, sediment total organic carbon (TOC) ranged from 0.4% to 3.5%, and the fines content (< 63 micron particle size) of the sediment ranged from 4.3% to 47.6%. Monitored populations ranged from a density of 59 to 6622 individuals per m2, with freshwater sites with a sediment fines content greater than 20% having the highest population densities. The sensitivity of the Corophium sp. was assessed by using copper chloride and ammonium chloride as reference toxicants in a 96-h static water-only test and a 10-day static sediment test. The LC50 for copper in freshwater-only exposures was 80 to 86 microg/L, using adult animals collected from the field. In contrast, the LC50 for copper in freshwater sediment and the sediment pore water were 840 mg/kg (dry weight) and 99 microg/L, respectively. The LC50 for ammonia (total) in freshwater-only at pH 7 was 5.5 mg/L. In contrast, the LC50 for ammonia (total) in freshwater sediment and the sediment pore water were 110 mg/kg (dry weight) and 6 mg/L, respectively. Laboratory cultures of 5 per thousand to 15 per thousand salinity were optimal for supporting the release of juveniles. Juveniles collected from laboratory cultures had a LC50 for copper in 5 per thousand and 10 per thousand salinity of 9 microg/L and 28.5 microg/L, respectively, in water-only exposures. The juveniles would be suitable for use in the development of a chronic sediment toxicity test with growth as the endpoint.

  14. Age-related thermal response: the cellular resilience of juveniles.

    PubMed

    Clark, M S; Thorne, M A S; Burns, G; Peck, L S

    2016-01-01

    Understanding species' responses to environmental challenges is key to predicting future biodiversity. However, there is currently little data on how developmental stages affect responses and also whether universal gene biomarkers to environmental stress can be identified both within and between species. Using the Antarctic clam, Laternula elliptica, as a model species, we examined both the tissue-specific and age-related (juvenile versus mature adult) gene expression response to acute non-lethal warming (12 h at 3 °C). In general, there was a relatively muted response to this sub-lethal thermal challenge when the expression profiles of treated animals, of either age, were compared with those of 0 °C controls, with none of the "classical" stress response genes up-regulated. The expression profiles were very variable between the tissues of all animals, irrespective of age with no single transcript emerging as a universal biomarker of thermal stress. However, when the expression profiles of treated animals of the different age groups were directly compared, a very different pattern emerged. The profiles of the younger animals showed significant up-regulation of chaperone and antioxidant transcripts when compared with those of the older animals. Thus, the younger animals showed evidence of a more robust cellular response to warming. These data substantiate previous physiological analyses showing a more resilient juvenile population.

  15. Juveniles tried as adults: the age of the juvenile matters.

    PubMed

    Semple, Jaclyn K; Woody, William Douglas

    2011-08-01

    Serious juvenile crimes require evaluation of a child as a criminal defendant in adult court. In such cases, it is crucial to understand jurors' attitudes, biases, and ability to follow legal instructions and maintain fairness. 308 undergraduate psychology students served as mock jurors, were randomly separated into four groups, and each group read the same realistic summary of a trial with the defendant's age presented as 13, 15, 17, or 21 years. Participants were asked to render guilty or not guilty verdicts and, if guilty, to suggest sentences. Chi-squared analysis indicated 13- and 15-year-old defendants were convicted less often than 17- and 21-year-old defendants, showing that jurors distinguished between juvenile defendants of different ages, but not minors and adults as defined by law. Additional analysis showed that age did not affect sentencing recommendations. Decision processes jurors use for juveniles tried as adults are discussed.

  16. Forensic aspects of juvenile violence.

    PubMed

    Haller, L H

    2000-10-01

    The juvenile justice system was created because it was recognized that youthful offenders needed to be managed differently from adults. They were to receive habilitation services instead of punishment. It is now more than a century since the creation of the first juvenile court. After 67 years, the US Supreme Court, in Kent v United States stated that the model was not working because juveniles in the criminal justice system received no treatment and they had no rights. Because the issue that had been appealed was the lack of rights (not lack of treatment), the Court mandated that juveniles, like adults, be given certain rights. The following year, in In re Gault, the Court expanded these rights. Subsequent Supreme Court cases have dealt with these kinds of issues--that is, whether juvenile offenders are entitled to the same rights as adults and subject to the same penalties. The Supreme Court has never heard a "right to treatment" case, which is the other part of the juvenile court system. Cases have been brought in lower courts (e.g., Nelson v. Heyne, 1972) alleging inadequate treatment services, but no national impact has resulted. Thus, in general, children in the juvenile court system do not have an enforceable right to treatment and can obtain only what services are available in their jurisdictions. The services often are woefully inadequate. Sentencing a youth to probation, with the requirement that he or she participate in counseling or mental health treatment, is meaningless if services are not available. Community-based, model programs that provide effective treatment do exist. They are, as yet, the rare exception rather than the norm and, therefore, are not available to most youthful offenders. Incarcerated juveniles, obviously, cannot avail themselves of community programs. Litigation to give these youth the same rights as adults in penal institutions is not the answer because incarcerated adults don't have a right to treatment, only a right to be free

  17. A New Mass Mortality of Juvenile Protoceratops and Size-Segregated Aggregation Behaviour in Juvenile Non-Avian Dinosaurs

    PubMed Central

    Hone, David W. E.; Farke, Andrew A.; Watabe, Mahito; Shigeru, Suzuki; Tsogtbaatar, Khishigjav

    2014-01-01

    Background Monodominant bonebeds are a relatively common occurrence for non-avian dinosaurs, and have been used to infer associative, and potentially genuinely social, behavior. Previously known assemblages are characterized as either mixed size-classes (juvenile and adult-sized specimens together) or single size-classes of individuals (only juveniles or only adult-sized individuals within the assemblage). In the latter case, it is generally unknown if these kinds of size-segregated aggregations characterize only a particular size stage or represent aggregations that happened at all size stages. Ceratopsians (“horned dinosaurs”) are known from both types of assemblages. Methods/Principal Findings Here we describe a new specimen of the ceratopsian dinosaur Protoceratops andrewsi, Granger and Gregory 1923 from Mongolia representing an aggregation of four mid-sized juvenile animals. In conjunction with existing specimens of groups of P. andrewsi that includes size-clustered aggregations of young juveniles and adult-sized specimens, this new material provides evidence for some degree of size-clustered aggregation behaviour in Protoceratops throughout ontogeny. This continuity of size-segregated (and presumably age-clustered) aggregation is previously undocumented in non-avian dinosaurs. Conclusions The juvenile group fills a key gap in the available information on aggregations in younger ceratopsians. Although we support the general hypothesis that many non-avian dinosaurs were gregarious and even social animals, we caution that evidence for sociality has been overstated and advocate a more conservative interpretation of some data of ‘sociality’ in dinosaurs. PMID:25426957

