Science.gov

Sample records for adverse effects toxicology

  1. Pharmacology, Toxicology, and Adverse Effects of Synthetic Cannabinoid Drugs.

    PubMed

    Gurney, S M R; Scott, K S; Kacinko, S L; Presley, B C; Logan, B K

    2014-01-01

    Synthetic cannabinoid drugs have become an established part of the recreational drug landscape in the United States and internationally. These drugs are manufactured in clandestine laboratories internationally and distributed in the United States in smoking mixtures, use of which produces effects very similar to use of marijuana. The adverse-effect profile of the drugs has not been studied in humans and infrequently in animal models, so much of the information about their toxicity comes from emergency department and treatment reports and forensic case studies. This review considers the discovery and characterization of the endocannabinoid system, approaches to receptor-binding studies of various synthetic cannabinoids from the first wave of naphthoylindoles (e.g., JWH-018) to the emerging adamantoylindole drugs (e.g., AKB-48), and their analogs, to evaluate the potential activity of drugs in this class. Currently employed approaches to assessing functional activity of the drugs using in vitro and in vivo models is also described, and comparisons made to the effects of THC. The physiological effects of activation of the endocannabinoid system in humans are reviewed, and the physiological effects of cannabinoid use are described. Case reports of adverse events including emergency department admissions, mental health admissions, and clinical and forensic case reports are presented in detail and discussed to summarize the current state of knowledge of adverse effects, both clinical and forensic in humans, including effects on driving ability, and tissue injury and death. The greatest weight is accorded to those reports that include toxicological confirmation of use. Finally, we discuss the current status of attempts to schedule and control the distribution of synthetic cannabinoids and the relevance of receptor binding and functional activity in this context. There is growing toxicological and pharmacological evidence of impairment, psychosis, tissue injury, and

  2. Identification and Characterization of Adverse Effects in 21st Century Toxicology

    EPA Science Inventory

    The ILSI Health and Environmental Sciences Institute Project Committee on Distinguishing Adverse from Non-Adverse / Adaptive Effects held a workshop in May 2011 to discuss approaches to identifying adverse effects in the context of the 2007 NRC committee report titled “Toxicity T...

  3. [Development and application of adverse outcome pathway in toxicology research].

    PubMed

    Wang, Yanhua; Duan, Huawei

    2015-12-01

    Adverse outcome pathway (AOP) was a conceptual construct that integrated existing knowledge concerning the pathway of causal linkages between a molecular initiating event (MIE) and a final adverse effect at individual or population levels. The AOP methodology could be used as a basis for effects extrapolation and was an approach towards providing a framework for collecting and evaluating relevant chemical, biological and toxicological information. The framework would play an important role in risk assessment. We reviewed the concept of AOP, the development and assessment of the framework and the established models in toxicology researches. And the prospects and challenges of its application in toxicology were also introduced. PMID:26887310

  4. The relationship of maternal and fetal toxicity in developmental toxicology bioassays with notes on the biological significance of the "no observed adverse effect level".

    EPA Science Inventory

    Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects and include dose levels that induce maternal toxicity. The work reported here was undertaken to evaluate the relationship of maternal and fetal toxicity. It co...

  5. Adverse outcome pathways (AOPs): A framework to support predictive toxicology

    EPA Science Inventory

    High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

  6. The adverse outcome pathway concept: a pragmatic tool in toxicology.

    PubMed

    Vinken, Mathieu

    2013-10-01

    Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies. PMID:23978457

  7. Adverse outcome pathways (AOPs): A framework to support predictive toxicology (presentation)

    EPA Science Inventory

    High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

  8. Advancing adverse outcome pathways for integrated toxicology and regulatory applications

    EPA Science Inventory

    Recent regulatory efforts in many countries have focused on a toxicological pathway-based vision for human health assessments relying on in vitro systems and predictive models to generate the toxicological data needed to evaluate chemical hazard. A pathway-based vision is equally...

  9. Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes

    PubMed Central

    Leung, Maxwell C.K.; Phuong, Jimmy; Baker, Nancy C.; Sipes, Nisha S.; Klinefelter, Gary R.; Martin, Matthew T.; McLaurin, Keith W.; Setzer, R. Woodrow; Darney, Sally Perreault; Judson, Richard S.; Knudsen, Thomas B.

    2015-01-01

    Background: Trends in male reproductive health have been reported for increased rates of testicular germ cell tumors, low semen quality, cryptorchidism, and hypospadias, which have been associated with prenatal environmental chemical exposure based on human and animal studies. Objective: In the present study we aimed to identify significant correlations between environmental chemicals, molecular targets, and adverse outcomes across a broad chemical landscape with emphasis on developmental toxicity of the male reproductive system. Methods: We used U.S. EPA’s animal study database (ToxRefDB) and a comprehensive literature analysis to identify 774 chemicals that have been evaluated for adverse effects on male reproductive parameters, and then used U.S. EPA’s in vitro high-throughput screening (HTS) database (ToxCastDB) to profile their bioactivity across approximately 800 molecular and cellular features. Results: A phenotypic hierarchy of testicular atrophy, sperm effects, tumors, and malformations, a composite resembling the human testicular dysgenesis syndrome (TDS) hypothesis, was observed in 281 chemicals. A subset of 54 chemicals with male developmental consequences had in vitro bioactivity on molecular targets that could be condensed into 156 gene annotations in a bipartite network. Conclusion: Computational modeling of available in vivo and in vitro data for chemicals that produce adverse effects on male reproductive end points revealed a phenotypic hierarchy across animal studies consistent with the human TDS hypothesis. We confirmed the known role of estrogen and androgen signaling pathways in rodent TDS, and importantly, broadened the list of molecular targets to include retinoic acid signaling, vascular remodeling proteins, G-protein coupled receptors (GPCRs), and cytochrome P450s. Citation: Leung MC, Phuong J, Baker NC, Sipes NS, Klinefelter GR, Martin MT, McLaurin KW, Setzer RW, Darney SP, Judson RS, Knudsen TB. 2016. Systems toxicology of male

  10. Towards the regulation of aerosol emissions by their potential health impact: Assessing adverse effects of aerosols from wood combustion and ship diesel engine emissions by combining comprehensive data on the chemical composition and their toxicological effects on human lung cells

    NASA Astrophysics Data System (ADS)

    Zimmermann, R.; Streibel, T.; Dittmar, G.; Kanashova, T.; Buters, J.; Öder, S.; Paur, H. R.; Dilger, M.; Weiss, C.; Harndorf, H.; Stengel, B.; Hirvonen, M. R.; Jokiniemi, J.; Hiller, K.; Sapcariu, S.; Sippula, O.; Orasche, J.; Müller, L.; Rheda, A.; Passig, J.; Radischat, C.; Czech, H.; Tiita, P.; Jalava, P.; Kasurinen, S.; Schwemer, T.; Yli-Prilä, P.; Tissari, J.; Lamberg, H.; Schnelle-Kreis, J.

    2014-12-01

    Ship engine emissions are important regarding lung and cardiovascular diseases in coastal regions worldwide. Bio mass burning is made responsible for adverse health effects in many cities and rural regions. The Virtual Helmholtz Institute-HICE (www.hice-vi.eu) addresses chemical & physical properties and health effects of anthropogenic combustion emissions. Typical lung cell responses to combustion aerosols include inflammation and apoptosis, but a molecular link with the specific chemical composition in particular of ship emissions has not been established. Through an air-liquid interface exposure system (ALI), we exposed human lung cells at-site to exhaust fumes from a ship engine running on common heavy fuel oil (HFO) and cleaner-burning diesel fuel (DF) as well as to emissions of wood combustion compliances. A special field deployable ALI-exposition system and a mobile S2-biological laboratory were developed for this study. Human alveolar basal epithelial cells (A549 etc.) are ALI-exposed to fresh, diluted (1:40-1:100) combustion aerosols and subsequently were toxicologically and molecular-biologically characterized. Advanced chemical analyses of the exhaust aerosols were combined with transcriptional, proteomic and metabolomic profiling to characterise the cellular responses. The HFO ship emissions contained high concentrations of toxic compounds (transition metals, organic toxicants) and particle masses. The cellular responses included inflammation and oxidative stress. Surprisingly, the DF ship emissions, which predominantly contain rather "pure" carbonaceous soot and much less known toxicants, induced significantly broader biological effects, affecting essential cellular pathways (e.g., mitochondrial function and intracellular transport). Therefore the use of distillate fuels for shipping (this is the current emission reduction strategy of the IMO) appears insufficient for diminishing health effects. The study suggests rather reducing the particle emissions

  11. Developmental Toxicology##

    EPA Science Inventory

    Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...

  12. Biologics in dermatology: adverse effects.

    PubMed

    Sehgal, Virendra N; Pandhi, Deepika; Khurana, Ananta

    2015-12-01

    Biologics are a group of drugs that precisely affect certain specific steps in the immune response and are an extremely useful group when used in an appropriate setting. However, their use can often be a double-edged sword. Careful patient selection and thorough knowledge of adverse effects is a key to their successful use in various disorders. The initial enthusiasm has gradually given way to a more cautious approach wherein a balance is sought between clinical usefulness and expected side effects. The adverse effects of the biologics most commonly used in dermatology have been carefully listed for ready reference. The plausible causes of the adverse reactions are succinctly outlined along with their incriminating factor(s). Besides, in brief, the attention has been focused on their management. The content should provide an essential didactic content for educating the practitioner. PMID:26147909

  13. Cardiovascular adverse effects of phenytoin.

    PubMed

    Guldiken, B; Rémi, J; Noachtar, Soheyl

    2016-05-01

    Phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus. One of its main advantages over benzodiazepines is the less sedative effect. However, the possibility of cardiovascular adverse effects with the intravenous use of phenytoin cause a reluctance to its usage, and this has lead to a search for safer anticonvulsant drugs. In this study, we aimed to review the studies which evaluated the safety of phenytoin with respect to cardiovascular adverse effects. The original clinical trials and case reports listed in PUBMED in English language between the years of 1946-2014 were evaluated. As the key words, "phenytoin, diphenylhydantoin, epilepsy, seizure, cardiac toxicity, asystole, arrhythmia, respiratory arrest, hypotension, death" were used. Thirty-two clinical trials and ten case reports were identified. In the case reports, a rapid infusion rate (>50 mg/min) of phenytoin appeared as the major cause of increased mortality. In contrast, no serious cardiovascular adverse effects leading to death were met in the clinical trials which applied the recommended infusion rate and dosages. An infusion rate of 50 mg/min was reported to be safe for young patients. For old patients and patients with a cardiovascular co-morbidity, a slower infusion rate was recommended with a careful follow-up of heart rhythm and blood pressure. No cardiovascular adverse effect was reported in oral phenytoin overdoses except one case with a very high serum phenytoin level and hypoalbuminemia. Phenytoin is an effective and well tolerated drug in the treatment of epilepsy. Intravenous phenytoin is safe when given at recommended infusion rates and doses. PMID:26645393

  14. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects. PMID:27357302

  15. Adverse Effects of Electroconvulsive Therapy.

    PubMed

    Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

    2016-09-01

    Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. PMID:27514303

  16. Toxicological Effects of Fullerenes on Caenorhabditis elegans

    NASA Astrophysics Data System (ADS)

    Schomaker, Justin; Snook, Renee; Howell, Carina

    2014-03-01

    The nematode species Caenorhabditis elegans is a useful genetic model organism due to its simplicity and the substantial molecular, genetic, and developmental knowledge about the species. In this study, this species was used to test the toxicological effects of C60 fullerene nanoparticles. In previous studies using rats, a solution of C60 fullerenes in olive oil proved to extend the life of the subjects. The purpose of this experiment was to subject C. elegans to varying concentrations of C60 fullerenes and observe their toxicological effects. Initial findings indicate a link between fullerene exposure and enlargement of the vulva as well as the formation of a small nodule at the base of the tail in some individuals. While the fullerenes are not lethally toxic in C. elegans, results will be presented that pertain to changes in life span and progeny of the nematodes exposed to varying concentrations of fullerenes as well as the mechanisms of toxicity. High magnification imaging via SEM and/or AFM will be used to characterize the fullerene nanoparticles. Testing the toxicity of fullerenes in a wide variety of organisms will lead to a more complete understanding of the effects of fullerenes on living organisms to ultimately understand their effects in humans. This work was supported by National Science Foundation grants DUE-1058829, DMR-0923047, DUE-0806660 and Lock Haven FPDC grants.

  17. Adverse effects of plasma transfusion.

    PubMed

    Pandey, Suchitra; Vyas, Girish N

    2012-05-01

    Plasma utilization has increased over the past two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions after infusion of fresh-frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: 1) transfusion-related acute lung injury, 2) transfusion-associated circulatory overload, and 3) allergic and/or anaphylactic reactions. Other less common risks include 1) transmission of infections, 2) febrile nonhemolytic transfusion reactions, 3) red blood cell alloimmunization, and 4) hemolytic transfusion reactions. The effects of pathogen inactivation or reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice. PMID:22578374

  18. Developmental exposure to a mixture of two mechanistically distinct antiandrogens results in cumulative adverse reproductive effects in adult male rats

    EPA Science Inventory

    Typically, toxicological studies have focused on the adverse effects from exposure to single chemicals. However, endocrine disrupting chemicals (EDCs) are detected in the environment as mixtures. Empirical evidence suggests that mixtures of EDCs with the same mechanism of action...

  19. Adverse Outcome Pathways-Organizing Toxicological Information to Improve Decision Making.

    PubMed

    Edwards, Stephen W; Tan, Yu-Mei; Villeneuve, Daniel L; Meek, M E; McQueen, Charlene A

    2016-01-01

    The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High-throughput screening commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP) concept has emerged as a framework for connecting high-throughput toxicity testing (HTT) and other results to potential impacts on human and wildlife populations. As a result of international efforts, the AOP development process is now well-defined and efforts are underway to broaden the participation through outreach and training. One key principle is that AOPs represent the chemical-agnostic portions of pathways to increase the generalizability of their application from early key events to overt toxicity. The closely related mode of action framework extends the AOP as needed when evaluating the potential risk of a specific chemical. This in turn enables integrated approaches to testing and assessment (IATA), which incorporate results of assays at various levels of biologic organization such as in silico; HTT; chemical-specific aspects including absorption, distribution, metabolism, and excretion (ADME); and an AOP describing the biologic basis of toxicity. Thus, it is envisaged that provision of limited information regarding both the AOP for critical effects and the ADME for any chemical associated with any adverse outcome would allow for the development of IATA and permit more detailed AOP and ADME research, where higher precision is needed based on the decision context. PMID:26537250

  20. Aviation combustion toxicology: an overview.

    PubMed

    Chaturvedi, Arvind K

    2010-01-01

    Aviation combustion toxicology is a subspecialty of the field of aerospace toxicology, which is composed of aerospace and toxicology. The term aerospace, that is, the environment extending above and beyond the surface of the Earth, is also used to represent the combined fields of aeronautics and astronautics. Aviation is another term interchangeably used with aerospace and aeronautics and is explained as the science and art of operating powered aircraft. Toxicology deals with the adverse effects of substances on living organisms. Although toxicology borrows knowledge from biology, chemistry, immunology, pathology, physiology, and public health, the most closely related field to toxicology is pharmacology. Economic toxicology, environmental toxicology, and forensic toxicology, including combustion toxicology, are the three main branches of toxicology. In this overview, a literature search for the period of 1960-2007 was performed and information related to aviation combustion toxicology collected. The overview included introduction; combustion, fire, and smoke; smoke gas toxicity; aircraft material testing; fire gases and their interactive effects; result interpretation; carboxyhemoglobin and blood cyanide ion levels; pyrolytic products of aircraft engine oils, fluids, and lubricants; and references. This review is anticipated to be an informative resource for aviation combustion toxicology and fire-related casualties. PMID:20109297

  1. Toxicology

    NASA Technical Reports Server (NTRS)

    Macewen, J. W.

    1973-01-01

    Oxygen toxicity is examined, including the effects of oxygen partial pressure variations on toxicity and oxygen effects on ozone and nitrogen dioxide toxicity. Toxicity of fuels and oxidizers, such as hydrazines, are reported. Carbon monoxide, spacecraft threshold limit values, emergency exposure limits, spacecraft contaminants, and water quality standards for space missions are briefly summarized.

  2. Environmental toxicology and health effects associated with dinitrotoluene exposure.

    PubMed

    Tchounwou, Paul B; Newsome, Cecilia; Glass, Konsuela; Centeno, Jose A; Leszczynski, Jerzy; Bryant, Joseph; Okoh, Joseph; Ishaque, Ali; Brower, Marius

    2003-01-01

    Dinitrotoluenes (DNTs) are nitroaromatic compounds appearing as pale yellow crystalline solids at room temperature. Dinitrotoluenes exist as a mixture of 2 to 6 isomers, with 2,4-DNT, and 2,6-DNT being the most significant. About 500 persons are estimated to be potentially exposed yearly to 2,4-DNT and 2,6-DNT during the production of munitions and explosives. The main route of human exposure at ammunition facilities is inhalation, but dermal contact and inadvertent ingestion can also be substantial. In factory workers, exposure to DNTs has been linked to many adverse health effects, including cyanosis, vertigo, headache, metallic taste, dyspnea, weakness and lassitude, loss of appetite, nausea, and vomiting. Other symptoms including pain or parasthesia in extremities, abdominal discomfort, tremors, paralysis, chest pain, and unconsciousness have also been reported. The primary targets of DNT toxicity are the hematopoietic system (pallor, cyanosis, anemia, and leukocytosis), the cardiovascular system (ischemic heart disease), the nervous system (muscular weakness, headache, dizziness, nausea, insomnia, and tingling pains in the extremities) and the reproductive system (reduction of sperm counts, alteration of sperm morphology, and aspermatogenesis). An association between DNT exposure and increased risk of hepatocellular carcinomas and subcutaneous tumors in rats, as well as renal tumors in mice, has been established. Epidemiologic studies of DNT toxicity have been limited to small groups of workers who had been occupationally exposed at various ammunitions production facilities. Clearly defining the health effects of DNTs with a high degree of confidence has therefore been difficult because of the multigenic nature of occupational exposure. In an attempt to update the toxicologic profile of the DNTs, we hereby provide a critical review of the environmental and toxicologic pathology of DNTs, with a special emphasis on their potential implications for public health

  3. TOXICOLOGY OF MALE REPRODUCTIVE DEVELOPMENT: PROFILING 774 CHEMICALS FOR MOLECULAR TARGETS AND ADVERSE OUTCOMES (SOT)

    EPA Science Inventory

    Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male...

  4. Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes

    EPA Science Inventory

    Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male...

  5. Misuse of the Naranjo Adverse Drug Reaction Probability Scale in toxicology

    PubMed Central

    Seger, Donna; BARKER, Kimberly; McNAUGHTON, Candace D.

    2014-01-01

    Context When an adverse event occurs in an overdose patient, it may be difficult to determine whether the event was caused by the ingested drug or by medical therapy. Naranjo and colleagues developed a probability scale, the Naranjo Adverse Drug Reaction Probability Scale (Naranjo Scale), to assess the probability that a drug administered in therapeutic doses caused an adverse event thereby classifying the event as an adverse drug reaction (ADR). Although Naranjo et al. specifically excluded the application of this scale to adverse events in overdose patients, case reports demonstrate that authors continue to apply the Naranjo Scale to events in these patients. Objective The World Health Organization defines an ADR as occurring only when drugs are administered in therapeutic doses. Yet ADRs continue to be reported in overdose patients. We sought to examine the use of the Naranjo scale in case reports of overdose patients to assess the potential consequences of that application. Methods A Medline search via PubMed without language limits, through September 2012, using the search terms “Naranjo” and “overdose” or “poisoning” yielded 146 publications. Additional searches were performed to find articles with keywords of the Naranjo Scale development, current applications and validity of application in specific populations such as critically ill and overdose patients. Results From the 146 publications, we identified 17 case reports or series of overdose patients in which the Naranjo Scale was applied to a clinical complication to support a causal relationship between an administered drug and the clinical complication and thereby classify the clinical complication as an ADR. We also identified a recent publication in which the Naranjo Scale was applied to a new treatment modality (lipid emulsion) that is currently administered to overdose patients. Conclusion Adverse events that occur in overdose patients are excluded from the definition of ADR. Yet in case

  6. [Acute adverse effects of dialysis].

    PubMed

    Opatrný, K

    2003-02-01

    Adverse reactions to dialyzers are a not very frequent, but because of the serious, sometimes fatal course, a dreaded complication of haemodialysis treatment. Most important among these reactions are hypersensitive reactions (anaphylactoid, reaction type A to dialyzer), which develop as a rule within the 10th minute of the procedure, and the reaction caused by the action of perfluorohydrocarbon which develop hours after onset or even completion of haemodialysis. Explanation of the development of hypersensitive reactions (HSR) by complement activation and formation of anaphylatoxins C3a and C5a during contact of blood with the bioincompatible dialysis membrane has been abandoned. Evidence of the etiological role of ethylene oxide (ETO) in the development of HSR influenced the selection of materials for the production of dialyzers and sterilization during manufacture, it emphasized the importance of rinsing of the dialyzer in the dialysis centre and led to the wide application of alternative methods of sterilization by gamma radiation and steam. HSR may be also caused by overproduction of bradykinin and inhibition of its degradation or degradation of its metabolites. Excessive bradykinin production caused by dialysis membranes with a negative charge is potentiated e.g. by a lower pH and increased plasma dilution in the initial stage of haemodialysis. Inhibition of bradykinin degradation develops during treatment with angiotensin converting enzyme inhibitors (ACEI). In prevention of HSR associated with bradykinin in addition to elimination of a combination of a negatively charged dialysis membrane and ACEI treatment a part is played also by rinsing of the dialyzer before haemodialysis with a bicarbonate solution and the modification of the membrane surface (implemented by the manufacturer) which reduces its negative charge. The first reaction to the dialyzer in conjunction with perfluorohydrocarbon (PF-5070), used in production of some dialyzers for testing the

  7. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

    Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, β-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use. PMID:24872675

  8. Aloe vera: A review of toxicity and adverse clinical effects.

    PubMed

    Guo, Xiaoqing; Mei, Nan

    2016-04-01

    The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects of Aloe vera whole leaf extract, gel, and latex. PMID:26986231

  9. Perspective on Lithotripsy Adverse Effects

    NASA Astrophysics Data System (ADS)

    Knoll, Thomas; Wendt-Nordahl, Gunnar

    2008-09-01

    Shock wave lithotripsy (SWL) is an effective and without any doubt the least invasive procedure to treat upper urinary tract calculi. Acute complications are rarely reported and do not require specific treatment in most cases. However, one should be aware that energy levels sufficient for stone breakage are capable of damaging tissue as well, and significant hematoma—not only in the kidney but as well in surrounding organs—has been observed. Furthermore, only little is known about the long-term effects of SWL. Some authors have reported an increased incidence of hypertension and possibly also diabetes mellitus. Such chronic diseases—if indeed related to prior SWL—may be a late result of acute SWL-related trauma but the discussion on the underlying pathogenesis is controversial. Many factors have to be considered, such as the natural history of recurrent stone formers, technical principles of SWL, and differences in treatment protocols. Promising studies are currently underway to optimize stone breakage while limiting potential collateral damage. With this progress, SWL remains a safe treatment option for most urinary calculi.

  10. Quantification of toxicological effects for dichloromethane. Draft report (Final)

    SciTech Connect

    Not Available

    1990-04-01

    The source documents for background information used to develop the report on the quantification of toxicological effects for dichloromethane are the health assessment document (HAD) for dichloromethane and a subsequent addendum to the HAD (U.S. EPA, 1985b). In addition, some references published since 1985 are discussed. To summarize the results of the quantification of toxicological effects, a One-day Health Advisory of 10,000 ug/L for a 10-kg child was calculated, based on an acute oral study in rats reported by Kimura et al. (1971). No suitable data for the derivation of a Ten-day Health Advisory were found in the available literature.

  11. Toxicological effects of nanoparticles from photocopiers

    NASA Astrophysics Data System (ADS)

    Khatri, Madhu

    , potential in-vitro cytotoxicity and induction of cytokines of the collected NP generated during photocopying was studied. Furthermore, airborne fine PM collected from copy center was evaluated for their capability to induce in-vitro cytotoxicity and induction of cytokines. The research addresses one major knowledge gap between possible adverse effects on human health caused due to NP exposure. Additionally, this would help develop useful biomarkers for such exposures. These biomarkers could then assists in early detection of such effects and can potentially be used to assess human health risk from exposures to such NPs and device effective interventions if needed.

  12. Adverse Effects of Psychotropic Medications on Sleep.

    PubMed

    Doghramji, Karl; Jangro, William C

    2016-09-01

    Psychotropic medications such as antidepressants, antipsychotics, stimulants, and benzodiazepines are widely prescribed. Most of these medications are thought to exert their effects through modulation of various monoamines as well as interactions with receptors such as histamine and muscarinic cholinergic receptors. Through these interactions, psychotropics can also have a significant impact on sleep physiology, resulting in both beneficial and adverse effects on sleep. PMID:27514301

  13. Adverse effects of fillers and their histopathology.

    PubMed

    Haneke, Eckart

    2014-12-01

    Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options. PMID:25536126

  14. 77 FR 72858 - Toxicological Review of Inorganic Arsenic (Cancer and Noncancer Effects): In Support of Summary...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-06

    ... AGENCY Toxicological Review of Inorganic Arsenic (Cancer and Noncancer Effects): In Support of Summary... toxicological review of inorganic arsenic (cancer and noncancer effects) in support of the IRIS program. SUMMARY... toxicological review of chronic exposure to iAs (cancer and noncancer effects), which EPA intends to post in...

  15. Biomarkers in Computational Toxicology

    EPA Science Inventory

    Biomarkers are a means to evaluate chemical exposure and/or the subsequent impacts on toxicity pathways that lead to adverse health outcomes. Computational toxicology can integrate biomarker data with knowledge of exposure, chemistry, biology, pharmacokinetics, toxicology, and e...

  16. Lewisite: its chemistry, toxicology, and biological effects.

    PubMed

    Goldman, M; Dacre, J C

    1989-01-01

    routes for inducing teratogenicity is also problematical. Recently, Lewisite has been shown not to be teratogenic in either rats or rabbits. A monograph on arsenic, succinctly states that "no human epidemiological investigations have been conducted on the carcinogenicity of organic arsenic compounds" (WHO 1981). Indeed, the lack of such evidence eminating from epidemiological sources or from animal studies is resounding. At present, there is no evidence that Lewisite is either carcinogenic, mutagenic or teratogenic. A review of toxicological studies of other organic arsenicals has produced no evidence that they might be carcinogenic, mutagenic or teratogenic. PMID:2692088

  17. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence. PMID:23850228

  18. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors. PMID:26070758

  19. Environmental Perchlorate Exposure: Potential Adverse Thyroid Effects

    PubMed Central

    Leung, Angela M.; Pearce, Elizabeth N.; Braverman, Lewis E.

    2014-01-01

    Purpose of review This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Recent findings Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant IQ in groups who would be particularly susceptible to perchlorate effects. An update regarding the recent proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. Summary The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants. PMID:25106002

  20. Toxicology and cellular effect of manufactured nanomaterials

    DOEpatents

    Chen, Fanqing

    2014-07-22

    The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

  1. [Adverse drug effects in the community pharmacy].

    PubMed

    Arnet, Isabelle; Seidling, Hanna M; Hersberger, Kurt E

    2015-12-01

    Community pharmacists represent an important pillar for the identification and the reporting of adverse drug effects (ADE}. Thanks to their broad view on the pharmacotherapy, over-the-counter medication included, they contribute greatly to the improvement of drug safety. In principle, the community pharmacy will face three groups of ADE which require specific attention. This article deals with these specific ADE groups and presents some illustrative examples from daily practice. Furthermore, we suggest some solutions to identify potential relevant interactions - including herbal-drug interactions - and give tips for daily practice, along with some often overseen cutaneous ADE. PMID:26654812

  2. Fingolimod-Associated Peripheral Vascular Adverse Effects.

    PubMed

    Russo, Margherita; Guarneri, Claudio; Mazzon, Emanuela; Sessa, Edoardo; Bramanti, Placido; Calabrò, Rocco Salvatore

    2015-10-01

    Fingolimod is the first oral disease-modifying drug approved for the treatment of multiple sclerosis. The drug is usually well tolerated, and common adverse effects include bradycardia, headache, influenza, diarrhea, back pain, increased liver enzyme levels, and cough. Fingolimod is thought to provide therapeutic benefit by preventing normal lymphocyte egress from lymphoid tissues, thus reducing the infiltration of autoaggressive lymphocytes into the central nervous system. However, because the drug acts on different sphingosine-1-phosphate receptors, it may induce several biological effects by influencing endothelial cell-cell adhesion, angiogenesis, vascular development, and cardiovascular function. We describe a patient with multiple sclerosis who, after 3 weeks of fingolimod administration, developed purplish blotches over the dorsal surface of the distal phalanges of the second and fifth digits and the middle phalanx of the fourth ray, itching, and edema on his left hand, without other evident clinical manifestations. When fingolimod therapy was discontinued, the clinical picture regressed within a few days but reappeared after a rechallenge test. Physicians should be aware of unexpected peripheral vascular adverse effects due to fingolimod use, and patients with vascular-based acropathies should be carefully screened and monitored when taking this drug. PMID:26349949

  3. Managing the adverse effects of radiation therapy.

    PubMed

    Berkey, Franklin J

    2010-08-15

    Nearly two thirds of patients with cancer will undergo radiation therapy as part of their treatment plan. Given the increased use of radiation therapy and the growing number of cancer survivors, family physicians will increasingly care for patients experiencing adverse effects of radiation. Selective serotonin reuptake inhibitors have been shown to significantly improve symptoms of depression in patients undergoing chemotherapy, although they have little effect on cancer-related fatigue. Radiation dermatitis is treated with topical steroids and emollient creams. Skin washing with a mild, unscented soap is acceptable. Cardiovascular disease is a well-established adverse effect in patients receiving radiation therapy, although there are no consensus recommendations for cardiovascular screening in this population. Radiation pneumonitis is treated with oral prednisone and pentoxifylline. Radiation esophagitis is treated with dietary modification, proton pump inhibitors, promotility agents, and viscous lidocaine. Radiation-induced emesis is ameliorated with 5-hydroxytryptamine3 receptor antagonists and steroids. Symptomatic treatments for chronic radiation cystitis include anticholinergic agents and phenazopyridine. Sexual dysfunction from radiation therapy includes erectile dysfunction and vaginal stenosis, which are treated with phosphodiesterase type 5 inhibitors and vaginal dilators, respectively. PMID:20704169

  4. Enhancing high throughput toxicology - development of putative adverse outcome pathways linking US EPA ToxCast screening targets to relevant apical hazards.

    EPA Science Inventory

    High throughput toxicology programs, such as ToxCast and Tox21, have provided biological effects data for thousands of chemicals at multiple concentrations. Compared to traditional, whole-organism approaches, high throughput assays are rapid and cost-effective, yet they generall...

  5. [The undesirable, psychologically adverse effects of screening].

    PubMed

    Döbrössy, Bence; Kovács, Attila; Budai, András; Cornides, Agnes; Döbrössy, Lajos

    2007-09-01

    The psychological adverse effects might play an important role in the non-compliance with the offered screening examination. The possible sources of them are three-fold: 1. The general human attitude, such as the rejection of health interventions, particularly those aiming at the prevention of eventual future health problems instead of handling existing complaints and symptoms at present; the screening can be seen as a "future-oriented" intervention. 2. The cultural image of cancer and the disbelief of its curability. 3. The subjective experiences in relation to the screening process. The providers have to do their best to eliminate these causes: by means of a) health education addressing people of various ages, social classes and cultural levels, promoting the understanding of the importance of disease prevention, and, changing their negative, defeatist attitude towards cancer; b) minimizing the psychological adverse effects of all kinds. This can be done by proper organisation of the screening process; optimizing the quality of work, and, provision of good quality of information and advice to the screenees before, during and after the screening. PMID:17766222

  6. Management of adverse effects of mood stabilizers.

    PubMed

    Murru, Andrea; Popovic, Dina; Pacchiarotti, Isabella; Hidalgo, Diego; León-Caballero, Jordi; Vieta, Eduard

    2015-08-01

    Mood stabilizers such as lithium and anticonvulsants are still standard-of-care for the acute and long-term treatment of bipolar disorder (BD). This systematic review aimed to assess the prevalence of their adverse effects (AEs) and to provide recommendations on their clinical management. We performed a systematic research for studies reporting the prevalence of AEs with lithium, valproate, lamotrigine, and carbamazepine/oxcarbazepine. Management recommendations were then developed. Mood stabilizers have different tolerability profiles and are eventually associated to cognitive, dermatological, endocrine, gastrointestinal, immunological, metabolic, nephrogenic, neurologic, sexual, and teratogenic AEs. Most of those can be transient or dose-related and can be managed by optimizing drug doses to the lowest effective dose. Some rare AEs can be serious and potentially lethal, and require abrupt discontinuation of medication. Integrated medical attention is warranted for complex somatic AEs. Functional remediation and psychoeducation may help to promote awareness on BD and better medication management. PMID:26084665

  7. Adverse Effects of Common Drugs: Adults.

    PubMed

    Lewis, Peter R; Karpa, Kelly Dowhower; Felix, Todd Matthew

    2015-09-01

    Although drugs can be an essential and lifesaving component of the care of adult patients, their use frequently is accompanied by adverse effects and life-threatening adverse drug reactions that can result in significant disability and mortality. The potential for drug-related severe morbidity and mortality is compounded during periods of hospitalization, when high-risk drugs such as anticoagulants or insulin are used, and when care in an intensive care unit is required. Patient factors in adults that can increase the risk of drug harms include immunosuppression, cognitive impairment, depression, alcoholism and other substance abuse disorders, chronic kidney disease, hepatic dysfunction, coagulopathies, limited English proficiency, institutional/nursing home care, and underinsurance or lack of insurance. Physician factors that can increase the risk of drug harms include inappropriate prescribing of drugs (including to pregnant and breastfeeding women), failure to appropriately discontinue/deprescribe drugs, insufficient drug reconciliation, failure to coordinate care among multiple prescribing clinicians, and failure to elicit and incorporate into health histories and clinical decision-making the widespread use of nonprescription drugs, herbal products, and dietary supplements. PMID:26375995

  8. Risk assessment and toxicology databases for health effects assessment

    SciTech Connect

    Lu, P.Y.; Wassom, J.S.

    1990-12-31

    Scientific and technological developments bring unprecedented stress to our environment. Society has to predict the results of potential health risks from technologically based actions that may have serious, far-reaching consequences. The potential for error in making such predictions or assessment is great and multiplies with the increasing size and complexity of the problem being studied. Because of this, the availability and use of reliable data is the key to any successful forecasting effort. Scientific research and development generate new data and information. Much of the scientific data being produced daily is stored in computers for subsequent analysis. This situation provides both an invaluable resource and an enormous challenge. With large amounts of government funds being devoted to health and environmental research programs and with maintenance of our living environment at stake, we must make maximum use of the resulting data to forecast and avert catastrophic effects. Along with the readily available. The most efficient means of obtaining the data necessary for assessing the health effects of chemicals is to utilize applications include the toxicology databases and information files developed at ORNL. To make most efficient use of the data/information that has already been prepared, attention and resources should be directed toward projects that meticulously evaluate the available data/information and create specialized peer-reviewed value-added databases. Such projects include the National Library of Medicine`s Hazardous Substances Data Bank, and the U.S. Air Force Installation Restoration Toxicology Guide. These and similar value-added toxicology databases were developed at ORNL and are being maintained and updated. These databases and supporting information files, as well as some data evaluation techniques are discussed in this paper with special focus on how they are used to assess potential health effects of environmental agents. 19 refs., 5 tabs.

  9. Space Toxicology

    NASA Technical Reports Server (NTRS)

    James, John T.

    2011-01-01

    Safe breathing air for space faring crews is essential whether they are inside an Extravehicular Mobility Suit (EMU), a small capsule such as Soyuz, or the expansive International Space Station (ISS). Sources of air pollution can include entry of propellants, excess offgassing from polymeric materials, leakage of systems compounds, escape of payload compounds, over-use of utility compounds, microbial metabolism, and human metabolism. The toxicological risk posed by a compound is comprised of the probability of escaping to cause air pollution and the magnitude of adverse effects on human health if escape occurs. The risk from highly toxic compounds is controlled by requiring multiple levels of containment to greatly reduce the probability of escape; whereas compounds that are virtually non-toxic may require little or no containment. The potential for toxicity is determined by the inherent toxicity of the compound and the amount that could potentially escape into the breathing air.

  10. Toxicological dose assessment and acute health effect criteria

    SciTech Connect

    Stalker, A.C.; White, B.

    1992-01-01

    The use of hazardous materials requires the means of assessing doses from postulated accidental exposures to the hazardous materials. Hazardous materials include radiological and toxicological substances. Health effects are often divided into either acute (short term exposure) or chronic (long-term-exposure)-categories. Dose assessments and health effects are used in Hazard Classification, Safety Analysis Reports and Unreviewed Safety Question Determinations. The use of hazardous substances requires a means of assessing the potential health effects from exposure. Two types of toxicological data exist. The first is measured effects from human exposure, either accidentally or studies. The second consists of data from toxicity and lethality studies on mammals, often mice or rats. Because the data for human exposure is severely limited, an approach is needed that uses basic toxicity and lethality data from animal studies to estimate acute health effects in humans. The approach chosen is the one suggested jointly by the EPA, FEMA, and DOT in their Technical Guidance for Hazards Analysis'', December 1987.

  11. Toxicological dose assessment and acute health effect criteria

    SciTech Connect

    Stalker, A.C.; White, B.

    1992-09-01

    The use of hazardous materials requires the means of assessing doses from postulated accidental exposures to the hazardous materials. Hazardous materials include radiological and toxicological substances. Health effects are often divided into either acute (short term exposure) or chronic (long-term-exposure)-categories. Dose assessments and health effects are used in Hazard Classification, Safety Analysis Reports and Unreviewed Safety Question Determinations. The use of hazardous substances requires a means of assessing the potential health effects from exposure. Two types of toxicological data exist. The first is measured effects from human exposure, either accidentally or studies. The second consists of data from toxicity and lethality studies on mammals, often mice or rats. Because the data for human exposure is severely limited, an approach is needed that uses basic toxicity and lethality data from animal studies to estimate acute health effects in humans. The approach chosen is the one suggested jointly by the EPA, FEMA, and DOT in their ``Technical Guidance for Hazards Analysis``, December 1987.

  12. The NAS Perchlorate Review: Adverse Effects?

    SciTech Connect

    Johnston, Richard B.; Corley, Richard; Cowan, Linda; Utiger, Robert D.

    2005-11-01

    To the editor: Drs. Ginsberg and Rice argue that the reference dose for perchlorate of 0.0007 mg/kg per day recommended by the National Academies’ Committee to Assess the Health Implications of Perchlorate Ingestion is not adequately protective. As members of the committee, we disagree. Ginsberg and Rice base their conclusion on three points. The first involves the designation of the point of departure as a NOEL (no-observed-effect level) versus a LOAEL (lowest-observed-adverse- effect level). The committee chose as its point of departure a dose of perchlorate (0.007 mg/kg per day) that when given for 14 days to 7 normal subjects did not cause a significant decrease in the group mean thyroid iodide uptake (Greer et al. 2002). Accordingly, the committee considered it a NOEL. Ginsberg and Rice focus on the fact that only 7 subjects were given that dose, and they 1seem to say that attention should be paid only to the results in those subjects in whom there was a 1fall in thyroid iodide uptake, and that the results in those in whom there was no fall or an increase should be ignored. They consider the dose to be a LOAEL because of the fall in uptake in those few subjects. It is important to note that a statistically significant decrease of, for example, 5% or even 10%, would not be biologically important and, more important, would not be sustained. For example, in another study (Braverman et al. 2004), administration of 0.04 mg/kg per day to normal subjects for 6 months had no effect on thyroid iodide uptake when measured at 3 and 6 months, and no effect on serum thyroid hormone or thyrotropin concentrations measured monthly (inspection of Figure 5A in the paper by Greer et al. suggests that this dose would inhibit thyroid iodide uptake by about 25% if measured at 2 weeks). The second issue involves database uncertainty. In clinical studies, perchlorate has been administered prospectively to 68 normal subjects for 2 weeks to 6 months. In one study (Brabant et al. 1992

  13. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  14. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  15. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  16. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  17. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  18. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  19. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  20. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  1. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  2. Neuropsychiatric Adverse Effects of Interferon-α

    PubMed Central

    Raison, Charles L.; Demetrashvili, Marina; Capuron, Lucile; Miller, Andrew H.

    2005-01-01

    Recombinant preparations of the cytokine interferon (IFN)-α are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFNα induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFNα, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFNα-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21–58% of patients receiving IFNα, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFNα dosage and treatment duration. The available data support two approaches to the pharmacological management of IFNα-induced depression: antidepressant pretreatment or symptomatic treatment once IFNα has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFNα-induced depression once it has developed, allowing the vast majority of

  3. Transformation of Air Quality Monitor Data from the International Space Station into Toxicological Effect Groups

    NASA Technical Reports Server (NTRS)

    James, John T.; Zalesak, Selina M.

    2011-01-01

    The primary reason for monitoring air quality aboard the International Space Station (ISS) is to determine whether air pollutants have collectively reached a concentration where the crew could experience adverse health effects. These effects could be near-real-time (e.g. headache, respiratory irritation) or occur late in the mission or even years later (e.g. cancer, liver toxicity). Secondary purposes for monitoring include discovery that a potentially harmful compound has leaked into the atmosphere or that air revitalization system performance has diminished. Typical ISS atmospheric trace pollutants consist of alcohols, aldehydes, aromatic compounds, halo-carbons, siloxanes, and silanols. Rarely, sulfur-containing compounds and alkanes are found at trace levels. Spacecraft Maximum Allowable Concentrations (SMACs) have been set in cooperation with a subcommittee of the National Research Council Committee on Toxicology. For each compound and time of exposure, the limiting adverse effect(s) has been identified. By factoring the analytical data from the Air Quality Monitor (AQM), which is in use as a prototype instrument aboard the ISS, through the array of compounds and SMACs, the risk of 16 specific adverse effects can be estimated. Within each adverse-effect group, we have used an additive model proportioned to each applicable 180-day SMAC to estimate risk. In the recent past this conversion has been performed using archival data, which can be delayed for months after an air sample is taken because it must be returned to earth for analysis. But with the AQM gathering in situ data each week, NASA is in a position to follow toxic-effect groups and correlate these with any reported crew symptoms. The AQM data are supplemented with data from real-time CO2 instruments aboard the ISS and from archival measurements of formaldehyde, which the AQM cannot detect.

  4. Cutaneous Adverse Effects of Neurologic Medications.

    PubMed

    Bahrani, Eman; Nunneley, Chloe E; Hsu, Sylvia; Kass, Joseph S

    2016-03-01

    Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication. PMID:26914914

  5. Migraine treatment: a chain of adverse effects.

    PubMed

    Veloso, Tiago Sousa; Cambão, Mariana Seixas

    2015-01-01

    This clinical vignette presents a 14 years old female, with a past medical history relevant only for migraine with typical aura of less than monthly frequency, complaining of a severe unilateral headache with rising intensity for the previous 4 h, associated with nausea, vomiting, photophobia and phonophobia. This episode of migraine with aura in a patient with recurrent migraine was complicated by side effects of medical diagnostic and therapeutic procedures (extrapyramidal symptoms, delirium, post-lumbar puncture headache, hospital admission) all of which could have been prevented-quaternary prevention. This case illustrates several important messages in migraine management: (1) use of acetaminophen is not based in high-quality evidence and better options exist; (2) among youngsters, domperidone should be preferred over metoclopramide because it does not cross the blood-brain barrier; (3) moderate to severe migraine crisis can be managed with triptans in teenagers over 12 years old; (4) it is important to recognize adverse drug effects; (5) harmful consequences of medical interventions do occur; (6) the school community must be informed about chronic diseases of the young. PMID:26266080

  6. Reproductive Toxicology Testing with EDCS

    EPA Science Inventory

    An introduction to reproductive toxicology: the basic approaches to testing chemicals for adverse effects using multigenerational studies with rats and how the regulatory agencies used the data in risk assessments. Case studies were presented of how endocrine or genomic data were...