  18. The toxicity of diaminodiphenoxyalkanes.

    PubMed

    GOODWIN, L G; RICHARDS, W H; UDALL, V

    1957-12-01

    Representative members of a series of schistosomicidal diaminodiphenoxyalkanes were examined for their toxic effects in laboratory animals. Primary amino-derivatives were, in general, more toxic than secondary methylamino-compounds; tertiary compounds were less toxic than either. Large doses given by mouth or by injection to mice or rabbits produced intravascular haemolysis; the haemoglobin and erythrocyte counts began to increase again about a week after the dose. Mice which had been given large doses of diaminodiphenoxyalkanes developed symmetrical bald patches 2 to 3 weeks after treatment. The exposed skin appeared normal and new fur grew to cover the hairless areas in about 6 weeks. Large doses of drug delayed water diuresis in mice.Many compounds of the series caused visual impairment when given to cats. In order to obtain a quantitative assessment of retinotoxic potency, a method was devised in which the ability of the retina of the frog to resynthesize rhodopsin was measured in treated and control animals. Compounds that produced blindness in cats also inhibited rhodopsin synthesis in frogs; the most toxic compounds were primary amines. Treatment with some tertiary amines caused retinal damage if the drugs were given for long periods. Diaminodiphenoxyalkanes may perhaps interfere in some way with the biological activity of vitamin A. However, toxic effects on the hair and retina were not prevented by supplements of synthetic or natural vitamin A.

  19. The toxicity of diaminodiphenoxyalkanes

    PubMed Central

    Goodwin, L. G.; Richards, W. H. G.; Udall, V.

    1957-01-01

    Representative members of a series of schistosomicidal diaminodiphenoxyalkanes were examined for their toxic effects in laboratory animals. Primary amino-derivatives were, in general, more toxic than secondary methylamino-compounds; tertiary compounds were less toxic than either. Large doses given by mouth or by injection to mice or rabbits produced intravascular haemolysis; the haemoglobin and erythrocyte counts began to increase again about a week after the dose. Mice which had been given large doses of diaminodiphenoxyalkanes developed symmetrical bald patches 2 to 3 weeks after treatment. The exposed skin appeared normal and new fur grew to cover the hairless areas in about 6 weeks. Large doses of drug delayed water diuresis in mice. Many compounds of the series caused visual impairment when given to cats. In order to obtain a quantitative assessment of retinotoxic potency, a method was devised in which the ability of the retina of the frog to resynthesize rhodopsin was measured in treated and control animals. Compounds that produced blindness in cats also inhibited rhodopsin synthesis in frogs; the most toxic compounds were primary amines. Treatment with some tertiary amines caused retinal damage if the drugs were given for long periods. Diaminodiphenoxyalkanes may perhaps interfere in some way with the biological activity of vitamin A. However, toxic effects on the hair and retina were not prevented by supplements of synthetic or natural vitamin A. ImagesFIG. 2 PMID:13489176

  20. Toxicity of the herbicide glyphosate to Chordodes nobilii (Gordiida, Nematomorpha).

    PubMed

    Achiorno, Cecilia L; Villalobos, Cristina de; Ferrari, Lucrecia

    2008-05-01

    Nematomorpha (horsehair worms) is a poorly known group of worm-like animals similar to nematodes. Adults are free-living and reproduction takes place in freshwater environments, where preparasitic larvae undergo development. All species have a parasitic juvenil stage and infection may result in the host's death, insects being the most frequent host. Most of the life cycle occurs in freshwater environments, which are often contaminated by different pollutants. Based on the lack of information on the toxicity of herbicides to horsehair worms, the objective of this study is to evaluate the effect of different concentrations of glyphosate (technical grade and formulated product) on Chordodes nobilii (Gordiida, Nematomorpha). Bioassays were performed with embryos and larvae (preparasitic stages), and adults (postparasitic stage). Test organisms were exposed for a short period of time to concentrations ranging between 0.1 and 8 mga.e.l(-1) of glyphosate (technical and formulated). Although embryo development was not inhibited, there was a significant decrease in the infective capacity of larvae derived from eggs that had been exposed to >or= 0.1mg/l. Similar results were obtained for directly exposed larvae. No differences in toxicity were detected between the active ingredient and formulated product. Adult exposed for 96 h to 1.76 mgl(-1) formulated Gly shown a mortality of 50%. Results indicate that C. nobilii is affected at glyphosate concentrations lower than those expected to be found in freshwater environments and those specified in the legislation.

  1. Workshop Report: Juvenile toxicity testing protocols for chemicals

    EPA Science Inventory

    There is increased awareness of the specific position of children when it comes to hazards of xenobiotic exposures. Children are not small adults, since their exposure patterns, compound kinetics and metabolism, and sensitivity of their developing organs may differ extensively fr...

  2. Workshop Report: Juvenile toxicity testing protocols for chemicals

    EPA Science Inventory

    There is increased awareness of the specific position of children when it comes to hazards of xenobiotic exposures. Children are not small adults, since their exposure patterns, compound kinetics and metabolism, and sensitivity of their developing organs may differ extensively fr...

  3. Genetics Home Reference: juvenile polyposis syndrome

    MedlinePlus

    ... and symptoms of the disorder. Juvenile polyposis of infancy is characterized by polyps that occur throughout the gastrointestinal tract during infancy. Juvenile polyposis of infancy is the most severe ...

  4. Recidivism of juvenile homicide offenders.

    PubMed

    Vries, Anne M; Liem, Marieke

    2011-01-01

    Serious offenses against persons perpetrated by juveniles raise fundamental questions about the background, causes, and prevention of future crime. The current study addresses the potential of future crime of all juvenile homicide offenders (JHOs) in the Netherlands in the period 1992-2007. In contrast to former research on recidivism of JHOs, which has been merely descriptive, the present study integrates theoretical perspectives as to why some of these juveniles turn back to crime, while others do not. To this end, relationships are investigated between recidivism behavior and risk factors. Results indicate that male JHOs, and JHOs who maintain relationships with delinquents, run a greater risk of reoffending. Copyright © 2011 John Wiley & Sons, Ltd.