  7. Adverse immunologic effects of antithyroid drugs.

    PubMed Central

    Wing, S S; Fantus, I G

    1987-01-01

    Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299

  8. Adverse effects of IgG therapy.

    PubMed

    Berger, Melvin

    2013-01-01

    IgG is widely used for patients with immune deficiencies and in a broad range of autoimmune and inflammatory disorders. Up to 40% of intravenous infusions of IgG may be associated with adverse effects (AEs), which are mostly uncomfortable or unpleasant but often are not serious. The most common infusion-related AE is headache. More serious reactions, including true anaphylaxis and anaphylactoid reactions, occur less frequently. Most reactions are related to the rate of infusion and can be prevented or treated just by slowing the infusion rate. Medications such as nonsteroidal anti-inflammatory drugs, antihistamines, or corticosteroids also may be helpful in preventing or treating these common AEs. IgA deficiency with the potential of IgG or IgE antibodies against IgA increases the risk of some AEs but should not be viewed as a contraindication if IgG therapy is needed. Potentially serious AEs include renal dysfunction and/or failure, thromboembolic events, and acute hemolysis. These events usually are multifactorial, related to combinations of constituents in the IgG product as well as risk factors for the recipient. Awareness of these factors should allow minimization of the risks and consequences of these AEs. Subcutaneous IgG is absorbed more slowly into the circulation and has a lower incidence of AEs, but awareness and diligence are necessary whenever IgG is administered. PMID:24565701

  9. Toxicological profile for selenium. (Update)

    SciTech Connect

    1996-08-01

    Each profile includes: (1) The examination, summary, and interpretation of available toxicologic information and epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human exposure for the substance and the associated acute, subacute, and chronic health effects; (2) A determination of whether adequate information on the health effects of each substance is available or in the process of development to determine levels of exposure that present a significant risk to human health of acute, subacute, and chonic health effects; and (3) Where appropriate, identification of toxicologic testing needed to identify the types or levels of exposure that may present significant risk of adverse health effects in humans.

  10. Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms.

    PubMed

    Steiner, Sandro; Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

    2016-07-01

    Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially concerning the nature of the components of diesel exhaust responsible for the effects and how they could be eliminated from the exhaust. This review describes the fundamental properties of diesel exhaust as well as the human respiratory tract and concludes that adverse health effects of diesel exhaust not only emerge from its chemical composition, but also from the interplay between its physical properties, the physiological and cellular properties, and function of the human respiratory tract. Furthermore, the primary molecular and cellular mechanisms triggered by diesel exhaust exposure, as well as the fundamentals of the methods for toxicological testing of diesel exhaust toxicity, are described. The key aspects of adverse effects induced by diesel exhaust exposure described herein will be important for regulators to support or ban certain technologies or to legitimate incentives for the development of promising new technologies such as catalytic diesel particle filters. PMID:27165416

  11. Toxicological effects of polycyclic aromatic hydrocarbons and their derivatives on respiratory cells

    NASA Astrophysics Data System (ADS)

    Koike, Eiko; Yanagisawa, Rie; Takano, Hirohisa

    2014-11-01

    Polycyclic aromatic hydrocarbons (PAHs) are found in ambient aerosols and particulate matter. Experimental studies have shown that PAHs and related chemicals can induce toxicological effects. The present study aimed to investigate the effects of PAHs and their derivatives on the respiratory and immune systems and the underlying mechanisms. The human bronchial epithelial cell line BEAS-2B was exposed to PAHs and their derivatives, and the cytotoxicity and proinflammatory protein expression were then investigated. A cytotoxic effect was observed in BEAS-2B exposed to PAH derivatives such as naphthoquinone (NQ), phenanthrenequinone (PQ), 1-nitropyrene (1-NP), and 1-aminopyrene (1-AP). In addition, 1,2-NQ and 9,10-PQ showed more effective cytotoxicity than 1,4-NQ and 1,4-PQ, respectively. Pyrene showed a weak cytotoxic effect. On the other hand, naphthalene and phenanthrene showed no significant effects. Pyrene, 1-NP, and 1-AP also increased intercellular adhesion molecule-1 expression and interleukin-6 production in BEAS-2B. The increase was partly suppressed by protein kinase inhibitors such as the epidermal growth factor receptor-selective tyrosine kinase inhibitor and nuclear receptor antagonists such as the thyroid hormone receptor antagonist. The present study suggests that the toxicological effects of chemicals may be related to the different activities resulting from their structures, such as numbers of benzene rings and functional groups. Furthermore, the chemical-induced increase in proinflammatory protein expression in bronchial epithelial cells was possibly a result of the activation of protein kinase pathways and nuclear receptors. The increase may partly contribute to the adverse health effects of atmospheric PAHs.

  12. The adverse health effects of chronic cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2014-01-01

    This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment. PMID:23836598

  13. Adverse effects of human immunoglobulin therapy.

    PubMed

    Stiehm, E Richard

    2013-07-01

    Human immunoglobulin (IG) is used for IgG replacement therapy in primary and secondary immunodeficiency, for prevention and treatment of certain infections, and as an immunomodulatory agent for autoimmune and inflammatory disorders. IG has a wide spectrum of antibodies to microbial and human antigens. Several high-titered IGs are also available enriched in antibodies to specific viruses or bacterial toxins. IG can be given intravenously (IGIV), intramuscularly (IGIM) or by subcutaneous infusions (SCIG). Local adverse reactions such as persistent pain, bruising, swelling and erythema are rare with IGIV infusions but common (75%) with SCIG infusions. By contrast, adverse systemic reactions are rare with SCIG infusions but common with IGIV infusions, occurring as often as 20% to 50% of patients and 5% to 15% of all IGIV infusions. Systemic adverse reactions can be immediate (60% of reactions) occurring within 6 hours of an infusion, delayed (40% of reactions) occurring 6 hours-1 week after an infusion, and late (less than 1% of reactions), occurring weeks and months after an infusion. Immediate systemic reactions such as head and body aches, chills and fever are usually mild and readily treatable. Immediate anaphylactic and anaphylactoid reactions are uncommon. The most common delayed systemic reaction is persistent headache. Less common but more serious delayed reactions include aseptic meningitis, renal failure, thromboembolism, and hemolytic reactions. Late reactions are uncommon but often severe, and include lung disease, enteritis, dermatologic disorders and infectious diseases. The types, incidence, causes, prevention, and management of these reactions are discussed. PMID:23835249

  14. Effectiveness of adverse effects search filters: drugs versus medical devices

    PubMed Central

    Farrah, Kelly; Mierzwinski-Urban, Monika; Cimon, Karen

    2016-01-01

    Objective The study tested the performance of adverse effects search filters when searching for safety information on medical devices, procedures, and diagnostic tests in MEDLINE and Embase. Methods The sensitivity of 3 filters was determined using a sample of 631 references from 131 rapid reviews related to the safety of health technologies. The references were divided into 2 sets by type of intervention: drugs and nondrug health technologies. Keyword and indexing analysis were performed on references from the nondrug testing set that 1 or more of the filters did not retrieve. Results For all 3 filters, sensitivity was lower for nondrug health technologies (ranging from 53%–87%) than for drugs (88%–93%) in both databases. When tested on the nondrug health technologies set, sensitivity was lower in Embase (ranging from 53%–81%) than in MEDLINE (67%–87%) for all filters. Of the nondrug records that 1 or more of the filters missed, 39% of the missed MEDLINE records and 18% of the missed Embase records did not contain any indexing terms related to adverse events. Analyzing the titles and abstracts of nondrug records that were missed by any 1 filter, the most commonly used keywords related to adverse effects were: risk, complications, mortality, contamination, hemorrhage, and failure. Conclusions In this study, adverse effects filters were less effective at finding information about the safety of medical devices, procedures, and tests compared to information about the safety of drugs. PMID:27366123

  15. Using Literature-Based Discovery to Explain Adverse Drug Effects.

    PubMed

    Hristovski, Dimitar; Kastrin, Andrej; Dinevski, Dejan; Burgun, Anita; Žiberna, Lovro; Rindflesch, Thomas C

    2016-08-01

    We report on our research in using literature-based discovery (LBD) to provide pharmacological and/or pharmacogenomic explanations for reported adverse drug effects. The goal of LBD is to generate novel and potentially useful hypotheses by analyzing the scientific literature and optionally some additional resources. Our assumption is that drugs have effects on some genes or proteins and that these genes or proteins are associated with the observed adverse effects. Therefore, by using LBD we try to find genes or proteins that link the drugs with the reported adverse effects. These genes or proteins can be used to provide insight into the processes causing the adverse effects. Initial results show that our method has the potential to assist in explaining reported adverse drug effects. PMID:27318993

  16. Contribution of new technologies to characterization and prediction of adverse effects.

    PubMed

    Rouquié, David; Heneweer, Marjoke; Botham, Jane; Ketelslegers, Hans; Markell, Lauren; Pfister, Thomas; Steiling, Winfried; Strauss, Volker; Hennes, Christa

    2015-02-01

    Identification of the potential hazards of chemicals has traditionally relied on studies in laboratory animals where changes in clinical pathology and histopathology compared to untreated controls defined an adverse effect. In the past decades, increased consistency in the definition of adversity with chemically-induced effects in laboratory animals, as well as in the assessment of human relevance has been reached. More recently, a paradigm shift in toxicity testing has been proposed, mainly driven by concerns over animal welfare but also thanks to the development of new methods. Currently, in vitro approaches, toxicogenomic technologies and computational tools, are available to provide mechanistic insight in toxicological Mode of Action (MOA) of the adverse effects observed in laboratory animals. The vision described as Tox21c (Toxicity Testing in the 21st century) aims at predicting in vivo toxicity using a bottom-up-approach, starting with understanding of MOA based on in vitro data to ultimately predict adverse effects in humans. At present, a practical application of the Tox21c vision is still far away. While moving towards toxicity prediction based on in vitro data, a stepwise reduction of in vivo testing is foreseen by combining in vitro with in vivo tests. Furthermore, newly developed methods will also be increasingly applied, in conjunction with established methods in order to gain trust in these new methods. This confidence is based on a critical scientific prerequisite: the establishment of a causal link between data obtained with new technologies and adverse effects manifested in repeated-dose in vivo toxicity studies. It is proposed to apply the principles described in the WHO/IPCS framework of MOA to obtain this link. Finally, an international database of known MOAs obtained in laboratory animals using data-rich chemicals will facilitate regulatory acceptance and could further help in the validation of the toxicity pathway and adverse outcome pathway

  17. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Significant adverse environmental... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Environmental Effects § 970.701 Significant adverse environmental effects. (a) Activities with no...

  18. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Significant adverse environmental... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Environmental Effects § 970.701 Significant adverse environmental effects. (a) Activities with no...

  19. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Significant adverse environmental... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Environmental Effects § 970.701 Significant adverse environmental effects. (a) Activities with no...

  20. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  1. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  2. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  3. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  4. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  5. Nonlinear neural mapping analysis of the adverse effects of drugs.

    PubMed

    Domine, D; Guillon, C; Devillers, J; Lacroix, R; Lacroix, J; Doré, J C

    1998-01-01

    Numerous drugs have been identified as presenting adverse effects towards the driving of vehicles. A large set of these drugs was compiled and classified into ten categories. Nonlinear neural mapping (N2M) was used to derive a typology of these molecules and also to link their adverse effects to therapeutic categories and structural information. PMID:9517012

  6. Paradoxical bronchospasm: a potentially life threatening adverse effect of albuterol.

    PubMed

    Raghunathan, Kalpana; Nagajothi, Nagapradeep

    2006-03-01

    We report a case of paradoxical bronchospasm to both levalbuterol and albuterol. While the exact mechanism for this known adverse effect of albuterol is not known, awareness of this adverse effect can be life saving to the patient. To our knowledge, this is the first reported case of paradoxical bronchospasm to levalbuterol inhalation solution. PMID:16553105

  7. Multiple adverse effects of pyridium: a case report.

    PubMed

    Haigh, Charles; Dewar, James C

    2006-01-01

    Pyridium (phenazopyridine hydrochloride) is often prescribed as an analgesic in patients following trauma, surgery, or infections of the urinary tract. Pyridium toxicity has been previously reported, however, most cases result in a single adverse effect. Herein the authors describe an elderly patient who presented with simultaneous multiple adverse effects, including a previously undocumented myelosuppressive pancytopenia. PMID:16466130

  8. Adverse Effects of Systemic Immunosuppression in Keratolimbal Allograft

    PubMed Central

    Krakauer, M.; Welder, J. D.; Pandya, H. K.; Nassiri, N.; Djalilian, A. R.

    2012-01-01

    Purpose. Keratolimbal allograft (KLAL) is a treatment for limbal stem cell deficiency. One disadvantage is systemic immunosuppression to avoid rejection. Our purpose was to examine the adverse effects of systemic immunosuppression in KLAL. Methods. A retrospective case review of 16 patients with KLAL who received systemic immunosuppression consisting of a corticosteroid, an antimetabolite, and/or a calcineurin inhibitor was performed. Patients were monitored for signs, symptoms, or laboratory evidence of toxicity. Results. Eleven of 16 patients (68%) experienced an adverse effect. The average age of those with adverse effects was 43.5 years and without was 31.4 years. Ten of 11 patients (91%) had resolution during mean followup of 16.4 months. No serious adverse effects occurred. The most common included anemia, hyperglycemia, elevated creatinine, and elevated liver function tests. Prednisone and tacrolimus were responsible for the most adverse effects. Patients with comorbidities were more likely to experience an adverse effect (82% versus 20%, P = 0.036). Conclusions. KLAL requires prolonged systemic immunosuppression. Our data demonstrated that systemic immunosuppression did not result in serious adverse effects in our population and is relatively safe with monitoring for toxicity. In addition, we demonstrated that adverse effects are more likely in older patients with comorbidities. PMID:22523651

  9. [Haematological adverse effects caused by psychiatric drugs].

    PubMed

    Mazaira, Silvina

    2008-01-01

    Almost all clases of psychiatric drugs (typical and atypical antipsychotics, antidepressants, mood stabilizers, benzodiazepines) have been reported as possible causes of haematological toxicity. This is a review of the literature in which different clinical situations involving red blood cells, white blood cells, platelets and impaired coagulation are detailed and the drugs more frequently involved are listed. The haematological adverse reactions detailed here include: aplastic anemia, haemolitic anemia, leukopenia, agranulocytosis, leukocytosis, eosinophilia, thrombocytosis, thrombocytopenia, disordered platelet function and impaired coagulation. The haematologic toxicity profile of the drugs more frequently involved: lithium, clozapine, carbamazepine, valproic acid and SSRI antidepressants is mentioned. PMID:19424521

  10. Spaceflight Toxicology

    NASA Technical Reports Server (NTRS)

    Meyers, Valerie

    2008-01-01

    This viewgraph presentation provides a review of NASA Johnson Space Center's Toxicology program. The mission of this program is to protect crews from toxic exposures during spaceflight. The presentation reviews some of the health hazards. A toxicological hazard level chart is presented that reviews the rating of hazard level, irritancy, systemic effects and containability. The program also participates in the Lunar Airborne Dust Toxicity Advisory Group.

  11. Pharmacological and Toxicological Effects of Lithium in Zebrafish

    PubMed Central

    2014-01-01

    Lithium is the paradigmatic treatment for bipolar disorder and has been widely used as a mood stabilizer due to its ability to reduce manic and depressive episodes, efficiency in long-term mood stabilization, and effectiveness in reducing suicide risks. Despite many decades of clinical use, the molecular targets of lithium are not completely understood. However, they are credited at least partially to glycogen synthase kinase 3 (GSK3) inhibition, mimicking and exacerbating Wnt signaling pathway activation. There has been a great effort to characterize lithium cellular and system actions, aiming to improve treatment effectiveness and reduce side effects. There is also a growing concern about lithium’s impact as an environmental contaminant and its effects on development. In this scenario, zebrafish is a helpful model organism to gather more information on lithium’s effects in different systems and developmental stages. The rapid external development, initial transparency, capacity to easily absorb substances, and little space required for maintenance and experimentation, among other advantages, make zebrafish a suitable model. In addition, zebrafish has been established as an effective model organism in behavioral and neuropharmacological studies, reacting to a wide range of psychoactive drugs, including lithium. So far only a limited number of studies evaluated the toxicological impact of lithium on zebrafish development and demonstrated morphological, physiological, and behavioral effects that may be informative regarding human findings. Further studies dedicated to characterize and evaluate the underlying mechanisms of the toxic effects and the potential impact of exposure on developing and adult individuals are necessary to establish safe clinical management guidelines for women with bipolar disorder of childbearing age and safety disposal guidelines for pharmaceutical neuroactive compounds. PMID:24798681

  12. Adverse Effects of Common Drugs: General Concepts.

    PubMed

    Karpa, Kelly Dowhower; Lewis, Peter R; Felix, Todd Matthew

    2015-09-01

    Adverse drug reactions (ADRs) contribute to substantial morbidity and mortality and add to rising health care costs. Many ADRs are preventable with appropriate prescribing and monitoring because they often occur as an extension of a drug's mechanism of action or known drug interactions. Patients at higher risk of ADRs include those at the extremes of age, those with multiple comorbidities, those taking multiple drugs, and patients admitted to intensive care units or experiencing transitions of care. Because the risk of ADRs becomes greater as the number of drugs and dietary supplements taken increases, it is imperative that prescribers be vigilant about the prescribing cascade and take steps to discontinue drugs that are likely to be more harmful than helpful. Pharmacists serve as important partners in clinical care environments by conducting comprehensive drug reviews, aiding in drug/dosage selection, and developing therapeutic monitoring plans. Although the potential exists for clinicians to use electronic health record systems to aid in clinical decision making through drug safety decision support tools, computer systems should never replace clinical judgment. Clinicians also are encouraged to report ADRs to the Food and Drug Administration Adverse Event Reporting System. PMID:26375993

  13. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR part 68) and applicable guidelines, to avoid adverse effects. (c) Consulting party review. If the... (36 CFR part 68) and applicable guidelines; (iii) Removal of the property from its historic location... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse...

  14. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CFR part 68) and applicable guidelines, to avoid adverse effects. (c) Consulting party review. If the... (36 CFR part 68) and applicable guidelines; (iii) Removal of the property from its historic location... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Assessment of adverse...

  15. Toxicological Benchmarks for Wildlife

    SciTech Connect

    Sample, B.E. Opresko, D.M. Suter, G.W.

    1993-01-01

    Ecological risks of environmental contaminants are evaluated by using a two-tiered process. In the first tier, a screening assessment is performed where concentrations of contaminants in the environment are compared to no observed adverse effects level (NOAEL)-based toxicological benchmarks. These benchmarks represent concentrations of chemicals (i.e., concentrations presumed to be nonhazardous to the biota) in environmental media (water, sediment, soil, food, etc.). While exceedance of these benchmarks does not indicate any particular level or type of risk, concentrations below the benchmarks should not result in significant effects. In practice, when contaminant concentrations in food or water resources are less than these toxicological benchmarks, the contaminants may be excluded from further consideration. However, if the concentration of a contaminant exceeds a benchmark, that contaminant should be retained as a contaminant of potential concern (COPC) and investigated further. The second tier in ecological risk assessment, the baseline ecological risk assessment, may use toxicological benchmarks as part of a weight-of-evidence approach (Suter 1993). Under this approach, based toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. Other sources of evidence include media toxicity tests, surveys of biota (abundance and diversity), measures of contaminant body burdens, and biomarkers. This report presents NOAEL- and lowest observed adverse effects level (LOAEL)-based toxicological benchmarks for assessment of effects of 85 chemicals on 9 representative mammalian wildlife species (short-tailed shrew, little brown bat, meadow vole, white-footed mouse, cottontail rabbit, mink, red fox, and whitetail deer) or 11 avian wildlife species (American robin, rough-winged swallow, American woodcock, wild turkey, belted kingfisher, great blue heron, barred owl, barn owl, Cooper's hawk, and red-tailed hawk

  16. Adverse effects of spinal manipulation: a systematic review

    PubMed Central

    Ernst, E

    2007-01-01

    Objective To identify adverse effects of spinal manipulation. Design Systematic review of papers published since 2001. Setting Six electronic databases. Main outcome measures Reports of adverse effects published between January 2001 and June 2006. There were no restrictions according to language of publication or research design of the reports. Results The searches identified 32 case reports, four case series, two prospective series, three case-control studies and three surveys. In case reports or case series, more than 200 patients were suspected to have been seriously harmed. The most common serious adverse effects were due to vertebral artery dissections. The two prospective reports suggested that relatively mild adverse effects occur in 30% to 61% of all patients. The case-control studies suggested a causal relationship between spinal manipulation and the adverse effect. The survey data indicated that even serious adverse effects are rarely reported in the medical literature. Conclusions Spinal manipulation, particularly when performed on the upper spine, is frequently associated with mild to moderate adverse effects. It can also result in serious complications such as vertebral artery dissection followed by stroke. Currently, the incidence of such events is not known. In the interest of patient safety we should reconsider our policy towards the routine use of spinal manipulation. PMID:17606755

  17. Rare and very rare adverse effects of clozapine

    PubMed Central

    De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

    2015-01-01

    Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

  18. Computational Toxicology (S)

    EPA Science Inventory

    The emerging field of computational toxicology applies mathematical and computer models and molecular biological and chemical approaches to explore both qualitative and quantitative relationships between sources of environmental pollutant exposure and adverse health outcomes. Th...

  19. Role of adverse effects in medication nonadherence in bipolar disorder.

    PubMed

    Mago, Rajnish; Borra, Dileep; Mahajan, Rajeev

    2014-01-01

    Nonadherence to medications is common and associated with poor or limited clinical outcomes in the treatment of bipolar disorder. A review of the literature discloses that adverse effects are one of the commonly reported reasons for nonadherence to mood stabilizers by patients with bipolar disorder. Nevertheless, other than such broad summaries, relatively little attention has been given to the role of adverse effects in relation to nonadherence. This review article is the first to consolidate the available data on this topic. Weight gain, perceived cognitive impairment, tremors, and sedation are the adverse effects most likely to lead to nonadherence. Further research is needed to anticipate, identify, manage, and potentially minimize the impact of adverse effects. PMID:25377611

  20. Teaching Toxicology as a Basic Medical Science

    ERIC Educational Resources Information Center

    Gralla, Edward J.

    1976-01-01

    A 4-year effort at Yale University School of Medicine to teach toxicology as an elective basic science from the standpoint of organ-specific toxic effects is described. The objective of the successful multidisciplinary program is to prepare physicians to understand, recognize, and manage adverse effects from drugs and other environmental…

  1. TOXLINE (TOXICOLOGY INFORMATION ONLINE)

    EPA Science Inventory

    TOXLINE? (TOXicology information onLINE) are the National Library of Medicines extensive collection of online bibliographic information covering the pharmacological, biochemical, physiological, and toxicological effects of drugs and other chemicals. TOXLINE and TOXLINE65 together...

  2. Adverse effects of herbal medicines: an overview of systematic reviews.

    PubMed

    Posadzki, Paul; Watson, Leala K; Ernst, Edzard

    2013-02-01

    This overview of systematic reviews (SRs) aims to evaluate critically the evidence regarding the adverse effects of herbal medicines (HMs). Five electronic databases were searched to identify all relevant SRs, with 50 SRs of 50 different HMs meeting our inclusion criteria. Most had only minor weaknesses in methods. Serious adverse effects were noted only for four HMs: Herbae pulvis standardisatus, Larrea tridentate, Piper methysticum and Cassia senna. The most severe adverse effects were liver or kidney damage, colon perforation, carcinoma, coma and death. Moderately severe adverse effects were noted for 15 HMs: Pelargonium sidoides, Perna canaliculus, Aloe vera, Mentha piperita, Medicago sativa, Cimicifuga racemosa, Caulophyllum thalictroides, Serenoa repens, Taraxacum officinale, Camellia sinensis, Commifora mukul, Hoodia gordonii, Viscum album, Trifolium pratense and Stevia rebaudiana. Minor adverse effects were noted for 31 HMs: Thymus vulgaris, Lavandula angustifolia Miller, Boswellia serrata, Calendula officinalis, Harpagophytum procumbens, Panax ginseng, Vitex agnus-castus, Crataegus spp., Cinnamomum spp., Petasites hybridus, Agave americana, Hypericum perforatum, Echinacea spp., Silybum marianum, Capsicum spp., Genus phyllanthus, Ginkgo biloba, Valeriana officinalis, Hippocastanaceae, Melissa officinalis, Trigonella foenum-graecum, Lagerstroemia speciosa, Cnicus benedictus, Salvia hispanica, Vaccinium myrtillus, Mentha spicata, Rosmarinus officinalis, Crocus sativus, Gymnema sylvestre, Morinda citrifolia and Curcuma longa. Most of the HMs evaluated in SRs were associated with only moderately severe or minor adverse effects. PMID:23472485

  3. Adverse Biological Effect of TiO₂ and Hydroxyapatite Nanoparticles Used in Bone Repair and Replacement.

    PubMed

    Wang, Jiangxue; Wang, Liting; Fan, Yubo

    2016-01-01

    The adverse biological effect of nanoparticles is an unavoidable scientific problem because of their small size and high surface activity. In this review, we focus on nano-hydroxyapatite and TiO₂ nanoparticles (NPs) to clarify the potential systemic toxicological effect and cytotoxic response of wear nanoparticles because they are attractive materials for bone implants and are widely investigated to promote the repair and reconstruction of bone. The wear nanoparticles would be prone to binding with proteins to form protein-particle complexes, to interacting with visible components in the blood including erythrocytes, leukocytes, and platelets, and to being phagocytosed by macrophages or fibroblasts to deposit in the local tissue, leading to the formation of fibrous local pseudocapsules. These particles would also be translocated to and disseminated into the main organs such as the lung, liver and spleen via blood circulation. The inflammatory response, oxidative stress, and signaling pathway are elaborated to analyze the potential toxicological mechanism. Inhibition of the oxidative stress response and signaling transduction may be a new therapeutic strategy for wear debris-mediated osteolysis. Developing biomimetic materials with better biocompatibility is our goal for orthopedic implants. PMID:27231896

  4. Adverse Health Effects of Nighttime Lighting

    NASA Astrophysics Data System (ADS)

    Motta, M.

    2012-06-01

    The effects of poor lighting and glare on public safety are well-known, as are the harmful environmental effects on various species and the environment in general. What is less well-known is the potential harmful medical effects of excessive poor nighttime lighting. A significant body of research has been developed over the last few years regarding this problem. One of the most significant effects is the startling increased risk for breast cancer by excessive exposure to nighttime lighting. The mechanism is felt to be by disruption of the circadian rhythm and suppression of melatonin production from the pineal gland. Melatonin has an anticancer effect that is lost when its production is disrupted. I am in the process of developing a monograph that will summarize this important body of research, to be presented and endorsed by the American Medical Association, and its Council of Science and Public health. This paper is a brief overall summary of this little known potential harmful effect of poor and excessive nighttime lighting.

  5. [Thyrostatic treatment and its adverse effects].

    PubMed

    Dokupilová, A; Payer, J

    2013-11-01

    Antithyroid drugs are relatively simple molecules known as thionamides, which contain a sulfhydryl group and a thiourea moiety within a heterocyclic structure. Propylthiouracil (6- propyl 2- sulfanylidene 1,2,3,4- tetrahydropyrimidin4- one) and methimazole (1- metyl 2,3- dihydro1H imidazole 2- thione) are the antithyroid drugs used in the United States. Methimazole is used in most of Europe and Asia, and carbimazole -  methimazole analogue, is used in the United Kingdom and parts of the former British Commonwealth. Their primary effect is to inhibit thyroid hormone synthesis by interfering with thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin and is an important step in the synthesis of thyroxine and triiodothyronine. Propylthiouracil (but not methimazole or carbimazole), can block the conversion of thyroxine to triiodothyronine within the thyroid and in peripheral tissues. Antithyroid drugs may have clinically important immunosuppressive effects. Side effects of thionamides are usually mild, serious untoward effects are observed in < 5% of cases, more frequently during the initial phases of treatment, when the drug daily dose is higher. PMID:24279443

  6. Potential adverse health effects of wood smoke.

    PubMed

    Pierson, W E; Koenig, J Q; Bardana, E J

    1989-09-01

    The use of wood stoves has increased greatly in the past decade, causing concern in many communities about the health effects of wood smoke. Wood smoke is known to contain such compounds as carbon monoxide, nitrogen oxides, sulfur oxides, aldehydes, polycyclic aromatic hydrocarbons, and fine respirable particulate matter. All of these have been shown to cause deleterious physiologic responses in laboratory studies in humans. Some compounds found in wood smoke--benzo[a]pyrene and formaldehyde--are possible human carcinogens. Fine particulate matter has been associated with decreased pulmonary function in children and with increased chronic lung disease in Nepal, where exposure to very high amounts of wood smoke occurs in residences. Wood smoke fumes, taken from both outdoor and indoor samples, have shown mutagenic activity in short-term bioassay tests. Because of the potential health effects of wood smoke, exposure to this source of air pollution should be minimal. PMID:2686171

  7. Potential adverse health effects of wood smoke.

    PubMed Central

    Pierson, W E; Koenig, J Q; Bardana, E J

    1989-01-01

    The use of wood stoves has increased greatly in the past decade, causing concern in many communities about the health effects of wood smoke. Wood smoke is known to contain such compounds as carbon monoxide, nitrogen oxides, sulfur oxides, aldehydes, polycyclic aromatic hydrocarbons, and fine respirable particulate matter. All of these have been shown to cause deleterious physiologic responses in laboratory studies in humans. Some compounds found in wood smoke--benzo[a]pyrene and formaldehyde--are possible human carcinogens. Fine particulate matter has been associated with decreased pulmonary function in children and with increased chronic lung disease in Nepal, where exposure to very high amounts of wood smoke occurs in residences. Wood smoke fumes, taken from both outdoor and indoor samples, have shown mutagenic activity in short-term bioassay tests. Because of the potential health effects of wood smoke, exposure to this source of air pollution should be minimal. PMID:2686171

  8. Ecological and toxicological effects of inorganic nitrogen pollution in aquatic ecosystems: A global assessment.

    PubMed

    Camargo, Julio A; Alonso, Alvaro

    2006-08-01

    We provide a global assessment, with detailed multi-scale data, of the ecological and toxicological effects generated by inorganic nitrogen pollution in aquatic ecosystems. Our synthesis of the published scientific literature shows three major environmental problems: (1) it can increase the concentration of hydrogen ions in freshwater ecosystems without much acid-neutralizing capacity, resulting in acidification of those systems; (2) it can stimulate or enhance the development, maintenance and proliferation of primary producers, resulting in eutrophication of aquatic ecosystems; (3) it can reach toxic levels that impair the ability of aquatic animals to survive, grow and reproduce. Inorganic nitrogen pollution of ground and surface waters can also induce adverse effects on human health and economy. Because reductions in SO2 emissions have reduced the atmospheric deposition of H2SO4 across large portions of North America and Europe, while emissions of NOx have gone unchecked, HNO3 is now playing an increasing role in the acidification of freshwater ecosystems. This acidification process has caused several adverse effects on primary and secondary producers, with significant biotic impoverishments, particularly concerning invertebrates and fishes, in many atmospherically acidified lakes and streams. The cultural eutrophication of freshwater, estuarine, and coastal marine ecosystems can cause ecological and toxicological effects that are either directly or indirectly related to the proliferation of primary producers. Extensive kills of both invertebrates and fishes are probably the most dramatic manifestation of hypoxia (or anoxia) in eutrophic and hypereutrophic aquatic ecosystems with low water turnover rates. The decline in dissolved oxygen concentrations can also promote the formation of reduced compounds, such as hydrogen sulphide, resulting in higher adverse (toxic) effects on aquatic animals. Additionally, the occurrence of toxic algae can significantly

  9. Adverse health effects of indoor moulds.

    PubMed

    Piecková, Elena

    2012-12-01

    Building associated illnesses - sick building syndrome (SBS) as a common example - are associated with staying in buildings with poor indoor air quality. The importance of indoor fungal growth in this phenomenon continues to be evident, even though no causative relation has been established so far. Indoor humidity is strongly associated with the symptoms of SBS. Fungal metabolites that may induce ill health in susceptible occupants comprise beta-D-glucan, mycotoxins, and volatile organic compounds as known irritants and/or immunomodulators. Indoor toxic fungal metabolites might be located in micromycetal propagules (endometabolites), in (bio-)aerosol, detritus, and house dust (exometabolites) as their particular carriers. It is highly probable that hyphal fragments, dust, and particles able to reach the alveoli have the strongest depository and toxic potential. Most fungal spores are entrapped by the upper respiratory tract and do not reach further than the bronchi because of their size, morphology, and the mode of propagation (such as slime heads and aggreggation). This is why studies of the toxic effects of fungal spores prefer directly applying metabolite mixtures over mimicking real exposure. Chronic low-level exposure to a mixture of fungal toxicants and other indoor stressors may have synergistic effects and lead to severe neuroendocrineimmune changes. PMID:23334050

  10. Chemical Hair Relaxers Have Adverse Effects a Myth or Reality

    PubMed Central

    Shetty, Vinma H; Shetty, Narendra J; Nair, Dhanya Gopinath

    2013-01-01

    Context: Hair plays an important role in one's personality and builds confidence. Now-a-days, chemical hair relaxers are used very commonly in the society. We document the adverse effects reported by the sample that have used any one of the professional chemical hair relaxers. Aim: To study the adverse effects reported by the sample who underwent repeated chemical hair relaxing. Settings and Design: Cross-sectional questionnaire based study done on a sample taken from a medical college and hospital campus in Mangalore. Materials and Methods: The sample was restricted to females and to those who underwent it more than once. A questionnaire was given to a sample of 90, which matched our criteria. Statistical Analysis: SPSS software 17. Results: Adverse effects reported by the sample after undergoing the procedure were found to be a high 95.56%, out of which the following are the common adverse effects reported; frizzy hair in 67%, dandruff in 61%, hair loss in 47%, thinning and weakening of hair in 40%, greying of hair 22%, and split ends in only 17%. Conclusions: Very few studies have been conducted on the adverse effects of hair straightening products in India. From our study, it can be stated that most of the samples had adverse effects, which was as high as 95.56%. Hence from the details elicited from this study, we can conclude that, usage of chemical hair relaxers does cause adverse effects and is “not a myth.” Thus, it is necessary to make available a less harmful chemical hair relaxer to the society. PMID:23960393

  11. Assessment of the potential for long-term toxicological effects of the Exxon Valdez oil spill on birds and mammals

    SciTech Connect

    Hartung, R.

    1995-12-31

    This paper assesses the potential for direct long-term toxicological effects of exposures to oils in birds and mammals by tracing exposures and effects form the initial cute phases through the sub-chronic to the eventual long-term exposures. The immediate effects of oil spills are physical, the oil acting on the plumage of birds or the fur of mammals. This causes a loss of entrained air and a concomitant reduction in buoyancy and thermal insulation. Animals that escape the immediate impacts may be isolated from their food supply and often ingest large amounts of oil while attempting to clean themselves. At the comparatively high dose levels involved, these exposures can result in toxicologically significant responses in many organ systems. In the course of an oil pollution incident, the amounts of biologically available oils decrease steadily, and simultaneously the composition of the oils shifts towards those components that have low volatility, and that resist photo- and bio-degradation. As this occurs, the primary pathways of exposure change from direct intakes to indirect routes involving the food supply. Although laboratory studies often report finding some adverse effects, the dose rates employed in many of these studies are extremely high when compared with those that are potentially available to animals in the wild, and very few actually use weathered oils. An assessment of the toxicological literature and of the available empirical data on the Exxon Valdez oil spill leads to the conclusion that long-term sub-lethal toxic effects of crude oils on wildlife in such marine spills appear to be very unlikely. 111 refs., 4 figs., 1 tab.

  12. Chloroquine cardiomyopathy: beyond ocular adverse effects

    PubMed Central

    Lopez-Ruiz, Nilson; Uribe, Carlos Esteban

    2014-01-01

    A 36-year-old woman who had received long-term treatment with chloroquine for systemic lupus erythematosus developed a third degree atrioventricular block and required a permanent pacemaker. Notably, left ventricular thickening and mild systolic dysfunction were noticed on echocardiography as well as on cardiac MRI. As there was no clear explanation for myocardial findings, the patient underwent an endomyocardial biopsy that demonstrated vacuolar degeneration of myocytes on light microscopy and curvilinear bodies on electron microscopy, both findings consistent with chloroquine toxicity. The drug was withheld and treatment with candesartan and carvedilol was prescribed. At 2-year follow-up, the patient remained asymptomatic and left ventricular systolic function had improved. Physicians who prescribe antimalarial drugs for rheumatic diseases should be aware of the potentially life-threatening effects of chloroquine on the heart. PMID:25225192

  13. Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

    PubMed Central

    Ajaltouni, Jean

    2015-01-01

    The misuse of nootropics—any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters—may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of our knowledge this has not been previously reported in the formal medical literature. We briefly describe the most common classes of nootropics, including their postulated or proven methods of actions, their desired effects, and their adverse side effects, and provide a brief discussion of the cases. Our objective is to raise awareness among physicians in general and psychiatrists and addiction specialists in particular of the potentially dangerous phenomenon of unsupervised nootropic use among young adults who may be especially vulnerable to nootropics’ negative effects. PMID:27222762

  14. Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases.

    PubMed

    Talih, Farid; Ajaltouni, Jean

    2015-01-01

    The misuse of nootropics-any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters-may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of our knowledge this has not been previously reported in the formal medical literature. We briefly describe the most common classes of nootropics, including their postulated or proven methods of actions, their desired effects, and their adverse side effects, and provide a brief discussion of the cases. Our objective is to raise awareness among physicians in general and psychiatrists and addiction specialists in particular of the potentially dangerous phenomenon of unsupervised nootropic use among young adults who may be especially vulnerable to nootropics' negative effects. PMID:27222762

  15. Blood transcriptomics: applications in toxicology

    PubMed Central

    Joseph, Pius; Umbright, Christina; Sellamuthu, Rajendran

    2015-01-01

    The number of new chemicals that are being synthesized each year has been steadily increasing. While chemicals are of immense benefit to mankind, many of them have a significant negative impact, primarily owing to their inherent chemistry and toxicity, on the environment as well as human health. In addition to chemical exposures, human exposures to numerous non-chemical toxic agents take place in the environment and workplace. Given that human exposure to toxic agents is often unavoidable and many of these agents are found to have detrimental human health effects, it is important to develop strategies to prevent the adverse health effects associated with toxic exposures. Early detection of adverse health effects as well as a clear understanding of the mechanisms, especially at the molecular level, underlying these effects are key elements in preventing the adverse health effects associated with human exposure to toxic agents. Recent developments in genomics, especially transcriptomics, have prompted investigations into this important area of toxicology. Previous studies conducted in our laboratory and elsewhere have demonstrated the potential application of blood gene expression profiling as a sensitive, mechanistically relevant and practical surrogate approach for the early detection of adverse health effects associated with exposure to toxic agents. The advantages of blood gene expression profiling as a surrogate approach to detect early target organ toxicity and the molecular mechanisms underlying the toxicity are illustrated and discussed using recent studies on hepatotoxicity and pulmonary toxicity. Furthermore, the important challenges this emerging field in toxicology faces are presented in this review article. PMID:23456664

  16. Adverse Health Effects in Relation to Urban Residential Soundscapes

    NASA Astrophysics Data System (ADS)

    SKÅNBERG, A.; ÖHRSTRÖM, E.

    2002-02-01

    Noise pollution from road traffic in residential areas is a growing environmental problem. New approaches to turn the negative trend are needed. The programme “Soundscape Support to Health” will achieve new knowledge about the adverse health effects of noise pollution on humans and will investigate the link between well-being and health and perceived soundscapes for optimizing the acoustic soundscapes in urban residential areas. This paper will briefly present the programme and presents preliminary results from the first study of how various adverse health effects are related to individual noise exposures among individuals in residential areas with and without access to a quiet side of the dwelling.

  17. Translational toxicology: a developmental focus for integrated research strategies

    PubMed Central

    2013-01-01

    Background Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean? Discussion Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures. The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan 2) Defining modes of action and relevance of data from animal models 3) Use of mathematical models to develop plausible predictions as the basis for 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development. Summary Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics. PMID:24079609

  18. Amiodarone-induced hypothyroidism and other adverse effects.

    PubMed

    Mosher, Mary C

    2011-01-01

    Amiodarone is a class III antiarrhythmic agent that is frequently prescribed today for the treatment of ventricular and atrial arrhythmias. Amiodarone has many adverse effects, and one of them is thyroid dysfunction. Advanced practice and staff nurses need to be vigilant, recognizing early signs and symptoms of thyroid dysfunction to prevent adverse drug reactions. Often, the signs and symptoms of amiodarone-induced hypothyroidism are overlooked because of the complexity of the patient's condition. The purpose of this article was to review a case study, present differential diagnoses and testing, discuss risk factors associated with amiodarone-induced hypothyroidism, discuss its pathogenesis, and review clinical management. PMID:21307683

  19. Skin-lightening cosmetics: frequent, potentially severe adverse effects.

    PubMed

    2011-09-01

    Skin-lightening cosmetics are used by many women and men around the world. The products contain a variety of substances, which are often unknown to the users. Most of these products include topical corticosteroids, hydroquinone and mercury salts. Many other substances may be added. Several surveys and cohort studies, including several thousand individuals, have shown that regular application of skin-lightening cosmetics to large surface areas can have irreversible cutaneous adverse effects, such as patchy hyper- or hypopigmentation, skin atrophy, stretch marks and delayed wound healing, and can also mask or, on the contrary, promote or reactivate skin infections. Cases of skin cancer have been attributed to skin-lightening cosmetics. A Senegalese cohort study of 147 women showed a statistically significant increase in the risk of hypertension and diabetes linked to the use of skin-lightening agents. Other systemic adverse effects attributed to skin-lightening cosmetics include Cushing's syndrome, adrenal insufficiency, nephrotic syndrome, neurological disorders, and ocular disorders. Hypersensitivity reactions, including anaphylaxis, have also been attributed to these products. Many skin-lightening cosmetics contain substances that can harm the unborn child. For example, tretinoin is teratogenic while salicylic acid is feto-toxic. In practice, users are often unaware of the risk of severe adverse effects associated with skin-lightening cosmetics. Users should be informed of these adverse effects and encouraged to stop using these products, especially when skin disorders appear. PMID:21954516

  20. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... no significant adverse environmental effect. NOAA believes that exploration-type activities, as listed in the license regulations (15 CFR 970.701), require no further environmental assessment. (e... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY...

  1. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... no significant adverse environmental effect. NOAA believes that exploration-type activities, as listed in the license regulations (15 CFR 970.701), require no further environmental assessment. (e... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY...

  2. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental impact... listed in the license regulations (15 CFR 970.701), require no further environmental assessment....

  3. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental impact... listed in the license regulations (15 CFR 970.701), require no further environmental assessment....

  4. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental impact... listed in the license regulations (15 CFR 970.701), require no further environmental assessment....

  5. Mixed-effects Poisson regression analysis of adverse event reports

    PubMed Central

    Gibbons, Robert D.; Segawa, Eisuke; Karabatsos, George; Amatya, Anup K.; Bhaumik, Dulal K.; Brown, C. Hendricks; Kapur, Kush; Marcus, Sue M.; Hur, Kwan; Mann, J. John

    2008-01-01

    SUMMARY A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)’s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system. PMID:18404622

  6. Effect of wettability on adverse mobility immiscible floods

    SciTech Connect

    Vives, M.T.; Chang, Y.C.; Mohanty, K.K.

    1995-12-31

    Many immiscible displacements in reservoirs occur at adverse mobility. Effect of wettability on these displacements is not well understood and often ignored in reservoir simulation. Recent macroscopic theories of viscous fingering treat adverse immiscible flows similar to miscible flows, the mixing in the fingered region being controlled by a Todd-Longstaff-type functional form. The wettability of the medium is taken into account only through the use of appropriate relative permeabilities. The goal of this paper is to understand the macroscopic bypassing in adverse mobility immiscible floods. Immiscible displacements are conducted in a quarter 5-spot model in both drainage and imbibition modes at similar effective mobility ratios and viscous-to-gravity numbers. The level of bypassing and gravity override is visualized and measured. Tertiary water-alternating-gas (WAG) displacements are also conducted at various WAG ratios and viscosity ratios. Fractional flow analysis and numerical simulation are used to understand these displacements. Experiments show that macroscopic viscous fingering is present in adverse viscosity immiscible displacements where no saturation shock is expected from 1-D fractional flow theory. Bypassing due to both fingering and gravity override is higher in the drainage mode than in the imbibition mode, with other key parameters being the same. Optimum WAG ratio in water-wet rock is a function of oil/solvent viscosity ratio. The macroscopic flow theory needs to include capillarity and viscous fingering to match these experimental findings.

  7. TOXICOLOGICAL EFFECTS OF PARTICULATE MATTER DERIVED FROM THE DESTRUCTION OF THE WORLD TRADE CENTER

    EPA Science Inventory

    May 15, 2002
    Abstract submitted by Stephen H. Gavett for American Association for Aerosol Research (AAAR) annual meeting October 7-11, 2002 in Charlotte, NC.

    TOXICOLOGICAL EFFECTS OF PARTICULATE MATTER DERIVED FROM THE DESTRUCTION OF THE WORLD TRADE CENTER
    Stephen H ...

  8. Thai traditional massage: Issues causing possible adverse effects.

    PubMed

    Wiwanitkit, Viroj

    2015-01-01

    Thai traditional massage is a widely used massage technique in Thailand and is presently accepted by local Thai Ministry of Public Health. The technique is promoted but not well accepted internationally. There is a concern about the effectiveness as well as safety of this local wisdom. After a recent episode of concurrent acute heart attack and Thai traditional massage in a patient, the issue of possible adverse effects of Thai traditional massage is being widely discussed. PMID:26865746

  9. Thai traditional massage: Issues causing possible adverse effects

    PubMed Central

    Wiwanitkit, Viroj

    2015-01-01

    Thai traditional massage is a widely used massage technique in Thailand and is presently accepted by local Thai Ministry of Public Health. The technique is promoted but not well accepted internationally. There is a concern about the effectiveness as well as safety of this local wisdom. After a recent episode of concurrent acute heart attack and Thai traditional massage in a patient, the issue of possible adverse effects of Thai traditional massage is being widely discussed. PMID:26865746

  10. Energy Drink Consumption: Beneficial and Adverse Health Effects

    PubMed Central

    Alsunni, Ahmed Abdulrahman

    2015-01-01

    Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents. PMID:26715927

  11. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Toxic or adverse effect incident... Information § 159.184 Toxic or adverse effect incident reports. (a) General. Information about incidents... organism suffered a toxic or adverse effect, or may suffer a delayed or chronic adverse effect in...

  12. The adverse effects of sorafenib in patients with advanced cancers.

    PubMed

    Li, Ye; Gao, Zu-Hua; Qu, Xian-Jun

    2015-03-01

    Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in long-term efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers. PMID:25495944

  13. Adverse effects of common medications on male fertility.

    PubMed

    Samplaski, Mary K; Nangia, Ajay K

    2015-07-01

    An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic-pituitary-gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility. PMID:26101108

  14. The effects of air pollution on adverse birth outcomes

    PubMed Central

    Ha, Sandie; Hu, Hui; Roussos-Ross, Dikea; Haidong, Kan; Roth, Jeffrey; Xu, Xiaohui

    2014-01-01

    Background Air pollution has been shown to have adverse effects on many health outcomes including cardiorespiratory diseases and cancer. However, evidence on the effects of prenatal exposure is still limited. The purpose of this retrospective cohort study is to evaluate the effects of prenatal exposure to air pollutants including particulate matter with aerodynamic diameter less than 2.5 micrometer (PM2.5) and ozone (O3) on the risk of adverse birth outcomes (ABOs) including term low birth weight (LBW), preterm delivery (PTD) and very PTD (VPTD). Methods Singleton births from 2004–2005 in Florida were included in the study (N=423,719). Trimester-specific exposures to O3 and PM2.5 at maternal residence at delivery were estimated using the National Environmental Public Health Tracking Network data, which were interpolated using Hierarchical Bayesian models. Results After adjustment for potential confounders such as demographics, medical and lifestyle factors PM2.5 exposures in all trimesters were found to be significantly and positively associated with the risk of all ABOs. Second-trimester exposure had the strongest effects. For an interquartile range (IQR) increase in PM2.5 during the second trimester, the risk of term LBW, PTD and VPTD increased by 3% [95% confidence interval (CI): 1–6%)], 12% (11–14%) and 22% (18–25%), respectively. O3 was also found to be positively associated with PTD and VPTD with the strongest effects over the whole pregnancy period [3% (1–5%) for PTD and 13% (7–19%) for VPTD for each IQR increase]. However, O3 was observed to have protective effects on term LBW. Results were consistent for multi-pollutant models. Conclusion PM2.5 has consistent adverse effects on ABOs whereas O3 has inconsistent effects. These findings warrant further investigation. PMID:25173052

  15. Moving Upstream: Evaluating Adverse Upstream Endpoints for Improved Risk Assessment and Decision-Making

    EPA Science Inventory

    Background: Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and ...

  16. A Review of Epidemiological Research on Adverse Neurological Effects of Exposure to Ambient Air Pollution

    PubMed Central

    Xu, Xiaohui; Ha, Sandie Uyen; Basnet, Rakshya

    2016-01-01

    There is a growing body of epidemiological research reporting the neurological effects of ambient air pollution. We examined current evidence, identified the strengths and weaknesses of published epidemiological studies, and suggest future directions for research in this area. Studies were identified through a systematic search of online scientific databases, in addition to a manual search of the reference lists from the identified papers. Despite being a relatively new area of investigation, overall, there is mounting evidence implicating adverse effects of air pollution on neurobehavioral function in both adults and children. Further research is needed to expand our understanding of these relationships, including improvement in the accuracy of exposure assessments; focusing on specific toxicants and their relationships to specific health endpoints, such as neurodevelopmental disorders and neurodegenerative diseases; investigating the combined neurological effects of multiple air pollutants; and further exploration of genetic susceptibility for neurotoxicity of air pollution. In order to achieve these goals collaborative efforts are needed from multidisciplinary teams, including experts in toxicology, biostatistics, geographical science, epidemiology, and neurology. PMID:27547751

  17. A Review of Epidemiological Research on Adverse Neurological Effects of Exposure to Ambient Air Pollution.

    PubMed

    Xu, Xiaohui; Ha, Sandie Uyen; Basnet, Rakshya

    2016-01-01

    There is a growing body of epidemiological research reporting the neurological effects of ambient air pollution. We examined current evidence, identified the strengths and weaknesses of published epidemiological studies, and suggest future directions for research in this area. Studies were identified through a systematic search of online scientific databases, in addition to a manual search of the reference lists from the identified papers. Despite being a relatively new area of investigation, overall, there is mounting evidence implicating adverse effects of air pollution on neurobehavioral function in both adults and children. Further research is needed to expand our understanding of these relationships, including improvement in the accuracy of exposure assessments; focusing on specific toxicants and their relationships to specific health endpoints, such as neurodevelopmental disorders and neurodegenerative diseases; investigating the combined neurological effects of multiple air pollutants; and further exploration of genetic susceptibility for neurotoxicity of air pollution. In order to achieve these goals collaborative efforts are needed from multidisciplinary teams, including experts in toxicology, biostatistics, geographical science, epidemiology, and neurology. PMID:27547751

  18. Genetic toxicology: web resources.

    PubMed

    Young, Robert R

    2002-04-25

    Genetic toxicology is the scientific discipline dealing with the effects of chemical, physical and biological agents on the heredity of living organisms. The Internet offers a wide range of online digital resources for the field of Genetic Toxicology. The history of genetic toxicology and electronic data collections are reviewed. Web-based resources at US National Library of Medicine (NLM), including MEDLINE, PUBMED, Gateway, Entrez, and TOXNET, are discussed. Search strategies and Medical Subject Headings (MeSH) are reviewed in the context of genetic toxicology. The TOXNET group of databases are discussed with emphasis on those databases with genetic toxicology content including GENE-TOX, TOXLINE, Hazardous Substances Data Bank, Integrated Risk Information System, and Chemical Carcinogenesis Research Information System. Location of chemical information including chemical structure and linkage to health and regulatory information using CHEMIDPLUS at NLM and other databases is reviewed. Various government agencies have active genetic toxicology research programs or use genetic toxicology data to assist fulfilling the agency's mission. Online resources at the US Food and Drug Administration (FDA), the US Environmental Protection Agency (EPA), the National Institutes of Environmental Health Sciences, and the National Toxicology Program (NTP) are outlined. Much of the genetic toxicology for pharmaceuticals, industrial chemicals and pesticides that is performed in the world is regulatory-driven. Regulatory web resources are presented for the laws mandating testing, guidelines on study design, Good Laboratory Practice (GLP) regulations, and requirements for electronic data collection and reporting. The Internet provides a range of other supporting resources to the field of genetic toxicology. The web links for key professional societies and journals in genetic toxicology are listed. Distance education, educational media resources, and job placement services are also

  19. Some adverse effects of antipsychotics: prevention and treatment.

    PubMed

    Lader, M

    1999-01-01

    Antipsychotic medication causes a wide range of adverse effects, which can be serious and may further imperil both the physical and psychological health of schizophrenic patients. The range of side effects patients commonly encounter includes weight gain, endocrine disturbances, sedation, anticholinergic effects, hypotension, seizures, and extrapyramidal symptoms. Less common and unpredictable reactions are blood dyscrasias, cardiotoxicity, sudden death, and the neuroleptic malignant syndrome. Antipsychotic drugs differ significantly regarding their propensity to cause these reactions. Patients should undergo comprehensive health checks before an antipsychotic is prescribed, and drug therapy should be individualized to take account of any preexisting symptoms. Side effects and the wider implications of drug treatment, such as effects on occupational and social functioning, should be discussed with the patient before initiating therapy. Patients should be regularly monitored for side effects during treatment and switched to alternative therapy if side effects are serious and/or persistent. PMID:10372605

  20. The combined toxicological effects of titanium dioxide nanoparticles and bisphenol A on zebrafish embryos

    PubMed Central

    2014-01-01

    Environmental pollutants co-exist and exhibit interaction effects that are different from those associated with a single pollutant. As one of the more commonly manufactured nanomaterials, titanium dioxide nanoparticles (TiO2-NPs) are most likely to bind to other contaminants in water. In this paper, we aimed to study the combined toxicological effects of TiO2-NPs and bisphenol A (BPA) on organism. First, in vitro adsorption experiments were conducted to determine the adsorptive interaction between TiO2-NPs and BPA. Second, zebrafish embryo toxicity tests were performed to monitor for changes in the toxicological effects associated with the two chemicals. The study results demonstrated that adsorptive interactions exist between the two chemicals and increased toxicity effects which included an advanced toxicological effect time, decreased survival, increased morphological abnormalities, and delayed embryo hatching. Also, we suggest that the mode of combined action has a synergistic effect. Based on this, we postulate that concomitant exposure to TiO2-NPs and BPA increased BPA bioavailability and uptake into cells and organisms. Further studies are required to understand the mechanisms of interactions of this mixture. PMID:25177222

  1. The combined toxicological effects of titanium dioxide nanoparticles and bisphenol A on zebrafish embryos

    NASA Astrophysics Data System (ADS)

    Yan, Jun; Lin, Bencheng; Hu, Chuanlu; Zhang, Huashan; Lin, Zhiqing; Xi, Zhuge

    2014-08-01

    Environmental pollutants co-exist and exhibit interaction effects that are different from those associated with a single pollutant. As one of the more commonly manufactured nanomaterials, titanium dioxide nanoparticles (TiO2-NPs) are most likely to bind to other contaminants in water. In this paper, we aimed to study the combined toxicological effects of TiO2-NPs and bisphenol A (BPA) on organism. First, in vitro adsorption experiments were conducted to determine the adsorptive interaction between TiO2-NPs and BPA. Second, zebrafish embryo toxicity tests were performed to monitor for changes in the toxicological effects associated with the two chemicals. The study results demonstrated that adsorptive interactions exist between the two chemicals and increased toxicity effects which included an advanced toxicological effect time, decreased survival, increased morphological abnormalities, and delayed embryo hatching. Also, we suggest that the mode of combined action has a synergistic effect. Based on this, we postulate that concomitant exposure to TiO2-NPs and BPA increased BPA bioavailability and uptake into cells and organisms. Further studies are required to understand the mechanisms of interactions of this mixture.

  2. Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population-Level Effects

    SciTech Connect

    Kramer, Vincent J.; Etterson, Matthew A.; Hecker, Markus; Murphy, Cheryl A.; Roesijadi, Guritno; Spade, Daniel J.; Spromberg, Julann A.; Wang, Magnus; Ankley, Gerald T.

    2010-11-24

    The viability of populations of plants and animals is a key focus for environmental regulation. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-specifics, competitors, predators, prey, habitat and other biotic and abiotic factors. Models of population-level effects of contaminants can integrate information from lower levels of biological organization and feed that information into higher-level community and ecosystem models. As individual-level endpoints are utilized to predict population responses, this requires that biological responses at lower levels of organization be translated into a form that is useable by the population modeler. In this paper we describe how mechanistic data, as captured in adverse outcome pathways, can be translated into modeling focused on population-level risk assessments. First, we present a succinct overview of different approaches to population modeling, and discuss the types of data needed for these models. Then we discuss how toxicity data are used currently for population modeling, and provide recommendations as to how testing might be modified to better generate information to support modeling. From this we describe how different key processes measured at the level of the individual serve as the bridge between mechanistic toxicology data and predictions of population status, and provide case examples of how this linkage has been/can be achieved.

  3. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  4. Genetics of Common Antipsychotic-Induced Adverse Effects.

    PubMed

    MacNeil, Raymond R; Müller, Daniel J

    2016-07-01

    The effectiveness of antipsychotic drugs is limited due to accompanying adverse effects which can pose considerable health risks and lead to patient noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual susceptibility to antipsychotic-induced adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on findings that have been independently replicated and which have additionally been listed to be of interest by PGx expert panels. Gene-drug associations meeting these criteria primarily pertain to metabolic dysregulation, extrapyramidal symptoms (EPS), and tardive dyskinesia (TD). Regarding metabolic dysregulation, results have reaffirmed HTR2C as a strong candidate with potential clinical utility, while MC4R and OGFR1 gene loci have emerged as new and promising biomarkers for the prediction of weight gain. As for EPS and TD, additional evidence has accumulated in support of an association with CYP2D6 metabolizer status. Furthermore, HSPG2 and DPP6 have been identified as candidate genes with the potential to predict differential susceptibility to TD. Overall, considerable progress has been made within the field of psychiatric PGx, with inroads toward the development of clinical tools that can mitigate AAEs. Going forward, studies placing a greater emphasis on multilocus effects will need to be conducted. PMID:27606321

  5. Adverse health effects of anabolic-androgenic steroids.

    PubMed

    van Amsterdam, Jan; Opperhuizen, Antoon; Hartgens, Fred

    2010-06-01

    Anabolic-androgenic steroids (AAS) are synthetic drugs derived from testosterone. Illegally, these drugs are regularly self-administered by body builders and power lifters to enhance their sportive performance. Adverse side effects of AAS include sexual dysfunction, alterations of the cardiovascular system, psyche and behavior, and liver toxicity. However, severe side effects appear only following prolonged use of AAS at high dose and their occurrence is limited. Occasionally, AAS abuse may be linked to certain social and psychological traits of the user, like low self-esteem, low self-confidence, suffered hostility, childhood conduct disorder, and tendency to high-risk behavior. The overwhelming stereotype about AAS is that these compounds cause aggressive behavior in males. However, the underlying personality traits of a specific subgroup of the AAS abusers, who show aggression and hostility, may be relevant, as well. Use of AAS in combination with alcohol largely increases the risk of violence and aggression. The dependence liability of AAS is very low, and withdrawal effects are relatively mild. Based on the scores for acute and chronic adverse health effects, the prevalence of use, social harm and criminality, AAS were ranked among 19 illicit drugs as a group of drugs with a relatively low harm. PMID:20153798

  6. Countermeasures for space radiation induced adverse biologic effects

    NASA Astrophysics Data System (ADS)

    Kennedy, A. R.; Wan, X. S.

    2011-11-01

    Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

  7. Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products

    PubMed Central

    Bersani, F. Saverio; Coviello, Marialuce; Imperatori, Claudio; Francesconi, Marta; Hough, Christina M.; Valeriani, Giuseppe; De Stefano, Gianfranco; Bolzan Mariotti Posocco, Flaminia; Santacroce, Rita; Minichino, Amedeo; Corazza, Ornella

    2015-01-01

    Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs) as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs) often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications. PMID:26457296

  8. Vaginal douching and adverse health effects: a meta-analysis.

    PubMed Central

    Zhang, J; Thomas, A G; Leybovich, E

    1997-01-01

    OBJECTIVES: The meta-analysis described here reviewed the current literature on adverse health effects of vaginal douching. METHODS: Papers published in English from 1965 through 1995 were potentially eligible. RESULTS: One third of White women and two thirds of Black women of reproductive age reported douching regularly. Analyses indicated that vaginal douching increases the overall risk of pelvic inflammatory disease by 73% and the risk of ectopic pregnancy by 76%. Frequent douching was shown to be highly associated with pelvic inflammatory disease and modestly associated with cervical cancer. CONCLUSIONS: Current literature suggests that frequent douching increases the risk of pelvic inflammatory disease, ectopic pregnancy, and, possibly, cervical cancer. PMID:9240115

  9. Palmar-plantar erythrodysesthesia: An uncommon adverse effect of everolimus

    PubMed Central

    Arora, Shalabh; Akhil, Rajendra; Chacko, Raju Titus; George, Renu

    2016-01-01

    Mammalian target of rapamycin inhibitor everolimus is a novel agent used in endocrine therapy resistant hormone receptor positive metastatic breast cancer. Its use has been associated with clinically significant improvement in the otherwise dismal outcomes of this subset of patients. Rash is a common adverse effect associated with everolimus. However, Hand-foot syndrome is an uncommon toxicity with the use of this drug. We report a case of Grade 3 hand-foot syndrome following institution of everolimus therapy and describe its successful management. PMID:27168711

  10. CN-15ADVERSE EFFECTS OF BEVACIZUMAB IN BRAIN TUMOR PATIENTS

    PubMed Central

    Pawar, Tushar; Ladha, Harshad; Mandel, Jacob; Gilbert, Mark; O'Brien, Barbara; Hamza, Mohamed; Armstrong, Terri

    2014-01-01

    BACKGROUND: Bevacizumab is humanized monoclonal antibody inhibiting angiogenesis and the only FDA approved treatment for recurrent glioblastoma. The aim of this study was to look at the occurrence of various adverse effects associated with use of bevacizumab in recurrent glioblastoma. METHODS: In this retrospective chart review, we studied 280 patients with recurrent glioblastoma treated with Bevacizumab between 2005-2011 to characterize the known adverse effects of bevacizumab including hypertension, grade 3-4 myelosuppression, wound healing complications, thrombo-embolic events, stroke, hemorrhage and gastrointestinal complications. RESULTS: The study population included 168 males and 112 females. The median age was 53.5 years(range 8.1-81.3). TREATMENT: Bevacizumab only(58), Bevacizumab + CPT(11), Bevacizumab + TMZ(32) or Bevacizumab + Other(34). Patients were treated at recurrence(1st = 96; 2nd = 126, 3rd = 58). Hypertension was the most common adverse effect occurring in 131(49%). The median duration from treatment start to development was 82 days (Range 7-1143). However, only 33(25%) were started on antihypertensive medication. Grade 3-4 Myelosuppression occurred in 52(19%)causing treatment discontinuation in 8. Thrombo-embolic events were reported in 5%(15) patients including DVT(9), PE(2), Central venous thrombosis(1) and Stroke(3). Thirty-six patients (13%) were on anti-coagulant medication at bevacizumab initiation. Median time to a thromboembolic complication was 113 days (Range 8-1145). Wound healing complications were noted in 7(3%) patients, 3 craniotomy dehiscence and 4 at soft tissue sites. Five patients (2%) developed GI complications, including perforations(3), pancreatitis(1), and diverticulitis(1). Median time to development was 92 days(Range 10-651). There was a high rate 46%(129) of grade 3-4 lymphocytopenia; median time to develop lymphocytopenia was 50 days(Range = 3-564). CONCLUSION: The range of toxicities was similar to other reports

  11. Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products.

    PubMed

    Bersani, F Saverio; Coviello, Marialuce; Imperatori, Claudio; Francesconi, Marta; Hough, Christina M; Valeriani, Giuseppe; De Stefano, Gianfranco; Bolzan Mariotti Posocco, Flaminia; Santacroce, Rita; Minichino, Amedeo; Corazza, Ornella

    2015-01-01

    Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs) as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs) often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications. PMID:26457296

  12. COMPUTATIONAL TOXICOLOGY

    EPA Science Inventory

    Over the last several years, there has been increased pressure to utilize novel technologies derived from computational chemistry, molecular biology and systems biology in toxicological risk assessment. This new area has been referred to as "Computational Toxicology". Our resear...

  13. Adverse effects of antiretroviral therapy for HIV infection.

    PubMed

    Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

    2004-01-20

    Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. PMID:14734438

  14. An argument for the chicken embryo as a model for the developmental toxicological effects of the polyhalogenated aromatic hydrocarbons (PHAHs)

    SciTech Connect

    Henshel, D.S.

    1996-12-31

    This article will present the argument that the chicken embryo is especially appropriate as an animal model for studying the mechanism of the developmental toxicological effects of the polyhalogenated aromatic hydrocarbons (PHAHs). The PHAHs are a group of toxicologically related compounds including, in part, the polychlorinated dibenzodioxins, dibenzofurans and biphenyls. The chicken (Gallus gallus) embryo is relatively sensitive to the toxicological effects of the PHAHs being approximately two orders of magnitude more sensitive than the mature bird. The chicken embryo has been used to demonstrate general toxicological teratogeneicity, hepatotoxicity and neurotoxicity. Many of these effects, or analogous effects, have also been observed in mammals and fish. Thus, most animals appear to respond to the PHAHs with a similar toxicological profile, indicating that many of the biomarkers used for the PHAHs are valid across a number of species, including the chicken. Furthermore, the chicken embryo is relatively inexpensive to use for toxicity testing. In addition, all effects detected are due to direct effects on the embryo and are not complicated by maternal interactions. In short, for sensitivity, ease of use, cost and applicability of results to other animals, the chicken embryo is an excellent animal model for evaluation of the mechanism underlying the developmental toxicological effects of the PHAHs.

  15. Potential health effects of gasoline and its constituents: A review of current literature (1990-1997) on toxicological data.

    PubMed Central

    Caprino, L; Togna, G I

    1998-01-01

    We reviewed toxicological studies, both experimental and epidemiological, that appeared in international literature in the period 1990-1997 and included both leaded and unleaded gasolines as well as their components and additives. The aim of this overview was to select, arrange, and present references of scientific papers published during the period under consideration and to summarize the data in order to give a comprehensive picture of the results of toxicological studies performed in laboratory animals (including carcinogenic, teratogenic, or embryotoxic activity), mutagenicity and genotoxic aspects in mammalian and bacterial systems, and epidemiological results obtained in humans in relation to gasoline exposure. This paper draws attention to the inherent difficulties in assessing with precision any potential adverse effects on health, that is, the risk of possible damage to man and his environment from gasoline. The difficulty of risk assessment still exists despite the fact that the studies examined are definitely more technically valid than those of earlier years. The uncertainty in overall risk determination from gasoline exposure also derives from the conflicting results of different studies, from the lack of a correct scientific approach in some studies, from the variable characteristics of the different gasoline mixtures, and from the difficulties of correctly handling potentially confounding variables related to lifestyle (e.g., cigarette smoking, drug use) or to preexisting pathological conditions. In this respect, this paper highlights the need for accurately assessing the conclusive explanations reported in scientific papers so as to avoid the spread of inaccurate or misleading information on gasoline toxicity in nonscientific papers and in mass-media messages. PMID:9452413

  16. Adverse effects of outdoor pollution in the elderly

    PubMed Central

    Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  17. Adverse effects of outdoor pollution in the elderly.

    PubMed

    Simoni, Marzia; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  18. Mechanisms and assessment of statin-related muscular adverse effects

    PubMed Central

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-01-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

  19. Adverse effects of gentamicin in scarlet macaws and galahs.

    PubMed

    Flammer, K; Clark, C H; Drewes, L A; Wilson, R C; Fiorello-Barrett, J

    1990-03-01

    The adverse effects of administration of gentamicin (5 mg/kg of body weight, IM, q 12 h) for 7 days were studied in healthy scarlet macaws (Ara macao) and galahs (Eolophus roseicapillus; cockatoos). Polydipsia and polyuria developed in each species, but were greater and persisted longer in the cockatoos. Peak water intake in the cockatoos more than quadrupled, and remained increased for 23 days after cessation of gentamicin administration. Plasma aspartate transaminase activity increased significantly (P less than 0.05) after treatment in the macaws, and plasma aspartate transaminase and lactate dehydrogenase activities increased in the cockatoos. Single IM administration of gentamicin (5 mg/kg) resulted in mean (+/- SEM) plasma concentration of 20.6 (+/- 1.85) micrograms/ml at 0.5 hour for either species of birds. There were no significant differences between mean plasma gentamicin concentrations for cockatoos and macaws at any time after drug administration, except at 12 hours, when values for cockatoos were significantly (P less than 0.05) greater than those for macaws. The elimination half-life for gentamicin after IM administration of 5 and 10 mg/kg was 1.17 and 1.07 hours, respectively, for macaws and 1.23 and 1.44 hours, respectively, for cockatoos. Correlation between drug disposition and adverse side effects could not be detected. PMID:2316918

  20. Adverse effects associated with arginine alpha-ketoglutarate containing supplements.

    PubMed

    Prosser, J M; Majlesi, N; Chan, G M; Olsen, D; Hoffman, R S; Nelson, L S

    2009-05-01

    The athletic performance supplement industry is a multibillion-dollar business and one popular category claims to increase nitric oxide (NO) production. We report three patients presenting to the emergency department with adverse effects. A 33-year-old man presented with palpitations, dizziness, vomiting, and syncope, after the use of NO(2) platinum. His examination and electrocardiogram (ECG) were normal. The dizziness persisted, requiring admission overnight. A 21-year-old man with palpitations and near syncope had used a "nitric oxide" supplement. He was tachycardic to 115 bpm with otherwise normal examination. Laboratory values including methemoglobin, and ECG were unremarkable. He was treated with 1 L of saline with no change in heart rate. He was admitted for observation. A 24-year-old man presented after taking NO-Xplode with palpitations and a headache. His examination, laboratory values, and ECG were normal. He was discharged. The purported active ingredient in these products is arginine alpha-ketoglutarate (AAKG), which is claimed to increase NO production by supplying the precursor L-arginine. The symptoms could be due to vasodilation from increased levels of NO, though other etiologies cannot be excluded. AAKG containing supplements may be associated with adverse effects requiring hospital admission. PMID:19755457

  1. [Analgesics in geriatric patients. Adverse side effects and interactions].

    PubMed

    Gosch, Markus

    2015-07-01

    Pain is a widespread symptom in clinical practice. Older adults and chronically ill patients are particularly affected. In multimorbid geriatric patients, pharmacological pain treatment is an extension of a previously existing multimedication. Besides the efficacy of pain treatment, drug side effects and drug-drug interactions have to be taken into account to minimize the health risk for these patients. Apart from the number of prescriptions, the age-related pharmacokinetic and pharmacodynamic changes significantly increase the risk among older adults. The use of non-steroidal anti-inflammatory drugs (NSAID) is widespread but NSAIDs have the highest risk of adverse drug reactions and drug interactions. In particular, the gastrointestinal, cardiovascular, renal and coagulation systems are affected. Apart from the known toxic effect on the liver (in high doses), paracetamol (acetaminophen) has similar risks although to a lesser degree. According to current data, metamizol is actually better than its reputation suggests. The risk of potential drug interactions seems to be low. Apart from the risk of sedation in combination with other drugs, tramadol and other opioids can induce the serotonin syndrome. Among older adults, especially in the case of polypharmacy, an individualized approach should be considered instead of sticking to the pain management recommended by the World Health Organization (WHO) in order to minimize drug-drug interactions and adverse drug reactions. PMID:26152872

  2. Toxicological effects of chlorpyrifos on growth, enzyme activity and chlorophyll a synthesis of freshwater microalgae.

    PubMed

    Chen, Shangchao; Chen, Mindong; Wang, Zhuang; Qiu, Weijian; Wang, Junfeng; Shen, Yafei; Wang, Yajun; Ge, Shun

    2016-07-01

    This paper aims to acquire the experimental data on the eco-toxicological effects of agricultural pollutants on the aquatic plants and the data can support the assessment of toxicity on the phytoplankton. The pesticide of Chlorpyrifos used as a good model to investigate its eco-toxicological effect on the different microalgae in freshwater. In order to address the pollutants derived from forestry and agricultural applications, freshwater microalgae were considered as a good sample to investigate the impact of pesticides such as Chlorpyrifos on aquatic life species. Two microalgae of Chlorella pyrenoidosa and Merismopedia sp. were employed to evaluate toxicity of Chlorpyrifos in short time and long time by means of measuring the growth inhibition rate, the redox system and the content of chlorophyll a, respectively. In this study, the results showed that EC50 values ranging from 7.63 to 19.64mg/L, indicating the Chlorpyrifos had a relatively limited to the growth of algae during the period of the acute toxicity experiment. Moreover, when two kinds of algae were exposed to a medium level of Chlorpyrifos, SOD and CAT activities were importantly advanced. Therefore, the growth rate and SOD and CAT activities can be highly recommended for the eco-toxicological assessment. In addition, chlorophyll a also could be used as a targeted parameter for assessing the eco-toxicity of Chlorpyrifos on both Chlorella pyrenoidosa and Merismopedia sp. PMID:27314761

  3. Comprehensive approach for predicting toxicological effects of ionic liquids on several biological systems using unified descriptors.

    PubMed

    Cho, Chul-Woong; Stolte, Stefan; Yun, Yeoung-Sang

    2016-01-01

    The challenge and opportunity for design of environmentally-benign ionic liquids (ILs) would start from prediction of their toxicological effects on several endpoints solely based on the structural formulas. Especially, a comprehensive yet simple equation able to predict several biological responses to IL toxicity is of much advantage. Therefore, based on 50 toxicity testing systems on ILs a comprehensively approachable prediction method was developed. For the modelling, approximately 1600 toxicity values measured by several biological systems and an amended linear free energy relationship (LFER) model were used. Since the toxicological activities of an IL could be differently described according to sensitivity of toxicity testing systems, the sensitivity of each of toxicity testing systems was also estimated in the modelling. By statistical analysis with the calculated descriptors, a LFER model was built. Also the sensitivity value of each system on the basis of the comprehensively approachable model was numerically estimated. In results, it was observed that the combination of single model and sensitivity terms was able to predict each of 50 toxicological effects of ILs with R(2) of 0.593~0.978, and SE of 0.098~0.699 log unit, and the total data set with R(2) of 0.901 and SE of 0.426 log unit. PMID:27624396

  4. Quantification of toxicological effects for dichloromethane. Final report

    SciTech Connect

    Not Available

    1992-01-01

    The document discusses the quantification of non-carcinogenic effects and carcinogenic effects for dichloromethane. The evaluation of non-carcinogenic effects includes a study of short and long term effects in animals and humans, as well as the development of the one-day, ten-day, and long term health advisories. The evaluation of carcinogenic effects includes a categorization of carcinogenic potential and risks estimates. There is a brief discussion on existing guidelines or standards and special considerations such as high risk groups.

  5. Adverse testicular effects of Botox® in mature rats

    SciTech Connect

    Breikaa, Randa M.; Mosli, Hisham A.; Nagy, Ayman A.; Abdel-Naim, Ashraf B.

    2014-03-01

    Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicular function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause. - Highlights: • Botox® injections are the trend nowadays, for both medical and non-medical uses. • They were recently suggested for cryptorchidism and

  6. Adverse Biological Effect of TiO2 and Hydroxyapatite Nanoparticles Used in Bone Repair and Replacement

    PubMed Central

    Wang, Jiangxue; Wang, Liting; Fan, Yubo

    2016-01-01

    The adverse biological effect of nanoparticles is an unavoidable scientific problem because of their small size and high surface activity. In this review, we focus on nano-hydroxyapatite and TiO2 nanoparticles (NPs) to clarify the potential systemic toxicological effect and cytotoxic response of wear nanoparticles because they are attractive materials for bone implants and are widely investigated to promote the repair and reconstruction of bone. The wear nanoparticles would be prone to binding with proteins to form protein-particle complexes, to interacting with visible components in the blood including erythrocytes, leukocytes, and platelets, and to being phagocytosed by macrophages or fibroblasts to deposit in the local tissue, leading to the formation of fibrous local pseudocapsules. These particles would also be translocated to and disseminated into the main organs such as the lung, liver and spleen via blood circulation. The inflammatory response, oxidative stress, and signaling pathway are elaborated to analyze the potential toxicological mechanism. Inhibition of the oxidative stress response and signaling transduction may be a new therapeutic strategy for wear debris–mediated osteolysis. Developing biomimetic materials with better biocompatibility is our goal for orthopedic implants. PMID:27231896

  7. Adverse effects of drugs on the immature kidney.

    PubMed

    Guignard, J P; Gouyon, J B

    1988-01-01

    The immature kidney may be adversely affected by a variety of vasoactive or diuretic drugs, either administered to the mother during pregnancy, or to the neonate. Inhibitors of the angiotensin-converting enzyme administered to the hypertensive pregnant woman can severely and sometimes definitely impair renal function in the fetus, leading to postnatal anuria. Pathogenesis involves interference with the renin-angiotensin system and the prostaglandins. Beta-adrenergic agents administered during labor depress glomerular filtration rate transiently. Tolazoline, an alpha-adrenergic blocking agent useful in the treatment of persistent pulmonary hypertension of the neonate induces intense renal vasoconstriction with consequent hypoperfusion. Indomethacin, a prostaglandin synthetase inhibitor used for the pharmacological closure of a patent ductus arteriosus, also increases renal vascular resistance, and decreases urine output. Furosemide, the drug most often used in oliguric neonates, may also adversely affect the newborn infant. Its use has been associated with an increase in the incidence of patent ductus arteriosus, hypercalciuria, nephrocalcinosis and secondary hyperparathyroidism. These observations demonstrate that the proper use of drugs requires that the therapeutic endpoint be clearly defined and the predictable side effects be anticipated. PMID:2901276

  8. Characterization of Soy Biodiesel Exhaust and Toxicological Effects in Mice

    EPA Science Inventory

    Although biofuel use across the world is increasing, very little is known about possible health effects resulting from biofuel exhaust (BE) from this relatively new source of transportation fuel. The U.S. EPA has instigated an in vivo screening approach in rodents to examine whet...

  9. HYGROSCOPIC GROWTH: ITS EFFECT ON AEROSOL THERAPY AND INHALATION TOXICOLOGY

    EPA Science Inventory

    The success of an aerosol therapy protocol is contingent upon a proper quantity of drug being delivered to an appropriate site within the respiratory tract to elicit a therapeutic effect. Likewise, an accurate risk assessment of the threat to human health presented by airborne po...

  10. TOXICOLOGICAL EFFECTS OF CHLORINE DIOXIDE, CHLORITE AND CHLORATE

    EPA Science Inventory

    Review of the available literature obtained from both acute and chronic experiments utilizing rats, mice and chickens treated with Cl02, Cl02 and Cl03 in drinking water has demonstrated alterations in hematologic parameters in all species tested. The effects were usually dose rel...

  11. Does Cannabidiol Protect Against Adverse Psychological Effects of THC?

    PubMed

    Niesink, Raymond J M; van Laar, Margriet W

    2013-01-01

    The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD). A literature search was performed in the bibliographic databases PubMed, PsycINFO, and Web of Science using the keyword "cannabidiol." After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone's individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users. PMID:24137134

  12. Does Cannabidiol Protect Against Adverse Psychological Effects of THC?

    PubMed Central

    Niesink, Raymond J. M.; van Laar, Margriet W.

    2013-01-01

    The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD). A literature search was performed in the bibliographic databases PubMed, PsycINFO, and Web of Science using the keyword “cannabidiol.” After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone’s individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users. PMID:24137134

  13. Discovery of thiazolylpyridinone SCD1 inhibitors with preferential liver distribution and reduced mechanism-based adverse effects.

    PubMed

    Sun, Shaoyi; Zhang, Zaihui; Raina, Vandna; Pokrovskaia, Natalia; Hou, Duanjie; Namdari, Rostam; Khakh, Kuldip; Ratkay, Leslie G; McLaren, David G; Mork, Monica; Fu, Jianmin; Ferreira, Suzie; Hubbard, Brian; Winther, Michael D; Dales, Natalie

    2014-01-15

    We discovered a series of novel and potent thiazolylpyridinone-based SCD1 inhibitors based on a 2-aminothiazole HTS hit by replacing the amide bond with a pyridinone moiety. Compound 19 demonstrated good potency against SCD1 in vitro and in vivo. The mouse liver microsomal SCD1 in vitro potency for 19 was improved by more than 240-fold compared to the original HTS hit. Furthermore, 19 demonstrated a dose-dependent reduction of plasma desaturation index with an ED50 of 6.3 mg/kg. Compound 19 demonstrated high liver to plasma and liver to eyelid exposures, indicating preferential liver distribution. The preliminary toxicology study with compound 19 did not demonstrate adverse effects related to SCD1 inhibition, suggesting a wide safety margin with respect to other known SCD1 inhibitors with wider distribution profiles. PMID:24370012

  14. Toxicology research for precautionary decision-making and the role of Human & Experimental Toxicology.

    PubMed

    Grandjean, P

    2015-12-01

    A key aim of toxicology is the prevention of adverse effects due to toxic hazards. Therefore, the dissemination of toxicology research findings must confront two important challenges: one being the lack of information on the vast majority of potentially toxic industrial chemicals and the other being the strict criteria for scientific proof usually required for decision-making in regard to prevention. The present study ascertains the coverage of environmental chemicals in four volumes of Human & Experimental Toxicology and the presentation and interpretation of research findings in published articles. Links in SciFinder showed that the 530 articles published in four selected volumes between 1984 and 2014 primarily dealt with metals (126 links) and other toxicants that have received substantial attention in the past. Thirteen compounds identified by US authorities in 2006 as high-priority substances, for which toxicology documentation is badly needed, were not covered in the journal issues at all. When reviewing published articles, reliance on p values was standard, and non-significant findings were often called 'negative.' This tradition may contribute to the perceived need to extend existing research on toxic hazards that have already been well characterized. Several sources of bias towards the null hypothesis can affect toxicology research, but are generally not considered, thus adding to the current inclination to avoid false positive findings. In this regard, toxicology is particularly prone to bias because of the known paucity of false positives and, in particular, the existence of a vast number of toxic hazards which by default are considered innocuous due to lack of documentation. The Precautionary Principle could inspire decision-making on the basis of incomplete documentation and should stimulate a change in toxicology traditions and in toxicology research publication. PMID:26614810

  15. What are the toxicological effects of mercury in Arctic biota?

    PubMed

    Dietz, Rune; Sonne, Christian; Basu, Niladri; Braune, Birgit; O'Hara, Todd; Letcher, Robert J; Scheuhammer, Tony; Andersen, Magnus; Andreasen, Claus; Andriashek, Dennis; Asmund, Gert; Aubail, Aurore; Baagøe, Hans; Born, Erik W; Chan, Hing M; Derocher, Andrew E; Grandjean, Philippe; Knott, Katrina; Kirkegaard, Maja; Krey, Anke; Lunn, Nick; Messier, Francoise; Obbard, Marty; Olsen, Morten T; Ostertag, Sonja; Peacock, Elizabeth; Renzoni, Aristeo; Rigét, Frank F; Skaare, Janneche Utne; Stern, Gary; Stirling, Ian; Taylor, Mitch; Wiig, Øystein; Wilson, Simon; Aars, Jon

    2013-01-15

    This review critically evaluates the available mercury (Hg) data in Arctic marine biota and the Inuit population against toxicity threshold values. In particular marine top predators exhibit concentrations of mercury in their tissues and organs that are believed to exceed thresholds for biological effects. Species whose concentrations exceed threshold values include the polar bears (Ursus maritimus), beluga whale (Delphinapterus leucas), pilot whale (Globicephala melas), hooded seal (Cystophora cristata), a few seabird species, and landlocked Arctic char (Salvelinus alpinus). Toothed whales appear to be one of the most vulnerable groups, with high concentrations of mercury recorded in brain tissue with associated signs of neurochemical effects. Evidence of increasing concentrations in mercury in some biota in Arctic Canada and Greenland is therefore a concern with respect to ecosystem health. PMID:23231888

  16. Prolonged Ventricular Asystole: A Rare Adverse Effect of Hydrocodone Use

    PubMed Central

    Sudhakaran, Sivakumar; Surani, Saherish S.; Surani, Salim R.

    2014-01-01

    Patient: Female, 56 Final Diagnosis: Ventricular asystole Symptoms: Dizziness, headache, near-syncope, weakness Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background: Prolonged ventricular asystole is a rare vagal reaction caused by hydrocodone use. Sinus bradycardia is a characteristic presentation of the vasovagal response; examples of other presentations include arrest or atrioventricular block. Physicians need to be aware of ventricular asystole due to vagally-mediated atrioventricular block caused by hydrocodone or other opiates. Case Report: We present a case of prolonged ventricular asystole in a young patient due to a vasovagal reaction caused by the hydrocodone found in the hydrocodone/acetaminophen combination. Conclusions: Ventricular asystole can be a rare complication of hydrocodone found in hydrocodone/acetaminophen. Physicians need to be aware of this adverse effect, rather then resorting to expensive diagnostic interventions. PMID:25330933

  17. Toxicological effects of multi-walled carbon nanotubes on Saccharomyces cerevisiae: The uptake kinetics and mechanisms and the toxic responses.

    PubMed

    Zhu, Song; Zhu, Bin; Huang, Aiguo; Hu, Yang; Wang, Gaoxue; Ling, Fei

    2016-11-15

    Using Saccharomyces cerevisiae as an experimental model, the potential toxicological effects of oxidized multi-walled carbon nanotubes (MWCNTs) were investigated following exposure to 0-600mg/L for 24h. Results indicated that MWCNTs (>100mg/L) had adverse effects on the cell proliferation. MWCNTs were clearly visible in lysosome, vacuole, endosome, mitochondria, multivesicular body and localization in the perinuclear region. The uptake kinetics data demonstrated that the maximum MWCNTs content (209.61mg/g) was reached at 3h, and a steady state was reached after 18h. Based on the combined results of transmission electron microscope, endocytosis inhibition experiments and endocytosis-related genes (END3, END6, Sla2 and Rsp5) expression analysis, we elucidated MWCNTs uptake mechanism: (i) via a direct penetration of single MWCNTs; (ii) via endocytosis of single MWCNTs; and (iii) via endocytosis of MWCNTs aggregates. The percentage of apoptosis was significant increased at 600mg/L. The decrease of mitochondrial transmembrane potential and the leakage of cytochrome c shown dose-dependent manners. Interestingly, there was no significant increase of reactive oxygen species (ROS). The apoptosis-related genes (SOD1, SOD2, Yca1, Nma111 and Nuc1) were significant changed. These results obtained in our study demonstrated that oxidized MWCNTs induce Saccharomyces cerevisiae apoptosis via mitochondrial impairment pathway. PMID:27475463

  18. Proteomics for systems toxicology

    PubMed Central

    Titz, Bjoern; Elamin, Ashraf; Martin, Florian; Schneider, Thomas; Dijon, Sophie; Ivanov, Nikolai V.; Hoeng, Julia; Peitsch, Manuel C.

    2014-01-01

    Current toxicology studies frequently lack measurements at molecular resolution to enable a more mechanism-based and predictive toxicological assessment. Recently, a systems toxicology assessment framework has been proposed, which combines conventional toxicological assessment strategies with system-wide measurement methods and computational analysis approaches from the field of systems biology. Proteomic measurements are an integral component of this integrative strategy because protein alterations closely mirror biological effects, such as biological stress responses or global tissue alterations. Here, we provide an overview of the technical foundations and highlight select applications of proteomics for systems toxicology studies. With a focus on mass spectrometry-based proteomics, we summarize the experimental methods for quantitative proteomics and describe the computational approaches used to derive biological/mechanistic insights from these datasets. To illustrate how proteomics has been successfully employed to address mechanistic questions in toxicology, we summarized several case studies. Overall, we provide the technical and conceptual foundation for the integration of proteomic measurements in a more comprehensive systems toxicology assessment framework. We conclude that, owing to the critical importance of protein-level measurements and recent technological advances, proteomics will be an integral part of integrative systems toxicology approaches in the future. PMID:25379146

  19. Toxicological profile for methyl t-butyl ether

    SciTech Connect

    1996-08-01

    Each profile includes: (1) The examination, summary, and interpretation of available toxicologic information and epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human exposure for the substance and the associated acute, subacute, and chronic health effects; (2) A determination of whether adequate information on the health effects of each substance is available or in the process of development to determine levels of exposure that present a significant risk to human health of acute, subacute, and chonic health effects; and (3) Where appropriate, identification of toxicologic testing needed to identify the types or levels of exposure that may present significant risk of adverse health effects in humans.