  5. Comparative bacteriology of juvenile periodontitis.

    PubMed Central

    Moore, W E; Holdeman, L V; Cato, E P; Smibert, R M; Burmeister, J A; Palcanis, K G; Ranney, R R

    1985-01-01

    Statistical comparisons of the floras associated with juvenile periodontitis, severe periodontitis, and moderate periodontitis indicated that differences in the bacterial compositions of affected sites in these populations were not statistically significant. The subgingival flora of affected juvenile periodontitis sites was statistically significantly different from the adjacent supragingival flora and from the subgingival floras of people with healthy gingiva and of children with developing (experimental) gingivitis. However, the subgingival flora of affected juvenile periodontitis sites was not significantly different from the flora of sites with gingival index scores of 1 or 2 in adults with developing (experimental) gingivitis. Of 357 bacterial taxa among over 18,000 isolates, 54 non-treponemal species, 2 treponemal species, and mycoplasma were most associated with diseased periodontal sulci. These species comprised an increasing proportion of the flora during developing gingivitis and constituted over half of the cultivable flora of diseased sites. PMID:3988344

  6. Altered Sensory Code Drives Juvenile-to-Adult Behavioral Maturation in Caenorhabditis elegans

    PubMed Central

    Pantazis, Alexandros K.

    2016-01-01

    Abstract Adults perform better than juveniles in food-seeking tasks. Using the nematode Caenorhabditis elegans to probe the neural mechanisms underlying behavioral maturation, we found that adults and juveniles require different combinations of sensory neurons to generate age-specific food-seeking behavior. We first show that adults and juveniles differ in their response to and preference for food-associated odors, and we analyze genetic mutants to map the neuronal circuits required for those behavioral responses. We developed a novel device to trap juveniles and record their neuronal activity. Activity measurements revealed that adult and juvenile AWA sensory neurons respond to the addition of diacetyl stimulus, whereas AWB, ASK, and AWC sensory neurons encode its removal specifically in adults. Further, we show that reducing neurotransmission from the additional AWB, ASK, and AWC sensory neurons transforms odor preferences from an adult to a juvenile-like state. We also show that AWB and ASK neurons drive behavioral changes exclusively in adults, providing more evidence that age-specific circuits drive age-specific behavior. Collectively, our results show that an odor-evoked sensory code is modified during the juvenile-to-adult transition in animal development to drive age-appropriate behavior. We suggest that this altered sensory code specifically enables adults to extract additional stimulus features and generate robust behavior. PMID:28083560

  7. Lidocaine toxicity.

    PubMed

    Mehra, P; Caiazzo, A; Maloney, P

    1998-01-01

    Local anesthetics are the most commonly used drugs in dentistry. The number of adverse reactions reported, particularly toxic reactions, are extraordinarily negligible. This article reports a case of lidocaine toxicity with its typical manifestation in a 37-yr-old healthy male. The toxic reaction followed transoral/transpharyngeal topical spraying of lidocaine preoperatively during preparation for general anesthesia. A review of dosages of the most commonly used local anesthetic drugs in dentistry and the management of a toxic reaction is presented. Clinicians need to be in a position to recognize and successfully manage this potential adverse reaction.

  8. Aminophylline toxicity.

    PubMed

    Albert, S

    1987-02-01

    Aminophylline therapy has undergone change in the past decade. With the changes in usage and dosage forms, the frequency of toxicity in the pediatric population, especially in adolescents, has increased dramatically. Two distinct patterns, chronic and acute, have been recognized and treatment methods for both are changing. Table 4 summarizes the emerging state-of-the-art therapy for aminophylline toxicity. Judging from the activity seen in the literature, investigation into aminophylline toxicity will continue to be a priority. We will see a greater understanding of the disease process and a refining of the therapeutic process. The ultimate goal is the elimination of mortality and the minimization of morbidity from aminophylline toxicity.

  9. Core decompression for juvenile osteonecrosis.

    PubMed

    Herrera-Soto, José A; Price, Charles T

    2011-07-01

    Core decompression may be used as adjunct for treatment in some cases of Legg-Calvé-Perthes disease (LCPD). The primary application is for patients with onset at 12 years of age or older. We recommend classifying these older patients as idiopathic juvenile osteonecrosis and treating them similarly to adults with avascular necrosis. Juvenile osteonecrosis may benefit from core decompression combined with shelf acetabuloplasty during the early stages of necrosis. Younger children with LCPD may benefit from decompression by fenestration of the femoral head. Experience in adult-onset osteonecrosis and our early experience suggest that some patients may benefit from these adjunctive treatments. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Juvenile Myelomonocytic Leukemia (JMML) (For Parents)

    MedlinePlus

    ... TV, Video Games, and the Internet Juvenile Myelomonocytic Leukemia (JMML) KidsHealth > For Parents > Juvenile Myelomonocytic Leukemia (JMML) ... Treatment Coping en español Leucemia mielomonocítica juvenil About Leukemia Leukemia is a type of cancer that affects ...

  11. School-Related Characteristics of Male Juveniles.

    ERIC Educational Resources Information Center

    Sapp, Gary L.; Abbott, Gypsy A.

    School-related characteristics of 256 male juveniles under the jurisdiction of a Family Court system were examined by perusing court records and conducting individual interviews with the juveniles. Results indicated that most juveniles last attended eighth grade, more than 81% had failed at least once, and more than half had fought frequently at…

  12. Do Juveniles Bully More than Young Offenders?

    ERIC Educational Resources Information Center

    Ireland, Jane L.

    2002-01-01

    Study compares bullying behavior among juvenile and young offenders. Ninety-five male juvenile and 196 male young offenders completed two questionnaires, measuring bullying directly and behaviors indicative of "being bullied" or of "bullying others". Juveniles perceived a higher extent of bullying and reported significantly…

  13. Intensive Reading Instruction in Juvenile Correctional Settings

    ERIC Educational Resources Information Center

    Williams, Jacob L.; Wexler, Jade; Roberts, Greg; Carpenter, Clint

    2011-01-01

    Despite 60 years of evidence linking juvenile illiteracy and delinquency, practitioners and policymakers have been painfully slow in the implementation of evidence-based reading interventions for incarcerated juveniles. We will present the Texas Juvenile Justice Tiered Instructional Model, an evidence-based reading program model created…

  14. The Juvenile Court: Changes and Challenges.

    ERIC Educational Resources Information Center

    Feld, Barry C.