  20. Genetic toxicology of phthalate esters: mutagenic and other genotoxic effects.

    PubMed Central

    Douglas, G R; Hugenholtz, A P; Blakey, D H

    1986-01-01

    The effects of DEHP on sperm morphology and on peripheral blood micronuclei were studied for 12 weeks following five subacute IP injections of DEHP at 1/6, 1/12, and 1/60 of the LD50 per day. Sperm morphology was examined in both adult mice and rats, while peripheral blood micronuclei were scored in mice up to 4 weeks after treatment. In mice, DEHP at 1/6 LD50 significantly depressed body weight gain for up to 12 weeks after treatment, and reduced epididymal sperm number by 4 weeks. Numbers of morphologically abnormal sperm did not differ from controls in the 12 weeks following treatment. In addition, DEHP did not increase the numbers of peripheral blood micronuclei. Studies in the rat indicated that exposure to doses of 1/6 and 1/12 of the LD50 per day of DEHP resulted in a reduced gain in body weight compared to controls. Testis weight, sperm number, and numbers of morphologically abnormal sperm were unaffected by DEHP following treatment. In separate experiments, DEHP did not induce sister chromatid exchange (SCE) or DNA damage in Chinese hamster ovary (CHO) cells. Although DEHP is known to cause testicular atrophy in rats and to a lesser extent in mice, it did not cause an increase in abnormal sperm in either species. Together with the CHO and micronucleus data, these findings suggest that DEHP has a low probability of causing genetic damage capable of being transmitted through the male germ line. PMID:3709450

  1. [Toxicological effects of nitrate: biological study in human and animal].

    PubMed

    Boukerche, S; Aouacheri, W; Saka, S

    2007-01-01

    In order to evaluate the effects of the nitrates toxicity, a study has been carried out on 45 workers of storage and distribution agricultural manures, exposed to nitrate derivatives. Another experimental study has carried out in laboratory on male Albinos wistar rats. These latter were treated with ammonium nitrate (NH(4)NO(3)) introduced by gavage with three increasing concentrations 200, 400 and 600 mg/kg of body weight during three weeks. The biochemical and hematological results on workers showed that no poisoning was announced within this complex, in spite of the observation of kidneys inflammations among about 50% of the population. The chemical treatment of the rats causes a variation in the biochemical and biological parameters: an increase of the hepato-somatic ratio especially in the rats treated by important doses. Moreover, the serum concentration in glucose, cholesterol, creatinin, lactate dehydrogenase and in transaminases (GOT, GPT) was increased significantly compared to the witness in all the treated rats. At the end, the results obtained highlight the detoxifier potential expressed by the reduction in the glutathione level in the deferent organs such as the liver, the kidneys, the spleen, the intestines and the testicles. According to the obtained results, it can be concluded that: (1) living organism can adapt to the lows doses of nitrate for a long time. This is observed in the workers exposed to deferent derivatives of nitrates; (2) high nitrate amounts involve important biological variations even if the exposure time is short. This is proven in the laboratory animals. PMID:17627919

  2. Exposures of children to organophosphate pesticides and their potential adverse health effects.

    PubMed Central

    Eskenazi, B; Bradman, A; Castorina, R

    1999-01-01

    Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children

  3. The Adverse Effects of Air Pollution on the Nervous System

    PubMed Central

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  4. Parenteral Lipid Tolerance and Adverse Effects: Fat Chance for Trouble?

    PubMed

    Wanten, Geert J A

    2015-09-01

    Lipid emulsions (LEs) are indispensable sources of fuel calories and (essential) fatty acids (FAs) in modern parenteral nutrition formulations. The use of LE, however, also remains associated with the development of adverse effects. Intolerance for LE mostly becomes apparent upon the development of patient complaints or disturbed blood function tests, mainly of the liver. These issues may be associated with the composition, stability, or the infusion rate of the emulsion. Also, altered balances of (anti)oxidants or the presence or absence of protective or toxic bioactive agents such as phytosterols and tocopherol in LE may lead to complications, especially in already vulnerable patients with an inflammatory condition. While the oldest available LEs are based on pure soybean oil (SO-LE), rich in the proinflammatory ω-6 polyunsaturated fatty acid linoleic acid, more recent next-generation LEs where alternative FA sources such as olive and fish oil (partially) replace soybean oil to lower the content of linoleic acid seem safe and effective. Especially LEs containing fish oil (FO-LE) have less proinflammatory characteristics that promise to convey beneficial effects on immune system and organ functions, although much of the available evidence awaits more robust clinical validation. PMID:26177663

  5. Soy isoflavones ameliorate the adverse effects of chemotherapy in children.

    PubMed

    Tacyildiz, Nurdan; Ozyoruk, Derya; Yavuz, Gulsan; Unal, Emel; Dincaslan, Handan; Dogu, Figen; Sahin, Kazim; Kucuk, Omer

    2010-01-01

    Genistein sensitizes cancer cells to chemotherapy and radiation by modulating cell survival pathways. At the same time, genistein's antioxidant and anti-inflammatory effects may protect normal tissues from adverse effects of chemotherapy and radiation, which are largely due to oxygen-free radicals and inflammation. We conducted a small pilot study with a soy isoflavone mixture containing 8 mg of genistein in children receiving chemotherapy and/or radiation to investigate genistein's potential toxicity preventive effect. We monitored clinical and laboratory parameters in children with cancer who received their first cycle of chemotherapy without genistein and the subsequent cycles with genistein. Patients served as their own controls, and the clinical-laboratory data from the first cycle were compared to the data from subsequent cycles. Nine cycles of chemotherapy were administered without genistein and 57 cycles with genistein. Patients experienced less myelosuppression, mucositis, and infection when they received genistein with chemotherapy. During supplementation, serum genistein levels were 2 to 6 times higher compared to presupplementation levels. Patients who received abdominal radiation reported less pain and diarrhea when they took the genistein supplement. Further clinical investigation of soy isoflavones in pediatric cancer patients receiving chemotherapy and/or radiation should be conducted. PMID:20924976

  6. Agricultural sources of contaminants of emerging concern and adverse health effects on freshwater fish

    USGS Publications Warehouse

    Tillitt, Donald E.; Buxton, Herbert T.

    2011-01-01

    Agricultural contaminants of emerging concern (CECs) are generally thought of as certain classes of chemicals associated with animal feeding and production facilities. Veterinary pharmaceuticals used in animal food production systems represent one of the largest groups of CECs. In our review, we discuss the extensive increase in use of antibiotics in animal feeding operations (AFOs) around the world. AFOs are a major consumer of antibiotics and other veterinary pharmaceuticals and over the past decade there has been growing information on the occurrence, release, and fate of CECs from animal food production operations, including the application of pharmaceutical-containing manure to agricultural fields and releases from waste lagoons. Concentrations of CECs in surface and ground water in proximity to AFOs correspond to their presence in the AFO wastes. In many cases, the environmental concentrations of agriculturally-derived CECs are below toxicity thresholds. Hormones and hormone replacement compounds are a notable exception, where chemical concentrations near AFOs can exceed concentrations known to cause adverse effects on endocrine-related functions in fish. In addition, some agricultural pesticides, once thought to be safe to non-target organisms, have demonstrated endocrine-related effects that may pose threats to fish populations in agricultural regions. That is, we have pesticides with emerging concerns, thus, the concern is emerging and not necessarily the chemical. In this light, one must consider certain agricultural pesticides to be included in the list of CECs. Even though agricultural pesticides are routinely evaluated in regulatory testing schemes which have been used for decades, the potential hazards of some pesticides have only recently been emerging. Emerging concerns of pesticides in fish include interference with hormone signaling pathways; additive (or more than additive) effects from pesticide mixtures; and adverse population-level effects at

  7. CORAL: model for no observed adverse effect level (NOAEL).

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Pizzo, Fabiola; Lombardo, Anna; Gadaleta, Domenico; Benfenati, Emilio

    2015-08-01

    The in vivo repeated dose toxicity (RDT) test is intended to provide information on the possible risk caused by repeated exposure to a substance over a limited period of time. The measure of the RDT is the no observed adverse effect level (NOAEL) that is the dose at which no effects are observed, i.e., this endpoint indicates the safety level for a substance. The need to replace in vivo tests, as required by some European Regulations (registration, evaluation authorization and restriction of chemicals) is leading to the searching for reliable alternative methods such as quantitative structure-activity relationships (QSAR). Considering the complexity of the RDT endpoint, for which data quality is limited and depends anyway on the study design, the development of QSAR for this endpoint is an attractive task. Starting from a dataset of 140 organic compounds with NOAEL values related to oral short term toxicity in rats, we developed a QSAR model based on optimal descriptors calculated with simplified molecular input-line entry systems and the graph of atomic orbitals by the Monte Carlo method, using CORAL software. Three different splits into the training, calibration, and validation sets are studied. The mechanistic interpretation of these models in terms of molecular fragment with positive or negative contributions to the endpoint is discussed. The probabilistic definition for the domain of applicability is suggested. PMID:25850638

  8. Neurological Adverse Effects after Radiation Therapy for Stage II Seminoma.

    PubMed

    Ebbeskov Lauritsen, Liv; Meidahl Petersen, Peter; Daugaard, Gedske

    2012-05-01

    We report 3 cases of patients with testicular cancer and stage II seminoma who developed neurological symptoms with bilateral leg weakness about 4 to 9 months after radiation therapy (RT). They all received RT to the para-aortic lymph nodes with a total dose of 40 Gy (36 Gy + 4 Gy as a boost against the tumour bed) with a conventional fractionation of 2 Gy/day, 5 days per week. RT was applied as hockey-stick portals, also called L-fields. In 2 cases, the symptoms fully resolved. Therapeutic irradiation can cause significant injury to the peripheral nerves of the lumbosacral plexus and/or to the spinal cord. RT is believed to produce plexus injury by both direct toxic effects and secondary microinfarction of the nerves, but the exact pathophysiology of RT-induced injury is unclear. Since reported studies of radiation-induced neurological adverse effects are limited, it is difficult to estimate their frequency and outcome. The treatment of neurological symptoms due to RT is symptomatic. PMID:22949908

  9. Management of the adverse effects associated with intravenous bisphosphonates.

    PubMed

    Tanvetyanon, T; Stiff, P J

    2006-06-01

    Intravenous bisphosphonates are widely used to treat hypercalcemia and to reduce skeletal-related morbidity among cancer patients. However, serious complications, generally occurring in less than 2% of patients participated in phase III clinical trials, including acute systemic inflammatory reaction, ocular inflammation, renal failure, nephrotic syndrome, electrolyte imbalance, and osteonecrosis of the maxilla and mandible have all been increasingly reported. Yet, strategies to deal with these complications are becoming clear. Acute systemic inflammatory reaction is often self-limited and becomes less intense during subsequent treatments. For patients who develop ocular symptoms, prompt ophthalmologic evaluation is crucial to determine the safety of a subsequent bisphosphonate therapy. Patients who receive long-term pamidronate should be evaluated at intervals for early sign of nephritic syndrome as timely cessation of the agent may result in a full recovery. To reduce the risk of severe electrolyte abnormalities, particularly hypocalcemia, correcting any pre-treatment electrolyte abnormality and supplementing vitamin D and calcium may be helpful. Finally, to reduce the risk of osteonecrosis of the maxilla and mandible, obtaining a full dental evaluation before treatment and avoidance of invasive dental procedures is suggested. The three commonly used intravenous bisphosphonates (pamidronate, zoledronic acid, and ibandronate), are generally safe; ibandronate has to date been the least reported to be associated with renal side effects. As clinical indications of intravenous bisphosphonates continue to expand, prescribing clinicians should be familiar with these possible adverse effects and discuss them with patients before commencing or continuing on therapy. PMID:16547070

  10. Shocking Results on the Adverse Effects of CO2 Exposures

    NASA Technical Reports Server (NTRS)

    James, John T.

    2012-01-01

    Carbon dioxide (CO2) is released in large quantities from humans while they live and work in spacecraft or work outside the spacecraft during extravehicular activity (EVA). Removal of this anthropogenic pollutant requires major resources, and these resources increase dramatically as the levels of CO2 set to protect human health and performance are reduced. The current Spacecraft Maximum Allowable Concentration of CO2 aboard the ISS is 0.7% or 5.3 mmHg; however, according to Chits (mission action requests), NASA and its international partners have agreed to control CO2 levels to less than 4 mmHg. In the meantime, retrospective investigations attempting to associate crew symptoms with elevated CO2 levels over the life if the International Space Station (ISS) are underway to determine if this level is sufficient to protect against health and performance decrements. Anecdotal reports suggest that crewmembers are not able to perform complex tasks as readily in spaceflight as they were able during ground-based training. While physiological effects of CO2 have been studied for many decades, it is only recently that the effects of CO2 on higher reasoning capabilities have been studied. The initial results are shocking. For example, one study published in the respected journal Environmental Health Perspectives showed obvious adverse effects of CO2 exposures on higher reasoning at 1.9 mmHg. The implications and limitations of this study are paramount in determining future CO2 SMACs for human spaceflight, both aboard the ISS and in exploration-class missions. Key Words: carbon dioxide, spacecraft, air quality, toxic effects

  11. IDENTIFICATION OF EMERGING SUB-POPULATIONS SUSCEPTIBLE TO ADVERSE HEALTH EFFECTS ASSOCIATED WITH AIR PARTICULATE EXPOSURE

    EPA Science Inventory

    The overall weight of evidence from panel, clinical, and toxicological studies has demonstrated the ability of ambient air particulate matter (PM) exposure to induce a variety of extra-pulmonary effects ranging from alterations in hematological parameters to cardiac function. Alt...

  12. Weighing the adverse cardiac effects of fluoroquinolones: A risk perspective.

    PubMed

    Mehrzad, Raman; Barza, Michael

    2015-11-01

    A rare side effect of fluoroquinolone (FQ) antibiotics is QT prolongation, which may result in serious arrhythmias. Most published comparative trials describe the relative risks among the drug class but do not focus on the incidence of serious arrhythmias. It is important for the prescriber to have a sense not only of relative risk but also of incidence to balance the risks against the other attributes of the individual members of the drug class. A review of English-language literature was performed to identify trials that provide data on the relative risk and, when able to be calculated, the incidence of adverse cardiac events among the commonly used FQs. Moxifloxacin had a several-fold higher risk of cardiac arrhythmias than levofloxacin or ciprofloxacin in randomized trials. However, the actual event rate was low in 2 of 3 studies. Given inconsistencies among the studies and the relative rarity of the events, the clinician need not base the choice of drug primarily on concern for a cardiac arrhythmia except in patients at the highest risk of such an event. PMID:26011799

  13. Second-Generation Antipsychotics and Extrapyramidal Adverse Effects

    PubMed Central

    Jakovcevski, Igor

    2014-01-01

    Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability. PMID:24995318

  14. Adverse effects and safety of SGLT-2 inhibitors.

    PubMed

    Halimi, S; Vergès, B

    2014-12-01

    In type 2 diabetes (T2DM), glycaemic control delays the development and slows the progression of complications. Although there are numerous glucose-lowering agents in clinical use, only approximately half of T2DM patients achieve glycaemic control, while undesirable side-effects, such as hypoglycaemia and body weight gain, often impede treatment in those taking these medications. Thus, there is a need for novel agents and treatment options. Sodium-glucose cotransporter-2 inhibitors (SGLT-2-i) have recently been developed for the treatment of T2DM. The available data suggest a good tolerability profile for the three available drugs - canagliflozin, dapagliflozin and empagliflozin - approved by the US Food and Drug Administration (FDA) for the American market as well as in other countries. The most frequently reported adverse events with SGLT-2-i are female genital mycotic infections, urinary tract infections and increased urination. The pharmacodynamic response to SGLT-2-i declines with increasing severity of renal impairment, requiring dosage adjustments or restrictions with moderate-to-severe renal dysfunction. Most patients treated with SGLT-2-i also have a modest reduction in blood pressure and modest effects on serum lipid profiles, some of which are beneficial (increased high-density lipoprotein cholesterol and decreased triglycerides) and others which are not (increased low-density lipoprotein cholesterol, LDL-C). A number of large-scale and longer-term cardiovascular trials are now ongoing. In patients treated with dapagliflozin, a non-significant excess number of breast and bladder cancers has been reported; considered as due to a bias, this is nevertheless being followed in the ongoing trials. No other significant safety issues have been reported so far. Although there is some benefit for several cardiovascular risk factors such as HbA1c, high blood pressure, obesity and increases in LDL-C, adequately powered trials are still required to determine the

  15. Eco-toxicological effects of the avermectin family with a focus on abamectin and ivermectin.

    PubMed

    Bai, Shahla Hosseini; Ogbourne, Steven

    2016-07-01

    Avermectin family members are categorised as highly effective but toxic natural products that are used as pharmaceuticals in both humans and animals and for crop protection. Abamectin and ivermectin are the two most commonly used compounds from this family with abamectin the only compound to be used for both crop protection and pharmaceutical purposes. Avermectins are produced by the soil dwelling actinomycetes Streptomyces avermitilis and despite having complex chemical structures, they are manufactured via synthesis in large scales for commercial use. Although the extent of the eco-toxicological effects of avermectins is not well documented, reports of eco-toxicity exist. Avermectins have short half-lives and their residues can be eliminated through different food processing methods. However, avermectins can persist in water, sediment, soil and food products and therefore management practices that reduce the potential risks associated with eco-toxicity of these highly toxic compounds need to be further developed. This manuscript provides a critical review of the eco-toxicological risks and the potential for food contamination associated with avermectin use. PMID:27058912

  16. Investigation of toxicological effects of Shuanghuanglian injection in Beagle dogs by metabonomic and traditional approaches.

    PubMed

    Yan, Guangyan; Zhao, Yinglan; Deng, Pengchi; Lv, Lei; Wang, Yanli; Bu, Qian; Liu, Bin; Hu, Chunyan; Zhuo, Yanqiang; Yang, Xunning; Wang, Li; Cen, Xiaobo

    2010-11-01

    In this study, clinical biochemistry, hematology, histopathology and (1)H nuclear magnetic resonance spectroscopy-based metabonomic approaches were applied to investigate the toxicological effects of Shuanghuanglian (SHL) injection after intravenous administration (dosed at 4, 12 and 36 mL stock/kg) in Beagle dogs for 30 d. Decreases in red blood cells, hemoglobin, mean cell volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were observed in the high-dose group. Elevated reticulocytes, total bilirubin and direct bilirubin were also observed in this group. Moreover, significant hemosiderosis and Prussian blue positivity were detected in the liver, spleen and kidney from high-dose group animals, and transmission electron microscopy examination revealed an appreciable number of acanthrocytes in the liver. These results collectively indicate that SHL injection has the potential to cause hemolytic anemia. Metabonomic analysis showed increases in serum lactate, choline and phosphocholine but a decrease in taurine in treated groups and these findings may underlie the toxicological mechanism of SHL injection. In summary, SHL injection shows hemolytic effects in Beagle dogs; moreover, serum choline and phosphocholine as well as lactate and taurine may be the biomarkers for hemolytic anemia induced by SHL injection. PMID:20864460

  17. Dispersant use as a response to oil spills: toxicological effects on fish cardiac performance.

    PubMed

    Milinkovitch, Thomas; Thomas-Guyon, Hélène; Lefrançois, Christel; Imbert, Nathalie

    2013-04-01

    Dispersant use is a controversial technique used to respond to oil spills in nearshore areas. In order to assess the toxicity of this technique, this study evaluated the cardiac toxicological effects on juvenile golden grey mullets Liza aurata exposed for 48 h to either dispersant alone, chemically dispersed oil, mechanically dispersed oil, the water-soluble fraction of oil or a control condition. Following exposure, the positive inotropic effects of adrenaline were assessed in order to evaluate a potential impairment on the cardiac performance. The results revealed an impairment of the positive inotropic effects of adrenaline for all the contaminants (single dispersant, dispersed and undispersed oil, water-soluble fraction of oil). This suggests that: (1) cardiac performance is a valuable parameter to study the physiopathological effects of dispersed oil; (2) dispersant application is likely to impair cardiac performance. PMID:22976195

  18. Adverse effects of acupuncture. Which are clinically significant?

    PubMed Central

    Chung, Ainee; Bui, Luke; Mills, Edward

    2003-01-01

    OBJECTIVE: To review potentially serious adverse events associated with acupuncture. QUALITY OF EVIDENCE: Studies in the medical literature primarily provide level II evidence from retrospective reviews, case reports, and prospective surveys of practitioners. MAIN MESSAGE: Both the general public and physicians are becoming more interested in the ancient Chinese medical practice of acupuncture. This paper discusses the basic philosophy of acupuncture and describes adverse events that might be associated with acupuncture treatment. Some events, such as nausea and syncope, can be mild and transient, but rare events, such as septicemia and hepatitis C infection, can be fatal. As the role of acupuncture in today's multidisciplinary clinics increases, the complications of acupuncture, although infrequent, cannot be overlooked. CONCLUSION: Responsible clinicians practising acupuncture and seeing patients who use acupuncture should be aware of the adverse events associated with it. PMID:12943357

  19. Dermatologic adverse effects of antiretroviral therapy: recognition and management.

    PubMed

    Luther, Jay; Glesby, Marshall J

    2007-01-01

    Despite the decrease in opportunistic infections associated with HIV in the highly active antiretroviral treatment (HAART) era, a significant number of patients still present with skin pathology, some of which can be attributed directly or indirectly to antiretroviral therapy. The non-nucleoside reverse transcriptase inhibitors exhibit a class effect with regard to skin adverse manifestations, and the spectrum of disease can vary from a mild morbilliform rash to Stevens-Johnson syndrome. Certain protease inhibitors are associated with rash, and indinavir causes retinoid-like manifestations such as paronychia, alopecia, ingrown toe-nails, and curling of straight hair. Abacavir, a nucleoside reverse transcriptase inhibitor, is notorious for causing a hypersensitivity reaction in select patients. The fusion inhibitor enfuvirtide causes injection-site reactions in the overwhelming majority of patients, although a new method of delivery has decreased the rate and severity of these reactions. A syndrome of lipoatrophy with or without lipohypertrophy, often termed lipodystrophy, has been described in patients receiving HAART. Potential management of lipoatrophy includes switching antiretrovirals and surgical treatment with facial fillers. Lastly, skin manifestations of the immune reconstitution inflammatory syndrome, including herpes zoster and warts, must be recognized and treated accordingly. In the evaluation of the individual HIV-infected patient receiving antiretroviral therapy who presents with a skin disorder, clinicians should consider the CD4 cell count as a marker of the degree of immunodeficiency, the specific antiretrovirals used, and the timing of the initiation of antiretroviral therapy in order to formulate a rational differential diagnosis. Management should be individualized based on the specific drug that is implicated and the severity of the reaction. PMID:17645377

  20. Process related effects on the chemical and toxicologic characteristics of coal derived fuels

    SciTech Connect

    Wright, C.W.; Chess, E.K.; Bean, R.M.; Mahlum, D.D.; Stewart, D.L.; Wilson, B.W.

    1986-01-01

    As a component of an ongoing program to assess the potential health effects of coal conversion materials, we have recently completed chemical and toxicologic studies of a sample set collected on selected days of a 25-day demonstration run of a catalytic two stage direct coal liquefaction (CTSL) process. There was an increase in heteroatomic, nitrogen containing polycyclic aromatic compounds (NPAC) and hydroxy-substituted PAC, compounds as the operation time of the pilot plant increased. The proportion of material which boiled above 975/sup 0/F also increased in the solids-free portion of the recycle slurry oil as pilot plant operation time increased. As anticipated from the increase in NPAC concentration during the run, the microbial mutagenic activity of selected process materials also increased as a function of run time. Likewise, the tumorigenicity of the materials produced later in the demonstration run was higher than that of those produced initially. These results support the view that catalyst deactivation during the course of the run gives rise not only to lower coal conversion, but also to increased toxicologic activity. 9 refs., 3 figs., 3 tabs.

  1. Handbook of toxicology

    SciTech Connect

    Haley, T.J.; Berndt, W.O.

    1987-01-01

    This book discusses the ongoing battle against the effects of pesticides, herbicides, fungicides, and other toxic agents. It points out gaps in present-day research, illustrate other diseases that can mimic chemical toxicity, and emphasize thorough consideration of all aspects in a given incident prior to administering an antidote. The book offers a compiled data on target organ toxicity involving the liver, kidneys, and lungs - detailing the rapid, recent progress in this area. The coverage also highlights reproductive toxicology, food additives, asphixiant gases, and pulmonary toxicology. The partial contents are: Absorption, distribution, Biotransformation, Conjugation, and Excretion of Xenobiotics, Hepatotoxicity, Pulmonary Toxiology, Reproductive and Perinatal toxicology, Toxicology of Insecticides, Rodenticides, Herbicides, and Fungicides, Mechanisms of Metal-Induced Cell Injury, Food Additives: A Benefit/Risk Dilemma, Animal Toxins, and Toxic Effects of Chemicals on the Immune System.

  2. Somatic and heritable effects of environmental genotoxins and the emergence of evolutionary toxicology

    SciTech Connect

    Bickham, J.W.; Smolen, M.J.

    1994-12-01

    The genetic effects of environmental pollutants include mutations in somatic cells or germinal cells that are the direct result of exposure to toxicants. Biomarkers that detect such mutagenic effects have been developed and tested in field studies on wildlife populations. However, another class of genetic effects resulting from pollution exposure exists. Specifically, changes in allele frequencies of populations will occur as a result of population bottlenecks, inbreeding, or selection at loci critical for survival in polluted environments. We describe how such genetic alterations can be studied at the population level using the techniques of molecular genetics, and we predict the development of a new field, evolutionary toxicology, that will address such issues. 26 refs., 1 fig., 1 tab.

  3. Somatic and heritable effects of environmental genotoxins and the emergence of evolutionary toxicology.

    PubMed Central

    Bickham, J W; Smolen, M J

    1994-01-01

    The genetic effects of environmental pollutants include mutations in somatic cells or germinal cells that are the direct result of exposure to toxicants. Biomarkers that detect such mutagenic effects have been developed and tested in field studies on wildlife populations. However, another class of genetic effects resulting from pollution exposure exists. Specifically, changes in allele frequencies of populations will occur as a result of population bottlenecks, inbreeding, or selection at loci critical for survival in polluted environments. We describe how such genetic alterations can be studied at the population level using the techniques of molecular genetics, and we predict the development of a new field, evolutionary toxicology, that will address such issues. PMID:7713028

  4. Toxicological and biochemical responses of the earthworm Eisenia fetida exposed to contaminated soil: Effects of arsenic species.

    PubMed

    Wang, Zhifeng; Cui, Zhaojie; Liu, Lei; Ma, Qianchi; Xu, Xiaoming

    2016-07-01

    Arsenic is a pollutant that can be detected in different chemical forms in soil. However, the toxicological effects of different arsenic species on organisms have received little attention. In this study, we exposed earthworms Eisenia fetida to artificial soils contaminated by arsenite [As(III)], arsenate [As(V)], monomethylarsonate (MMA) and dimethylarsinate (DMA) for 28 and 56 days. Three biomarkers including lipid peroxidation (LPO), metallothioneins (MTs) and lysosomal membrane stability (LMS) were analyzed in the organisms. In addition, the contents of total arsenic and arsenic species in earthworms were also determined to investigate the effects of bioaccumulation and biotransformation of arsenic on biomarkers and to evaluate the dose-response relationships. The results showed that the relationship between the three biomarkers and the two inorganic arsenic species were dose dependent, and the correlation levels between the biomarkers and As(III) were higher than that between the biomarkers and As(V). Trivalent arsenic species shows more toxicity than pentavalent arsenic on the earthworms at molecular and subcellular level, including oxidative damage, MTs induction and lysosomal membrane damage. The toxicity of MMA and DMA was lower than inorganic arsenic species. However, the occurrence of demethylation of organic arsenics could lead to the generation of highly toxic inorganic arsenics and induce adverse effects on organisms. The biotransformation of highly toxic inorganic arsenics to the less toxic organic species in the earthworms was also validated in this study. The biomarker responses of the earthworm to different arsenic species found in this study could be helpful in future environment monitoring programs. PMID:27045633

  5. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... under a license of scale-model mining systems which simulate commercial recovery could adversely affect... setting of instruments; (7) Sampling by box core, small diameter core or grab sampler, to determine seabed... mining tests under exploration licenses will be extremely small. (ii) Blanketing of benthic fauna...

  6. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... under a license of scale-model mining systems which simulate commercial recovery could adversely affect... setting of instruments; (7) Sampling by box core, small diameter core or grab sampler, to determine seabed... mining tests under exploration licenses will be extremely small. (ii) Blanketing of benthic fauna...

  7. Nifedipine versus terbutaline, tocolytic effectiveness and maternal and neonatal adverse effects: a randomized, controlled pilot trial.

    PubMed

    Padovani, Tania Regina; Guyatt, Gordon; Lopes, Luciane Cruz

    2015-03-01

    Although previous evidence suggests advantages of nifedipine over terbutaline as tocolytic agents, in some jurisdictions, terbutaline is approved for use and nifedipine is not. In women in preterm labour, we compared the impact of terbutaline versus nifedipine on inhibition of uterine contractions, preterm birth, neonatal sepsis, intracranial haemorrhage or necrotizing enterocolitis, death or admission to a neonatal intensive care unit and maternal adverse reactions. We randomized 32 women to nifedipine and 34 to terbutaline. We found no difference between groups in tocolysis or preterm birth. No serious maternal adverse effects or serious neonatal adverse outcome occurred in either group. Less serious maternal adverse effects less common with terbutaline included flushing (2.94% versus 43.7%) and headache (5.9% versus 31.2%). The administration of terbutaline increased tremor (76.4% versus 0%), nausea (58.8% versus 9.4%) and dizziness (29.4% versus 6.25%). The total number of side effects, and the proportion of women experiencing one or more side effects, proved greater with terbutaline. In this study, terbutaline and nifedipine performed similarly in their tocolytic effects. Each drug has specific side effects, although overall, nifedipine was associated with fewer adverse effects. PMID:25146233

  8. Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. II. Ninety-day study.

    PubMed

    Hardt, Daniel J; James, R Arden; Gut, Chester P; McInturf, Shawn M; Sweeney, Lisa M; Erickson, Richard P; Gargas, Michael L

    2015-02-01

    Carbon monoxide (CO), carbon dioxide (CO2) and low-level oxygen (O2) (hypoxia) are submarine atmosphere components of highest concern because of a lack of toxicological data available to address the potential effects from long-duration, combined exposures on female reproductive and developmental health. In this study, subchronic toxicity of mixed atmospheres of these three submarine air components was evaluated in rats. Male and female rats were exposed via inhalation to clean air (0.4 ppm CO; 0.13% CO2; 20.6% O2) (control), a low-dose (5.0 ppm CO; 0.41% CO2; 17.1% O2), a mid-dose (13.9 ppm CO; 1.19 or 1.20% CO2; 16.1% O2) and a high-dose (89.9 ppm CO; 2.5% CO2; 15.0% O2) gas mixture for 23 h per day for 70 d premating and a 14-d mating period. Impregnated dams continued exposure to gestation day 19. Adverse reproductive effects were not identified in exposed parents (P0) or first (F1) and second generation (F2) offspring during mating, gestation or parturition. No adverse changes to the estrous cycle or in reproductive hormone concentrations were identified. The exposure-related effects were reduced weight gains and adaptive up-regulation of erythropoiesis in male rats from the high-dose group. No adverse, dose-related health effects on clinical data or physiological data were observed. Neurobehavioral tests identified no apparent developmental deficits at the tested levels of exposure. In summary, subchronic exposures to the submarine atmosphere gases did not affect the ability of the exposed rats or their offspring to reproduce and did not appear to have any significant adverse health effects. PMID:25687554

  9. Toxicology - A primer on toxicology principles and applications

    SciTech Connect

    Kamrin, M.A.

    1988-01-01

    As the use of synthetic chemicals increased dramatically after World War II, concern about the possible adverse health and environmental effects of such use grew. The book opens with a discussion of the general principles of toxicology and how these general principles are applied in assessing the acute, subacute and chronic effects of chemicals. Both qualitative and quantitative measures of toxicity are addressed and the protocols for the various tests are described. Emphasis is placed on both the strengths and limitations of the techniques which are in current use. This is then followed by a discussion of risk assessment and risk management. Risk assessment deals with both the toxic potential of a chemical and the exposure likely to occur in specific situations. Risk management includes the steps taken to reduce or eliminate risks identified in the assessment process. The components of risk assessment are described in relation to a variety of possible toxic effects and exposure scenarios. The last part of the book provides a description and analysis of four case studies, each dealing with a different substance. These include the food additives, cyclamate and saccharin; asbestos; formaldehyde; and benzene. The basic toxicological information regarding each, and the different regulations to which they have been subject, provide the basis for exploring how the principles introduced in the first part of the book are applied in practice.

  10. Ocular and systemic adverse effects of ophthalmic and non ophthalmic medications.

    PubMed

    Izazola-Conde, C; Zamora-de la Cruz, D; Tenorio-Guajardo, G

    2011-01-01

    Information related to adverse drug effects caused by ocular medications and ocular adverse effects of systemically administered drugs has increased over the last several decades. Here we review the medical literature over the last four decades to both quantitatively and qualitatively determine the adverse effects of ocular drugs and ocular toxicity of non-ocular drugs. A systematic bibliographic review of the literature was performed with the following terms: "drug treatment", "drug therapy", "ocular adverse effects", "ocular side effects", "ocular toxicity", "systemic side effects", "systemic adverse effects", "systemic toxicity", "ocular drug" and "ophthalmic drug" using the Boolean operators or, and, not. Searches focused on: (1) Ocular side/adverse effects of ophthalmic drugs; (2) Ocular side/adverse effects of systemic drugs; (3) Systemic side/adverse effects of ophthalmic drugs. PubMed was used to perform searches. Limits included: species, human and field tag, abstract/title, dates from 01/01/1971 to 31/12/2010. A sub-selection of references was made by discarding articles that were irrelevant for the topics listed above. Adverse effects of alpha2-adrenergic agonists, beta-adrenergic antagonists, quinine derivatives and antituberculosis agents appear in the literature throughout the period of the review. Adverse effects of newer drugs such as amiodarone, phosphodiesterase 5 inhibitors, antiepileptics, tamoxifen, and its interactions have been published principally in the last two decades. It is imperative for patient safety that knowledge of the adverse effects of drugs on the eye whether topically or systemically administered, and the possible systemic effects of drugs given as ophthalmic medications be emphasized to clinicians. PMID:22423585

  11. Computational Toxicology

    EPA Science Inventory

    ‘Computational toxicology’ is a broad term that encompasses all manner of computer-facilitated informatics, data-mining, and modeling endeavors in relation to toxicology, including exposure modeling, physiologically based pharmacokinetic (PBPK) modeling, dose-response modeling, ...

  12. Endocrine and Metabolic Adverse Effects of Psychotropic Medications in Children and Adolescents

    ERIC Educational Resources Information Center

    Correll, Christoph U.; Carlson, Harold E.

    2006-01-01

    Objective: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. Method: Selective review of endocrine and metabolic effects of psychotropic…

  13. Toxicological effects of cinnabar in rats by NMR-based metabolic profiling of urine and serum

    SciTech Connect

    Wei Lai; Liao Peiqiu; Wu Huifeng; Li Xiaojing Pei Fengkui Li Weisheng; Wu Yijie

    2008-03-15

    Cinnabar, an important traditional Chinese mineral medicine, has been widely used as a Chinese patent medicine ingredient for sedative therapy. However, the pharmaceutical and toxicological effects of cinnabar, especially in the whole organism, were subjected to few investigations. In this study, an NMR-based metabolomics approach has been applied to investigate the toxicological effects of cinnabar after intragastrical administration (dosed at 0.5, 2 and 5 g/kg body weight) on male Wistar rats. Liver and kidney histopathology examinations and serum clinical chemistry analyses were also performed. The {sup 1}H NMR spectra were analyzed using multivariate pattern recognition techniques to show the time- and dose-dependent biochemical variations induced by cinnabar. The metabolic signature of urinalysis from cinnabar-treated animals exhibited an increase in the levels of creatinine, acetate, acetoacetate, taurine, hippurate and phenylacetylglycine, together with a decrease in the levels of trimethyl-N-oxide, dimethylglycine and Kreb's cycle intermediates (citrate, 2-oxoglutarate and succinate). The metabolomics analyses of serum showed elevated concentrations of ketone bodies (3-D-hydroxybutyrate and acetoacetate), branched-chain amino acids (valine, leucine and isoleucine), choline and creatine as well as decreased glucose, lipids and lipoproteins from cinnabar-treated animals. These findings indicated cinnabar induced disturbance in energy metabolism, amino acid metabolism and gut microflora environment as well as slight injury in liver and kidney, which might indirectly result from cinnabar induced oxidative stress. This work illustrated the high reliability of NMR-based metabolomic approach on the study of the biochemical effects induced by traditional Chinese medicine.

  14. Chlordecone exposure and adverse effects in French West Indies populations.

    PubMed

    Multigner, Luc; Kadhel, Philippe; Rouget, Florence; Blanchet, Pascal; Cordier, Sylvaine

    2016-01-01

    Chlordecone (Kepone) is an organochlorine insecticide that has been used as insecticide and fungicide. In the French West Indies, Guadeloupe and Martinique, it was intensively applied to banana fields from 1973 to 1993 to control root borers. This pesticide undergoes no significant biotic or abiotic degradation in the environment and is still present in soils where it was applied. It was only in 1999 that health and environmental authorities became aware of the extent of the chlordecone pollution of environmental media, including soils, waterways, and the food chain. Earlier observations and toxicological studies have demonstrated that chlordecone is a reproductive and developmental toxicant, neurotoxic and carcinogenic in rodents, and is an endocrine-disrupting chemical because of its estrogenic properties both in vitro and in vivo. Several surveys have confirmed that the French West Indian population continues to be exposed to this chemical though consumption of contaminated foodstuffs. Here, we report the findings of various epidemiological studies conducted in the French West Indies to assess the impact of environmental exposure to chlordecone on the health of the population. PMID:25940496

  15. Toxicology of chlorofluorocarbon replacements.

    PubMed Central

    Dekant, W

    1996-01-01

    Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements. PMID:8722112

  16. SOURCES OF VARIATION IN TOXICOLOGICAL STUDIES AND THEIR EFFECTS ON PRECISION OF RESULTS: INDIVIDUAL DIFFERENCES.

    EPA Science Inventory

    The ultimate goal of risk assessment is to estimate the adverse effects of exposures to environmental contaminants in the population. However, populations of humans and other species vary widely in many key factors such as age, genetic makeup, gender, and health status. Any or a...

  17. CONCENTRATED COARSE AIR PARTICLE EXPOSURE PRODUCES MILD TOXICOLOGICAL EFFECTS IN HEALTHY VOLUNTEERS

    EPA Science Inventory

    Epidemiological studies have shown that the adverse health effects of ambient particulate matter (PM) exposure to be in general more strongly associated with "fine" PM (<2.5 µM) originating from combustion processes than for "coarse" PM (>2.5 µM) from wind-blown dust, mechanical ...

  18. Methoxetamine, a novel psychoactive substance with serious adverse pharmacological effects: a review of case reports and preclinical findings.

    PubMed

    Zanda, Mary T; Fadda, Paola; Chiamulera, Cristiano; Fratta, Walter; Fattore, Liana

    2016-09-01

    An increasing number of novel psychoactive substances are currently available and sold as 'legal highs' or 'research chemicals' accompanied by the indication that they are 'not for human consumption'. Among those that have emerged in the last few years, methoxetamine (MXE) owes its wide popularity to its easy access on the Internet and its reputation of being a 'safe' drug. MXE is an arylcyclohexylamine with a chemical structure analogous to ketamine and phencyclidine, and similar noncompetitive glutamate N-methyl D-aspartate receptor antagonist properties. Yet, very recent preclinical data highlighted a stimulatory effect of MXE on dopamine neurotransmission within the mesolimbic pathway. The aim of this review is to provide an updated review of the behavioral and toxicological effects of MXE as well as the latest findings on its pharmacology that might explain sought effects and frequent occurrence of adverse effects. In light of the growing number of intoxications induced by MXE, knowledge of its short-term and long-term effects is urgently needed. However, the hypothetical rapid antidepressant activity of MXE suggested by its chemical analogy with ketamine and supported by recent preclinical findings deserves further investigation. PMID:27128862

  19. FEMALE SEX AND DISCONTINUATION OF ISONIAZID DUE TO ADVERSE EFFECTS DURING THE TREATMENT OF LATENT TUBERCULOSIS

    PubMed Central

    Pettit, April C.; Bethel, James; Hirsch-Moverman, Yael; Colson, Paul W.; Sterling, Timothy R.

    2013-01-01

    SUMMARY Objectives To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study. Methods The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007–September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression. Results Of 1,306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5–50.0%) completed treatment and 196 (15.0%, 95% CI 13.1–17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32–2.10, p<0.001) and current alcohol use (RR 1.41, 95% CI 1.13–1.77, p=0.003) were independently associated with isoniazid discontinuation due to adverse effects. Conclusions The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects. PMID:23845828

  20. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Pesticide Programs' Document Processing Desk at the appropriate address as set forth in 40 CFR 150.17(a) or... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of...

  1. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Flagging of studies for potential adverse effects. 158.34 Section 158.34 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES General Provisions § 158.34 Flagging of studies for potential adverse effects. (a)...

  2. Risk of Adverse Health and Performance Effects of Celestial Dust Exposure

    NASA Technical Reports Server (NTRS)

    Scully, Robert R.; Meyers, Valerie E.

    2015-01-01

    silica (Permissible Exposure Limit [PEL] 0.05 mg/m3) but more toxic than the nuisance dust titanium dioxide (TiO2 [PEL 5.0 mg/m3]). A PEL for episodic exposure to airborne lunar dust during a six-month stay on the lunar surface was established, in consultation with an independent, extramural panel of expert pulmonary toxicologists, at 0.3 mg/m3. The PEL provided for lunar dust is limited to the conditions and exposure specified therefore additional research remains to be accomplished with lunar dust to further address the issues of activation, address other areas of more unique lunar geology (Glotch et al., 2010; Greenhagen et al., 2010), examine potential toxicological effects of inhaled or ingested dust upon other organ systems, such cardiovascular, nervous systems, and examine effects of acute exposure to massive doses of dust such as may occur during off-nominal situations. Work to support the establishment of PELs for Martian dust and dusts of asteroids remains to be accomplished. The literature that describes health effects of exposure to toxic terrestrial dusts provides substantial basis for concern that prolonged exposure to respirable celestial dust could be detrimental to human health. Celestial bodies where a substantial portion of the dust is in the respirable range or where the dusts have large reactive surface areas or contain transition metals or volatile organics, represent greater risks of adverse effects from exposure to the dust. It is possible that in addition to adverse effects to the respiratory system, inhalation and ingestion of celestial dusts could pose risks to other systems

  3. Effects of hyperprolactinemia on toxicological parameters and proliferation of islet cells in male rats.

    PubMed

    Ose, Keiko; Miyata, Kaori; Yoshioka, Kaoru; Okuno, Yasuyoshi

    2009-04-01

    Prolactin has a wide variety of biological effects. Consequences of hyperprolactinemia on islet B cell proliferation as well as general toxicological parameters were here examined using anterior pituitary-grafted rats. Three or six anterior pituitary glands were implanted under single renal capsules of F344 male rats and left there for 13 weeks afterward. Clinical observation along with measurement of body weight and food consumption was conducted during the observation period, and subsequently hematology, blood biochemistry, gross pathology, organ weights and histopathology were examined. In addition, the proliferation rate of islet B cells was measured by a 5-bromo-2'-deoxy-uridine (BrdU) labeling technique. Serum prolactin concentrations at week 13 were 36, 70, 75 and 105 ng/ml in the sham-operated, 3-pituitary-grafted groups from male or female donors, and 6-pituitary-grafted group from male donors, respectively. Higher cholinesterase and total cholesterol values, lower trigriceride and leutenizing hormones (LH) values, and higher adrenal weights compared to those in the sham-operated group were apparent in the 3- and/or 6-pituitary-grafted groups. Also, the study revealed that mammary gland structure was transformed with change of differentiation from a male to a female acinar pattern. Furthermore a specific increase of islet cell proliferation rate was found, positively correlated with serum prolactin concentration. These findings suggest that elevation of serum prolactin level over 13 weeks induces islet cell proliferation and changes in toxicological parameters, including cholinesterase activity, elements of lipid metabolism and histopathology/morphology of the adrenals and mammary glands in male rats. PMID:19336972

  4. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment

    PubMed Central

    Kiff, Cara J.; Cortes, Rebecca; Lengua, Lilana; Kosterman, Rick; Hawkins, J. David; Mason, W. Alex

    2012-01-01

    Effects of Timing of Adversity on Adolescent and Young Adult Adjustment Abstract Exposure to adversity during childhood and adolescence predicts adjustment across development. Further, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal sample (N = 808) was followed from age 10 through 27. Perceptions of neighborhood in childhood predicted depression, alcohol use disorders, and HIV risk in young adulthood. Further, the timing of adversity was important in determining the type of problem experienced in adulthood. Youth adjustment predicted adult outcomes, and in some cases, mediated the relation between adversity and outcomes. These findings support the importance of adversity in predicting adjustment and elucidate factors that affect outcomes into young adulthood. PMID:22754271

  5. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment.

    PubMed

    Kiff, Cara J; Cortes, Rebecca; Lengua, Lilana; Kosterman, Rick; Hawkins, J David; Mason, W Alex

    2012-06-01

    Effects of Timing of Adversity on Adolescent and Young Adult Adjustment Abstract Exposure to adversity during childhood and adolescence predicts adjustment across development. Further, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal sample (N = 808) was followed from age 10 through 27. Perceptions of neighborhood in childhood predicted depression, alcohol use disorders, and HIV risk in young adulthood. Further, the timing of adversity was important in determining the type of problem experienced in adulthood. Youth adjustment predicted adult outcomes, and in some cases, mediated the relation between adversity and outcomes. These findings support the importance of adversity in predicting adjustment and elucidate factors that affect outcomes into young adulthood. PMID:22754271

  6. Toxicological effects of polychlorinated biphenyls (PCBs) on freshwater turtles in the United States.

    PubMed

    Ming-Ch'eng Adams, Clare Isabel; Baker, Joel E; Kjellerup, Birthe V

    2016-07-01

    Prediction of vertebrate health effects originating from persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) has remained a challenge for decades thus making the identification of bioindicators difficult. POPs are predominantly present in soil and sediment, where they adhere to particles due to their hydrophobic characteristics. Animals inhabiting soil and sediment can be exposed to PCBs via dermal exposure while others may obtain PCBs through contaminated trophic interaction. Freshwater turtles can serve as bioindicators due to their strong site fidelity, longevity and varied diet. Previous research observed the health effects of PCBs on turtles such as decreased bone mass, changed sexual development and decreased immune responses through studying both contaminated sites along with laboratory experimentation. Higher deformity rates in juveniles, increased mortality and slower growth have also been observed. Toxicological effects of PCBs vary between species of freshwater turtles and depend on the concertation and configuration of PCB congeners. Evaluation of ecotoxicological effects of PCBs in non-endangered turtles could provide important knowledge about the health effects of endangered turtle species thus inform the design of remediation strategies. In this review, the PCB presence in freshwater turtle habitats and the ecotoxicological effects were investigated with the aim of utilizing the health status to identify areas of focus for freshwater turtle conservation. PMID:27043381

  7. [Adverse or toxic effects of drugs in medical practice: a one-year follow-up].

    PubMed

    Grange, J C

    1990-01-01

    In order to analyse the response of pharmaceutical companies to adverse drug reaction reports, 37 suspected side effects were sent by mail to the 30 companies concerned. The time period involved was 1 year and corresponded to a total of 3341 consultations in general practice. Companies answered in 29 cases (78.3%), sent 21 reply forms and returned 3 evaluations of adverse drugs reactions to the reporting doctor. The high percentage of adverse drug reactions (1.07 per one hundred consultations), the doctor's work-load and poor feed-back lead one to reflect on the usefulness of systematic adverse drug reaction reporting by general practitioners. PMID:2399517

  8. A short history of the toxicology of inhaled particles

    PubMed Central

    2012-01-01

    Particle toxicology arose in order to understand the mechanisms of adverse effects of 3 major particle types that had historically exerted the greatest toll of ill-health—quartz, coal and asbestos. By the middle of the last century rat inhalation studies had been carried out and the pathology documented, but true mechanistic particle toxicology did not really take off until the 1970s when cell culture techniques became available. By the 1980s glass fibres were a major focus of interest and attempts to develop a structure-toxicity paradigm centred on biopersistence. In the 1990s environmental particles dominated the particle toxicology agenda and the cardiovascular system emerged as a target for inhaled particles, raising new challenges for particle toxicologists. We are currently in the era of nanotoxicology where a large and diverse range of new nanoparticles types are under scrutiny. PMID:22559156

  9. Toxicological effects of particulate emissions - A comparison of oil and wood fuels in small- and medium-scale heating systems

    NASA Astrophysics Data System (ADS)

    Kasurinen, Stefanie; Jalava, Pasi I.; Tapanainen, Maija; Uski, Oskari; Happo, Mikko S.; Mäki-Paakkanen, Jorma; Lamberg, Heikki; Koponen, Hanna; Nuutinen, Ilpo; Kortelainen, Miika; Jokiniemi, Jorma; Hirvonen, Maija-Riitta

    2015-02-01

    The use of wood instead of oil fuels in heating systems is strongly encouraged in many countries. Yet it is unknown to what extent such a large-scale change from oil to wood fuels in heating systems would contribute to any negative health effects from their emissions. We compared the toxicological properties of particulate matter (PM) emissions from wood and oil fuels from two small-scale and two medium-scale heating systems. To assess whether oil or wood combustion emissions cause adverse effects and which PM emissions' effects are more profound, we measured cell viability and proliferation, inflammatory markers, as well as DNA damage in RAW264.7 mouse macrophages. We found that the medium-scale oil-fueled heating system induced a dose-dependent increase of DNA damage, short-term cytotoxic effects, and a cell cycle arrest in the G2/M-phase. We did not detect an induction of DNA damage by the medium-scale wood-fired system. However, we detected significant short-term cytotoxicity. We found that both oil and wood combustion emission samples from the small-scale heating systems induced DNA damage. However, the short-term cytotoxic effects were greater for the PM emissions from the oil-fired heating system. PM mass emissions differed significantly between the tested heating systems. The lowest emissions, 0.1 mg/MJ, were produced by the small-scale oil-fired heating system; the highest emissions, 20.3 mg/MJ, by the medium-scale oil-fired heating system. The wood-fired heating systems' PM mass emissions were in between these concentrations, complicating the direct comparison of the emissions' health related toxic effects. Conclusively, our results indicate that the emissions from both the small- and the medium-scale wood-fueled heating systems cause overall less cytotoxicity and DNA damage in a cell model than the emissions from the corresponding oil-fueled heating systems. Hence, controlled wood-fueled heating systems may be good alternatives to heating systems fired

  10. Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

    EPA Science Inventory

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe res...

  11. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... the criteria of 40 CFR 158.34 for flagging studies for potential adverse effects to the results of the... exceeds criteria. I have applied the criteria of 40 CFR 158.34 for flagging studies for potential adverse... section. (b) The following table indicates the study types and the criteria to be applied to each....

  12. Effect of Two Different Methods of Initiating Atomoxetine on the Adverse Event Profile of Atomoxetine

    ERIC Educational Resources Information Center

    Greenhill, Laurence L.; Newcorn, Jeffrey H.; Gao, Haitao; Feldman, Peter D.

    2007-01-01

    Objective: To compare the effects of two different methods for initiating atomoxetine in terms of the incidence of early adverse events. Method: Data on atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were analyzed from five randomized, double-blind, placebo-controlled, acute-phase studies. Two studies involve…

  13. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the criteria of 40 CFR 158.34 for flagging studies for potential adverse effects to the results of the... exceeds criteria. I have applied the criteria of 40 CFR 158.34 for flagging studies for potential adverse... at any dose level, compared to concurrent control animals of the same sex; or 2 An increase in...

  14. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the criteria of 40 CFR 158.34 for flagging studies for potential adverse effects to the results of the... exceeds criteria. I have applied the criteria of 40 CFR 158.34 for flagging studies for potential adverse... at any dose level, compared to concurrent control animals of the same sex; or 2 An increase in...

  15. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the criteria of 40 CFR 158.34 for flagging studies for potential adverse effects to the results of the... exceeds criteria. I have applied the criteria of 40 CFR 158.34 for flagging studies for potential adverse... incidence of neoplasms in males or females which increases with dose (positive trend p≤ 0.05); or 1...

  16. Separate and Cumulative Effects of Adverse Childhood Experiences in Predicting Adult Health and Health Care Utilization

    ERIC Educational Resources Information Center

    Chartier, Mariette J.; Walker, John R.; Naimark, Barbara

    2010-01-01

    Objectives: Objectives of this population-based study were: (1) to examine the relative contribution of childhood abuse and other adverse childhood experiences to poor adult health and increased health care utilization and (2) to examine the cumulative effects of adverse childhood experiences on adult health and health care utilization. Methods:…

  17. Toxicology and epidemiology: improving the science with a framework for combining toxicological and epidemiological evidence to establish causal inference.

    PubMed

    Adami, Hans-Olov; Berry, Sir Colin L; Breckenridge, Charles B; Smith, Lewis L; Swenberg, James A; Trichopoulos, Dimitrios; Weiss, Noel S; Pastoor, Timothy P

    2011-08-01

    Historically, toxicology has played a significant role in verifying conclusions drawn on the basis of epidemiological findings. Agents that were suggested to have a role in human diseases have been tested in animals to firmly establish a causative link. Bacterial pathogens are perhaps the oldest examples, and tobacco smoke and lung cancer and asbestos and mesothelioma provide two more recent examples. With the advent of toxicity testing guidelines and protocols, toxicology took on a role that was intended to anticipate or predict potential adverse effects in humans, and epidemiology, in many cases, served a role in verifying or negating these toxicological predictions. The coupled role of epidemiology and toxicology in discerning human health effects by environmental agents is obvious, but there is currently no systematic and transparent way to bring the data and analysis of the two disciplines together in a way that provides a unified view on an adverse causal relationship between an agent and a disease. In working to advance the interaction between the fields of toxicology and epidemiology, we propose here a five-step "Epid-Tox" process that would focus on: (1) collection of all relevant studies, (2) assessment of their quality, (3) evaluation of the weight of evidence, (4) assignment of a scalable conclusion, and (5) placement on a causal relationship grid. The causal relationship grid provides a clear view of how epidemiological and toxicological data intersect, permits straightforward conclusions with regard to a causal relationship between agent and effect, and can show how additional data can influence conclusions of causality. PMID:21561883

  18. Toxicology and Epidemiology: Improving the Science with a Framework for Combining Toxicological and Epidemiological Evidence to Establish Causal Inference

    PubMed Central

    Adami, Hans-Olov; Berry, Sir Colin L.; Breckenridge, Charles B.; Smith, Lewis L.; Swenberg, James A.; Trichopoulos, Dimitrios; Weiss, Noel S.; Pastoor, Timothy P.

    2011-01-01

    Historically, toxicology has played a significant role in verifying conclusions drawn on the basis of epidemiological findings. Agents that were suggested to have a role in human diseases have been tested in animals to firmly establish a causative link. Bacterial pathogens are perhaps the oldest examples, and tobacco smoke and lung cancer and asbestos and mesothelioma provide two more recent examples. With the advent of toxicity testing guidelines and protocols, toxicology took on a role that was intended to anticipate or predict potential adverse effects in humans, and epidemiology, in many cases, served a role in verifying or negating these toxicological predictions. The coupled role of epidemiology and toxicology in discerning human health effects by environmental agents is obvious, but there is currently no systematic and transparent way to bring the data and analysis of the two disciplines together in a way that provides a unified view on an adverse causal relationship between an agent and a disease. In working to advance the interaction between the fields of toxicology and epidemiology, we propose here a five-step “Epid-Tox” process that would focus on: (1) collection of all relevant studies, (2) assessment of their quality, (3) evaluation of the weight of evidence, (4) assignment of a scalable conclusion, and (5) placement on a causal relationship grid. The causal relationship grid provides a clear view of how epidemiological and toxicological data intersect, permits straightforward conclusions with regard to a causal relationship between agent and effect, and can show how additional data can influence conclusions of causality. PMID:21561883

  19. Adverse effects of extra-articular corticosteroid injections: a systematic review

    PubMed Central

    2010-01-01

    Background To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue) corticosteroid injection. Methods A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case reports were included, as were prospective and retrospective studies that reported adverse events of corticosteroid injection. All clinical trials which used extra-articular corticosteroid injections were examined. We divided the reported adverse events into major (defined as those needing intervention or not disappearing) and minor ones (transient, not requiring intervention). Results The search yielded 87 relevant studies:44 case reports, 37 prospective studies and 6 retrospective studies. The major adverse events included osteomyelitis and protothecosis; one fatal necrotizing fasciitis; cellulitis and ecchymosis; tendon ruptures; atrophy of the plantar fat was described after injecting a neuroma; and local skin effects appeared as atrophy, hypopigmentation or as skin defect. The minor adverse events effects ranged from skin rash to flushing and disturbed menstrual pattern. Increased pain or steroid flare after injection was reported in 19 studies. After extra-articular injection, the incidence of major adverse events ranged from 0-5.8% and that of minor adverse events from 0-81%. It was not feasible to pool the risk for adverse effects due to heterogeneity of study populations and difference in interventions and variance in reporting. Conclusion In this literature review it was difficult to accurately quantify the incidence of adverse effects after extra-articular corticosteroid injection. The reported adverse events were relatively mild, although one fatal reaction was reported. PMID:20836867

  20. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis

    PubMed Central

    Trindade, E; Menon, D; Topfer, L A; Coloma, C

    1998-01-01

    BACKGROUND: The use of antidepressant medications and the resulting costs have increased dramatically in recent years, partly because of the introduction of selective serotonin reuptake inhibitors (SSRIs). An assessment of the clinical and economic aspects of SSRIs compared with the older tricyclic antidepressants (TCAs) was initiated to generate information for purchasers of these drugs as well as clinicians. One component of this study was an examination of the adverse effects associated with the use of these drugs. METHODS: Searches of bibliographic databases (for January 1980 through May 1996) and manual scanning of both peer-reviewed publications and other documents were used to identify double-blind, randomized controlled trials involving at least one SSRI and one TCA. For the study of adverse effects, only trials that had at least 20 patients in each trial arm and that reported rates of adverse effects in both arms were retained. In total 84 trials reporting on 18 adverse effects were available. Meta-analyses were undertaken to calculate pooled differences in rates of adverse effects. The question of whether the method of eliciting information from patients about adverse effects made a difference in the findings was also examined. Finally, differences in drop-out rates due to adverse effects were calculated. RESULTS: The crude rates of occurrence of adverse effects ranged from 4% (palpitations) to 26% (nausea) for SSRIs and from 4% (diarrhea) to 27% (dry mouth) for TCAs. The differences in the rates of adverse effects between the 2 types of drugs ranged from 14% more with SSRIs (for nausea) to 11% more with TCAs (for constipation). The results did not depend on the method of eliciting information from patients. There were no statistically significant differences between drug classes in terms of drop-outs due to adverse effects. INTERPRETATION: SSRIs and TCAs are both associated with adverse effects, although the key effects differ between the drug classes

  1. Effectiveness of Micro-Blowing Technique in Adverse Pressure Gradients

    NASA Technical Reports Server (NTRS)

    Welch, Gerard E.; Larosiliere, Louis M.; Hwang, Danny P.; Wood, Jerry R.

    2001-01-01

    The impact of the micro-blowing technique (MBT) on the skin friction and total drag of a strut in a turbulent, strong adverse-pressure-gradient flow is assessed experimentally over a range of subsonic Mach numbers (0.3 less than M less than 0.7) and reduced blowing fractions (0 less than or equal to 2F/C (sub f,o) less than or equal to 1.75). The MBT-treated strut is situated along the centerline of a symmetric 2-D diffuser with a static pressure rise coefficient of 0.6. In agreement with presented theory and earlier experiments in zero-pressure-gradient flows, the effusion of blowing air reduces skin friction significantly (e.g., by 60% at reduced blowing fractions near 1.75). The total drag of the treated strut with blowing is significantly lower than that of the treated strut in the limit of zero-blowing; further, the total drag is reduced below that of the baseline (solid-plate) strut, provided that the reduced blowing fractions are sufficiently high. The micro-blowing air is, however, deficient in streamwise momentum and the blowing leads to increased boundary-layer and wake thicknesses and shape factors. Diffuser performance metrics and wake surveys are used to discuss the impact of various levels of micro-blowing on the aerodynamic blockage and loss.

  2. Adverse Effects of Common Drugs: Children and Adolescents.

    PubMed

    Karpa, Kelly Dowhower; Felix, Todd Matthew; Lewis, Peter R

    2015-09-01

    Drug use and harms are increasingly common among newborns, infants, children, and adolescents during ambulatory practice, emergency department, and in-hospital treatment, including treatment in pediatric intensive care units. The pharmacokinetic and pharmacodynamic parameters of drugs often are different for children compared with adults and must be considered before prescribing. Drug exposure and the potential for harms also should be considered for fetuses and breastfeeding infants. As with adult patients, a thorough drug and allergy history (including nonprescription drugs and herbal and dietary supplements) should be obtained and reviewed at each medical visit. Children and adolescents are increasingly at risk of drug harm/overdose through accidental or intentional ingestion of nonprescription and prescription drugs (eg, cough and cold preparations, candy-appearing vitamins, stimulants, narcotics). Parents and caregivers should receive training in the proper use, storage, and administration of all drugs. Prescribing clinicians should be vigilant in withholding unnecessary drugs, such as antibiotics for viral infections. When prescribing, clinicians should be aware of common drugs frequently associated with adverse reactions, including stimulants, antipsychotics, analgesics, asthma therapies, acne therapies, and tumor necrosis factor inhibitors. Scientifically based prescribing practices should be used and consultation with evidence-based resources and pharmacists sought as needed. PMID:26375994

  3. [Are there cardiovascular adverse effects of inhaled anticholinergics?].

    PubMed

    Nagy, László Béla

    2015-08-01

    The purpose of this review is to discuss the cardiovascular risk associated with inhaled anticholinergics in chronic obstructive pulmonary disease. Several meta-analyses of data for tiotropium raised the possibility of an increased risk for arrhythmia, angina, myocardial infarction, etc. This review includes the data of retrospective studies of databases using databases, randomized controlled trials, and meta-analyses of clinical trials. The conclusions of studies were inconsistent. In most clinical trials the incidence of cardiovascular adverse events was similar in active treatment and placebo groups, especially in patients with previous cardiovascular diseases. Considering meta-analyses, there is little, if any, evidence for the association between anticholinergics and the development of cardiovascular symptoms. The author discusses the presence and function of cholinergic receptor subtypes in human heart, and cardiac functions controlled by the autonomic nervous system via these receptors, their possible role, and pharmacokinetic properties of inhaled anticholinergics. The author concludes that it is not possible to find evidence of increased cardiovascular harm of inhaled anticholinergics. PMID:26211748

  4. Multidisciplinary approach to identification and remedial intervention for adverse late effects of cancer therapy

    SciTech Connect

    McCalla, J.L.

    1985-03-01

    Because of advances in surgical technique, radiation therapy, and combined chemotherapy regimens, there has been a dramatic improvement in the survival of children with pediatric malignancies. All treatment modalities are associated with adverse effects that may be manifested months to years after therapy. This article has provided an overview of the physiologic and psychologic adverse effects of antineoplastic therapy and described the multidisciplinary approach used by one institution to identify and initiate appropriate remedial intervention. Nurses can learn to assist in the identification of adverse late effects, provide support to the family, and facilitate appropriate intervention.

  5. Toxicology: Old Art, New Science.

    ERIC Educational Resources Information Center

    Timbrell, John A.

    1983-01-01

    Examines the need for a science of toxicology and training at both the undergraduate and graduate levels in response to legislation controlling drugs, food additives and toxic substances in the work environment, and concern about effects on man. Stresses need for putting toxicology on a scientific base with adequate funding. (JM)

  6. The lifelong effects of early childhood adversity and toxic stress.

    PubMed

    Shonkoff, Jack P; Garner, Andrew S

    2012-01-01

    Advances in fields of inquiry as diverse as neuroscience, molecular biology, genomics, developmental psychology, epidemiology, sociology, and economics are catalyzing an important paradigm shift in our understanding of health and disease across the lifespan. This converging, multidisciplinary science of human development has profound implications for our ability to enhance the life prospects of children and to strengthen the social and economic fabric of society. Drawing on these multiple streams of investigation, this report presents an ecobiodevelopmental framework that illustrates how early experiences and environmental influences can leave a lasting signature on the genetic predispositions that affect emerging brain architecture and long-term health. The report also examines extensive evidence of the disruptive impacts of toxic stress, offering intriguing insights into causal mechanisms that link early adversity to later impairments in learning, behavior, and both physical and mental well-being. The implications of this framework for the practice of medicine, in general, and pediatrics, specifically, are potentially transformational. They suggest that many adult diseases should be viewed as developmental disorders that begin early in life and that persistent health disparities associated with poverty, discrimination, or maltreatment could be reduced by the alleviation of toxic stress in childhood. An ecobiodevelopmental framework also underscores the need for new thinking about the focus and boundaries of pediatric practice. It calls for pediatricians to serve as both front-line guardians of healthy child development and strategically positioned, community leaders to inform new science-based strategies that build strong foundations for educational achievement, economic productivity, responsible citizenship, and lifelong health. PMID:22201156

  7. The behavior and toxicological effects of decabromodiphenyl ether (BDE209) in a soil-earthworm system.

    PubMed

    Zhang, Wei; Li, Jing; Liu, Kou; Lin, Kuangfei

    2015-12-15

    Decabromodiphenyl ether (BDE209) is easily absorbed by soil particles but barely degraded over time. Its potential ecological risk has received extensive attention. Here we supplemented natural soil with three different levels of BDE209 (1, 10 and 100 mg kg(-1) dry weight (i.e., dw)) to focus on the behavior and toxicological effects of BDE209 in a soil-earthworm system. Results demonstrated that earthworms accumulated BDE209 quickly, followed by biphasic elimination. The uptake rate constant (ku) values ranged from 0.156 to 0.232 mg soil kg(-1)worm d(-1), while the depuration rate (kd) values ranged from 0.228 to 0.239 d(-1). Biota-soil accumulation factor (BSAF) was also calculated in the present study, and the BSAF values for BDE209 ranged from 0.074 to 0.123. Throughout 28-d exposure, the concentrations of BDE209 among soil, worm casts and earthworms reached steady-state equilibrium. BDE209 content in worm casts might be a good indicator of actual concentration in soil. Neutral red retention time (NRRT) was also conducted to assess the lysosomal membrane stability, and it declined during the uptake phase when BDE209 gradually accumulated in earthworms, indicating a good dose-response relationship. These observations provide new insights into the potential ecological effects of BDE209 in a model soil-earthworm system. PMID:26282772

  8. Toxicological effects of nanometer titanium dioxide (nano-TiO2) on Chlamydomonas reinhardtii.

    PubMed

    Chen, Lanzhou; Zhou, Lina; Liu, Yongding; Deng, Songqiang; Wu, Hao; Wang, Gaohong

    2012-10-01

    The toxicological effects of nanometer titanium dioxide (nano-TiO2) on a unicellular green alga Chlamydomonas reinhardtii were assessed by investigating the changes of the physiology and cyto-ultrastructure of this species under treatment. We found that nano-TiO2 inhibited photosynthetic efficiency and cell growth, but the content of chlorophyll a content in algae did not change, while carotenoid and chlorophyll b contents increased. Malondialdehyde (MDA) content reached maximum values after 8h exposure and then decreased to a moderately low level at 72 h. Electron microscopy images indicated that as concentrations of nano-TiO2 increased, a large number of C. reinhardtii cells were noted to be damaged: the number of chloroplasts declined, various other organelles were degraded, plasmolysis occurred, and TiO2 nanoparticles were found to be located inside cell wall and membrane. It was also noted that cell surface was surrounded by TiO2 particles, which could present an obstacle to the exchange of substances between the cell and its surrounding environment. To sum up, the effect of nano-TiO2 on C. reinhardtii included cell surface aggregation, photosynthesis inhibition, lipid peroxidation and new protein synthesis, while the response of C. reinhardtii to nano-TiO2 was a rapid process which occurs during 24 h after exposing and may relate to physiological stress system to mitigate damage. PMID:22883605

  9. The Useage of Opioids and their Adverse Effects in Gastrointestinal Practice: A Review

    PubMed Central

    Khansari, MahmoudReza; Sohrabi, MasourReza; Zamani, Farhad

    2013-01-01

    Opium is one of the oldest herbal medicines currently used as an analgesic, sedative and antidiarrheal treatment. The effects of opium are principally mediated by the μ-, κ- and δ-opioid receptors. Opioid substances consist of all natural and synthetic alkaloids that are derived from opium. Most of their effects on gastrointestinal motility and secretion result from suppression of neural activity. Inhibition of gastric emptying, increase in sphincter tone, changes in motor patterns, and blockage of peristalsis result from opioid use. Common adverse effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, dependency and tolerance, and respiratory depression. The most common adverse effect of opioid use is constipation. Although stool softeners are frequently used to decrease opioid-induced bowel dysfunction, however they are not efficacious. Possibly, the use of specific opioid receptor antagonists is a more suitable approach. Opioid antagonists, both central and peripheral, could affect gastrointestinal function and visceromotor sensitivity, which suggests an important role for endogenous opioid peptides in the control of gastrointestinal physiology. Underlying diseases or medications known to influence the central nervous system (CNS) often accelerate the opioid’s adverse effects. However, changing the opioid and/or route of administration could also decrease their adverse effects. Appropriate patient selection, patient education and discussion regarding potential adverse effects may assist physicians in maximizing the effectiveness of opioids, while reducing the number and severity of adverse effects. PMID:24829664

  10. Aerospace Toxicology and Microbiology

    NASA Technical Reports Server (NTRS)

    James, John T.; Parmet, A. J.; Pierson, Duane L.

    2007-01-01

    Toxicology dates to the very earliest history of humanity with various poisons and venom being recognized as a method of hunting or waging war with the earliest documentation in the Evers papyrus (circa 1500 BCE). The Greeks identified specific poisons such as hemlock, a method of state execution, and the Greek word toxos (arrow) became the root of our modern science. The first scientific approach to the understanding of poisons and toxicology was the work during the late middle ages of Paracelsus. He formulated what were then revolutionary views that a specific toxic agent or "toxicon" caused specific dose-related effects. His principles have established the basis of modern pharmacology and toxicology. In 1700, Bernardo Ramazzini published the book De Morbis Artificum Diatriba (The Diseases of Workers) describing specific illnesses associated with certain labor, particularly metal workers exposed to mercury, lead, arsenic, and rock dust. Modern toxicology dates from development of the modern industrial chemical processes, the earliest involving an analytical method for arsenic by Marsh in 1836. Industrial organic chemicals were synthesized in the late 1800 s along with anesthetics and disinfectants. In 1908, Hamilton began the long study of occupational toxicology issues, and by WW I the scientific use of toxicants saw Haber creating war gases and defining time-dosage relationships that are used even today.

  11. Short-term adverse effects in humans of ingested mineral oils, their additives and possible contaminants--a review.

    PubMed

    Hard, G C

    2000-03-01

    The toxicological databases for petroleum refinery products such as mineral oils, as well as for their potential contaminants and additives, were reviewed for human cases of poisoning by the oral route. The aim was to determine whether any overlooked adulterant in the oil implicated as the cause of the 1981 outbreak of Toxic Oil Syndrome (TOS) in Spain, may have been responsible for the unusual symptomatology characterizing this disease. The essential features of TOS were peripheral eosinophilia, pulmonary oedema and endothelial damage in the acute phase; myalgia, sensory neuropathy, hepatic injury, skin oedema and sicca in the intermediate phase; and peripheral neuropathy, muscle wasting, scleroderma and hepatopathy in the chronic phase. Of the more than 70 chemical entities and mixtures reviewed here, none had been reported as producing adverse toxic effects upon ingestion resembling the specific set of symptoms and progression that characterized TOS. Because of their viscosity, the most commonly recorded disease process associated with oral ingestion of petroleum refinery products was lipid pneumonia, implicating lung exposure via aspiration. The mineral oil additives and contaminants comprised a highly diverse range of chemical entities, producing a variety of symptoms in instances of poisoning. Specifically, no chemical entity amongst the refinery products, additives or contaminants was described as inducing a syndrome involving vasculitis accompanied by thrombotic events, along with immunological consequences (such as T-lymphocyte activation and cytokine release), as is considered to be the cellular basis of TOS. PMID:10889514

  12. Preventive Effects of Multi-Lamellar Emulsion on Low Potency Topical Steroid Induced Local Adverse Effect

    PubMed Central

    Sul, Geun Dong; Park, Hyun Jung; Bae, Jong Hwan; Hong, Keum Duck; Park, Byeong Deog; Chun, Jaesun; Jeong, Se Kyoo; Lee, Seung Hun; Ahn, Sung Ku

    2013-01-01

    Background Topical steroid treatment induces diverse local Wand systemic adverse effects. Several approaches have been tried to reduce the steroid-induced adverse effects. Simultaneous application of physiological lipid mixture is also suggested. Objective Novel vehicles for topical glucocorticoids formulation were evaluated for the efficacy of reducing side-effects and the drug delivery properties of desonide, a low potency topical steroid. Methods Transcutaneous permeation and skin residual amount of desonide were measured using Franz diffusion cells. The in vivo anti-inflammatory activity was evaluated using murine model. Results Topical steroids formulation containing desonide, in either cream or lotion form, were prepared using multi-lamellar emulsion (MLE), and conventional desonide formulations were employed for comparison. MLE formulations did not affect the anti-inflammatory activity of the desonide in phobol ester-induced skin inflammation model, compared with conventional formulations. While the penetrated amounts of desonide were similar for all the tested formulations at 24 hours after application, the increased lag time was observed for the MLE formulations. Interestingly, residual amount of desonide in epidermis was significantly higher in lotion type MLE formulation. Steroid-induced adverse effects, including permeability barrier function impairment, were partially prevented by MLE formulation. Conclusion Topical desonide formulation using MLE as a vehicle showed a better drug delivery with increased epidermal retention. MLE also partially prevented the steroid-induced side effects, such as skin barrier impairment. PMID:23467730

  13. Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

    PubMed Central

    Pirela, Sandra V.; Lu, Xiaoyan; Miousse, Isabelle; Sisler, Jennifer D.; Qian, Yong; Guo, Nancy; Koturbash, Igor; Castranova, Vincent; Thomas, Treye; Godleski, John; Demokritou, Philip

    2016-01-01

    Incorporation of engineered nanomaterials (ENMs) into toners used in laser printers has led to countless quality and performance improvements. However, the release of ENMs during printing (consumer use) has raised concerns about their potential adverse health effects. The aim of this study was to use “real world” printer-emitted particles (PEPs), rather than raw toner powder, and assess the pulmonary responses following exposure by intratracheal instillation. Nine-week old male Balb/c mice were exposed to various doses of PEPs (0.5, 2.5 and 5 mg/kg body weight) by intratracheal instillation. These exposure doses are comparable to real world human inhalation exposures ranging from 13.7 to 141.9 h of printing. Toxicological parameters reflecting distinct mechanisms of action were evaluated, including lung membrane integrity, inflammation and regulation of DNA methylation patterns. Results from this in vivo toxicological analysis showed that while intratracheal instillation of PEPs caused no changes in the lung membrane integrity, there was a pulmonary immune response, indicated by an elevation in neutrophil and macrophage percentage over the vehicle control and low dose PEPs groups. Additionally, exposure to PEPs upregulated expression of the Ccl5 (Rantes), Nos1 and Ucp2 genes in the murine lung tissue and modified components of the DNA methylation machinery (Dnmt3a) and expression of transposable element (TE) LINE-1 compared to the control group. These genes are involved in both the repair process from oxidative damage and the initiation of immune responses to foreign pathogens. The results are in agreement with findings from previous in vitro cellular studies and suggest that PEPs may cause immune responses in addition to modifications in gene expression in the murine lung at doses that can be comparable to real world exposure scenarios, thereby raising concerns of deleterious health effects. PMID:26989787

  14. In vitro toxicological effects of estrogenic mycotoxins on human placental cells: Structure activity relationships

    SciTech Connect

    Prouillac, Caroline; Lecoeur, Sylvaine

    2012-03-15

    Zearalenone (ZEN) is a non-steroid estrogen mycotoxin produced by numerous strains of Fusarium which commonly contaminate cereals. After oral administration, ZEN is reduced via intestinal and hepatic metabolism to α- and β-zearalenol (αZEL and βZEL). These reduced metabolites possess estrogenic properties, αZEL showing the highest affinity for ERs. ZEN and reduced metabolites cause hormonal effects in animals, such as abnormalities in the development of the reproductive tract and mammary gland in female offspring, suggesting a fetal exposure to these contaminants. In our previous work, we have suggested the potential impact of ZEN on placental cells considering this organ as a potential target of xenobiotics. In this work, we first compared the in vitro effects of αZEL and βΖΕL on cell differentiation to their parental molecule on human trophoblast (BeWo cells). Secondly, we investigated their molecular mechanisms of action by investigating the expression of main differentiation biomarkers and the implication of nuclear receptor by docking prediction. Conversely to ZEN, reduced metabolites did not induce trophoblast differentiation. They also induced significant changes in ABC transporter expression by potential interaction with nuclear receptors (LXR, PXR, PR) that could modify the transport function of placental cells. Finally, the mechanism of ZEN differentiation induction seemed not to involve nuclear receptor commonly involved in the differentiation process (PPARγ). Our results demonstrated that in spite of structure similarities between ZEN, αZEL and βZEL, toxicological effects and toxicity mechanisms were significantly different for the three molecules. -- Highlights: ► ZEN and metabolites have differential effect on trophoblast differentiation. ► ZEN and metabolites have differential effect on ABC transporter expression. ► ZEN and metabolites effects involved nuclear receptors interaction.

  15. Comprehensive evaluations of the adverse effects of drugs: importance of appropriate study selection and data sources

    PubMed Central

    Golder, Su P.; Vandenbroucke, Jan P.

    2011-01-01

    While systematic reviews and meta-analyses are at the top of the evidence hierarchy, most of the methodology has focused on assessing treatment benefit. Hence, we propose a structured framework for the initial steps of searching and identifying relevant data sources so that adverse effects can be evaluated in a comprehensive, unbiased manner. The unique methodological challenges stem from the difficulties of addressing diverse outcomes encompassing common, mild symptoms to rare, fatal events. Retrieval of the most appropriate studies should be specifically tailored to fit the nature of the adverse effects, according to the primary objective and study question. In our framework, the structure of the review takes different forms depending on whether the main aim is on scoping/hypothesis generation, or evaluating statistically the magnitude of risk (hypothesis testing), or clarifying characteristics and risk factors of the adverse effect. The wide range of data sources covering adverse effects all have distinct strengths and limitations, and selection of appropriate sources depends on characteristics of the adverse effect (e.g. background incidence and effect size of the drug, clinical presentation, time of onset after drug exposure). Reviewers need to retrieve particular study designs that are most likely to yield robust data on the adverse effects of interest, rather than rely on studies that cannot reliably detect adverse effects, and may yield ‘false negatives’. Type II errors (a particular problem when evaluating rare adverse effects) can lull us into a false sense of security (e.g. wrongly concluding that there was no significant difference in harm between drug and control, with the drug erroneously judged as safe). Given the rapid rate at which methodological improvements occur, this proposed framework is by no means definitive, but aims to stimulate further debate and discussion amongst the pharmacoepidemiological and systematic review communities to reach

  16. Saraca indica Bark Extract Shows In Vitro Antioxidant, Antibreast Cancer Activity and Does Not Exhibit Toxicological Effects

    PubMed Central

    Yadav, Navneet Kumar; Saini, Karan Singh; Hossain, Zakir; Omer, Ankur; Sharma, Chetan; Gayen, Jiaur R.; Singh, Poonam; Arya, K. R.; Singh, R. K.

    2015-01-01

    Medicinal plants are used as a complementary and alternative medicine in treatment of various diseases including cancer worldwide, because of their ease of accessibility and cost effectiveness. Multicomposed mixture of compounds present in a plant extract has synergistic activity, increases the therapeutic potential many folds, compensates toxicity, and increases bioavailability. Saraca indica (family Caesalpiniaceae) is one of the most ancient sacred plants with medicinal properties, exhibiting a number of pharmacological effects. Antioxidant, antibreast cancer activity and toxicological evaluation of Saraca indica bark extract (SIE) were carried out in the present study. The results of the study indicated that this herbal preparation has antioxidant and antibreast cancer activity. Toxicological studies suggest that SIE is safer to use and may have a potential to be used as complementary and alternative medicine for breast cancer therapy. PMID:25861411

  17. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  18. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... water samples, percent surface water source by specific surface water sources to water supply system(s... adverse reproductive effects or in residual disability. (C) H-C: If the person alleged or...

  19. Evaluation of the adverse effect of low concentration of cadmium on interleukin-4 induced class switch recombination in Burkett's lymphoma Raji cell line.

    PubMed

    Poltoratsky, Vladimir

    2014-01-01

    Affinity maturation of B lymphocytes, a process that includes somatic hypermutation and class switch recombination, initiates global DNA rearrangements. The interruption of this process has an adverse effect on human health and results in immunodeficiency and autoimmune disease. Class switch recombination is a fundamental factor of the human adaptive immunity. Evaluation of the class switch recombination efficiency is an important component of laboratory diagnostic of immunotoxic components. Here, we describe a method for testing the efficiency of the class switch recombination. Cultivation of Raji Burkett's lymphoma cell line with anti-CD40 antibodies and recombinant interleukin-4 (IL-4) triggers a cascade of signal transduction network events that lead to switching the immunoglobulin isotopes from IgM to IgE. This chapter describes the methodology of class switch recombination assay for assessment of the effect of the environmental pollutants in toxicological laboratory diagnostics. PMID:24908303

  20. Science: Aquatic Toxicology Matures, Gains Importance.

    ERIC Educational Resources Information Center

    Dagani, Ron

    1980-01-01

    Reviews recent advances in aquatic toxicology, whose major goal is to protect diverse aquatic organisms and whole ecological communities from the dire effects of man-made chemicals. Current legislation is reviewed. Differences in mammalian and aquatic toxicology are listed, and examples of research in aquatic toxicology are discussed. (CS)

  1. Historical perspectives on cadmium toxicology

    SciTech Connect

    Nordberg, Gunnar F.

    2009-08-01

    The first health effects of cadmium (Cd) were reported already in 1858. Respiratory and gastrointestinal symptoms occurred among persons using Cd-containing polishing agent. The first experimental toxicological studies are from 1919. Bone effects and proteinuria in humans were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from Cd-pollution were issued in the 1970's. Reproductive and carcinogenic effects were studied at an early stage, but a quantitative assessment of these effects in humans is still subject to considerable uncertainty. The World Health Organization in its International Program on Chemical Safety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134, IPCS. WHO, Geneva, 1-280.) identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's and 2000 several epidemiological studies have reported adverse health effects, sometimes at low environmental exposures to Cd, in population groups in Japan, China, Europe and USA (reviewed in other contributions to the present volume). The early identification of an important role of metallothionein in cadmium toxicology formed the basis for recent studies using biomarkers of susceptibility to development of Cd-related renal dysfunction such as gene expression of metallothionein in peripheral lymphocytes and autoantibodies against metallothionein in blood plasma. Findings in these studies indicate that very low exposure levels to cadmium may give rise to renal dysfunction among sensitive subgroups of human populations such as persons with diabetes.

  2. Effect of oxygenated fuels on physicochemical and toxicological characteristics of diesel particulate emissions.

    PubMed

    Zhang, Zhi-Hui; Balasubramanian, Rajasekhar

    2014-12-16

    A systematic study was conducted to make a comparative evaluation of the effects of blending five different oxygenates (diglyme (DGM), palm oil methyl ester (PME), dimethyl carbonate (DMC), diethyl adipate (DEA), and butanol (Bu)) with ultralow sulfur diesel (ULSD) at 2% and 4% oxygen levels on physicochemical and toxicological characteristics of particulate emissions from a nonroad diesel engine. All blended fuels led to an overall decrease in the particulate mass concentration and elemental carbon (EC) emissions, which was strongly associated with the oxygen content in fuels and the specific type of fuels used. In general, the proportion of particulate-bound organic carbon (OC) and water-soluble organic carbon (WSOC) increased while using oxygenated fuel blends. Compared to ULSD, all fuel blends showed different emission factors of particle-phase PAHs and n-alkanes, slight alterations in soot nanostructure, lower soot ignition temperature, and lower activation energy. The total counts of particles (≤ 560 nm diameter) emitted decreased gradually for ULSD blended with DMC, DEA, and Bu, while they increased significantly for other fuel blends. The in vitro toxicity of particulates significantly increased with ULSD blended with DMC and DEA, while it decreased when ULSD was blended with PME, DGM, and Bu. PMID:25383974

  3. Geochemical properties of coal wastes and the toxicological effects on aquatic life. Environmental geology notes

    SciTech Connect

    Roy, W.R.; Krapac, I.G.; Griffin, R.A.; Dickerson, D.R.; Schuller, R.M.

    1984-01-01

    Leachates from solid wastes generated by coal mining, cleaning, and gasification are potentially harmful to the environment. The toxicological effects of leachates on aquatic organisms have not been adequately assessed. In this investigation, samples of seven coal-related wastes were charcterized chemically and mineralogically. Laboratory extracts of each sample, obtained by a variety of extraction methods, were used in both acute and chronic bioassay. A coal-slurry sample (coarse fraction) and two samples of coal-cleaning refuse were chemically and mineralogically similar; they generated acidic water-waste systems, both in the laboratory and in the field. Two mine-spoil samples, essentially shale, tended to generate water-waste systems that were neutral in pH; consequently, they released lower quantities of potential pollutants than the acidic wastes. Each extract was tested for acute toxicity with four species of fresh-water aquatic organisms; the green sunfish (Lepomis cyanellus), the fathead minnow, (Pimephales promelas), a crustacean (Daphia magna), and a snail (Physa anatina). The extracts of the two mine spoil samples and of the gasification residue were not toxic to any of the organisms; whereas the extracts from the acidic refuse and slurry samples were acutely toxic to all the organisms.

  4. Relationships of maternal and fetal weight changes in developmental toxicology bioassays

    EPA Science Inventory

    Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects in the embryo/fetus. Guidelines require the inclusion of a dose level(s) that induces “overt maternal toxicity”. The common occurrence of dose levels at which ...

  5. Maternal and fetal toxicity in developmental toxicology bioassays: Weight changes and their biological significance

    EPA Science Inventory

    Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects in the embryo/fetus. Guidelines call for the inclusion of a dose level(s) that induces “overt maternal toxicity.” The possibility that general maternal toxicit...

  6. SIMPLE, INEXPENSIVE HEART RATE MONITOR AND ARRHYTHMIA DETECTOR FOR USE IN TOXICOLOGICAL STUDIES

    EPA Science Inventory

    Many toxic agents have been reported to produce acute, adverse effects on cardiac function. Often these data are neglected in toxicological studies because of the difficulty and expense of monitoring cardiac parameters. We have developed a simple, inexpensive heart rate monitor (...

  7. Toxicological assays for testing effects of an epigenetic drug on development, fecundity and survivorship of malaria mosquitoes.

    PubMed

    Sharma, Atashi; Anderson, Troy D; Sharakhov, Igor V

    2015-01-01

    Insecticidal resistance poses a major problem for malaria control programs. Mosquitoes adapt to a wide range of changes in the environment quickly, making malaria control an omnipresent problem in tropical countries. The emergence of insecticide resistant populations warrants the exploration of novel drug target pathways and compounds for vector mosquito control. Epigenetic drugs are well established in cancer research, however not much is known about their effects on insects. This study provides a simple protocol for examining the toxicological effects of 3-Deazaneplanocin A (DZNep), an experimental epigenetic drug for cancer therapy, on the malaria vector, Anopheles gambiae. A concentration-dependent increase in mortality and decrease in size was observed in immature mosquitoes exposed to DZNep, whereas the compound reduced the fecundity of adult mosquitoes relative to control treatments. In addition, there was a drug-dependent decrease in S-adenosylhomocysteine (SAH) hydrolase activity in mosquitoes following exposure to DZNep relative to control treatments. These protocols provide the researcher with a simple, step-by-step procedure to assess multiple toxicological endpoints for an experimental drug and, in turn, demonstrate a unique multi-prong approach for exploring the toxicological effects of water-soluble epigenetic drugs or compounds of interest against vector mosquitoes and other insects. PMID:25650701

  8. Tissue-specific toxicological effects of cadmium in green mussels (Perna viridis): nuclear magnetic resonance-based metabolomics study.