    2000-01-01

    Explores the changes in the juvenile court system, in particular, the juvenile waiver and sentencing laws, as it transformed from a social welfare agency into a type of criminal court system for young offenders. Addresses whether states should create an integrated juvenile and criminal justice system. (CMK)

  15. On the Prevention of Juvenile Crime

    ERIC Educational Resources Information Center

    Lelekov, V. A.; Kosheleva, E. V.

    2008-01-01

    Crimes committed by juveniles are among the most urgent social problems. Juvenile crime is as prevalent as crime itself is, and it has not been solved completely in any society and cannot be solved through law enforcement measures alone. In this article, the authors discuss the dynamics and structure of juvenile crime in Russia and present data…

  16. Guidelines for Juvenile Information Sharing. OJJDP Report

    ERIC Educational Resources Information Center

    Mankey, Jennifer; Baca, Patricia; Rondenell, Stephanie; Webb, Marilyn; McHugh, Denise

    2006-01-01

    The juvenile information sharing (JIS) guidelines were prepared by the Center for Network Development (CND) for the Office of Juvenile Justice and Delinquency Prevention (OJJDP). The guidelines suggest a course of action for key agency and organization stakeholders involved in a state or local effort to implement and sustain juvenile information…

  17. On the Prevention of Juvenile Crime

    ERIC Educational Resources Information Center

    Lelekov, V. A.; Kosheleva, E. V.

    2008-01-01

    Crimes committed by juveniles are among the most urgent social problems. Juvenile crime is as prevalent as crime itself is, and it has not been solved completely in any society and cannot be solved through law enforcement measures alone. In this article, the authors discuss the dynamics and structure of juvenile crime in Russia and present data…

  18. Sex Differences in Attributions of Juvenile Delinquency.

    ERIC Educational Resources Information Center

    Sagatun, Inger J.

    This paper is an application of attribution theory to the processing of juvenile delinquents in an attempt to understand the differential treatment of female and male offenders within the juvenile justice system. The paper explores the attributions of juvenile delinquency both by male and female minors, by male and female parents, and by male and…

  19. Intensive Reading Instruction in Juvenile Correctional Settings

    ERIC Educational Resources Information Center

    Williams, Jacob L.; Wexler, Jade; Roberts, Greg; Carpenter, Clint

    2011-01-01

    Despite 60 years of evidence linking juvenile illiteracy and delinquency, practitioners and policymakers have been painfully slow in the implementation of evidence-based reading interventions for incarcerated juveniles. We will present the Texas Juvenile Justice Tiered Instructional Model, an evidence-based reading program model created…

  20. Disability and Juvenile Delinquency: Issues and Trends

    ERIC Educational Resources Information Center

    Morris, Kimberly A.; Morris, Richard J.

    2006-01-01

    The US juvenile justice system has gone through many changes since its inception in the late 1890s. Even with these changes and more than 100 years of empirical research, there is a paucity of literature published on juvenile delinquents with disabilities. The present article focuses on juvenile delinquents with disabilities, addressing…

  1. Reforming Our Expectations about Juvenile Justice

    ERIC Educational Resources Information Center

    Rodriguez, Pamela F.; Baille, Daphne M.

    2010-01-01

    Typing the term "juvenile justice reform" into a Google[TM] search will result in 60 pages of entries. But what is meant by juvenile justice reform? What does it look like? How will one know when it is achieved? This article defines juvenile justice reform, discusses the principles of effective reform, and describes the practice of…

  2. Effects of the herbicide imazapyr on juvenile Oregon spotted frogs

    USGS Publications Warehouse

    Yahnke, Amy E.; Grue, Christian E.; Hayes, Marc P.; Troiano, Alexandra T.

    2013-01-01

    Conflict between native amphibians and aquatic weed management in the Pacific Northwest is rarely recognized because most native stillwater-breeding amphibian species move upland during summer, when herbicide application to control weeds in aquatic habitats typically occurs. However, aquatic weed management may pose a risk for aquatic species present in wetlands through the summer, such as the Oregon spotted frog (OSF, Rana pretiosa), a state endangered species in Washington. Acute toxicity of herbicides used to control aquatic weeds tends to be low, but the direct effects of herbicide tank mixes on OSFs have remained unexamined. We exposed juvenile OSFs to tank mixes of the herbicide imazapyr, a surfactant, and a marker dye in a 96-h static-renewal test. The tank mix was chosen because of its low toxicity to fish and its effectiveness in aquatic weed control. Concentrations were those associated with low-volume (3.5 L/ha) and high-volume (7.0 L/ha) applications of imazapyr and a clean-water control. Following exposure, frogs were reared for two months in clean water to identify potential latent effects on growth. Endpoints evaluated included feeding behavior, growth, and body and liver condition indices. We recorded no mortalities and found no significant differences for any end point between the herbicide-exposed and clean-water control frogs. The results suggest that imazapyr use in wetland restoration poses a low risk of direct toxic effects on juvenile OSFs.

  3. Effects of the herbicide imazapyr on juvenile Oregon spotted frogs.

    PubMed

    Yahnke, Amy E; Grue, Christian E; Hayes, Marc P; Troiano, Alexandra T

    2013-01-01

    Conflict between native amphibians and aquatic weed management in the Pacific Northwest is rarely recognized because most native stillwater-breeding amphibian species move upland during summer, when herbicide application to control weeds in aquatic habitats typically occurs. However, aquatic weed management may pose a risk for aquatic species present in wetlands through the summer, such as the Oregon spotted frog (OSF, Rana pretiosa), a state endangered species in Washington. Acute toxicity of herbicides used to control aquatic weeds tends to be low, but the direct effects of herbicide tank mixes on OSFs have remained unexamined. We exposed juvenile OSFs to tank mixes of the herbicide imazapyr, a surfactant, and a marker dye in a 96-h static-renewal test. The tank mix was chosen because of its low toxicity to fish and its effectiveness in aquatic weed control. Concentrations were those associated with low-volume (3.5 L/ha) and high-volume (7.0 L/ha) applications of imazapyr and a clean-water control. Following exposure, frogs were reared for two months in clean water to identify potential latent effects on growth. Endpoints evaluated included feeding behavior, growth, and body and liver condition indices. We recorded no mortalities and found no significant differences for any end point between the herbicide-exposed and clean-water control frogs. The results suggest that imazapyr use in wetland restoration poses a low risk of direct toxic effects on juvenile OSFs. Copyright © 2012 SETAC.

  4. Prevention of Serious and Violent Juvenile Offending. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Wasserman, Gail A.; Miller, Laurie S.; Cothern, Lynn

    This bulletin explores the proximal risk factors for juvenile offending, reviews the early developmental precursors to violent offending, and summarizes approaches to prevention. It also discusses components of intervention programs, limitations of single-focus prevention, examples of multi systemic interventions, and limitations of prevention…

  5. Race as a Factor in Juvenile Arrests. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Pope, Carl E.; Snyder, Howard E.

    This bulletin examines the effect of race on police decisions to take juvenile offenders into custody. Analysis of 1997 and 1998 data on 17 states from the Federal Bureau of Investigation's National Incident-Based Reporting System indicates that there is no evidence to support the hypothesis that police are more likely to arrest nonwhite juvenile…

  6. Mobilizing Communities To Prevent Juvenile Crime. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Bownes, Donna; Ingersoll, Sarah

    Through Title V Incentive Grants for Local Delinquency Prevention Programs (Community Prevention Grants), the Office of Juvenile Justice and Delinquency Prevention (OJJDP) allocated $20 million in fiscal year 1997 to states to complement law enforcement and justice system efforts by helping local communities foster strong families and nurture…

  7. Special Education and the Juvenile Justice System. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Burrell, Sue; Warboys, Loren

    This bulletin summarizes provisions of federal law as they pertain to special education and juvenile justice. It discusses provisions of the Individuals with Disabilities Education Act 1997 including: the definition of disability; free appropriate public education; identification, referral, and evaluation; the individualized education program…

  8. Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio).

    PubMed

    Praskova, E; Voslarova, E; Siroka, Z; Plhalova, L; Macova, S; Marsalek, P; Pistekova, V; Svobodova, Z

    2011-01-01

    The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 +/- 9.8 mg/L in juvenile Danio rerio, and 6.11 +/- 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P < 0.05) in embryonic stages compared to the juvenile fish.

  9. Effects of different food doses on cadmium toxicity to Daphnia magna

    SciTech Connect

    Kluettgen, B.; Ratte, H.T. )

    1994-10-01

    Chronic toxicity tests were conducted with Daphnia magma using cadmium concentrations of 0, 0.5, 1, 2, and 5 [mu]g/L Cd with algae doses of 0.8, 4, 8, and 16 [center dot] 10[sup 6] cells/d of Chlorella saccharophila for each. In this way, the authors were able to determine the effects of cadmium on the life-table data of individuals, under different nutritional conditions. The development of juveniles was found to be inhibited by cadmium at low food doses, whereas body length and reproduction were strongly affected at higher food levels. The molting interval of adults and the development rate of embryos proved to be unaffected by cadmium. Cadmium-stressed animals lived longer than did the unstressed controls. The intrinsic rate of natural increase was generally reduced by cadmium, independent of the food dose.

  10. Tungsten toxicity.

    PubMed

    Witten, Mark L; Sheppard, Paul R; Witten, Brandon L

    2012-04-05

    There is emerging evidence that tungsten has toxic health effects. We summarize the recent tungsten toxicity research in this short review. Tungsten is widely used in many commercial and military applications because it has the second highest melting temperature of any element. Consequently, it is important to elucidate the potential health effects of tungsten.

  11. Toxic Encephalopathy

    PubMed Central

    Kim, Jae Woo

    2012-01-01

    This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

  12. Long-wavelength (red) light produces hyperopia in juvenile and adolescent tree shrews.

    PubMed

    Gawne, Timothy J; Ward, Alexander H; Norton, Thomas T

    2017-08-29

    In infant tree shrews, exposure to narrow-band long-wavelength (red) light, that stimulates long-wavelength sensitive cones almost exclusively, slows axial elongation and produces hyperopia. We asked if red light produces hyperopia in juvenile and adolescent animals, ages when plus lenses are ineffective. Animals were raised in fluorescent colony lighting (100-300 lux) until they began 13days of red-light treatment at 11 (n=5, "infant"), 35 (n=5, "juvenile") or 95 (n=5, "adolescent") days of visual experience (DVE). LEDs provided 527-749 lux on the cage floor. To control for the higher red illuminance, a fluorescent control group (n=5) of juvenile (35 DVE) animals was exposed to ∼975 lux. Refractions were measured daily; ocular component dimensions at the start and end of treatment and end of recovery in colony lighting. These groups were compared with normals (n=7). In red light, the refractive state of both juvenile and adolescent animals became significantly (P<0.05) hyperopic: juvenile 3.9±1.0 diopters (D, mean±SEM) vs. normal 0.8±0.1D; adolescent 1.6±0.2D vs. normal 0.4±0.1D. The fluorescent control group refractions (0.6±0.3D) were normal. In red-treated juveniles the vitreous chamber was significantly smaller than normal (P<0.05): juvenile 2.67±0.03mmvs. normal 2.75±0.02mm. The choroid was also significantly thicker: juvenile 77±4μmvs. normal 57±3μm (P<0.05). Although plus lenses do not restrain eye growth in juvenile tree shrews, the red light-induced slowed growth and hyperopia in juvenile and adolescent tree shrews demonstrates that the emmetropization mechanism is still capable of restraining eye growth at these ages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Contrasting movement strategies among juvenile albatrosses and petrels

    NASA Astrophysics Data System (ADS)

    de Grissac, Sophie; Börger, Luca; Guitteaud, Audrey; Weimerskirch, Henri

    2016-05-01

    Animal movement is a fundamental eco-evolutionary process yet the behaviour of juvenile animals is largely unknown for many species, especially for soaring seabirds which can range widely over the oceans at low cost. We present an unprecedented dataset of 98 juvenile albatrosses and petrels (nine species), tracked for the first three months after independence. There was a startling diversity within and among species in the type and scale of post-natal movement strategies, ranging from area-restricted to nomadic patterns. Spatial scales were clustered in three groups that ranged from <3000 km to >6000 km from the natal nest. In seven of the nine species, the orientation of flight paths and other movement statistics showed strong similarities between juveniles and adults, providing evidence for innate orientation abilities. Our results have implications for understanding the development of foraging behaviour in naïve individuals and the evolution of life history traits such as survival, lifespan and breeding strategy.