    PubMed

    Wu, Huifeng; Wang, Wen-Xiong

    2011-04-01

    Toxicity tests for metals have traditionally focused on selected biomarkers to characterize the biological stress induced by metals in marine organisms. Here nuclear magnetic resonance (NMR)-based metabolomics, a system biology tool, was applied to the marine green mussel, Perna viridis, to investigate the toxicological effects of Cd in both digestive gland and adductor muscle tissues. After Cd exposure for either two or four weeks, there was no significant metabolic change in the mussels exposed to Cd at 2 µg/L. At 20 µg/L, there were major metabolite changes related to amino acids, osmolytes, and energy metabolites. Digestive gland tissue was more sensitive to Cd than adductor muscle tissue. The adductor muscle tissue showed elevated levels of glutamine, glutamate, and lactate, and reduced levels of branched chain amino acids, aspartate, phenylalanine, and tyrosine. Overall, four weeks of Cd exposure produced neurotoxicity and metabolic disturbances and disturbed osmoregulation. These results suggest that the adductor muscle tissue of mussels may be a suitable supplemental biomarker for exposure to toxicants. In addition, the results demonstrate that (1) H-NMR-based metabolomic analysis can provide a systematic view of the toxicological effects of metals on mussels, suggesting that it might be employed to investigate the toxicological effects of other marine pollutants. PMID:21184531

  9. Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

    PubMed Central

    Koch, Karoline; Havermann, Susannah; Büchter, Christian

    2014-01-01

    Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research. PMID:24895670

  10. Possible sertraline-induced extrapyramidal adverse effects in an adolescent.

    PubMed

    Wang, Lian-Fang; Huang, Jin-Wen; Shan, Si-Yang; Ding, Jia-Hong; Lai, Jian-Bo; Xu, Yi; Hu, Shao-Hua

    2016-01-01

    Sertraline has been considered to be a relatively safe selective serotonin reuptake inhibitor for adolescents for a long time. We report herein a case of a 16-year-old Chinese boy with depression who experienced extrapyramidal-like effects, for example, facial spasm, upper limb dystonia, akathisia, and other disturbed behaviors, while being treated with sertraline 200 mg per day. His movement symptoms were significantly alleviated after the discontinuation of sertraline and the administration of scopolamine. This finding indicates that albeit infrequent, sertraline may cause severe extrapyramidal symptoms in adolescent patients, suggesting that clinicians should be alert to the neurological side effects of sertraline in young patients. PMID:27226717

  11. Possible sertraline-induced extrapyramidal adverse effects in an adolescent

    PubMed Central

    Wang, Lian-fang; Huang, Jin-wen; Shan, Si-yang; Ding, Jia-hong; Lai, Jian-bo; Xu, Yi; Hu, Shao-hua

    2016-01-01

    Sertraline has been considered to be a relatively safe selective serotonin reuptake inhibitor for adolescents for a long time. We report herein a case of a 16-year-old Chinese boy with depression who experienced extrapyramidal-like effects, for example, facial spasm, upper limb dystonia, akathisia, and other disturbed behaviors, while being treated with sertraline 200 mg per day. His movement symptoms were significantly alleviated after the discontinuation of sertraline and the administration of scopolamine. This finding indicates that albeit infrequent, sertraline may cause severe extrapyramidal symptoms in adolescent patients, suggesting that clinicians should be alert to the neurological side effects of sertraline in young patients. PMID:27226717

  12. Toxicology and Chemical Safety.

    ERIC Educational Resources Information Center

    Hall, Stephen K.

    1983-01-01

    Topics addressed in this discussion of toxicology and chemical safety include routes of exposure, dose/response relationships, action of toxic substances, and effects of exposure to chemicals. Specific examples are used to illustrate the principles discussed. Suggests prudence in handling any chemicals, whether or not toxicity is known. (JN)

  13. The (Adverse) Effects of Expanding Higher Education: Evidence from Italy

    ERIC Educational Resources Information Center

    Oppedisano, Veruska

    2011-01-01

    Over the period 1995-1998 Italy experienced an expansion of its higher education supply with the aim of reducing regional differences in educational attainment. This paper evaluates the effects of this policy on enrolment, drop out and academic performance. The paper combines differences across provinces in the number of campuses constructed with…

  14. 36 CFR 800.7 - Failure to resolve adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) If a THPO terminates consultation regarding an undertaking occurring on or affecting historic... terminating consultation to seek to resolve issues concerning the undertaking and its effects on historic... additional advisory comments upon an undertaking for which a memorandum of agreement will be executed....

  15. Abuse potential and adverse cognitive effects of mitragynine (kratom).

    PubMed

    Yusoff, Nurul H M; Suhaimi, Farah W; Vadivelu, Raja K; Hassan, Zurina; Rümler, Anne; Rotter, Andrea; Amato, Davide; Dringenberg, Hans C; Mansor, Sharif M; Navaratnam, Visweswaran; Müller, Christian P

    2016-01-01

    Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug. PMID:25262913

  16. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... that the Commission make an initial determination on the adverse environmental effects requirements in...)(1), proposed measures to mitigate the adverse environmental effects found. (3)(i) The Commission... determination on whether a project has a substantial adverse effect on the environment (AEE petition)....

  17. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  18. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  19. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  20. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  1. In silico toxicology for the pharmaceutical sciences

    SciTech Connect

    Valerio, Luis G.

    2009-12-15

    The applied use of in silico technologies (a.k.a. computational toxicology, in silico toxicology, computer-assisted tox, e-tox, i-drug discovery, predictive ADME, etc.) for predicting preclinical toxicological endpoints, clinical adverse effects, and metabolism of pharmaceutical substances has become of high interest to the scientific community and the public. The increased accessibility of these technologies for scientists and recent regulations permitting their use for chemical risk assessment supports this notion. The scientific community is interested in the appropriate use of such technologies as a tool to enhance product development and safety of pharmaceuticals and other xenobiotics, while ensuring the reliability and accuracy of in silico approaches for the toxicological and pharmacological sciences. For pharmaceutical substances, this means active and impurity chemicals in the drug product may be screened using specialized software and databases designed to cover these substances through a chemical structure-based screening process and algorithm specific to a given software program. A major goal for use of these software programs is to enable industry scientists not only to enhance the discovery process but also to ensure the judicious use of in silico tools to support risk assessments of drug-induced toxicities and in safety evaluations. However, a great amount of applied research is still needed, and there are many limitations with these approaches which are described in this review. Currently, there is a wide range of endpoints available from predictive quantitative structure-activity relationship models driven by many different computational software programs and data sources, and this is only expected to grow. For example, there are models based on non-proprietary and/or proprietary information specific to assessing potential rodent carcinogenicity, in silico screens for ICH genetic toxicity assays, reproductive and developmental toxicity, theoretical

  2. Pulmonary adverse effects of welding fume in automobile assembly welders.

    PubMed

    Sharifian, Seyed Akbar; Loukzadeh, Ziba; Shojaoddiny-Ardekani, Ahmad; Aminian, Omid

    2011-01-01

    Welding is one of the key components of numerous manufacturing industries, which has potential physical and chemical health hazards. Many components of welding fumes can potentially affect the lung function. This study investigates the effects of welding fumes on lung function and respiratory symptoms among welders of an automobile manufacturing plant in Iran. This historical cohort study assesses 43 male welders and 129 office workers by a questionnaire to record demographic data, smoking habits, work history and respiratory symptoms as well as lung function status by spirometry. The average pulmonary function values of welders were lower relative to controls with dose-effect relationship between work duration and pulmonary function impairment. The prevalence of chronic bronchitis was higher in welders than controls. Our findings suggest that welders are at risk for pulmonary disease. PMID:21598218

  3. Adverse effects of poor micronutrient status during childhood and adolescence.

    PubMed

    Kapil, Umesh; Bhavna, A

    2002-05-01

    Despite India's substantial progress in human development since its independence in 1947, 5-7% of its children have vitamin A deficiency disorders in selected geographic areas, 53% have iron deficiency anemia, and 9% have goiter. Three micronutrients--vitamin A, iron, and iodine--are among the most important of all the nutrients needed by the body because they are vital for developing normal learning and cognitive functions, immunity, work capacity, and reproductive health. The body cannot synthesize them, so they must be made available through the diet. Deficiencies of these three micronutrients are known to have devastating effects on health. PMID:12035866

  4. Adversity in Preschool-Aged Children: Effects on Salivary Interleukin-1β

    PubMed Central

    Tyrka, Audrey R.; Parade, Stephanie H.; Valentine, Thomas R.; Eslinger, Nicole M.; Seifer, Ronald

    2016-01-01

    Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary IL-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records, and contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. Number of past month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Post-challenge IL-1β displayed positive associations with each adversity variable, but were not significant. CRP was not significantly associated with any of the adversity variables. Given evidence suggesting involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

  5. The uses and adverse effects of beryllium on health

    PubMed Central

    Cooper, Ross G.; Harrison, Adrian P.

    2009-01-01

    Context: This review describes the health effects of beryllium exposure in the workplace and the environment. Aim: To collate information on the consequences of occupational and environmental exposure to beryllium on physiological function and well being. Materials and Methods: The criteria used in the current review for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability, and Health. Articles were classified based on acute and chronic exposure and toxicity of beryllium. Results: The proportions of utilized and nonutilized articles were tabulated. Years 2001–10 gave the greatest match (45.9%) for methodological parameters, followed by 27.71% for 1991–2000. Years 1971–80 and 1981–90 were not significantly different in the information published and available whereas years 1951–1960 showed a lack of suitable articles. Some articles were published in sources unobtainable through requests at the British Library, and some had no impact factor and were excluded. Conclusion: Beryllium has some useful but undoubtedly harmful effects on health and well-being. Measures need to be taken to prevent hazardous exposure to this element, making its biological monitoring in the workplace essential. PMID:20386622

  6. Correlating toxicological effects of ionic liquids on Daphnia magna with in silico calculated linear free energy relationship descriptors.

    PubMed

    Cho, Chul-Woong; Yun, Yeoung-Sang

    2016-06-01

    In silico prediction model for toxicological effects of ionic liquids (ILs) is useful to understand ILs' toxicological interactions and to design environmentally benign IL structures. Actually, it is essential since the types of ILs are extremely numerous. Accordingly, prediction models were developed in this study. For the modelling, well-defined linear free energy relationship (LFER) descriptors - i.e. excess molar refraction (E), dipolarity/polarizability (S), H-bonding acidity (A), H-bonding basicity (B), McGowan volume (V), cation interaction (J(+)) and anion interaction (J(-)) - were in silico calculated using density functional theory and conductor-like screening model. These descriptors were then correlated with the toxicological values of ILs to Daphnia magna. First, a model established by Hoover et al. (2007) using measured LFER descriptors of 97 neutral compounds was applied to the prediction of ILs' toxicity. As expected, the model by Hoover et al. (2007) needs to be amended for ILs. To that end, the difference in toxicological interactions between neutral compounds and ILs was addressed by additional single J(+) or five LFER descriptors of cation i.e. Ec, Sc, Bc, Vc, and J(+). Secondly, a prediction model for only ILs was developed by using the three LFER descriptors Ec, Bc, and J(+). The model had a reasonable predictability and robustness of R(2) = 0.880 for the training set, 0.848 for the test set, and 0.867 for the overall set. The established models can be used to design environmentally benign IL structures and to reduce labour, danger, time, and materials compared to the experiment-based study. PMID:26971173

  7. Adverse effects of bisphenol A on water louse (Asellus aquaticus).

    PubMed

    Plahuta, Maja; Tišler, Tatjana; Pintar, Albin; Toman, Mihael Jožef

    2015-07-01

    Experiments were performed to study the effects of short and long-term exposure to bisphenol A (BPA) on a freshwater crustacean isopod Asellus aquaticus (L.). Two life stages of isopods were exposed to a range of BPA concentrations, from aqueous and two dietary sources, in the form of with BPA spiked conditioned alder leaf (Alnus glutinosa) discs, or spiked formulated sediment, to determine the relative importance of each source of exposure on the uptake of this contaminant. Several lethal and sublethal endpoints were evaluated in this study to measure the potential effects of BPA on A. aquaticus, including mortality, growth and feeding rate inhibition, mobility inhibition, de-pigmentation and molting disturbances. They signify a correlation to BPA levels and a difference in BPA uptake efficiency from different uptake sources. Results of acute exposure to BPA show a greater sensitivity of test systems using juvenile specimens with a 96 h LC₅₀ of 8.6 mg L(-1) BPA in water medium and a 96 h LC₅₀ of 13.5 mg L(-1) BPA in sediment. In comparison, adult isopods show a 96 h LC₅₀ of 25.1 mg L(-1) BPA in water medium and a 96 h LC₅₀ of 65.1 mg L(-1) BPA in sediment. Observed endpoints of chronic exposures suggest the alder leave discs to be the most efficient uptake source of BPA, in contrast to uptake from water or heterogeneous sediment. Significant (p<0.05) growth inhibition, with a 21d NOEC of 0.5/2.5 mg L(-1) (for juvenile/adult organisms), and feeding rate inhibition, with a 21d NOEC of 0.5/1.0 mg L(-1) (for juvenile/adult organisms), were proven to be the most sensitive toxicity endpoints. An even more sensitive effect turned out to be molting frequency, which was significantly reduced; a 21d NOEC was 1.0 mg L(-1) of BPA for adult organisms and an even lower 21d NOEC of 0.05 mg L(-1) of BPA for juveniles. The observed endpoints are recorded at very low, non-toxic exposure concentrations, indicating that BPA acts as an endocrine disrupting compound, as

  8. Long-term antidepressant use: patient perspectives of benefits and adverse effects

    PubMed Central

    Cartwright, Claire; Gibson, Kerry; Read, John; Cowan, Ondria; Dehar, Tamsin

    2016-01-01

    Long-term antidepressant treatment has increased and there is evidence of adverse effects; however, little is known about patients’ experiences and views of this form of treatment. This study used mixed methods to examine patients’ views and experiences of long-term antidepressant treatment, including benefits and concerns. Data from 180 patients, who were long-term users of antidepressants (3–15 years), were extracted from an anonymous online survey of patients’ experiences of antidepressants in New Zealand. Participants had completed rating scales about the effectiveness of antidepressants, levels of depression before and during antidepressant use, quality of life, and perceived adverse effects. Two open-ended questions allowed participants to comment on personal experiences. The majority (89.4%) reported that antidepressants had improved their depression although 30% reported moderate-to-severe depression on antidepressants. Common adverse effects included withdrawal effects (73.5%), sexual problems (71.8%), and weight gain (65.3%). Adverse emotional effects, such as feeling emotionally numb (64.5%) and addicted (43%), were also common. While the majority of patients were pleased with the benefits of antidepressant treatment, many were concerned about these adverse effects. Some expressed a need for more information about long-term risks and increased information and support to discontinue. PMID:27528803

  9. Thermal Dose and the Probability of Adverse Effects from HIFU

    NASA Astrophysics Data System (ADS)

    Church, Charles C.

    2007-05-01

    The absorption of high-intensity, focused ultrasound (HIFU) by the body results in brief, intense heating capable of killing cells, tissues or entire organisms, thereby providing the basis for many applications in medical therapy. The object of such therapy is in assuring the destruction of diseased tissue while sparing adjacent, healthy tissue. However, even moderate heating to a few degrees above normal physiological temperatures can perturb biological systems, e.g., by altering normal metabolic processes. In modeling the bioeffects produced by ultrasound-induced heating, the physicist typically relies on bulk tissue properties and ultrasound exposure parameters to calculate the thermal `dose' delivered to the tissue. Although thermal dose is currently given in units of time rather than energy, the concept is quite useful, and its use in quantifying the probability and extent of biological effects expected from therapeutic exposures is demonstrated. The results demonstrate the need for additional experimental data to validate and advance existing theoretical approaches for HIFU exposures.

  10. Adverse health effects of air pollutants in a nonsmoking population.

    PubMed

    Pope, C A

    1996-07-17

    Utah Valley has provided an interesting and unique opportunity to evaluate the health effects of respirable particulate air pollution (PM10). Residents of this valley are predominantly nonsmoking members of the Church of Jesus Christ of Latter-day Saints (Mormons). The area has moderately high average PM10 levels with periods of highly elevated PM10 concentrations due to local emissions being trapped in a stagnant air mass near the valley floor during low-level temperature inversion episodes. Due to a labor dispute, there was intermittent operation of the single largest pollution source, an old integrated steel mill. Levels of other common pollutants including sulfur dioxide, ozone, and acidic aerosol are relatively low. Studies specific to Utah Valley have observed that elevated PM10 concentrations are associated with: (1) decreased lung function; (2) increased incidence of respiratory symptoms; (3) increased school absenteeism; (4) increased respiratory hospital admissions; and (5) increased mortality, especially respiratory and cardiovascular mortality. PMID:8711730

  11. The use of fluoroquinolones in neutropenic patients--analysis of adverse effects.

    PubMed

    Rubinstein, E; Potgieter, P; Davey, P; Norrby, S R

    1994-07-01

    The fluoroquinolones have been extensively used in the neutropenic patient. When fluoroquinolone monotherapy was used as prophylaxis, frequently for extended periods, the rate of adverse effect of ciprofloxacin (6.9%) ofloxacin (11.6%) and norfloxacin (5.5%) were significantly lower than those of the comparator agents--co-trimoxazole, vancomycin and polymycin. Rash and gastrointestinal upset were the commonest adverse effects associated with the fluoroquinolones. When used as monotherapy for bacterial infections, often intravenously and in high dosages, the cumulative rate of adverse effects caused by the fluoroquinolones (12.6%) was similar to that caused by the comparator agents (10.3%), but significantly higher than reported for non-neutropenic patients (6.4%) and for prophylactic use. The main adverse events were also rashes (15.4%) and gastrointestinal upset (6.1%). When fluoroquinolones were used as therapy of bacterial infections in combination with other agents, the incidence of adverse events was 14.9%, which was similar to the comparator agents (13.5%). Adverse events were also similar except that nephrotoxicity was commonest with comparator combinations (4.0%). The data suggest that fluoroquinolone prophylaxis in neutropenic patients, even for prolonged periods, is safer than the comparator agents, but is associated with more frequent adverse events than in non-neutropenic patients. Fluoroquinolone therapy, frequently with high dosages, is associated with similar rate of adverse events as the comparator agents. When used in combination with the other antibiotics, fluoroquinolones are as safe as the comparator agents. PMID:7961217

  12. The adverse effects of obesity on conception and implantation.

    PubMed

    Brewer, Christopher J; Balen, Adam H

    2010-09-01

    Whilst many multiparous women are obese (body mass index >30 kg/m(2)), obesity has been associated with impaired fecundity; however, the mechanism which links obesity to reduced fertility remains to be fully elucidated. Obese women, particularly those with central obesity, are less likely to conceive per cycle. Obese women suffer perturbations to the hypothalamic-pituitary-ovarian axis, menstrual cycle disturbance and are up to three times more likely to suffer oligo-/anovulation. A fine hormonal balance regulates follicular development and oocyte maturation, and it has been observed that obesity can alter the hormonal milieu. Leptin, a hormone produced by adipocytes, is elevated in obese women, and raised leptin has been associated with impaired fecundity. Obesity impairs ovulation but has also been observed to detrimentally affect endometrial development and implantation. The expression of polycystic ovary syndrome (PCOS) is regulated, in part, by weight, and so obese women with PCOS often have a more severe phenotype and experience more subfertility. Obesity also impairs the response of women to assisted conception treatments. Weight loss through lifestyle modification or bariatric surgery has been demonstrated to restore menstrual cyclicity and ovulation and improve the likelihood of conception. In this article, we will discuss the effect of obesity upon key reproductive mechanisms and its relation to fertility treatments. PMID:20395425

  13. Remembering Statins: Do Statins Have Adverse Cognitive Effects?

    PubMed

    Bitzur, Rafael

    2016-08-01

    The issue of statin-associated cognitive impairment has been a hot topic among both patients and health care providers, especially since the U.S. Food and Drug Administration (FDA) issued a statement regarding rare postmarketing reports of ill-defined cognitive impairment associated with statin use. This statement was based on case reports, and no objective measures of cognitive function were used. Nevertheless, many patients at high risk of cardiovascular disease have expressed concerns about possible cognitive decline and may have opted to forgo statin therapy. In this overview, the evidence leading to the statement by the FDA is reviewed. Potential mechanisms of the effect of LDL cholesterol reduction and statin therapy on cognition are discussed. Evidence from observational and prospective randomized trials is summarized, leading to the conclusion that as for now, there is no good evidence that statins cause cognitive impairment to a significant degree. Reported cases seem to be rare, and a causal relationship has not been established. PMID:27440840

  14. High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)

    PubMed Central

    Marescotti, Diego; Gonzalez Suarez, Ignacio; Acali, Stefano; Johne, Stephanie; Laurent, Alexandra; Frentzel, Stefan; Hoeng, Julia; Peitsch, Manuel C.

    2016-01-01

    Cigarette smoke (CS) is a major risk factor for cardiovascular and lung diseases. Because CS is a complex aerosol containing more than 7,000 chemicals1 it is challenging to assess the contributions of individual constituents to its overall toxicity. Toxicological profiles of individual constituents as well as mixtures can be however established in vitro, by applying high through-put screening tools, which enable the profiling of Harmful and Potentially Harmful Constituents (HPHCs) of tobacco smoke, as defined by the U.S. Food and Drug Administration (FDA).2 For an initial assessment, an impedance-based instrument was used for a real-time, label-free assessment of the compound's toxicity. The instrument readout relies on cell adhesion, viability and morphology that all together provide an overview of the cell status. A dimensionless parameter, named cell index, is used for quantification. A set of different staining protocols was developed for a fluorescence imaging-based investigation and a HCS platform was used to gain more in-depth information on the kind of cytotoxicity elicited by each HPHC. Of the 15 constituents tested, only five were selected for HCS-based analysis as they registered a computable LD50 (< 20 mM). These included 1-aminonaphtalene, Arsenic (V), Chromium (VI), Crotonaldehyde and Phenol. Based on their effect in the HCS, 1-aminonaphtalene and Phenol could be identified to induce mitochondrial dysfunction, and, together with Chromium (VI) as genotoxic based on the increased histone H2AX phosphorylation. Crotonaldehyde was identified as an oxidative stress inducer and Arsenic as a stress kinase pathway activator. This study demonstrates that a combination of impedance-based and HCS technologies provides a robust tool for in vitro assessment of CS constituents. PMID:27228213

  15. High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC).

    PubMed

    Marescotti, Diego; Gonzalez Suarez, Ignacio; Acali, Stefano; Johne, Stephanie; Laurent, Alexandra; Frentzel, Stefan; Hoeng, Julia; Peitsch, Manuel C

    2016-01-01

    Cigarette smoke (CS) is a major risk factor for cardiovascular and lung diseases. Because CS is a complex aerosol containing more than 7,000 chemicals it is challenging to assess the contributions of individual constituents to its overall toxicity. Toxicological profiles of individual constituents as well as mixtures can be however established in vitro, by applying high through-put screening tools, which enable the profiling of Harmful and Potentially Harmful Constituents (HPHCs) of tobacco smoke, as defined by the U.S. Food and Drug Administration (FDA). For an initial assessment, an impedance-based instrument was used for a real-time, label-free assessment of the compound's toxicity. The instrument readout relies on cell adhesion, viability and morphology that all together provide an overview of the cell status. A dimensionless parameter, named cell index, is used for quantification. A set of different staining protocols was developed for a fluorescence imaging-based investigation and a HCS platform was used to gain more in-depth information on the kind of cytotoxicity elicited by each HPHC. Of the 15 constituents tested, only five were selected for HCS-based analysis as they registered a computable LD50 (< 20 mM). These included 1-aminonaphtalene, Arsenic (V), Chromium (VI), Crotonaldehyde and Phenol. Based on their effect in the HCS, 1-aminonaphtalene and Phenol could be identified to induce mitochondrial dysfunction, and, together with Chromium (VI) as genotoxic based on the increased histone H2AX phosphorylation. Crotonaldehyde was identified as an oxidative stress inducer and Arsenic as a stress kinase pathway activator. This study demonstrates that a combination of impedance-based and HCS technologies provides a robust tool for in vitro assessment of CS constituents. PMID:27228213

  16. Toxicological Benchmarks for Screening Potential Contaminants of Concern for Effects on Sediment-Associated Biota

    SciTech Connect

    Hull, R.N.

    1993-01-01

    A hazardous waste site may contain hundreds of chemicals; therefore, it is important to screen contaminants of potential concern for the ecological risk assessment. Often this screening is done as part of a screening assessment, the purpose of which is to evaluate the available data, identify data gaps, and screen contaminants of potential concern. Screening may be accomplished by using a set of toxicological benchmarks. These benchmarks are helpful in determining whether contaminants warrant further assessment or are at a level that requires no further attention. If a chemical concentration or the reported detection limit exceeds a proposed lower benchmark, further analysis is needed to determine the hazards posed by that chemical. If, however, the chemical concentration falls below the lower benchmark value, the chemical may be eliminated from further study. The use of multiple benchmarks is recommended for screening chemicals of concern in sediments. Integrative benchmarks developed for the National Oceanic and Atmospheric Administration and the Florida Department of Environmental Protection are included for inorganic and organic chemicals. Equilibrium partitioning benchmarks are included for screening nonionic organic chemicals. Freshwater sediment effect concentrations developed as part of the U.S. Environmental Protection Agency's (EPA's) Assessment and Remediation of Contaminated Sediment Project are included for inorganic and organic chemicals (EPA 1996). Field survey benchmarks developed for the Ontario Ministry of the Environment are included for inorganic and organic chemicals. In addition, EPA-proposed sediment quality criteria are included along with screening values from EPA Region IV and Ecotox Threshold values from the EPA Office of Solid Waste and Emergency Response. Pore water analysis is recommended for ionic organic compounds; comparisons are then made against water quality benchmarks. This report is an update of three prior reports (Jones et al

  17. Road traffic and adverse effects on respiratory health in children.

    PubMed Central

    Wjst, M; Reitmeir, P; Dold, S; Wulff, A; Nicolai, T; von Loeffelholz-Colberg, E F; von Mutius, E

    1993-01-01

    OBJECTIVES--To examine whether road traffic in a big city has a direct effect on pulmonary function and respiratory symptoms in children. DESIGN--Cross sectional study. SETTING--Of all 7445 fourth grade children (aged 9-11 years) in Munich, 6537 were examined. Of the children with German nationality and the same residence during the past five years and known exposure data, 4678 questionnaires and 4320 pulmonary function tests could be analysed. MAIN OUTCOME MEASURES--Variables of pulmonary function by forced expiration and respiratory symptoms reported in a questionnaire; census data on car traffic collected in the school district. RESULTS--Density of car traffic ranged from 7000 to 125,000 cars per 24 hours. Multiple regression analysis of peak expiratory flow showed a significant decrease of 0.71% (95% confidence interval 1.08% to 0.33%) per increase of 25,000 cars daily passing through the school district on the main road. Maximum expiratory flow when 25% vital capacity had been expired was decreased by 0.68% (1.11% to 0.25%). In contrast, response to cold air challenge was not increased. The adjusted odds ratio for the cumulative prevalence of recurrent wheezing with the same exposure was 1.08 (1.01 to 1.16). Cumulative prevalence of recurrent dyspnoea was increased, with an odds ratio of 1.10 (1.00 to 1.20). Lifetime prevalence of asthma (odds ratio 1.04; 0.89 to 1.21) and recurrent bronchitis (1.05; 0.98 to 1.12) were not significantly increased. CONCLUSIONS--High rates of road traffic diminish forced expiratory flow and increase respiratory symptoms in children. Images FIG 1 PMID:7691304

  18. Radiation exposure and adverse health effects of interventional cardiology staff.

    PubMed

    Kesavachandran, Chandrasekharan Nair; Haamann, Frank; Nienhaus, Albert

    2013-01-01

    To the best of our knowledge, this chapter constitutes the first systematic review of radiation exposure to eyes, thyroid, and hands for Interventional Cardiology (IC) staff. We have concluded from our review that these anatomical locations are likely to be exposed to radiation as a result of the limited use of personal protective equipment (PPE) among IC staff as shown in Fig. 8. Our review also reveals that, with the exception of three eye exposure cases, the annual radiation dose to eyes, thyroid, and hands among IC staff was within recommended levels and limits. The As Low As Reasonably Achievable (ALARA) limit was not achieved in three cases for fingers/hands and four cases for eyes. However, an increased incidence of cataracts were reported for IC staff, and this gives rise to the concern that low-dose or unnoticed exposures may increase the risk of developing cataracts among cardiology staff. Clearly, the formation of cataracts among IC staff may be an issue and should be studied in more depth. Our review also disclosed that the two groups who receive excessive radiation doses (i.e., exceed the recommended limit) are physicians-in-training and junior staff physicians who work in cardiac catheterization laboratories. In particular, more attention should be given to assessing the effects of radiation exposure among IC staff who work in the Asia Pacific countries, because our review indicates that the number of IC procedures performed by IC staff in these countries is higher than for other continents. There is a huge demand for procedures conducted by IC staff in the Asia-Pacific area, for both treating patients and consulting with specialists. Our review also disclosed that recommended limits for per-procedure radiation doses are needed for IC staff. We recommend that such limits be established by the appropriate national and international agencies that are responsible for occupational radiation exposure. Although our review indicates that the current

  19. High intake of dietary tyramine does not deteriorate glucose handling and does not cause adverse cardiovascular effects in mice.

    PubMed

    Carpéné, Christian; Schaak, Stéphane; Guilbeau-Frugier, Céline; Mercader, Josep; Mialet-Perez, Jeanne

    2016-09-01

    Tyramine is naturally occurring in food and induces pressor responses. Low-tyramine diets are recommended for patients treated with MAO inhibitors to avoid the fatal hypertensive crisis sadly known as "cheese effect". Hence, tyramine intake is suspected to have toxicological consequences in humans, while its administration to type 1 diabetic rodents has been reported to improve glucose tolerance. We investigated in mice whether prolonged tyramine ingestion could alter glucose homeostasis, insulin sensitivity, adipose tissue physiology or cardiovascular functions. Tyramine was added at 0.04 or 0.14 % in the drinking water since this was estimated to increase by 10- to 40-fold the spontaneous tyramine intake of control mice fed a standard diet. Ten to 12 weeks of such tyramine supplementation did not influence body weight gain, adiposity or food consumption. Both doses (reaching approx. 300 and 1100 μmol tyramine/kg bw/day) decreased nonfasting blood glucose but did not modify glucose tolerance or fasting levels of glucose, insulin or circulating lipids. Blood pressure was not increased in tyramine-drinking mice, while only the higher tested dose moderately increased heart rate without change in its variability. Markers of cardiac tissue injury or oxidative stress remained unaltered, except an increased hydrogen peroxide production in heart preparations. In isolated adipocytes, tyramine inhibited lipolysis similarly in treated and control groups, as did insulin. The lack of serious adverse cardiovascular effects of prolonged tyramine supplementation in normoglycemic mice together with the somewhat insulin-like effects found on adipose cells should lead to reconsider favourably the risk/benefit ratio of the intake of this dietary amine. PMID:26634369

  20. Pretreatment Predictors of Adverse Radiation Effects After Radiosurgery for Arteriovenous Malformation

    SciTech Connect

    Hayhurst, Caroline; Monsalves, Eric; Prooijen, Monique van; Cusimano, Michael; Tsao, May; Menard, Cynthia; Kulkarni, Abhaya V.; Schwartz, Michael; Zadeh, Gelareh

    2012-02-01

    Purpose: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. Methods and Materials: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzed to identify predictors of adverse radiation effects. Results: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm{sup 3}, above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Conclusions: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series suggest the

  1. Influence of experimental pulmonary emphysema on the toxicological effects from inhaled nitrogen dioxide and diesel exhaust

    SciTech Connect

    Mauderly, J.L.; Bice, D.E.; Cheng, Y.S.; Gillett, N.A.; Henderson, R.F.; Pickrell, J.A.; Wolff, R.K. )

    1989-10-01

    This project examined the influence of preexisting, experimentally induced pulmonary emphysema on the adverse health effects in rats of chronic inhalation exposure to either nitrogen dioxide or automotive diesel-engine exhaust. Previous reports indicated that humans with chronic lung disease were among those most severely affected by episodic exposures to high concentrations of airborne toxicants. There were no previous reports comparing the effects of chronic inhalation exposure to components of automotive emissions in emphysematous and normal animals. The hypothesis tested in this project was that rats with preexisting pulmonary emphysema were more susceptible than rats with normal lungs to the adverse effects of the toxicant exposures. Young adult rats were housed continuously in inhalation exposure chambers and exposed seven hours per day, five days per week, for 24 months to nitrogen dioxide at 9.5 parts per million (ppm)2, or to diesel exhaust at 3.5 mg soot/m3, or to clean air as control animals. These concentrations were selected to produce mild, but distinct, effects in rats with normal lungs. Pulmonary emphysema was induced in one-half of the rats by intratracheal instillation of the proteolytic enzyme elastase six weeks before the toxicant exposures began. Health effects were evaluated after 12, 18, and 24 months of exposure. The measurements included respiratory function, clearance of inhaled radiolabeled particles, pulmonary immune responses to instilled antigen, biochemistry and cytology of airway fluid, total lung collagen, histopathology, lung morphometry, and lung burdens of diesel soot. The significance of influences of emphysema and toxicant exposure, and interactions between influences of the two treatments, were evaluated by analysis of variance.

  2. Adverse effects of BCG vaccine 1173 P2 in Iran: A meta-analysis

    PubMed Central

    Mostaan, Saied; Yazdanpanah, Bahador; Moukhah, Rasool; Hozouri, Hamid Reza; Rostami, Manouchehr; Khorashadizadeh, Mohsen; Zerehsaz, Javad; Mahabadi, Ramin Pirhajati; Saadi, Arya; Khanahmad, Hossein; Pooya, Mohammad

    2016-01-01

    Although in the last two decades the World Health Organization (WHO) has introduced tuberculosis as “a threat to global”, the vaccination with the Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the only way for the prevention of this fatal infectious disease. Despite of the efficacy of BCG vaccine especially against infants’ meningitis, it has still some limitations due to a variety of adverse effects. Many studies have evaluated the side effects of different strains of BCG vaccines in different countries. In Iran, some studies have been done so far to evaluate the adverse effects of 1173 P2 strain which is used for BCG vaccination. Each of these studies have used different standardization and sampling methods. This review will survey all studies that have been published about adverse effects of 1173 P2 strain of BCG vaccine in Iran using data mining methods. PMID:27376038

  3. Toxicology of Biodiesel Combustion products

    EPA Science Inventory

    1. Introduction The toxicology of combusted biodiesel is an emerging field. Much of the current knowledge about biological responses and health effects stems from studies of exposures to other fuel sources (typically petroleum diesel, gasoline, and wood) incompletely combusted. ...

  4. Biochemical and toxicological evidence of neurological effects of pesticides: the example of Parkinson's disease.

    PubMed

    Moretto, A; Colosio, C

    2011-08-01

    Parkinson's disease (PD) is frequently reported to be associated with pesticide exposure but the issue has not yet been solved because the data are inconsistent and the studies suffer from several biases and limitations. The aim of this article is to summarise available biochemical and toxicological data on some pesticides, particularly on paraquat, that might help in the evaluation of epidemiological data. The nigrostriatal system appears to be particularly sensitive to oxidative damage caused by different mechanisms and agents, thus supporting the epidemiological evidence that Parkinson's disease is in fact an environmental disease. In available experimental studies, animals have been treated with a high single or a few doses of pesticide, and have been followed up for a few days or weeks after treatment. Moreover, experimental data indicate additive/synergistic effects of different pesticides that act on different targets within the dopaminergic system. In these conditions and to a different extent, pesticides such as paraquat, maneb and other dithiocarbamates, pyrethroids, rotenone, and dieldrin cause neurotoxic effects that may suggest a possible role in the development of a PD-like syndrome in animals. Although, all the characteristics of PD cannot be reproduced by any single chemical, these data can be of help for understanding the role of pesticide exposure in human PD development. On the other hand farmers are exposed for days or weeks during several years to much lower doses than those used in experimental studies. Therefore, a firm conclusion on the role of pesticide exposure on the increased risk of developing PD cannot be drawn. However, it is suggested that close follow up of survivors of acute poisonings by these pesticides, or identification in epidemiological studies of such subjects or of those reporting episodes of accidentally high exposure will certainly provide information useful for the understanding of the relevance of actual human exposure

  5. Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: A retrospective evaluation

    PubMed Central

    ASTOLFI, LAURA; GHISELLI, SARA; GUARAN, VALERIA; CHICCA, MILVIA; SIMONI, EDI; OLIVETTO, ELENA; LELLI, GIORGIO; MARTINI, ALESSANDRO

    2013-01-01

    Cisplatin is the most common antineoplastic drug used for the therapy of solid tumours. To date, researchers have focused on the dosage to be administered for each specific tumour, mainly considering the local adverse effects. The aim of this study was to correlate the severity of the adverse effects with: i) the dosage of cisplatin; ii) the specific site of the tumour; iii) the association with other drugs; and iv) the symptoms. We analysed data from 123 patients with 11 different tumour classes undergoing therapy from 2007 to 2008 at St. Anna Hospital (Ferrara, Italy), using the Spearman non-parametric correlation index. Even though significant correlations were found among the variables, the overall results showed that the main factor influencing the severity of the adverse effects was the dosage of cisplatin administered. PMID:23404427

  6. Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

    SciTech Connect

    Herrera, Higmar; Yanez, Elvia

    2010-12-07

    This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55{+-}13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher age (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).

  7. Identifying potential adverse effects using the web: a new approach to medical hypothesis generation

    PubMed Central

    Benton, Adrian; Ungar, Lyle; Hill, Shawndra; Hennessy, Sean; Mao, Jun; Chung, Annie; Leonard, Charles E.; Holmes, John H.

    2011-01-01

    Medical message boards are online resources where users with a particular condition exchange information, some of which they might not otherwise share with medical providers. Many of these boards contain a large number of posts and contain patient opinions and experiences that would be potentially useful to clinicians and researchers. We present an approach that is able to collect a corpus of medical message board posts, de-identify the corpus, and extract information on potential adverse drug effects discussed by users. Using a corpus of posts to breast cancer message boards, we identified drug event pairs using co-occurrence statistics. We then compared the identified drug event pairs with adverse effects listed on the package labels of tamoxifen, anastrozole, exemestane, and letrozole. Of the pairs identified by our system, 75–80% were documented on the drug labels. Some of the undocumented pairs may represent previously unidentified adverse drug effects. PMID:21820083

  8. A review of the adverse effects and safety of noradrenergic antidepressants.

    PubMed

    Whiskey, Eromona; Taylor, David

    2013-08-01

    There are a variety of noradrenergic antidepressants available, most of which act by inhibiting neuronal noradrenaline re-uptake, although few drugs are specific for this action. Where drugs have numerous actions the adverse effects of noradrenaline reuptake may be difficult to isolate, although in this respect the adverse effects of reboxetine, a specific noradrenaline re-uptake inhibitor, are illuminating. Noradrenergic antidepressants typically cause minor changes in blood and heart rate, sweating and insomnia. Other pharmacological actions shown by non-specific antidepressants may act to worsen or mitigate these adverse effects. Noradrenergic drugs are less likely than selective serotonin reuptake inhibitors (SSRIs) to cause sexual dysfunction but more likely to cause urinary hesitancy. Doubts remain over the relative propensity for antidepressants with different modes of action to cause diabetes and hyponatraemia. Noradrenergic actions do not seem to confer a risk of death in overdose. PMID:23784737

  9. Ocular adverse effects after facial cosmetic procedures: a review of case reports.

    PubMed

    Ricci, Lucas H; Navajas, Samia V; Carneiro, Paula R; Söderberg, Stephanie A; Ferraz, Caroline A

    2015-06-01

    To review indexed literature concerning adverse ocular effects of the most common aesthetic facial procedures (light-emitting therapy, dermal fillers injection, and botulinum toxin). Literature search using three online databases - PubMed, SciELO, and Capes - selecting case reports, series of cases and reviews, with no language restriction, published in a period of the last twenty years (1995-2015). After reviewing 48 case reports and most recent reviews, the authors found the most common ocular adverse effects of dermal fillers were related to vascular occlusion; light-emitting therapy was associated with pigmented tissue damage leading to anterior uveitis and iris atrophy, and ptosis presented the higher relative risk associated with botulinum toxin. Even though ocular adverse effects are not very frequent, some of them can lead to permanent ocular dysfunction and visual impairment. Professionals involved in cosmetic procedures should be aware of the risks. PMID:25790150

  10. The College Student and Marijuana: Research Findings Concerning Adverse Biological and Psychological Effects.

    ERIC Educational Resources Information Center

    Nicholi, Armand M., Jr.

    1983-01-01

    This paper focuses on current knowledge about adverse biological and psychological affects of marijuana use, with special reference to risks for college students. Short-term effects on intellectual functioning and perceptual-motor coordination and long-term effects on reproduction and motivation are highlighted. (PP)

  11. On the Likelihood of Single-Walled Carbon Nanotubes Causing Adverse Marine Ecological Effects

    EPA Science Inventory

    This brief article discusses the ecological effects of single-walled carbon nanotubes (SWNTs)in the marine environment. Based on new research and a review of the scientific literature, the paper concludes that SWNTs are unlikely to cause adverse ecological effects in the marine ...

  12. The value of glucocorticoid co-therapy in different rheumatic diseases - positive and adverse effects

    PubMed Central

    2014-01-01

    Glucocorticoids play a pivotal role in the management of many inflammatory rheumatic diseases. The therapeutic effects range from pain relief in arthritides, to disease-modifying effects in early rheumatoid arthritis, and to strong immunosuppressive actions in vasculitides and systemic lupus erythematosus. There are multiple indications that adverse effects are more frequent with the longer use of glucocorticoids and use of higher dosages, but high-quality data on the occurrence of adverse effects are scarce especially for dosages above 10 mg prednisone daily. The underlying rheumatic disease, disease activity, risk factors and individual responsiveness of the patient should guide treatment decisions. Monitoring for adverse effects should also be tailored to the patient. Continuously balancing the benefits and risks of glucocorticoid therapy is recommended. There is an ongoing quest for new drugs with glucocorticoid actions without the potential to cause harmful effects, such as selective glucocorticoid receptor agonists, but the application of a new compound in clinical practice will probably not occur within the next few years. In the meantime, basic research on glucocorticoid effects and detailed reports on therapeutic efficacy and occurrence of adverse effects will be valuable in weighing benefits and risks in clinical practice. PMID:25608693

  13. Effects of coal rank on the chemical composition and toxicological activity of coal liquefaction materials

    SciTech Connect

    Wright, C.W.; Dauble, D.D.

    1986-05-01

    This report presents data from the chemical analysis and toxicological testing of coal liquefaction materials from the EDS and H-Coal processes operated using different ranks of coal. Samples of recycle solvent from the bottoms recycle mode of the EDS direct coal liquefaction process derived from bituminous, sub-bituminous, and lignite coals were analyzed. In addition, the H-Coal heavy fuel oils derived from bituminous and sub-bituminous coals were analyzed. Chemical methods of analysis included adsoprtion column chromatography, high-resolution gas chromatography, gas chromatography/mass spectrometry, and low-voltage probe-inlet mass spectrometry. The toxicological activity of selected samples was evaluated using the standard microbial mutagenicity assay, an initiation/promotion assay for mouse-skin tumorigenicity, and a static bioassy with Daphnia magna for aquatic toxicity of the water-soluble fractions. 22 refs., 16 figs., 14 tabs.

  14. Influence of experimental pulmonary emphysema on the toxicological effects from inhaled nitrogen dioxide and diesel exhaust.

    PubMed

    Mauderly, J L; Bice, D E; Cheng, Y S; Gillett, N A; Henderson, R F; Pickrell, J A; Wolff, R K

    1989-10-01

    This project examined the influence of preexisting, experimentally induced pulmonary emphysema on the adverse health effects in rats of chronic inhalation exposure to either nitrogen dioxide or automotive diesel-engine exhaust. Previous reports indicated that humans with chronic lung disease were among those most severely affected by episodic exposures to high concentrations of airborne toxicants. There were no previous reports comparing the effects of chronic inhalation exposure to components of automotive emissions in emphysematous and normal animals. The hypothesis tested in this project was that rats with preexisting pulmonary emphysema were more susceptible than rats with normal lungs to the adverse effects of the toxicant exposures. Young adult rats were housed continuously in inhalation exposure chambers and exposed seven hours per day, five days per week, for 24 months to nitrogen dioxide at 9.5 parts per million (ppm)2, or to diesel exhaust at 3.5 mg soot/m3, or to clean air as control animals. These concentrations were selected to produce mild, but distinct, effects in rats with normal lungs. Pulmonary emphysema was induced in one-half of the rats by intratracheal instillation of the proteolytic enzyme elastase six weeks before the toxicant exposures began. Health effects were evaluated after 12, 18, and 24 months of exposure. The measurements included respiratory function, clearance of inhaled radiolabeled particles, pulmonary immune responses to instilled antigen, biochemistry and cytology of airway fluid, total lung collagen, histopathology, lung morphometry, and lung burdens of diesel soot. The significance of influences of emphysema and toxicant exposure, and interactions between influences of the two treatments, were evaluated by analysis of variance. The elastase treatment resulted in pulmonary emphysema that was manifested by enlarged alveoli and alveolar ducts, and by ruptured alveolar septa. There was no accompanying inflammation and no

  15. Topiramate-Induced Somnambulism in a Migraineur: A Probable Idiosyncratic Adverse Effect

    PubMed Central

    Mathew, Thomas; Sarma, G. R. K.; Nadig, Raghunandan; Varghese, Raji

    2012-01-01

    Somnambulism (sleepwalking) is a disorder of arousal that falls under “parasomnia” group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers.1 This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine. Citation: Mathew T; Sarma GRK; Nadig R; Varghese R. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect. J Clin Sleep Med 2012;8(2):197-198. PMID:22505867

  16. Oleoresin Capsicum toxicology evaluation and hazard review

    SciTech Connect

    Archuleta, M.M.