  14. Contrasting movement strategies among juvenile albatrosses and petrels

    PubMed Central

    de Grissac, Sophie; Börger, Luca; Guitteaud, Audrey; Weimerskirch, Henri

    2016-01-01

    Animal movement is a fundamental eco-evolutionary process yet the behaviour of juvenile animals is largely unknown for many species, especially for soaring seabirds which can range widely over the oceans at low cost. We present an unprecedented dataset of 98 juvenile albatrosses and petrels (nine species), tracked for the first three months after independence. There was a startling diversity within and among species in the type and scale of post-natal movement strategies, ranging from area-restricted to nomadic patterns. Spatial scales were clustered in three groups that ranged from <3000 km to >6000 km from the natal nest. In seven of the nine species, the orientation of flight paths and other movement statistics showed strong similarities between juveniles and adults, providing evidence for innate orientation abilities. Our results have implications for understanding the development of foraging behaviour in naïve individuals and the evolution of life history traits such as survival, lifespan and breeding strategy. PMID:27189182

  15. Contrasting movement strategies among juvenile albatrosses and petrels.

    PubMed

    de Grissac, Sophie; Börger, Luca; Guitteaud, Audrey; Weimerskirch, Henri

    2016-05-18

    Animal movement is a fundamental eco-evolutionary process yet the behaviour of juvenile animals is largely unknown for many species, especially for soaring seabirds which can range widely over the oceans at low cost. We present an unprecedented dataset of 98 juvenile albatrosses and petrels (nine species), tracked for the first three months after independence. There was a startling diversity within and among species in the type and scale of post-natal movement strategies, ranging from area-restricted to nomadic patterns. Spatial scales were clustered in three groups that ranged from <3000 km to >6000 km from the natal nest. In seven of the nine species, the orientation of flight paths and other movement statistics showed strong similarities between juveniles and adults, providing evidence for innate orientation abilities. Our results have implications for understanding the development of foraging behaviour in naïve individuals and the evolution of life history traits such as survival, lifespan and breeding strategy.

  16. Transfer of Juvenile Cases to Criminal Court.

    PubMed

    Lee, Soo Jung; Kraus, Louis J

    2016-01-01

    The first juvenile court was founded in 1899 with the focus on rehabilitation of a juvenile offender as opposed to punishment in adult court. Determining culpability and disposition for adolescents has become a source of much discussion. With serious crimes, juvenile delinquents may be transferred from juvenile court to adult criminal court; this practice became more prevalent in the past century. However, growing knowledge of adolescent development has mitigated the culpability of youth offenders and resulted in judicial decisions influential to juvenile dispositions. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Factors affecting attitudes toward juvenile sex offenders.

    PubMed

    Sahlstrom, Kimberly J; Jeglic, Elizabeth L

    2008-01-01

    This study investigated attitudes toward juvenile sex offenders and factors influencing those attitudes. Additionally, the influences of perpetrator characteristics such as age, gender, and ethnicity on societal attitudes towards intervention requirements were also investigated. Overall, attitudes toward juvenile sex offenders and their treatment amenability were negative. No differences in attitudes toward juvenile sex offenders were found between those who had been victims of sexual abuse and those that had not. Sex offenses committed by juvenile female sex offenders were viewed to be more serious and require more intervention than those committed by juvenile male sex offenders.

  18. Juvenile Justice and Substance Use

    ERIC Educational Resources Information Center

    Chassin, Laurie

    2008-01-01

    Laurie Chassin focuses on the elevated prevalence of substance use disorders among young offenders in the juvenile justice system and on efforts by the justice system to provide treatment for these disorders. She emphasizes the importance of diagnosing and treating these disorders, which are linked both with continued offending and with a broad…

  19. Juvenile Diabetes and Rehabilitation Counseling.

    ERIC Educational Resources Information Center

    Stone, J. Blair; Gregg, Charles H.

    1981-01-01

    Severe complications of diabetes are more likely to occur with the juvenile diabetic and problems of psychosocial adjustment are recurring and difficult. Implications for the rehabilitation counselor are discussed in terms of employment considerations, the effects of complications, genetic counseling, and cooperation with other professionals.…

  20. Juvenile Diabetes and Rehabilitation Counseling.

    ERIC Educational Resources Information Center

    Stone, J. Blair; Gregg, Charles H.

    1981-01-01

    Severe complications of diabetes are more likely to occur with the juvenile diabetic and problems of psychosocial adjustment are recurring and difficult. Implications for the rehabilitation counselor are discussed in terms of employment considerations, the effects of complications, genetic counseling, and cooperation with other professionals.…

  1. Types of Juvenile Sex Offenders

    ERIC Educational Resources Information Center

    Bauman, Sheri

    2002-01-01

    Although juvenile sex offenders (JSOs) account for a significant percentage of sex crimes committed in this country, researchers have only recently begun to study this population. One line of inquiry has been to investigate sub-types of offenders, in order to determine whether different types of offenders have different personality profiles and…

  2. Juvenile Criminals: Who Are They?

    ERIC Educational Resources Information Center

    Antonov, A. I.; Lebed, O. L.

    2005-01-01

    Many adolescents who were born in the late 1970s and 1980s in Russia became juvenile criminals due to the change in the social structure, the proclamation of the values of the comfortable way of life, the institution of property ownership and so forth. Many young people have to help relatives who are in need, and this as well often causes them to…

  3. Treatment of juvenile recurrent parotitis.

    PubMed

    Katz, Philippe; Hartl, Dana M; Guerre, Agnès

    2009-12-01

    Juvenile recurrent parotitis (JRP) can be a debilitating illness in children. Knowing how to recognize and diagnose it for early treatment avoids recurrences that could lead to significant destruction of the glandular parenchyma. This article discusses the various therapeutic modalities proposed in the literature (medical treatment or sialendoscopy) and describes the authors' treatment of choice of combining antibiotics and iodinated oil sialography.