    1995-10-01

    Oleoresin Capsicum (OC) is an extract of the pepper plant used for centuries as a culinary spice (hot peppers). This material has been identified as a safe and effective Less-Than- Lethal weapon for use by Law enforcement and security professionals against assault. The National Institute of Justice (NIJ) is currently also evaluating its use in conjunction with other Less-Than-Lethal agents such as aqueous foam for use in corrections applications. Therefore, a comprehensive toxicological review of the literature was performed for the National Institute of Justice Less-Than-Lethal Force program to review and update the information available on the toxicity and adverse health effects associated with OC exposure. The results of this evaluation indicate that exposure to OC can result in dermatitis, as well as adverse nasal, pulmonary, and gastrointestinal effects in humans. The primary effects of OC exposure include pain and irritation of the mucous membranes of the eyes, nose, and lining of the mouth. Blistering and rash have been shown to occur after chronic or prolonged dermal exposure. Ingestion of capsicum may cause acute stinging of the lips, tongue, and oral mucosa and may lead to vomiting and diarrhea with large doses. OC vapors may also cause significant pulmonary irritation and prolonged cough. There is no evidence of long term effects associated with an acute exposure to OC, and extensive use as a culinary additive and medicinal ointment has further provided no evidence of long term adverse effects following repeated or prolonged exposure.

  17. [Toxicologic estimation, an element of therapeutical progress].

    PubMed

    Fournier, P E

    1991-01-01

    The clinical toxicology plays a great part to the progresses of human therapy. It is an essential observation for a good clinical use of drugs and of materials used by physicians. It permits a better knowledge of the dose-effect relationship (in acute either in chronic adverse effects). It specifies the statement of the therapeutic efficacy between the threshold, a placebo effect with adverse disorders as those possibly related to any xenobiotic and the overdose where the nocivity predominates on the therapeutic results. A better detection of some individual responses as adverse or toxic reactions due to a genetic peculiarity belongs to clinical toxicogenetic studies in parallel with pharmacogenetics. The recent evolution of drugs needs a more scientific approach of the therapy for cytotoxic drugs largely used against cancers, in terms of tolerable doses, cumulative actions, interactions and cofactors. On the opposite, the bio-chemical variations of new bio-drugs acting as real bioprotheses of hormones or biomediators need specific toxicological studies according to the progresses and to the limits of biotechnologies. Among numerous drugs issued of chemical research one must separate the reversible functional drugs designed as enzyme-inhibitors or cellular receptors ligands very close to the dominant themes of biochemistry and experimental physiology from chemicals coined by synthetic "chance" which are for the time being plain xenobiotics whose dangers are often poorly evaluated but whose practical applications will take place either in disciplines related to pharmacopea like chemicals used in plant protection, either beginning their commercial trip very far from health concern in industrial preparations and being brought back to medicine as plastics, glues or metallic implants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1842171

  18. Radiological/toxicological sabotage assessments at the Savannah River Site

    SciTech Connect

    Johnson, H.D.; Pascal, M.D.; Richardson, D.L.

    1995-11-01

    This paper describes the methods being employed by Westinghouse Savannah River Company (WSRC) to perform graded assessments of radiological and toxicological sabotage vulnerability at Savannah River Site (SRS) facilities. These assessments are conducted to ensure that effective measures are in place to prevent, mitigate, and respond to a potential sabotage event which may cause an airborne release of radiological/toxicological material, causing an adverse effect on the health and safety of employees, the public, and the environment. Department of Energy (DOE) Notice 5630.3A, {open_quotes}Protection of Departmental Facilities Against Radiological and Toxicological Sabotage,{close_quotes} and the associated April 1993 DOE-Headquarters guidance provide the requirements and outline an eight-step process for hazardous material evaluation. The process requires the integration of information from a variety of disciplines, including safety, safeguards and security, and emergency preparedness. This paper summarizes WSRC`s approach towards implementation of the DOE requirements, and explains the inter-relationships between the Radiological and Toxicological Assessments developed using this process, and facility Hazard Assessment Reports (HAs), Safety Analysis Reports (SARs), and Facility Vulnerability Assessments (VAs).

  19. A replication of the study ‘Adverse effects of spinal manipulation: a systematic review’

    PubMed Central

    2012-01-01

    and related adverse effects. PMID:22998971

  20. Systems toxicology.

    PubMed

    Hartung, Thomas; van Vliet, Erwin; Jaworska, Joanna; Bonilla, Leo; Skinner, Nigel; Thomas, Russell

    2012-01-01

    The need for a more mechanistic understanding of the ways in which chemicals modulate biological pathways is urgent if we are to identify and better assess safety issues relating to a wide range of substances developed by the pharmaceutical, chemical, agri-bio, and cosmetic industries. Omics technologies provide a valuable opportunity to refine existing methods and provide information for so-called integrated testing strategies via the creation of signatures of toxicity. By mapping these signatures to underlying pathways of toxicity, some of which have been identified by toxicologists over the last few decades, and bringing them together with pathway information determined from biochemistry and molecular biology, a "systems toxicology" approach will enable virtual experiments to be conducted that can improve the prediction of hazard and the assessment of compound toxicity. PMID:22562485

  1. Effects of copy center particles on the lungs: A toxicological characterization using a Balb/c mice model

    PubMed Central

    Pirela, Sandra; Molina, Ramon; Watson, Christa; Cohen, Joel; Bello, Dhimiter; Demokritou, Philip; Brain, Joseph

    2015-01-01

    Context Printers and photocopiers release respirable particles into the air. Engineered nanomaterials (ENMs) have been recently incorporated into toner formulations but their potential toxicological effects have not been well studied. Objective To evaluate the biologic responses to copier-emitted particles in the lungs using a mouse model. Methods Particles from a university copy center were sampled and fractionated into three distinct sizes, two of which (PM0.1 and PM0.1–2.5) were evaluated in this study. The particles were extracted and dispersed in deionized water and RPMI/10% FBS. Hydrodynamic diameter and zeta potential were evaluated by dynamic light scattering. The toxicologic potential of these particles was studied using 8-week-old male Balb/c mice. Mice were intratracheally instilled with 0.2, 0.6, 2.0 mg/kg bw of the PM0.1 and PM0.1–2.5 size fractions. Fe2O3 and welding fumes were used as comparative materials, while RPMI/10% FBS was used as the vehicle control. Bronchoalveolar lavage (BAL) was performed 24 hours post-instillation. The BAL fluid was analyzed for total and differential cell counts, and biochemical markers of injury and inflammation. Results Particle size- and dose-dependent pulmonary effects were found. Specifically, mice instilled with PM0.1 (2.0 mg/kg bw) had significant increases in neutrophil number, lactate dehydrogenase and albumin compared to vehicle control. Likewise, pro-inflammatory cytokines were elevated in mice exposed to PM0.1 (2.0 mg/kg bw) compared to other groups. Conclusion Our results indicate that exposure to copier-emitted nanoparticles may induce lung injury and inflammation. Further exposure assessment and toxicological investigations are necessary to address this emerging environmental health pollutant. PMID:23895351

  2. Toxicological effects of short-term resuspension of metal-contaminated freshwater and marine sediments.

    PubMed

    Fetters, Kyle J; Costello, David M; Hammerschmidt, Chad R; Burton, G Allen

    2016-03-01

    Sediments in navigation-dominated waterways frequently are contaminated with a variety of particle-associated pollutants and are subject to frequent short-term resuspension events. There is little information documenting whether resuspension of metal-contaminated sediments has adverse ecological effects on resident aquatic organisms. Using a novel laboratory approach, the authors examined the mobilization of Zn, Cu, Cd, Pb, Ni, and Cr during resuspension of 1 freshwater and 2 coastal marine sediments and whether resuspension and redeposition resulted in toxicity to model organisms. Sediment flux exposure chambers were used to resuspend metal-contaminated sediments from 1 site in Lake DePue, Illinois (USA), and 2 sites in Portsmouth Naval Shipyard, Maine (USA). Short-term (4-h) resuspension of sediment at environmentally relevant suspended particulate matter concentrations (<1 g/L) resulted in metal mobilization to water that was sediment and metal specific. Overall, the net release of metals from suspended particles was limited, likely because of scavenging by organic matter and Fe oxides that formed during sediment interaction with oxic water. Minimal toxicity to organisms (survival of Hyalella azteca and Daphnia magna; survival, growth, and tissue metal concentration of Neanthes arenaceodentata; bioluminescence of Pyrocystis lunula) was observed during 4-h exposure to resuspended sediments and during 4-d to 10-d post-exposure recovery periods in uncontaminated water. Redeposited suspended particles exhibited increased metal bioavailability and toxicity to H. azteca, highlighting the potential for adverse ecological impacts because of changes in metal speciation. It is important to consider interactions between organisms' life histories and sediment disturbance regimes when assessing risks to ecosystems. PMID:26313755

  3. Adverse drug effects in hospitalized elderly: Data from the Healthcare Cost and Utilization Project

    PubMed Central

    Shamliyan, Tatyana

    2010-01-01

    We aimed to analyze trends in hospital admissions due to adverse drug effects between the years 2000 to 2007 among the elderly using the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project. We identified the discharges with the principal and all listed diagnoses related to adverse drug effects and associated hospital charges using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes. Between 2000 and 2007, 321,057 patients over 65 years were discharged with a principal diagnosis related to an adverse drug effect. Hospital charges were $5,329,276,300 or $666,159,537 annual cost. The number of discharges and total hospital charges did not change over the examined years, while mean charge per discharge increased on average by $1064 ± 384 per year. Total hospital charges for drug-induced gastritis with hemorrhage increased the most by $11,206,555 per year among those 66–84 years old and by $8,646,456 per year among those older than 85 years. During 2007, 791,931 elderly had adverse treatment effects among all listed diagnoses with hospital charges of $937,795,690. Effective drug management interventions are needed to improve safety of treatments in the elderly. PMID:22291486

  4. A critical review of the toxicological effects of carrageenan and processed eucheuma seaweed on the gastrointestinal tract.

    PubMed

    Cohen, Samuel M; Ito, Nobuyuki

    2002-09-01

    Carrageenan is a high-molecular-weight, strongly anionic polymer derived from several species of red seaweed that is used for the textural stabilization of foods. Processed Eucheuma Seaweed (PES) is a form of carrageenan with a higher cellulose content. Food-grade carrageenan has a weight average molecular weight greater than 100,000 Da, with a low percentage of smaller fragments. Carrageenan is not degraded to any extent in the gastrointestinal tract and is not absorbed from it in species examined, such as rodents, dogs, and non-human primates. Systemically administered carrageenan has been reported to have a variety of effects, particularly on the immune system, but these are not pertinent to orally administered carrageenan. The substance poligeenan (formerly referred to as degraded carrageenan) is not a food additive. It exhibits toxicological properties at high doses that do not occur with the food additive carrageenan. In-long term bioassays, carrageenan has not been found to be carcinogenic, and there is no credible evidence supporting a carcinogenic effect or a tumor-promoting effect on the colon in rodents. Also, like many dietary fibers, there is significant cecal enlargement in rodents when it is administered at high doses, but this does not appear to be associated with any toxicological consequences to the rodent. Many toxicological studies on carrageenan have involved administration at doses in excess of today's standards for dietary feeding levels in bioassays, and they are orders of magnitude in excess of those to which humans are exposed. Previous reviews of carrageenan and PES by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) have recommended a group allowable daily intake (ADI) of "not specified". The lack of carcinogenic, genotoxic, or tumor-promoting activity with carrageenan strongly supports continuing such an ADI, and JECFA, during its most recent review in 2001, continued this

  5. Late-onset Tay-Sachs disease: adverse effects of medications and implications for treatment.

    PubMed

    Shapiro, B E; Hatters-Friedman, S; Fernandes-Filho, J A; Anthony, K; Natowicz, M R

    2006-09-12

    The authors conducted a retrospective and brief prospective study of adverse effects of approximately 350 medications in 44 adults with late-onset Tay-Sachs disease (LOTS). Some medications were relatively safe, whereas others, particularly haloperidol, risperidone, and chlorpromazine, were associated with neurologic worsening. PMID:16966555

  6. ENVIRONMENTAL POLLUTANTS AND ADVERSE HUMAN HEALTH EFFECTS: HAZARD IDENTIFICATION USING INTERREGION COMPARISONS

    EPA Science Inventory

    Background: Associations between adverse health effects and environmental exposures are difficult to study, because exposures may be widespread, low-dose in nature, and common throughout the study population. Therefore, individual risk-factor epidemiology may not be the right to...

  7. A well known and important adverse effect of phenytoin in a neurosurgical patient.

    PubMed

    Tomar, Gaurav Singh; Saxena, Anudeep; Kumar, Niraj; Goyal, Keshav

    2015-01-01

    Gum hypertrophy is a well-known and important adverse effect of phenytoin therapy in a neurosurgical patient. We present an interesting case of a 21-year-old man who, following head injury after a road traffic accident, developed status epilepticus diagnosed with gum hypertrophy in the jaws, with ongoing antiepileptics. He was managed conservatively as per hospital protocol. PMID:26475882

  8. Adverse Effect of Child Abuse Victimization among Substance-Using Women in Treatment.

    ERIC Educational Resources Information Center

    Kang, Sung-Yeon; Magura, Stephen; Laudet, Alexandre; Whitney, Shirley

    1999-01-01

    Study examined adverse effects of childhood sexual/physical abuse among substance-abusing women with children. Several significant differences between abused and nonabused women were found in service outcomes. Abused women had more problems relating to drug use and psychiatric/psychological adjustment at follow-up. Findings support a need for…

  9. Method of protecting a radiochromic optical waveguide dosimeter from adverse temperature effects. Patent Application

    SciTech Connect

    Kronenberg, S.

    1985-09-26

    A radiochromic optical waveguide dosimeter is protected from the adverse temperature effects of exposure in the desired operational temperature range of -40 C to +60 C by flattening the round plastic tubing to be used for the fabrication of the dosimeter until the tubing attains an elliptical cross section and then fabricating the dosimeter from the tubing having the elliptical cross section.

  10. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... female, pregnant? (J) Exposure data: amount of pesticide; duration of exposure; weight of victim. (K) Was... adverse reproductive effects or in residual disability. (C) H-C: If the person alleged or exhibited... of systems supplied. (C) If finished water samples, water supply systems sampled. (D) If...

  11. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... female, pregnant? (J) Exposure data: amount of pesticide; duration of exposure; weight of victim. (K) Was... adverse reproductive effects or in residual disability. (C) H-C: If the person alleged or exhibited... of systems supplied. (C) If finished water samples, water supply systems sampled. (D) If...

  12. Caregiver Acceptance of Adverse Effects and Use of Cholinesterase Inhibitors in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Oremus, Mark; Wolfson, Christina; Vandal, Alain C.; Bergman, Howard; Xie, Qihao

    2007-01-01

    Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire…

  13. ARE ENVIRONMENTAL EXPOSURES TO CHLOROPHENOXY HERBICIDES ASSOCIATED WITH AN INCREASE IN ADVERSE HUMAN HEALTH EFFECTS?

    EPA Science Inventory

    Background: Associations between adverse health effects and environmental exposures are difficult to study because exposures may be widespread, low-dose in nature, and common throughout the study population. Individual risk-factor epidemiology may not be able to initially ident...

  14. Potassium fertilization mitigates the adverse effects of drought on selected Zea mays cultivars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the present study, the role of potassium (K) in mitigating the adverse effects of drought stress (DS) on 2 maize (Zea mays L.) cultivars, ‘Shaandan 9’ (S9; drought-tolerant) and ‘Shaandan 911’ (S911; drought-sensitive), was assessed. K application increased dry matter (DM) across all growth stage...

  15. Insulin Injection Site Dystrophic Calcification with Fat Necrosis: A Case Report of an Uncommon Adverse Effect

    PubMed Central

    Ramdas, Sharad; Ramdas, Anita; Ambroise, Moses

    2014-01-01

    We report a case of an uncommon adverse effect of insulin injection resulting in hard subcutaneous swelling in the lower abdomen of a 47-year-oldfemale with type 1 diabetes. Extensive dystrophic calcification and fat necrosis was revealed on histopathological examination. PMID:25374868

  16. 20 years of toxicology.

    PubMed Central

    Fisher, B E

    1998-01-01

    With over 80,000 chemicals being used in commerce worldwide, it is important to identify the human health effects of these chemicals and the levels of exposure at which they are harmful to humans. In order to address this need, the National Toxicology Program (NTP) was established in 1978; since then, the NTP has become the world's leader in designing, conducting, and interpreting various types of toxicity assays. PMID:9755149

  17. Mixed-effects Poisson regression analysis of adverse event reports: the relationship between antidepressants and suicide.

    PubMed

    Gibbons, Robert D; Segawa, Eisuke; Karabatsos, George; Amatya, Anup K; Bhaumik, Dulal K; Brown, C Hendricks; Kapur, Kush; Marcus, Sue M; Hur, Kwan; Mann, J John

    2008-05-20

    A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)'s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system. PMID:18404622

  18. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    PubMed Central

    Croft, Ashley M; Herxheimer, Andrew

    2002-01-01

    Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis. PMID:11914150

  19. [Analysis of the cardiac side effects of antipsychotics: Japanese Adverse Drug Event Report Database (JADER)].

    PubMed

    Ikeno, Takashi; Okumara, Yasuyuki; Kugiyama, Kiyotaka; Ito, Hiroto

    2013-08-01

    We analyzed the cases of side effects due to antipsychotics reported to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) from Jan. 2004 to Dec. 2012. We used the Japanese Adverse Drug Event Report Database (JADER) and analyzed 136 of 216,945 cases using the defined terms. We also checked the cardiac adverse effects listed in the package inserts of the antipsychotics involved. We found cases of Ikr blockade resulting in sudden death (49 cases), electrocardiogram QT prolonged (29 cases), torsade de pointes (TdP, 19 cases), ventricular fibrillation (VF, 10 cases). M2 receptor blockade was observed in tachycardia (8 cases) and sinus tachycardia (3 cases). Calmodulin blockade was involved in reported cardiomyopathy (3 cases) and myocarditis (1 case). Multiple adverse events were reported simultaneously in 14 cases. Our search of package inserts revealed warnings regarding electrocardiogram QT prolongation (24 drugs), tachycardia (23), sudden death (18), TdP (14), VF (3), myocarditis (1) and cardiomyopathy (1). We suggest that when an antipsychotic is prescribed, the patient should be monitored regularly with ECG, blood tests, and/or biochemical tests to avoid adverse cardiac effects. PMID:25069255

  20. Metabolomic application in toxicity evaluation and toxicological biomarker identification of natural product.

    PubMed

    Chen, Dan-Qian; Chen, Hua; Chen, Lin; Tang, Dan-Dan; Miao, Hua; Zhao, Ying-Yong

    2016-05-25

    Natural product plays a vital role in disease prevention and treatment since the appearance of civilization, but the toxicity severely hinders its wide use. In order to avoid toxic effect as far as possible and use natural product safely, more comprehensive understandings of toxicity are urgently required. Since the metabolome represents the physiological or pathological status of organisms, metabolomics-based toxicology is of significance to observe potential injury before toxins have caused physiological or pathological damages. Metabolomics-based toxicology can evaluate toxicity and identify toxicological biomarker of natural product, which is helpful to guide clinical medication and reduce adverse drug reactions. In the past decades, dozens of metabolomic researches have been implemented on toxicity evaluation, toxicological biomarker identification and potential mechanism exploration of nephrotoxicity, hepatotoxicity, cardiotoxicity and central nervous system toxicity induced by pure compounds, extracts and compound prescriptions. In this paper, metabolomic technology, sample preparation, data process and analysis, and metabolomics-based toxicological research of natural product are reviewed, and finally, the potential problems and further perspectives in toxicological metabolomic investigations of natural product are discussed. PMID:27041073

  1. Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China

    PubMed Central

    Wu, Junyi; Hu, Yanmei; Zhu, Yin; Yin, Ping; Litscher, Gerhard; Xu, Shifen

    2015-01-01

    As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world. PMID:26339265

  2. In silico assessment of adverse effects of a large set of 6-fluoroquinolones obtained from a study of tuberculosis chemotherapy.

    PubMed

    Tusar, Marjan; Minovski, Nikola; Fjodorova, Natalja; Novic, Marjana

    2012-09-01

    Among the different chemotherapeutic classes available today, the 6-fluoroquinolone (6-FQ) antibacterials are still one of the most effective cures in fighting tuberculosis (TB). Nowadays, the development of novel 6-FQs for treatment of TB mainly depends on understanding how the structural modifications of the main quinolone scaffold at specific positions affect the anti-mycobacterial activity. Alongside the structure-activity relationship (SAR) studies of the 6-FQ antibacterials, which can be considered as a golden rule in the development of novel active antitubercular 6-FQs, the structure side effects relationship (SSER) of these drugs must be also taken into account. In the present study we focus on a proficient implementation of the existing knowledge-based expert systems for design of novel 6-FQ antibacterials with possible enhanced biological activity against Mycobaterium tuberculosis as well as lower toxicity. Following the SAR in silico studies of the quinolone antibacterials against M. tuberculosis performed in our laboratory, a large set of 6-FQs was selected. Several new 6-FQ derivatives were proposed as drug candidates for further research and development. The 6- FQs identified as potentially effective against M. tuberculosis were subjected to an additional SSER study for prediction of their toxicological profile. The assessment of structurally-driven adverse effects which might hamper the potential of new drug candidates is mandatory for an effective drug design. We applied publicly available knowledge-based (expert) systems and Quantitative Structure-Activity Relationship (QSAR) models in order to prepare a priority list of active compounds. A preferred order of drug candidates was obtained, so that the less harmful candidates were identified for further testing. TOXTREE expert system as well as some QSAR models developed in the framework of EC funded project CAESAR were used to assess toxicity. CAESAR models were developed according to the OECD

  3. Adverse effects of small-volume red blood cell transfusions in the neonatal population

    PubMed Central

    2014-01-01

    Background Adverse transfusion reactions in the neonatal population are poorly understood and defined. The incidence and pattern of adverse effects due to red blood cell (RBC) transfusion are not well known, and there has been no systematic review of published adverse events. RBC transfusions continue to be linked to the development of morbidities unique to neonates, including chronic lung disease, retinopathy of prematurity, intraventricular haemorrhage and necrotising enterocolitis. Uncertainties about the exact nature of risks alongside benefits of RBC transfusion may contribute to evidence of widespread variation in neonatal RBC transfusion practice. Our review aims to describe clinical adverse effects attributed to small-volume (10–20 mL/kg) RBC transfusions and, where possible, their incidence rates in the neonatal population through the systematic identification of all relevant studies. Methods A comprehensive search of the following bibliographic databases will be performed: MEDLINE (PubMed/OVID which includes the Cochrane Library) and EMBASE (OVID). The intervention of interest is small-volume (10–20 mL/kg) RBC transfusions in the neonatal population. We will undertake a narrative synthesis of the evidence. If clinical similarity and data quantity and quality permit, we will also carry out meta-analyses on the listed outcomes. Discussion This systematic review will identify and synthesise the reported adverse effects and associations of RBC transfusions in the neonatal population. We believe that this systematic review is timely and will make a valuable contribution to highlight an existing research gap. Trial Registration PROSPERO, CRD42013005107 http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013005107 PMID:25143009

  4. Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib

    PubMed Central

    Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

    2016-01-01

    Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC. PMID:27257345

  5. Establishing Adverse Outcome Pathways of Thyroid Hormone Disruption in an Amphibian Model

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) provides a framework for understanding the relevance of toxicology data in ecotoxicological hazard assessments. The AOP concept can be applied to many toxicological pathways including thyroid hormone disruption. Thyroid hormones play a critical r...

  6. Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor.

    PubMed

    Gibson, William S; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P; Welker, Kirk M; Klassen, Bryan T; Min, Hoon-Ki; Lee, Kendall H

    2016-08-01

    Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson's disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal

  7. Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

    PubMed Central

    Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

    2016-01-01

    Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal

  8. Tissue Expander Placement to Prevent the Adverse Intestinal Effects of Radiotherapy in Malignant Pelvic Tumors.

    PubMed

    Uehara, Shuichiro; Oue, Takaharu; Adachi, Kana; Yoshioka, Yasuo; Nakahata, Kengo; Ueno, Takehisa; Okuyama, Hiroomi

    2016-03-01

    We herein report the findings of 3 patients with primary Ewing sarcoma in a pelvic lesion who underwent the placement of a tissue expander (TE) before radiation therapy to prevent the adverse effects of radiotherapy. The simulation study showed that the TE drastically reduced volume of the intestine that was irradiated at all dose levels. All patients could receive the scheduled dose of radiotherapy without any acute and late complications such as diarrhea, melena, the dislodging of the TE, infection, or the formation of fistulae. In the 4-year (minimum) observation period, we did not observe intestinal complications in any of our patients. TE placement is considered to be a safe and effective method for preventing the adverse effects of radiotherapy in pediatric malignant pelvic tumors. PMID:26479989

  9. Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Canadian Consensus Working Group Update (2016).

    PubMed

    Mancini, G B John; Baker, Steven; Bergeron, Jean; Fitchett, David; Frohlich, Jiri; Genest, Jacques; Gupta, Milan; Hegele, Robert A; Ng, Dominic; Pearson, Glen J; Pope, Janet; Tashakkor, A Yashar

    2016-07-01

    The Canadian Consensus Working Group has updated its evaluation of the literature pertaining to statin intolerance and adverse effects. This overview introduces a pragmatic definition of statin intolerance (goal-inhibiting statin intolerance) that emphasizes the effects of symptoms on achieving nationally vetted goals in patients fulfilling indications for lipid-lowering therapy and cardiovascular risk reduction. The Canadian Consensus Working Group provides a structured framework for avoiding, evaluating and managing goal-inhibiting statin intolerance. Particularly difficult practice situations are reviewed, including management in young and elderly individuals, and in athletes and labourers. Finally, targeted at specialty practitioners, more detailed analyses of specific but more unusual adverse effects ascribed to statins are updated including evidence regarding new-onset diabetes, cognitive dysfunction, cataracts, and the rare but important immune-mediated necrotizing myopathy. PMID:27342697

  10. General and specific effects of early-life psychosocial adversities on adolescent grey matter volume☆

    PubMed Central

    Walsh, Nicholas D.; Dalgleish, Tim; Lombardo, Michael V.; Dunn, Valerie J.; Van Harmelen, Anne-Laura; Ban, Maria; Goodyer, Ian M.

    2014-01-01

    Exposure to childhood adversities (CA) is associated with subsequent alterations in regional brain grey matter volume (GMV). Prior studies have focused mainly on severe neglect and maltreatment. The aim of this study was to determine in currently healthy adolescents if exposure to more common forms of CA results in reduced GMV. Effects on brain structure were investigated using voxel-based morphometry in a cross-sectional study of youth recruited from a population-based longitudinal cohort. 58 participants (mean age = 18.4) with (n = 27) or without (n = 31) CA exposure measured retrospectively from maternal interview were included in the study. Measures of recent negative life events (RNLE) recorded at 14 and 17 years, current depressive symptoms, gender, participant/parental psychiatric history, current family functioning perception and 5-HTTLPR genotype were covariates in analyses. A multivariate analysis of adversities demonstrated a general association with a widespread distributed neural network consisting of cortical midline, lateral frontal, temporal, limbic, and cerebellar regions. Univariate analyses showed more specific associations between adversity measures and regional GMV: CA specifically demonstrated reduced vermis GMV and past psychiatric history with reduced medial temporal lobe volume. In contrast RNLE aged 14 was associated with increased lateral cerebellar and anterior cingulate GMV. We conclude that exposure to moderate levels of childhood adversities occurring during childhood and early adolescence exerts effects on the developing adolescent brain. Reducing exposure to adverse social environments during early life may optimize typical brain development and reduce subsequent mental health risks in adult life. PMID:25061568

  11. Adverse effects of industrial multiwalled carbon nanotubes on human pulmonary cells

    PubMed Central

    Tabet, Lyes; Bussy, Cyrill; Amara, Nadia; Setyan, Ari; Grodet, Alain; Rossi, Michel J.; Pairon, Jean-Claude; Boczkowski, Jorge; Lanone, Sophie

    2009-01-01

    The aim of this study was to evaluate adverse effects of multi-walled carbon nanotubes (MWCNT) produced for industrial purposes, on the human epithelial cell line A549. MWCNT were dispersed in dipalmitoyl lecithin (DPL), a component of pulmonary surfactant, and the effects of dispersion in DPL were compared to those in 2 other media: ethanol (EtOH) and phosphate buffer saline (PBS). Effects of MWCNT were also compared to those of 2 asbestos fibers (chrysotile and crocidolite) and carbon black (CB) nanoparticles, not only in A549 cells, but also on mesothelial cells (MeT5A human cell line), used as an asbestos-sensitive cell type. MWCNT formed agglomerates on top of both cell lines (surface area 15–35 μm2), that were significantly larger and more numerous in PBS than in EtOH and DPL. Whatever the dispersion media, incubation with 100 μg/ml MWCNT induced a similar decrease in metabolic activity without changing cell membrane permeability or apoptosis. Neither MWCNT cellular internalization nor oxidative stress were observed. In contrast, asbestos fibers penetrated into the cells, decreased metabolic activity but not cell membrane permeability and increased apoptosis, without decreasing cell number. CB was internalized without any adverse effects. In conclusion, this study demonstrates that MWCNT produced for industrial purposes exert adverse effects without being internalized by human epithelial and mesothelial pulmonary cell lines. PMID:19034795

  12. The role of ADHD in academic adversity: disentangling ADHD effects from other personal and contextual factors.

    PubMed

    Martin, Andrew J

    2014-12-01

    Students with attention-deficit/hyperactivity disorder (ADHD) experience significant academic difficulties that can lead to numerous negative academic consequences. With a focus on adverse academic outcomes, this study seeks to disentangle variance attributable to ADHD from variance attributable to salient personal and contextual covariates. Responses from 136 students with ADHD and 3,779 non-ADHD peers from 9 high schools were analyzed using logistic regression. Dependent measures included academic failure, grade repetition, school refusal, changing classes and school, school exclusion, and schoolwork noncompletion. Covariates comprised personal (e.g., sociodemographics, personality, prior achievement, specific learning disabilities, motivation) and contextual (e.g., school size, school socioeconomic status, school average achievement) factors. Findings indicated that, after accounting for personal and contextual covariates, ADHD explained significant variance in numerous adversities (schoolwork noncompletion, school suspension, school expulsion, changing schools, grade repetition). Thus, beyond the effects of numerous personal and contextual covariates, ADHD has a distinct presence in students' academic adversity. Also interesting, after accounting for other personal and contextual factors, was academic adversity with which ADHD was not associated. Findings provide direction for educational intervention targeting ADHD and associated factors found to be significant in the study. PMID:24820011

  13. Distance learning in toxicology: resident and remote; Scotland, IPCS, IUPAC, and the world.

    PubMed

    Duffus, John H

    2005-09-01

    Globally, very few college or university chemistry courses incorporate toxicology although public perception of chemicals and the chemical industry as threats to health and the environment has had an adverse effect on chemistry and on the use of its products. The International Union for Pure and Applied Chemistry (IUPAC) through its Commission on Toxicology recognized this and, with the support of the Committee on the Teaching of Chemistry has used the IUPAC web site to promote distance learning in toxicology for chemists. After preparation of a thoroughly refereed consensus Glossary of Terms for Chemists of Terms Used in Toxicology, a textbook Fundamental Toxicology for Chemists and a set of educational modules entitled Essential Toxicology were compiled and put through the normal thorough review procedure of IUPAC before being approved by the organization. There is now an additional Glossary of Terms Used in Toxicokinetics. The modules are freely downloadable in Adobe PDF format and are designed to be used both by educators and by students. Educators are asked to select whatever is appropriate to their students and to use the material as they wish, adding content specifically relevant to their circumstances. For self-study, the web modules have self-assessment questions and model answers. Currently the original Glossary for Chemists of Terms Used in Toxicology is being revised and it is expected that this will lead to further developments. The currently available components of the IUPAC programme may be accessed through the IUPAC website at the Subcommittee on Toxicology and Risk Assessment page: http://www.iupac.org/divisions/VII/VII.C.2/index.html. PMID:15982692

  14. Distance learning in toxicology: Resident and remote; Scotland, IPCS, IUPAC, and the world

    SciTech Connect

    Duffus, John H. . E-mail: J.H.Duffus@btinternet.com

    2005-09-01

    Globally, very few college or university chemistry courses incorporate toxicology although public perception of chemicals and the chemical industry as threats to health and the environment has had an adverse effect on chemistry and on the use of its products. The International Union for Pure and Applied Chemistry (IUPAC) through its Commission on Toxicology recognized this and, with the support of the Committee on the Teaching of Chemistry has used the IUPAC web site to promote distance learning in toxicology for chemists. After preparation of a thoroughly refereed consensus Glossary of Terms for Chemists of Terms Used in Toxicology, a textbook Fundamental Toxicology for Chemists and a set of educational modules entitled Essential Toxicology were compiled and put through the normal thorough review procedure of IUPAC before being approved by the organization. There is now an additional Glossary of Terms Used in Toxicokinetics. The modules are freely downloadable in Adobe PDF format and are designed to be used both by educators and by students. Educators are asked to select whatever is appropriate to their students and to use the material as they wish, adding content specifically relevant to their circumstances. For self-study, the web modules have self-assessment questions and model answers. Currently the original Glossary for Chemists of Terms Used in Toxicology is being revised and it is expected that this will lead to further developments. The currently available components of the IUPAC programme may be accessed through the IUPAC website at the Subcommittee on Toxicology and Risk Assessment page: http://www.iupac.org/divisions/VII/VII.C.2/index.html.

  15. Acute toxicological effects on the earthworm Eisenia fetida of 18 common pharmaceuticals in artificial soil.

    PubMed

    Pino, Ma Rosa; Val, Jonatan; Mainar, Ana Ma; Zuriaga, Estefanía; Español, Cecilia; Langa, Elisa

    2015-06-15

    Following soil applications of recycled water and biosolids, pharmaceutical residues can eventually enter the terrestrial environment. In vitro and in vivo assays have largely focused on the acute ecotoxicity of these compounds in aquatic systems. However, studies on the ecotoxicological effects of pharmaceuticals in soil biota are especially scarce. The aim of this study was to investigate the acute toxicity of 18 pharmaceuticals (4 NSAIDs, 5 blood lipid-lowering agents, 6 β-blockers and 3 antibiotics) that are usually found in the environment by using an Eisenia fetida bioassay. In addition, the presence of these pharmaceuticals in artificial soil was verified at the end of the test. Our results indicate that seven of the studied drugs cause acute adverse effects in E. fetida, in particular, the NSAIDs and the blood lipid-lowering agents. Ibuprofen (LC50=64.80 mg/kg) caused the highest acute toxicity for all tested compounds, followed by diclofenac (LC50=90.49 mg/kg) and simvastatin (LC50=92.70 mg/kg). Other tested pharmaceuticals from NSAIDs and blood lipid-lowering families have toxicity effects, from a LC50=140.87 mg/kg for gemfibrozil to 795.07 mg/kg for lovastatin. Atorvastatin, bezafibrate, β-blockers and antibiotics showed no detectable lethality in E. fetida. The four NSAIDs showed evidence of modification of their original chemical structure after 14 days so the detected toxicity may be due to the original product as well as their degradation products. The three blood lipid-lowering agents seem to be more stable in soil. From an environmental perspective, the lethal concentrations of the tested drugs are much greater than those reported in wastewater and biosolids, therefore acute toxic effects may be improbable. However, little is known about the accumulation of these substances in soils after regular applications, so accumulative and chronic effects cannot be excluded. Moreover, more studies are needed to determine the role of the degradation

  16. Forensic toxicology.

    PubMed

    Drummer, Olaf H

    2010-01-01

    Forensic toxicology has developed as a forensic science in recent years and is now widely used to assist in death investigations, in civil and criminal matters involving drug use, in drugs of abuse testing in correctional settings and custodial medicine, in road and workplace safety, in matters involving environmental pollution, as well as in sports doping. Drugs most commonly targeted include amphetamines, benzodiazepines, cannabis, cocaine and the opiates, but can be any other illicit substance or almost any over-the-counter or prescribed drug, as well as poisons available to the community. The discipline requires high level skills in analytical techniques with a solid knowledge of pharmacology and pharmacokinetics. Modern techniques rely heavily on immunoassay screening analyses and mass spectrometry (MS) for confirmatory analyses using either high-performance liquid chromatography or gas chromatography as the separation technique. Tandem MS has become more and more popular compared to single-stage MS. It is essential that analytical systems are fully validated and fit for the purpose and the assay batches are monitored with quality controls. External proficiency programs monitor both the assay and the personnel performing the work. For a laboratory to perform optimally, it is vital that the circumstances and context of the case are known and the laboratory understands the limitations of the analytical systems used, including drug stability. Drugs and poisons can change concentration postmortem due to poor or unequal quality of blood and other specimens, anaerobic metabolism and redistribution. The latter provides the largest handicap in the interpretation of postmortem results. PMID:20358697

  17. Adverse health effects and unhealthy behaviors among medical students using Facebook.

    PubMed

    Al-Dubai, Sami Abdo Radman; Ganasegeran, Kurubaran; Al-Shagga, Mustafa Ahmed Mahdi; Yadav, Hematram; Arokiasamy, John T

    2013-01-01

    Little is known about the relationships between adverse health effects and unhealthy behaviors among medical students using Facebook. The aim of this study was to determine the associations between adverse health effects and unhealthy behaviors with Facebook use. A cross-sectional study was conducted in a private university in Malaysia among 316 medical students. A self-administered questionnaire was used. It included questions on sociodemographics, pattern of Facebook use, social relationship, unhealthy behaviors, and health effects. Mean age was 20.5 (±2.7) years. All students had a Facebook account. The average daily Facebook surfing hours were 2.5 (±1.7). Significant associations were found between average hours of Facebook surfing and the following factors: isolation from family members and community, refusing to answer calls, musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours spent on Facebook were significantly associated with holding urination and defecation while online, surfing Facebook until midnight, and postponing, forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook were associated with adverse health effects and unhealthy behaviors among medical students, as well as social isolation from the family and community. PMID:24453859

  18. Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.

    PubMed

    El-Sayed, Wael M; Al-Kahtani, Mohamed Ali

    2011-09-01

    Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats. PMID:21861687

  19. Adverse Health Effects and Unhealthy Behaviors among Medical Students Using Facebook

    PubMed Central

    Al-Dubai, Sami Abdo Radman; Al-Shagga, Mustafa Ahmed Mahdi; Yadav, Hematram; Arokiasamy, John T.

    2013-01-01

    Little is known about the relationships between adverse health effects and unhealthy behaviors among medical students using Facebook. The aim of this study was to determine the associations between adverse health effects and unhealthy behaviors with Facebook use. A cross-sectional study was conducted in a private university in Malaysia among 316 medical students. A self-administered questionnaire was used. It included questions on sociodemographics, pattern of Facebook use, social relationship, unhealthy behaviors, and health effects. Mean age was 20.5 (±2.7) years. All students had a Facebook account. The average daily Facebook surfing hours were 2.5 (±1.7). Significant associations were found between average hours of Facebook surfing and the following factors: isolation from family members and community, refusing to answer calls, musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours spent on Facebook were significantly associated with holding urination and defecation while online, surfing Facebook until midnight, and postponing, forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook were associated with adverse health effects and unhealthy behaviors among medical students, as well as social isolation from the family and community. PMID:24453859

  20. Technical evaluation report, AGARD Fluid Dynamics Panel Symposium on Effects of Adverse Weather on Aerodynamics

    NASA Technical Reports Server (NTRS)

    Reinmann, J. J.

    1991-01-01

    The purpose of the meeting on Effects of Adverse Weather on Aerodynamics was to provide an update of the stae-of-the-art with respect to the prediction, simulation, and measurement of the effects of icing, anti-icing fluids, and various precipitation on the aerodynamic characteristics of flight vehicles. Sessions were devoted to introductory and survey papers and icing certification issues, to analytical and experimental simulation of ice frost contamination and its effects of aerodynamics, and to the effects of heavy rain and deicing/anti-icing fluids.

  1. Adversity, cannabis use and psychotic experiences: evidence of cumulative and synergistic effects

    PubMed Central

    Morgan, Craig; Reininghaus, Ulrich; Reichenberg, Abraham; Frissa, Souci; Hotopf, Matthew; Hatch, Stephani L.

    2014-01-01

    Background There is robust evidence that childhood adversity is associated with an increased risk of psychosis. There is, however, little research on intervening factors that might increase or decrease risk following childhood adversity. Aims To investigate main effects of, and synergy between, childhood abuse and life events and cannabis use on odds of psychotic experiences. Method Data on psychotic experiences and childhood abuse, life events and cannabis use were collected from 1680 individuals as part of the South East London Community Health Study (SELCoH), a population-based household survey. Results There was strong evidence that childhood abuse and number of life events combined synergistically to increase odds of psychotic experiences beyond the effects of each individually. There was similar, but weaker, evidence for cannabis use (past year). Conclusions Our findings are consistent with the hypothesis that childhood abuse creates an enduring vulnerability to psychosis that is realised in the event of exposure to further stressors and risk factors. PMID:24627297

  2. A Cohort Study on Long-Term Adverse Effects of Parental Drinking: Background and Study Design

    PubMed Central

    Lund, Ingunn Olea; Bukten, Anne; Storvoll, Elisabet E; Moan, Inger Synnøve; Skurtveit, Svetlana; Handal, Marte; Nordfjærn, Trond; Brunborg, Geir Scott; Rossow, Ingeborg

    2015-01-01

    Although many studies have addressed adverse outcomes in children of parents with alcohol abuse/dependence, less is known about the possible long-term effects of more normative patterns of parental alcohol consumption, including drinking at lower risk levels and heavy episodic or binge drinking. The extent of harm from parental drinking may therefore be underestimated. With this research proposal, we describe a project that aims to assess possible long-term adverse effects of parental drinking by combining survey and nationwide registry data. Advantages of a longitudinal general population cohort design include that it allows for detailed information on parental drinking through survey data and identification of possible negative long-term health and social outcomes from exposure to parental drinking 1–19 years after exposure through continuously updated nationwide registers. The rich information available from combining survey and registry data allows us to take into account important confounders, mediators, and moderators. PMID:26688663

  3. Renal-related adverse effects of intravenous contrast media in computed tomography

    PubMed Central

    Leow, Kheng Song; Wu, Yi Wei; Tan, Cher Heng

    2015-01-01

    Renal-related adverse effects of intravascular contrast media (CM) include contrast-induced nephropathy in computed tomography and angiography. While large retrospective studies have been published, the exact pathogenesis of this condition is still unknown. We review the main international guidelines, including the American College of Radiology white paper and the guidelines of European Society of Urogenital Radiology, Royal College of Radiologists and Canadian Association of Radiologists, as well as their references, regarding this subject. We present a simplified, concise approach to renal-related adverse effects of CM, taking into consideration the basis for each recommendation in these published guidelines. This will allow the reader to better understand the rationale behind appropriate patient preparation for cross-sectional imaging. PMID:25917468

  4. Statistical Mining of Potential Drug Interaction Adverse Effects in FDA's Spontaneous Reporting System.

    PubMed

    Harpaz, Rave; Haerian, Krystl; Chase, Herbert S; Friedman, Carol

    2010-01-01

    Many adverse drug effects (ADEs) can be attributed to drug interactions. Spontaneous reporting systems (SRS) provide a rich opportunity to detect novel post-marketed drug interaction adverse effects (DIAEs), as they include populations not well represented in clinical trials. However, their identification in SRS is nontrivial. Most existing research have addressed the statistical issues used to test or verify DIAEs, but not their identification as part of a systematic large scale database-wide mining process as discussed in this work. This paper examines the application of a highly optimized and tailored implementation of the Apriori algorithm, as well as methods addressing data quality issues, to the identification of DIAEs in FDAs SRS. PMID:21346985

  5. Proximal muscular atrophy and weakness: An unusual adverse effect of deferasirox iron chelation therapy.

    PubMed

    Vill, K; Müller-Felber, W; Teusch, V; Blaschek, A; Gerstl, L; Huetker, S; Albert, M H

    2016-01-01

    Deferasirox is a standard treatment for chronic transfusional iron overload. Adverse effects of deferasirox have been reported in large prospective studies. We report two cases of monozygotic twins manifesting with proximal muscular atrophy and weakness under deferasirox. Discontinuation of deferasirox resulted in symptom improvement and ultimately in complete remission five months after successful haematopoietic stem cell transplantation. Broad diagnostic work-up could not bring evidence of another aetiology of muscular weakness. Iron overload or beta thalassemia itself as a cause is considered unlikely in our patients because the chronological coincidence of muscular symptoms was contra-directional to serum ferritin levels and significant clinical improvement was observed promptly after cessation of deferasirox even before transplantation. These observations suggest that the development of muscular weakness in patients on deferasirox should be recognised as a possible adverse effect of the drug. PMID:27068298

  6. A severe dermatologic adverse effect related with gefitinib: case report and review of the literature.

    PubMed

    Li, Yuan-Qing; Sun, Hong; Xue, Dong

    2013-09-01

    Gefitinib, a selective inhibitor of the epidermal growth factor receptor-tyrosine kinase, it's one of the most frequent drug-related adverse effects (AEs) reported in literature is dermatologic AEs. We report, a case of severe cutaneous adverse reactions induced by gefitinib as second-line treatment in a male patient with advanced non-small cell lung cancer after 1 month of treatment. Although tumor shrunk and patient got benefit from the treatment, gefitinib had to be stopped right away. We managed the symptoms of rash with a variety of treatments, including topical ethacridine lactate, antihistamine and so on. After the rash improved, we found his tumor were progress. Then he took gefitinib again without severe skin toxicity or disease progression. We think the development of gefitinib-induced rash may be a sign of effective and administrating it again maybe relieves the degree of rash. PMID:24135241

  7. Potential adverse effects of discontinuing psychotropic drugs. Part 3: Antipsychotic, dopaminergic, and mood-stabilizing drugs.