  4. Juvenile Court: Today and Tomorrow.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Discusses whether juveniles who commit criminal law violations should be tried in the same courts as adults. Addresses the issue of transfers that is a legal mechanism used to move youth to criminal court. Considers alternative proposals for handling youth brought to the judicial system and the role of the federal government. (CMK)

  5. [Sex-linked juvenile retinoschisis].

    PubMed

    François, P; Turut, P; Soltysik, C; Hache, J C

    1976-02-01

    About 13 observations of sexe linked juvenile retinoschisis, the authors describe the ophthalmoscopic, fluorographic and functional aspects of the disease whose caracteristics are:--its sexe linked recessive heredity; --its clinical characterestics associating: a microcystic macular degeneration, peripheral retinal lesions, vitreous body alterations, --an electroretinogram of the negative type.

  6. Juvenile Court: Today and Tomorrow.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Discusses whether juveniles who commit criminal law violations should be tried in the same courts as adults. Addresses the issue of transfers that is a legal mechanism used to move youth to criminal court. Considers alternative proposals for handling youth brought to the judicial system and the role of the federal government. (CMK)

  7. Juvenile Justice: A Bibliographic Essay.

    ERIC Educational Resources Information Center

    Kondak, Ann

    1979-01-01

    Provides information on the background and legal framework of the juvenile justice system, the issues that confront it, and the pressures for change, as well as noting some sources of information on the system. Available from American Association of Law Libraries, 53 West Jackson Blvd., Suite 1201, Chicago, Illinois 60604; sc $4.00. (Author/IRT)

  8. Juvenile Criminals: Who Are They?

    ERIC Educational Resources Information Center

    Antonov, A. I.; Lebed, O. L.

    2005-01-01

    Many adolescents who were born in the late 1970s and 1980s in Russia became juvenile criminals due to the change in the social structure, the proclamation of the values of the comfortable way of life, the institution of property ownership and so forth. Many young people have to help relatives who are in need, and this as well often causes them to…

  9. Activity patterns of biotransformation enzymes in juvenile chickens after in ovo dosage of PCB126.

    PubMed

    van den Hurk, Peter; Wiley, Faith E; Lavoie, Emma T; Grasman, Keith A; Bowerman, William W

    2007-09-01

    Little is known about the correlations between biotransformation enzymes in juvenile birds after exposure to environmental toxicants like PCBs. In this study eggs of domestic chicken (Gallus domesticus) were dosed with PCB126 in concentrations of 0.175-0.325 ng/g egg weight. Liver subcellular fractions were analyzed for activities of Phase 1 and Phase 2 biotransformation enzymes 2 and 5 weeks post-hatch. Ethoxyresorufin O-deethylase (EROD) activity was increased in both the 2-week and 5-week samples. Glutathione-S-transferase (GST) activity was increased in the 2-week samples only, but the 5-week samples showed an overall much higher GST activity, probably as a result of a still developing enzyme expression in maturing chickens. The same pattern was seen in the phenol-type UDP-glucuronosyltransferase (UGT) activity of the control animals. The week two samples showed a positive dose-response relationship for the UGT activity, but after 5 weeks this was reversed, possibly caused by inhibition of hydroxylated PCB metabolites. Phenol-type sulfotransferase (SULT) activities were not significantly correlated with time or dose. There was a strong positive regression between the Ah-receptor mediated EROD and UGT activities. The EROD activities were also positively correlated to the GST activities. Most interesting was a negative correlation between the UGT and SULT activities: an inhibited UGT activity appeared to be compensated by an increased SULT activity.

  10. Farm Animals

    MedlinePlus

    ... the Back of a Horse Chickens in the City Diseases Cat-Scratch Disease E. coli Infection Ringworm ... animals when even when they appear healthy and clean. Although it usually doesn’t make farm animals ...

  11. Animal Bites

    MedlinePlus

    Wild animals usually avoid people. They might attack, however, if they feel threatened, are sick, or are protecting their ... or territory. Attacks by pets are more common. Animal bites rarely are life-threatening, but if they ...

  12. Animal Bites

    MedlinePlus

    ... surrounding the bite. Bites from wild animals, especially bats but also skunks, raccoons, coyotes, and foxes, are much more dangerous than those from tame, immunized (against rabies) dogs and cats. The health of the animal ...

  13. Dominance hierarchy formation in juvenile crayfish procambarus clarkii

    PubMed

    Issa; Adamson; Edwards

    1999-12-01

    The formation of social dominance hierarchies was studied in groups of five juvenile crayfish, 1.3-1.8 cm in length. Animals were grouped together in a small, featureless aquarium after having lived in isolation for more than a month. The occurrence of each of four behavior patterns ('attack', 'approach', 'retreat' and 'escape') was recorded for each animal, together with the frequency of encounters and the frequency of wins and losses. The frequencies of wins and losses were used to calculate the relative dominance value of each animal in the group. High levels of fighting developed immediately upon grouping the animals, and a positive feedback relationship between attacking and winning enabled one animal in each group to emerge quickly as the superdominant. If that animal was the largest, it remained as the superdominant; otherwise, it was replaced as superdominant within the first few days by the largest animal. This form of dominance hierarchy, with one superdominant and four subordinates, persisted throughout the duration of the grouping. Fighting declined over the first hour and by 24 h had dropped to low levels. After the first day, approaches were used together with attacks, and retreats replaced escapes. Attack and approach were the behavior patterns displayed most frequently by animals with high dominance values, whereas retreat and escape were performed by animals of low dominance. All these trends continued to develop over the next 2 weeks as the number of agonistic encounters declined to a low level.

  14. Determination of minimum alveolar concentration of sevoflurane in juvenile swine.

    PubMed

    Moeser, Adam J; Blikslager, Anthony T; Swanson, Cliff

    2008-04-01

    Pigs are important animal models in veterinary and medical research and have been widely used in experiments requiring surgical anesthesia. Sevoflurane is an inhalant anesthetic with unique properties that make it an ideal anesthetic for mask induction and anesthesia maintenance. However, there are relatively few studies reporting the anesthetic requirements for sevoflurane in juvenile swine, an age group that is commonly used in research experiments. Therefore the objective of this study was to determine the Minimum Alveolar Concentration (MAC) for sevoflurane in juvenile swine. Sevoflurane anesthesia was induced in six Yorkshire-cross pigs of approximately 9 weeks-of-age and MAC for sevoflurane was determined. The sevoflurane MAC value was determined to be 3.5+/-0.1% which is notably higher than values reported in the literature for pigs. This discrepancy in MAC values may represent changes in anesthetic requirements between different age groups of pigs and differences in the type of stimulus used to determine MAC.

  15. Mortality, bioaccumulation and physiological responses in juvenile freshwater mussels (Lampsilis siliquoidea) chronically exposed to copper.

    PubMed

    Jorge, Marianna B; Loro, Vania L; Bianchini, Adalto; Wood, Chris M; Gillis, Patricia L

    2013-01-15

    Several studies have indicated that the early life stages of freshwater mussels are among the most sensitive aquatic organisms to inorganic chemicals, including copper. However, little is known about the toxic mode of action and sub-lethal effects of copper exposure in this group of imperiled animals. In this study, the physiological effects of long-term copper exposure (survival, growth, copper bioaccumulation, whole-body ion content, oxygen consumption, filtration rate, ATPase activities, and biomarkers of oxidative stress) were evaluated in juvenile (6 month old) mussels (Lampsilis siliquoidea). The mussels' recovery capacity and their ability to withstand further acute copper challenge were also evaluated in secondary experiments following the 28 day exposure by assessing survival, copper bioaccumulation and whole-body ion content. Mussels chronically exposed to 2 and 12 μg Cu/L showed significantly higher mortality than those held under control conditions (mortality 20.9, 69.9 and 12.5%, respectively), indicating that juvenile L. siliquoidea is underprotected by the U.S. Environmental Protection Agency (USEPA) biotic ligand model (BLM)-derived chronic water quality criteria (WQC) (2.18 μg Cu/L) and the hardness-derived USEPA WQC (12.16 μg Cu/L). Soft tissue copper burden increased equally for both copper exposures, suggesting that chronic toxicity is not associated with copper bioaccumulation. Several physiological disturbances were also observed during chronic copper exposure. Most relevant was a decrease in whole-body sodium content paralleled by an inhibition of Na(+) K(+)-ATPase activity, indicating a metal-induced ionoregulatory disturbance. Filtration and oxygen consumption rates were also affected. Redox parameters (reactive oxygen production, antioxidant capacity against peroxyl radicals, glutathione-S-transferase (GST) activity, and glutathione (GSH) concentration) did not show clear responses, but membrane damage as lipid peroxidation (LPO) was

  16. Antipredator vigilance of juvenile and adult thirteen-lined ground squirrels and the role of nutritional need.

    PubMed

    Arenz; Leger

    2000-03-01

    Juvenile thirteen-lined ground squirrels, Spermophilus tridecemlineatus, are less vigilant (i.e. they spend less time visually scanning the environment) than adults. To determine whether nutritional need was a potential cause of this difference, we supplemented two groups of free-ranging juveniles during the predispersal stage, while juveniles were still near and around the natal burrows. The high-energy food group (HEF: 11 squirrels) received peanut butter and oats while the low-energy food group (LEF: seven squirrels) received lettuce. Adults (14 squirrels) were also supplemented, but due to their greater home range sizes, it was not feasible to classify them as either HEF or LEF. To evaluate the effect of supplementation on antipredator vigilance, the behavioural act of visually scanning for predators, we videotaped individuals while they were foraging above ground during 5-min observation periods. Each squirrel was observed and weighed during three time periods over 23 days. From the videotape, we extracted measures of time spent vigilant, locomoting and foraging. All three categories of squirrels gained mass over the study period, but the HEF juveniles rapidly exceeded that of the LEF juveniles. Early in the study, LEF and HEF juveniles did not significantly differ in either body mass or time budgets, and, initially, both juvenile groups were similar to adults in the amount of time devoted to vigilance. Later in the study, the behaviour of HEF juveniles closely resembled that of adults (increased time devoted to vigilance and decreased time devoted to foraging), while LEF juveniles decreased vigilance and increased their foraging time. This study indicates that for thirteen-lined ground squirrels the lower vigilance of juveniles is due, at least in part, to the greater nutritional needs of young animals with consequent increases in foraging, which is largely incompatible with vigilance. Copyright 2000 The Association for the Study of Animal Behaviour.

  17. Juvenile Crime, Juvenile Justice. Panel on Juvenile Crime: Prevention, Treatment, and Control.

    ERIC Educational Resources Information Center

    McCord, Joan, Ed.; Widom, Cathy Spatz, Ed.; Crowell, Nancy A., Ed.

    This book discusses patterns and trends in crimes committed by children and adolescents, analyzing youth crime as a subset of general crime and studying the impact of race and gender. It evaluates different approaches to forecasting future crime rates. Data come from a national panel that examined what is known about juvenile crime and its…

  18. Juvenile Crime, Juvenile Justice. Panel on Juvenile Crime: Prevention, Treatment, and Control.

    ERIC Educational Resources Information Center

    McCord, Joan, Ed.; Widom, Cathy Spatz, Ed.; Crowell, Nancy A., Ed.

    This book discusses patterns and trends in crimes committed by children and adolescents, analyzing youth crime as a subset of general crime and studying the impact of race and gender. It evaluates different approaches to forecasting future crime rates. Data come from a national panel that examined what is known about juvenile crime and its…

  19. A Practical Approach to Juvenile Dermatomyositis and Juvenile Scleroderma.

    PubMed

    McCann, Liza J; Pain, Clare E

    2016-02-01

    Juvenile dermatomyositis and juvenile scleroderma are rare multisystem autoimmune disorders. Although they share some pathognomonic hallmarks with adult onset myositis or scleroderma, there are significant differences in presentation, characteristics and associated features when the diseases present in childhood. In view of this, and the rarity of the conditions, it is important for care to be led by teams with expertise in pediatric rheumatology conditions. Prognosis has improved significantly in the West; likely due to early diagnosis and aggressive treatment with immunosuppressive medications. However, this trend is not replicated in the developing world. Early recognition of these diseases is crucial to achieve rapid and sustained remission and prevent disease or medication associated complications. This article aims to provide a practical overview for recognition, diagnosis and treatment of these conditions.

  20. Entry, Descent, Landing Animation (Animation)

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for Entry, Descent, Landing animation

    This animation illustrates the path the Stardust return capsule will follow once it enters Earth's atmosphere.