    PubMed

    Howland, Robert H

    2010-08-01

    Abrupt discontinuation of antipsychotic drugs in patients with schizophrenia is associated with earlier, and often more severe, illness episodes than are seen with gradual discontinuation. Antipsychotic drugs can cause various abnormal motor syndromes, but abruptly stopping them has been associated with the seemingly paradoxical development of similar motor syndromes, such as withdrawal dyskinesias, parkinsonian symptoms, dystonias, and neuroleptic malignant syndrome. Dopamine-releasing and dopamine-agonist drugs are used to treat some of the motor syndromes caused by antipsychotic drugs, but their abrupt discontinuation can also be associated with abnormal syndromes. When antipsychotic drugs, lithium, or certain anticonvulsant drugs are used for treatment of bipolar disorder, rapid versus gradual discontinuation is more likely to lead to greater mood instability and manic relapse. If necessary, these medications should be gradually tapered to minimize all types of adverse discontinuation effects. Patients should be educated about the possible adverse effects of abrupt medication discontinuation. PMID:20669865

  8. Role of CNR1 polymorphisms in moderating the effects of psychosocial adversity on impulsivity in adolescents.

    PubMed

    Buchmann, Arlette F; Hohm, Erika; Witt, Stephanie H; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Schmidt, Martin H; Esser, Günter; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2015-03-01

    Enhanced endocannabinoid signaling has been implicated in typically adolescent behavioral features such as increased risk-taking, impulsivity and novelty seeking. Research investigating the impact of genetic variants in the cannabinoid receptor 1 gene (CNR1) and of early rearing conditions has demonstrated that both factors contribute to the prediction of impulsivity-related phenotypes. The present study aimed to test the hypothesis of an interaction of the two most studied CNR1 polymorphisms rs806379 and rs1049353 with early psychosocial adversity in terms of affecting impulsivity in 15-year-olds from an epidemiological cohort sample followed since birth. In 323 adolescents (170 girls, 153 boys), problems of impulse control and novelty seeking were assessed using parent-report and self-report, respectively. Exposure to early psychosocial adversity was determined in a parent interview conducted at the age of 3 months. The results indicated that impulsivity increased following exposure to early psychosocial adversity, with this increase being dependent on CNR1 genotype. In contrast, while individuals exposed to early adversity scored higher on novelty seeking, no significant impact of genotype or the interaction thereof was detected. This is the first evidence to suggest that the interaction of CNR1 gene variants with the experience of early life adversity may play a role in determining adolescent impulsive behavior. However, given that the reported findings are obtained in a high-risk community sample, results are restricted in terms of interpretation and generalization. Future research is needed to replicate these findings and to identify the mediating mechanisms underlying this effect. PMID:24980155

  9. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect.

    PubMed

    Mathew, Thomas; Sarma, G R K; Nadig, Raghunandan; Varghese, Raji

    2012-04-15

    Somnambulism (sleepwalking) is a disorder of arousal that falls under "parasomnia" group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers. This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine. PMID:22505867

  10. Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

    SciTech Connect

    Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark; Gentili, Fred; Heydarian, Mostafa; Tsao, May; Schwartz, Michael; Prooijen, Monique van; Millar, Barbara-Ann; Menard, Cynthia; Kulkarni, Abhaya V.; Laperriere, Norm; Zadeh, Gelareh

    2012-04-01

    Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; and trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.

  11. Pharmacokinetics, pharmacodynamics and toxicology of theranostic nanoparticles

    NASA Astrophysics Data System (ADS)

    Kang, Homan; Mintri, Shrutika; Menon, Archita Venugopal; Lee, Hea Yeon; Choi, Hak Soo; Kim, Jonghan

    2015-11-01

    Nanoparticles (NPs) are considered a promising tool in both diagnosis and therapeutics. Theranostic NPs possess the combined properties of targeted imaging and drug delivery within a single entity. While the categorization of theranostic NPs is based on their structure and composition, the pharmacokinetics of NPs are significantly influenced by the physicochemical properties of theranostic NPs as well as the routes of administration. Consequently, altered pharmacokinetics modify the pharmacodynamic efficacy and toxicity of NPs. Although theranostic NPs hold great promise in nanomedicine and biomedical applications, a lack of understanding persists on the mechanisms of the biodistribution and adverse effects of NPs. To better understand the diagnostic and therapeutic functions of NPs, this review discusses the factors that influence the pharmacokinetics, pharmacodynamics and toxicology of theranostic NPs, along with several strategies for developing novel diagnostic and therapeutic modalities.

  12. Mechanisms of nanosilver-induced toxicological effects: more attention should be paid to its sublethal effects.

    PubMed

    Wang, Zhe; Xia, Tian; Liu, Sijin

    2015-05-01

    Due to its unique physicochemical properties and remarkable antimicrobial activity, nanosilver (nAg) is increasingly being used in a wide array of fields, including medicine and personal care products. Despite substantial progress being made towards the understanding of the acute toxicity of nAg, large knowledge gaps still exist on the assessment of its chronic toxicity to humans. Chronic effects of nAg, typically at low doses (i.e. sublethal doses) should be different from the acute toxicity at high doses (i.e., lethal doses), which is analogous to other environmental pollutants. Although a few review papers have elaborated the findings on nAg-mediated toxicity, most of them only discussed overt toxicity of nAg at high-level exposure and failed to evaluate the chronic and cumulative effects of nAg at sublethal doses. Therefore, it is necessary to more stringently scrutinize the sublethal toxicity of nAg under environmentally relevant conditions. Herein, we recapitulated recent findings on the sublethal effects of nAg toxicity performed by our groups and others. We then discussed the molecular mechanisms by which nAg exerts its toxicity under low concentrations and compared that with nAg-induced cell death. PMID:25865054

  13. Mechanisms of nanosilver-induced toxicological effects: more attention should be paid to its sublethal effects

    PubMed Central

    Wang, Zhe; Xia, Tian; Liu, Sijin

    2015-01-01

    Due to its unique physicochemical properties and remarkable antimicrobial activity, nanosilver (nAg) is increasingly being used in a wide array of fields, including medicine and personal care products. Despite substantial progress being made towards the understanding of the acute toxicity of nAg, large knowledge gaps still exist on the assessment of its chronic toxicity to humans. Chronic effects of nAg, typically at low doses (i.e. sublethal doses) should be different from the acute toxicity at high doses (i.e., lethal doses), which is analogous to other environmental pollutants. Although a few review papers have elaborated the findings on nAg-mediated toxicity, most of them only discussed overt toxicity of nAg at high-level exposure and failed to evaluate the chronic and cumulative effects of nAg at sublethal doses. Therefore, it is necessary to more stringently scrutinize the sublethal toxicity of nAg under environmentally relevant conditions. Herein, we recapitulated recent findings on the sublethal effects of nAg toxicity performed by our groups and others. We then discussed the molecular mechanisms by which nAg exerts its toxicity under low concentrations and compared that with nAg-induced cell death. PMID:25865054

  14. Mechanisms of nanosilver-induced toxicological effects: more attention should be paid to its sublethal effects

    NASA Astrophysics Data System (ADS)

    Wang, Zhe; Xia, Tian; Liu, Sijin

    2015-04-01

    Due to its unique physicochemical properties and remarkable antimicrobial activity, nanosilver (nAg) is increasingly being used in a wide array of fields, including medicine and personal care products. Despite substantial progress being made towards the understanding of the acute toxicity of nAg, large knowledge gaps still exist on the assessment of its chronic toxicity to humans. Chronic effects of nAg, typically at low doses (i.e. sublethal doses) should be different from the acute toxicity at high doses (i.e., lethal doses), which is analogous to other environmental pollutants. Although a few review papers have elaborated the findings on nAg-mediated toxicity, most of them only discussed overt toxicity of nAg at high-level exposure and failed to evaluate the chronic and cumulative effects of nAg at sublethal doses. Therefore, it is necessary to more stringently scrutinize the sublethal toxicity of nAg under environmentally relevant conditions. Herein, we recapitulated recent findings on the sublethal effects of nAg toxicity performed by our groups and others. We then discussed the molecular mechanisms by which nAg exerts its toxicity under low concentrations and compared that with nAg-induced cell death.

  15. A strategy for regulatory action when new adverse effects of a licensed product emerge.

    PubMed

    Aronson, Jeffrey K; Price, Deirdre; Ferner, Robin E

    2009-01-01

    Regulatory agencies grant product licences (marketing authorizations) for medicinal products in the light of evidence that the balance between benefit and harm in the population is favourable. Here we consider a framework for allowing regulatory agencies to make rational decisions when reviewing product licences in the light of new information about harms that change that balance. The regulator can revoke the product licence, restrict the product's availability or change the 'label' in different ways. We examine the features of the adverse effect that may be relevant in making the decision: namely, individual differences in susceptibility; the possibility of monitoring; and the availability of protective strategies. The balance of benefit and harm, and the time-course and dose relation of the adverse effect play important roles in the decision-making process. We set out how these factors can help determine the logical response to new information on the balance between benefit and harm, and provide a series of relevant examples. We believe that when regulatory agencies have to decide how to amend the product licence of a drug when new serious adverse effects cause concern, they would find it useful to adopt a framework of this kind, using different strategies for different cases. Our proposed framework could also be useful in risk management planning during drug development. PMID:19236116

  16. Caregiver acceptance of adverse effects and use of cholinesterase inhibitors in Alzheimer's disease.

    PubMed

    Oremus, Mark; Wolfson, Christina; Vandal, Alain C; Bergman, Howard; Xie, Qihao

    2007-01-01

    Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire from 375 caregivers in Montreal. Sixty-four per cent of caregivers responded ( n = 201), and most (> or =59%) were willing to continue treatment if persons with Alzheimer's disease suffered from weight loss or loss of appetite. However, most (> or =53%) were not willing to continue treatment in the event of headache, dizziness, nausea, diarrhea, vomiting, drop in blood pressure, insomnia, muscle cramps, or stomach bleeding. The use of cholinesterase inhibitors by persons with Alzheimer's disease was positively associated with caregivers' willingness to accept greater numbers of adverse effects (adjusted relative risk = 1.97; 95% CI = 1.11 to 3.61). Caregivers appear to make a risk-benefit assessment when they decide whether or not care-recipients should continue pharmacotherapy in the event of adverse effects. PMID:18238727

  17. History of wildlife toxicology.

    PubMed

    Rattner, Barnett A

    2009-10-01

    The field of wildlife toxicology can be traced to the late nineteenth and early twentieth centuries. Initial reports included unintentional poisoning of birds from ingestion of spent lead shot and predator control agents, alkali poisoning of waterbirds, and die-offs from maritime oil spills. With the advent of synthetic pesticides in the 1930s and 1940s, effects of DDT and other pesticides were investigated in free-ranging and captive wildlife. In response to research findings in the US and UK, and the publication of Silent Spring in 1962, public debate on the hazards of pollutants arose and national contaminant monitoring programs were initiated. Shortly thereafter, population-level effects of DDT on raptorial and fish-eating birds were documented, and effects on other species (e.g., bats) were suspected. Realization of the global nature of organochlorine pesticide contamination, and the discovery of PCBs in environmental samples, launched long-range studies in birds and mammals. With the birth of ecotoxicology in 1969 and the establishment of the Society of Environmental Toxicology and Chemistry in 1979, an international infrastructure began to emerge. In the 1980s, heavy metal pollution related to mining and smelting, agrichemical practices and non-target effects, selenium toxicosis, and disasters such as Chernobyl and the Exxon Valdez dominated the field. Biomarker development, endocrine disruption, population modeling, and studies with amphibians and reptiles were major issues of the 1990s. With the turn of the century, there was interest in new and emerging compounds (pharmaceuticals, flame retardants, surfactants), and potential population-level effects of some compounds. Based upon its history, wildlife toxicology is driven by chemical use and misuse, ecological disasters, and pollution-related events affecting humans. Current challenges include the need to more thoroughly estimate and predict exposure and effects of chemical-related anthropogenic

  18. Multi-omic landscape of rheumatoid arthritis: re-evaluation of drug adverse effects

    PubMed Central

    Tieri, Paolo; Zhou, XiaoYuan; Zhu, Lisha; Nardini, Christine

    2014-01-01

    Objective: To provide a frame to estimate the systemic impact (side/adverse events) of (novel) therapeutic targets by taking into consideration drugs potential on the numerous districts involved in rheumatoid arthritis (RA) from the inflammatory and immune response to the gut-intestinal (GI) microbiome. Methods: We curated the collection of molecules from high-throughput screens of diverse (multi-omic) biochemical origin, experimentally associated to RA. Starting from such collection we generated RA-related protein-protein interaction (PPI) networks (interactomes) based on experimental PPI data. Pharmacological treatment simulation, topological and functional analyses were further run to gain insight into the proteins most affected by therapy and by multi-omic modeling. Results: Simulation on the administration of MTX results in the activation of expected (apoptosis) and adverse (nitrogenous metabolism alteration) effects. Growth factor receptor-bound protein 2 (GRB2) and Interleukin-1 Receptor Associated Kinase-4 (IRAK4, already an RA target) emerge as relevant nodes. The former controls the activation of inflammatory, proliferative and degenerative pathways in host and pathogens. The latter controls immune alterations and blocks innate response to pathogens. Conclusions: This multi-omic map properly recollects in a single analytical picture known, yet complex, information like the adverse/side effects of MTX, and provides a reliable platform for in silico hypothesis testing or recommendation on novel therapies. These results can support the development of RA translational research in the design of validation experiments and clinical trials, as such we identify GRB2 as a robust potential new target for RA for its ability to control both synovial degeneracy and dysbiosis, and, conversely, warn on the usage of IRAK4-inhibitors recently promoted, as this involves potential adverse effects in the form of impaired innate response to pathogens. PMID:25414848

  19. Strategic approaches to adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...

  20. Evaluating legacy contaminants and emerging chemicals in marine environments using adverse outcome pathways and biological effects-directed analysis.

    PubMed

    Hutchinson, Thomas H; Lyons, Brett P; Thain, John E; Law, Robin J

    2013-09-30

    important scientific, economic and health challenges. In order to meet these challenges and pursue cost-effective scientific approaches that can provide evidence necessary to support policy needs (e.g. the European Marine Strategy Framework Directive), it is widely recognised that there is a need to (i) provide marine exposure assessments for priority contaminants using a range of validated models, passive samplers and biomarkers; (ii) integrate chemical monitoring data with biological effects data across spatial and temporal scales (including quality controls); and (iii) strengthen the evidence base to understand the relationship between exposure to complex chemical mixtures, biological and ecological impacts through integrated approaches and molecular data (e.g. genomics, proteomics and metabolomics). Additionally, we support the widely held view that (iv) that rather than increasing the analytical chemistry monitoring of large number of emerging contaminants, it will be important to target analytical chemistry towards key groups of chemicals of concern using effects-directed analysis. It is also important to evaluate to what extent existing biomarkers and bioassays can address various classes of emerging chemicals using the adverse outcome pathway (AOP) approach now being developed by the Organization for Economic Cooperation and Development (OECD) with respect to human toxicology and ecotoxicology. PMID:23820191

  1. Human exposure to mercury: A critical assessment of the evidence of adverse health effects

    SciTech Connect

    Ratcliffe, H.E.; Swanson, G.M.; Fischer, L.J.

    1996-10-25

    The ubiquitous nature of mercury in the environment, its global atmospheric cycling, and its toxicity to humans at levels that are uncomfortably close to exposures experienced by a proportion of the population are some of the current concerns associated with this pollutant. The purpose of this review is to critically evaluate the scientific quality of published reports involving human exposures to mercury and associated health outcomes as an aid in the risk evaluation of this chemical. A comprehensive review of the scientific literature involving human exposures to mercury was performed and each publication evaluated using a defined set of criteria that are considered standards in epidemiologic and toxicologic research. Severe, sometimes fatal, effects of mercury exposure at high levels were primarily reported as case studies. The disasters in Minamata, Japan, in the 1950s and in Iraq in 1971-1972 clearly demonstrated neurologic effects associated with ingestion of methylmercury both in adults and in infants exposed in utero. The effects were convincingly Associated with methylmercury ingestion, despite limitations of the study design. Several well-conducted studies have investigated the effects of methylmercury at levels below those in the Iraq incident but have not provided clear evidence of an effect. The lower end of the dose-response curve constructed from the Iraq data therefore still needs to be confirmed. The studies of mercury exposure in the workplace were mainly of elemental or inorganic mercury, and effects that were observed at relatively low exposure levels were primarily neurologic and renal. Several studies have investigated effects associated with dental amalgam but have been rated as inconclusive because of methodologic deficiencies. In our overall evaluation, 29 of 110 occupational studies and 20 of 54 studies where exposure occurred in the natural environment provided at least suggestive evidence of an exposure-related effect. 259 refs., 4 tabs.

  2. IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR CHLOROETHANE

    EPA Science Inventory

    Toxicological data in the published literature on Chloroethane (CE) will be assimilated, reviewed, and integated into a Toxicological Review of CE (assessment document), which seeks to characterize the key cancer, and non cancer health effect hazards from environmental exposures...

  3. Toxicological approaches to complex mixtures.

    PubMed Central

    Mauderly, J L

    1993-01-01

    This paper reviews the role of toxicological studies in understanding the health effects of environmental exposures to mixtures. The approach taken is to review mixtures that have received the greatest emphasis from toxicology; major mixtures research programs; the toxicologist's view of mixtures and approaches to their study; and the complementary roles of toxicological, clinical, and epidemiological studies. Studies of tobacco smoke, engine exhaust, combustion products, and air pollutants comprise most of the past research on mixtures. Because of their great experimental control over subjects, exposures, and endpoints, toxicologists tend to consider a wider range of toxic interactions among mixture components and sequential exposures than is practical for human studies. The three fundamental experimental approaches used by toxicologists are integrative (studying the mixture as a whole), dissective (dissecting a mixture to determine causative constituents), and synthetic (studying interactions between agents in simple combinations). Toxicology provides information on potential hazards, mechanisms by which mixture constituents interact to cause effects, and exposure dose-effect relationships; but extrapolation from laboratory data to quantitative human health risks is problematic. Toxicological, clinical, and epidemiological approaches are complementary but are seldom coordinated. Fostering synergistic interactions among the disciplines in studying the risks from mixtures could be advantageous. PMID:7515806

  4. Pharmacogenetics of quetiapine in healthy volunteers: association with pharmacokinetics, pharmacodynamics, and adverse effects.

    PubMed

    Cabaleiro, Teresa; López-Rodríguez, Rosario; Román, Manuel; Ochoa, Dolores; Novalbos, Jesús; Borobia, Alberto; Carcas, Antonio; Abad-Santos, Francisco

    2015-03-01

    Quetiapine is an atypical antipsychotic used for treatment of schizophrenia. Variability in response to this drug may be associated with pharmacogenetics. The aim of this study was to identify genetic markers related to the pharmacokinetics, pharmacodynamics, and adverse effects of quetiapine. The study population comprised 79 healthy volunteers from two bioequivalence trials who were genotyped to identify polymorphisms in genes encoding enzymes, receptors, and transporters. Quetiapine plasma levels were quantified using high-performance liquid chromatography/mass spectrometry. Prolactin plasma levels were detected by indirect chemiluminescence. Possible adverse effects were recorded throughout the study. Factors with P value of 0.1 or less in the univariate analysis were included in a multiple regression analysis (logistic regression for adverse reactions). The area under the curve and clearance of quetiapine were affected by polymorphisms in CYP1A2 and DRD3, respectively. Men had a lower quetiapine area under the curve compared with women. Prolactin iC(max) was higher in volunteers harboring polymorphisms in CYP2C19 and AGT. An association was detected between polymorphisms in CYP1A1 and CYP2C9 and somnolence. Several polymorphisms are responsible for differences in the pharmacokinetics, pharmacodynamics, and safety of quetiapine in healthy individuals. PMID:25025989

  5. Evaluating the potential effectiveness of using computerized information systems to prevent adverse drug events.

    PubMed Central

    Anderson, J. G.; Jay, S. J.; Anderson, M.; Hunt, T. J.

    1997-01-01

    In this study a dynamic computer simulation model is used to estimate the effectiveness of various information systems applications designed to detect and prevent medication errors that result in adverse drug events (ADEs). The model simulates the four stages of the drug ordering and delivery system: prescribing, transcribing, dispensing and administering drugs. In this study we simulated interventions that have been demonstrated in prior studies to decrease error rates. The results demonstrated that a computerized information system that detected 26% of medication errors and prevented associated ADEs could save 1,226 days of excess hospitalization and $1.4 million in hospital costs annually. Those results suggest that such systems are potentially a cost-effective means of preventing ADEs in hospitals. The results demonstrated the importance of viewing adverse drug events from a systems perspective. Prevention efforts that focus on a single stage of the process had limited impact on the overall error rate. This study suggests that system-wide changes to the drug-ordering and delivery system are required to significantly reduce adverse drug events in a hospital setting. PMID:9357622

  6. Adverse Drug Effects and Preoperative Medication Factors Related to Perioperative Low-Dose Ketamine Infusions.

    PubMed

    Schwenk, Eric S; Goldberg, Stephen F; Patel, Ronak D; Zhou, Jon; Adams, Douglas R; Baratta, Jaime L; Viscusi, Eugene R; Epstein, Richard H

    2016-01-01

    High-dose opioid administration is associated with significant adverse events. Evidence suggests that low-dose ketamine infusions improve perioperative analgesia over conventional opioid management, but usage is highly variable. Ketamine's adverse drug effects (ADEs) are well known, but their prevalence during low-dose infusions in a clinical setting and how often they lead to infusion discontinuation are unknown. The purposes of this study were 3-fold: (1) to identify patient factors associated with initiation of ketamine infusions during spine surgery, (2) to identify specific spine procedures in which ketamine has been used most frequently, and (3) to identify ADEs associated with postoperative ketamine infusions and which ADEs most frequently led to discontinuation. Spine surgery was chosen because of its association with moderate to severe pain and a relatively high use of ketamine infusions in this population at our hospital. PMID:27281730

  7. Drag-Reduction Effectiveness of Riblet Films in Adverse Pressure Gradients

    NASA Astrophysics Data System (ADS)

    Boomsma, Aaron; Sotiropoulos, Fotis

    2013-11-01

    Riblet films are micro-grooved structures that are widely known to passively reduce skin friction. Past studies have almost solely focused on riblet performance in channel-flows. However, possible applications of riblets include wind turbine blades, gas turbine blades, and other complex bodies that are exposed to non-zero pressure gradient flows--specifically adverse pressure gradients. We use high-resolution large eddy simulations of turbulent flow over three-dimensional riblets under an adverse pressure gradient. We analyze the computed results to quantify drag reduction effectiveness for different riblet shapes and to examine pertinent turbulent structures to gain a fundamental understanding of riblet performance. Supported by the DOE Wind Energy Consortium

  8. Incidence of adverse biological effects within ranges of chemical concentrations in marine and estuarine sediments

    NASA Astrophysics Data System (ADS)

    Long, Edward R.; MacDonald, Donald D.; Smith, Sherri L.; Calder, Fred D.

    1995-01-01

    Matching biological and chemical data were compiled from numerous modeling, laboratory, and field studies performed in marine and estuarine sediments. Using these data, two guideline values (an effects range-low and an effects range-median) were determined for nine trace metals, total PCBs, two pesticides, 13 polynuclear aromatic hydrocarbons (PAHs), and three classes of PAHs. The two values defined concentration ranges that were: (1) rarely, (2) occasionally, or (3) frequently associated with adverse effects. The values generally agreed within a factor of 3 or less with those developed with the same methods applied to other data and to those developed with other effects-based methods. The incidence of adverse effects was quantified within each of the three concentration ranges as the number of cases in which effects were observed divided by the total number of observations. The incidence of effects increased markedly with increasing concentrations of all of the individual PAHs, the three classes of PAHs, and most of the trace metals. Relatively poor relationships were observed between the incidence of effects and the concentrations of mercury, nickel, total PCB, total DDT and p,p'-DDE. Based upon this evaluation, the approach provided reliable guidelines for use in sediment quality assessments. This method is being used as a basis for developing National sediment quality guidelines for Canada and informal, sediment quality guidelines for Florida.

  9. Parent Report of Antidepressant, Anxiolytic, and Antipsychotic Medication Use in Individuals with Williams Syndrome: Effectiveness and Adverse Effects

    ERIC Educational Resources Information Center

    Martens, Marilee A.; Seyfer, Daisha L.; Andridge, Rebecca R.; Foster, Jessica E. A.; Chowdhury, Monali; McClure, Kelsey E.; Coury, Daniel L.

    2012-01-01

    Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage…

  10. TOXNET (TOXICOLOGY DATA NETWORK)

    EPA Science Inventory

    TOXNET (Toxicology Data Network) is a computerized system of files oriented to toxicology and related areas. It is managed by the National Library of Medicines Toxicology and Environmental Health Information Program (TEHIP) and runs on a series of microcomputers in a networked cl...

  11. Effect of fuel zinc content on toxicological responses of particulate matter from pellet combustion in vitro.

    PubMed

    Uski, O; Jalava, P I; Happo, M S; Torvela, T; Leskinen, J; Mäki-Paakkanen, J; Tissari, J; Sippula, O; Lamberg, H; Jokiniemi, J; Hirvonen, M-R

    2015-04-01

    Significant amounts of transition metals such as zinc, cadmium and copper can become enriched in the fine particle fraction during biomass combustion with Zn being one of the most abundant transition metals in wood combustion. These metals may have an important role in the toxicological properties of particulate matter (PM). Indeed, many epidemiological studies have found associations between mortality and PM Zn content. The role of Zn toxicity on combustion PM was investigated. Pellets enriched with 170, 480 and 2300 mg Zn/kg of fuel were manufactured. Emission samples were generated using a pellet boiler and the four types of PM samples; native, Zn-low, Zn-medium and Zn-high were collected with an impactor from diluted flue gas. The RAW 264.7 macrophage cell line was exposed for 24h to different doses (15, 50,150 and 300 μg ml(-1)) of the emission samples to investigate their ability to cause cytotoxicity, to generate reactive oxygen species (ROS), to altering the cell cycle and to trigger genotoxicity as well as to promote inflammation. Zn enriched pellets combusted in a pellet boiler produced emission PM containing ZnO. Even the Zn-low sample caused extensive cell cycle arrest and there was massive cell death of RAW 264.7 macrophages at the two highest PM doses. Moreover, only the Zn-enriched emission samples induced a dose dependent ROS response in the exposed cells. Inflammatory responses were at a low level but macrophage inflammatory protein 2 reached a statistically significant level after exposure of RAW 264.7 macrophages to ZnO containing emission particles. ZnO content of the samples was associated with significant toxicity in almost all measured endpoints. Thus, ZnO may be a key component producing toxicological responses in the PM emissions from efficient wood combustion. Zn as well as the other transition metals, may contribute a significant amount to the ROS responses evoked by ambient PM. PMID:25553547

  12. Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

    PubMed Central

    Snow, Samantha J.; McGee, John; Miller, Desinia B.; Bass, Virginia; Schladweiler, Mette C.; Thomas, Ronald F.; Krantz, Todd; King, Charly; Ledbetter, Allen D.; Richards, Judy; Weinstein, Jason P.; Conner, Teri; Willis, Robert; Linak, William P.; Nash, David; Wood, Charles E.; Elmore, Susan A.; Morrison, James P.; Johnson, Crystal L.; Gilmour, Matthew Ian; Kodavanti, Urmila P.

    2014-01-01

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe. PMID:25239632

  13. Role of adapted physical activity to prevent the adverse effects of the sarcopenia. A pilot study.

    PubMed

    Marini, Mirca; Sarchielli, Erica; Brogi, Lucia; Lazzeri, Renzo; Salerno, Roberto; Sgambati, Eleonora; Monaci, Marco

    2008-01-01

    Sarcopenia is the physiological age related decline in muscle mass and strength. It is a main cause of muscle weakness and reduced locomotory ability and its adverse effects contributes to a reduction in physical function and performance with decreased independence and quality of life. In fact, sarcopenia has been associated with disability and morbidity in the elderly population. Therefore, prevention and treatment of sarcopenia are areas of intense interest. The studies suggest that the pathogenesis of sarcopenia is multifactorial, but the decreased physical activity with aging appears to be a key factor involved in producing this pathology. We investigated the role of adapted physical activity on the adverse effects of the sarcopenia: we examined the effect of a specific resistance training program in twenty sedentary older men, 60-80 years old, with sarcopenia. The program was performed three days a week for 18 total weeks with isotonic machines; in particular the exercises effected with leg press, chest press and vertical row were monitored using a Globus-Tesys dynamometer with Real Power. The maximum repetition test (1RM) was used to calculate the percentage of work and formulate the methodology. Our results demonstrated that the proposed training can improve the dynamic characteristics of muscle strength. In particular, we showed that a medium-low intensity training, structured in series and repetitions with gradual increased workload, produced a time-dependent improvement of strength. Our training increased the muscle strength mainly in the lower limbs reducing the risk of falls which frequently occurs in the elderly. Therefore, a planned resistance training could be an effective countermeasure to prevent or reduce the adverse effects of the sarcopenia improving the quality of life. The physical activity should be personalized and adapted to subject's age and/or disability. PMID:19507462

  14. Inhaled diesel emissions generated with cerium oxide nanoparticle fuel additive induce adverse pulmonary and systemic effects.

    PubMed

    Snow, Samantha J; McGee, John; Miller, Desinia B; Bass, Virginia; Schladweiler, Mette C; Thomas, Ronald F; Krantz, Todd; King, Charly; Ledbetter, Allen D; Richards, Judy; Weinstein, Jason P; Conner, Teri; Willis, Robert; Linak, William P; Nash, David; Wood, Charles E; Elmore, Susan A; Morrison, James P; Johnson, Crystal L; Gilmour, Matthew Ian; Kodavanti, Urmila P

    2014-12-01

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe. PMID:25239632

  15. Toxicological profile for beryllium. Final report

    SciTech Connect

    Not Available

    1988-12-01

    The ATSDR Toxicological Profile for Beryllium is intended to characterize succinctly the toxicological and health-effects information for the substance. It identifies and reviews the key literature. More comprehensive sources of specialty information are referenced. The profile begins with a public-health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in toxicologic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information.

  16. Reduction in adverse effect on pulmonary function after exposure to filtered diesel exhaust

    SciTech Connect

    Ulfvarson, U.; Alexandersson, R. )

    1990-01-01

    A statistically significant temporary reduction on pulmonary function was measured with spirometry in stevedores on a roll-on-roll-off ro-ro ship who were exposed to diesel exhausts from trucks during a work shift. When all trucks were equipped with specially designed microfilters mounted on the exhaust pipes, this impairment in pulmonary function was reduced. Removal of the particulate fraction of the exhausts by filtering is an important factor in reducing the adverse effect of diesel exhaust on pulmonary function. The particle fraction should be considered when designing an indicator of the biological effects of diesel exhausts.

  17. Hypomagnesemia as a potentially life-threatening adverse effect of omeprazole

    PubMed Central

    Hansen, Bent-Are; Bruserud, Øyvind

    2016-01-01

    Hypomagnesemia can be caused by a wide range of diseases (e.g. gastrointestinal disorders, kidney diseases or endocrine disorders), but it can also be a side effect of several drugs. It can be asymptomatic or cause many different clinical symptoms, and the clinical manifestations mainly depend on the rate of development rather than the actual serum magnesium concentration. We here present a 40-year-old female patient with Torsade de pointes ventricular tachycardia and cardiac arrest caused by severe hypomagnesemia as an adverse effect of the proton pump inhibitor omeprazole. PMID:27471598

  18. Detecting and Managing Adverse Effects of Antipsychotic Medications: Current State of Play.

    PubMed

    Ames, Donna; Carr-Lopez, Sian M; Gutierrez, Mary A; Pierre, Joseph M; Rosen, Jennifer A; Shakib, Susan; Yudofsky, Lynn M

    2016-06-01

    Antipsychotics are some of the most frequently prescribed medications not only for psychotic disorders and symptoms but also for a wide range of on-label and off-label indications. Because second-generation antipsychotics have largely replaced first-generation antipsychotics as first-line options due to their substantially decreased risk of extrapyramidal side effects, attention has shifted to other clinically concerning adverse events associated with antipsychotic therapy. The focus of this article is to update the nonextrapyramidal side effects associated with second-generation antipsychotics. Issues surrounding diagnosis and monitoring as well as clinical management are addressed. PMID:27216904

  19. Effect of adverse pressure gradient on high speed boundary layer transition

    NASA Astrophysics Data System (ADS)

    Franko, Kenneth J.; Lele, Sanjiva

    2014-02-01

    The effect of adverse pressure gradients (APG) on boundary layer stability, breakdown, and heat-transfer overshoot is investigated. Flat plate isothermal boundary layers initially at Mach 6 with APG imposed through the freestream boundary condition are simulated using suction and blowing to produce boundary layer instabilities. The three different transition mechanisms compared are first mode oblique breakdown, second mode oblique breakdown, and second mode fundamental resonance. For all of the transition mechanisms, an adverse pressure gradient increases the linear growth rates and quickens the transition to turbulence. However, the nonlinear breakdown for all three transition mechanisms is qualitatively the same as for a zero pressure gradient boundary layer. First mode oblique breakdown leads to the earliest transition location and an overshoot in heat transfer in the transitional region. Both types of Mack second mode forcing lead to a transitional boundary layer but even with the increased growth rates and N factors produced by the adverse pressure gradient, the breakdown process is still more gradual than first mode oblique breakdown because the primary Mack second mode instabilities saturate and produce streaks that breakdown further downstream.

  20. Physiologically-based Pharmacokinetic(PBPK) Models Application to Screen Environmental Hazards Related to Adverse Outcome Pathways(AOPs)

    EPA Science Inventory

    PBPK models are useful in estimating exposure levels based on in vitro to in vivo extrapolation (IVIVE) calculations. Linkage of large sets of chemically screened vitro signature effects to in vivo adverse outcomes using IVIVE is central to the concepts of toxicology in the 21st ...

  1. [My experience in mercury toxicology: behavioral teratology study of the effects of prenatal exposure to environmental pollutants].

    PubMed

    Satoh, Hiroshi

    2007-05-01

    I would like to express sincere thanks to all the people involved in awarding the 2005 Congress Award. It is a great honor to be given the prize. I have been interested in mercury toxicology since I was a graduate student and mercury toxicology has been my main subject of focus for 30 years. I am proud to continue the research in this field. In this presentation I would like to summarize some of my research works and to talk anecdotes related to the research works. Soon after I became involved in this research field, I came across "behavioral teratology", which is a novel field of study whose focus is understanding the postnatal consequences of exposure to harmful agents in utero. Spyker and her colleagues clearly showed postnatal behavioral deviations in mouse offspring exposed to a low dose of methylmercury prenatally. In various animal experiments, I elucidated the subtle consequences that appear postnatally. I found that these consequences are modified by many factors such as selenium status, PCBs, and heat, because the degree of exposure to produce these consequences can be extremely small. These experiments simulate actual human life and the results will be useful to assess the risk of methylmercury exposure through fish consumption in the human population, since fish eating populations are exposed to these factors at a low dose. Recently, cohort studies elucidating the possible effects of prenatal exposure to environmental pollutants in the postnatal period have been established and ongoing. When a conclusion is drawn, it is expected to serve as basic information that is useful for the risk assessment of methylmercury and other environmental pollutants. This will give great gratification to scientists in environmental health and preventive medicine. PMID:17575786

  2. Polytraumatization and Trauma Symptoms in Adolescent Boys and Girls: Interpersonal and Noninterpersonal Events and Moderating Effects of Adverse Family Circumstances

    ERIC Educational Resources Information Center

    Nilsson, Doris Kristina; Gustafsson, Per E.; Svedin, Carl Goran

    2012-01-01

    The objective of this study was to investigate the cumulative effect of interpersonal and noninterpersonal traumatic life events (IPEs and nIPEs, respectively) on the mental health of adolescents and to determine if the adverse impacts of trauma were moderated by adverse family circumstances (AFC). Adolescents (mean age 16.7 years) from the…

  3. Time-Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach.

    PubMed

    Vogs, Carolina; Altenburger, Rolf

    2016-07-19

    Chemicals affect unicellular algae as a result of toxicokinetic and toxicodynamic processes. The internal concentration of chemicals in algae cells typically reaches equilibrium within minutes, while damage cumulatively increases over hours. The time gap between the steady state of internal exposure and damage development is thus suspected to span up to hours, mainly due to toxicodynamic processes. The quantification of rate-limited toxicodynamic processes, aggregated as a progressive effect from an initiating molecular event through biological key events toward the adverse outcome on algae growth inhibition, might discriminate between different adverse outcome pathways (AOPs). To support our hypothesis, we selected six chemicals according to different physicochemical properties and three distinctly dissimilar AOPs. The time courses of internal concentrations were linked to the observed affected Scenedesmus vacuolatus growth using toxicokinetic-toxicodynamic modeling. Effects on cell growth were explained by effect progression and not by the time to reach internal equilibrium concentration. Effect progression rates ranged over 6 orders of magnitude for all chemicals but varied by less than 1 order of magnitude within similar AOP (photosystem II inhibitors > reactive chemicals > lipid biosynthesis inhibitors), meaning that inhibitors of photosystem II advance an effect toward algae growth fastest compared to reactive chemicals and inhibitors of lipid biosynthesis. PMID:27149222

  4. Vitamin D mitigates the adverse effects of obesity on breast cancer in mice.

    PubMed

    Swami, Srilatha; Krishnan, Aruna V; Williams, Jasmaine; Aggarwal, Abhishek; Albertelli, Megan A; Horst, Ronald L; Feldman, Brian J; Feldman, David

    2016-04-01

    Obesity is an established risk factor for postmenopausal breast cancer (BCa), insulin resistance, and vitamin D deficiency, and all contribute to increased synthesis of mammary estrogens, the drivers of estrogen receptor-positive (ER+) BCa growth. As both dietary vitamin D and calcitriol treatments inhibit breast estrogen synthesis and signaling, we hypothesized that vitamin D would be especially beneficial in mitigating the adverse effects of obesity on ER+BCa. To assess whether obesity exerted adverse effects on BCa growth and whether vitamin D compounds could reduce these unfavorable effects, we employed a diet-induced obesity (DIO) model in ovariectomized C57BL/6 mice. Breast tumor cells originally from syngeneic Mmtv-Wnt1 transgenic mice were then implanted into the mammary fat pads of lean and obese mice. DIO accelerated the initiation and progression of the mammary tumors. Treatments with either calcitriol or dietary vitamin D reduced the adverse effects of obesity causing a delay in tumor appearance and inhibiting continued tumor growth. Beneficial actions of treatments with vitamin D or calcitriol on BCa and surrounding adipose tissue included repressed Esr1, aromatase, and Cox2 expression; decreased tumor-derived estrogen and PGE2; reduced expression of leptin receptors; and increased adiponectin receptors. We demonstrate that vitamin D treatments decreased insulin resistance, reduced leptin, and increased adiponectin signaling and also regulated the LKB1/AMPK pathway contributing to an overall decrease in local estrogen synthesis in the obese mice. We conclude that calcitriol and dietary vitamin D, acting by multiple interrelated pathways, mitigate obesity-enhanced BCa growth in a postmenopausal setting. PMID:26817629

  5. Novel Associations between FAAH Genetic Variants and Postoperative Central Opioid related Adverse Effects

    PubMed Central

    Sadhasivam, Senthilkumar; Zhang, Xue; Chidambaran, Vidya; Mavi, Jagroop; Pilipenko, Valentina; Mersha, Tesfaye B.; Meller, Jaroslaw; Kaufman, Kenneth M.; Martin, Lisa J.; McAuliffe, John

    2014-01-01

    Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year in due to opioid induced respiratory depression in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype blinded observational study 259 healthy children between 6 and 15 years that received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, respiratory depression (RD), postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (PACU) due to RD and PONV were analyzed. Five specific FAAH SNPs had significant associations with more than 2 fold increased risk for refractory PONV (adjusted p<0.0018), and nominal associations (p<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. FAAH SNP, rs324420 is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related respiratory depression, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy. PMID:25558980

  6. Identifying Adverse Effects of HIV Drug Treatment and Associated Sentiments Using Twitter

    PubMed Central

    Adrover, Cosme; Bodnar, Todd; Huang, Zhuojie

    2015-01-01

    Background Social media platforms are increasingly seen as a source of data on a wide range of health issues. Twitter is of particular interest for public health surveillance because of its public nature. However, the very public nature of social media platforms such as Twitter may act as a barrier to public health surveillance, as people may be reluctant to publicly disclose information about their health. This is of particular concern in the context of diseases that are associated with a certain degree of stigma, such as HIV/AIDS. Objective The objective of the study is to assess whether adverse effects of HIV drug treatment and associated sentiments can be determined using publicly available data from social media. Methods We describe a combined approach of machine learning and crowdsourced human assessment to identify adverse effects of HIV drug treatment solely on individual reports posted publicly on Twitter. Starting from a large dataset of 40 million tweets collected over three years, we identify a very small subset (1642; 0.004%) of individual reports describing personal experiences with HIV drug treatment. Results Despite the small size of the extracted final dataset, the summary representation of adverse effects attributed to specific drugs, or drug combinations, accurately captures well-recognized toxicities. In addition, the data allowed us to discriminate across specific drug compounds, to identify preferred drugs over time, and to capture novel events such as the availability of preexposure prophylaxis. Conclusions The effect of limited data sharing due to the public nature of the data can be partially offset by the large number of people sharing data in the first place, an observation that may play a key role in digital epidemiology in general. PMID:27227141

  7. Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects.

    PubMed

    Sadhasivam, S; Zhang, X; Chidambaran, V; Mavi, J; Pilipenko, V; Mersha, T B; Meller, J; Kaufman, K M; Martin, L J; McAuliffe, J

    2015-10-01

    Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year because of opioid-induced respiratory depression (RD) in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype-blinded observational study in which 259 healthy children between 6 and 15 years of age who received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, RD, postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (postoperative anesthesia care unit, PACU) due to RD and PONV were analyzed. Five specific FAAH single nucleotide polymorphisms (SNPs) had significant associations with more than twofold increased risk for refractory PONV (adjusted P<0.0018), and nominal associations (P<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. The FAAH SNP, rs324420, is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related RD, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy. PMID:25558980

  8. Sub-chronic exposure of non-observable adverse effect dose of terbufos sulfone: neuroinflammation in diabetic and non-diabetic rats.

    PubMed

    Nurulain, Syed M; Adeghate, Ernest; Sheikh, Azimullah; Yasin, Javed; Kamal, Mohammad A; Sharma, Charu; Adem, Abdu; Ojha, Shreesh

    2014-01-01

    Neuroinflammation (NI) contributes to the pathogenesis of several neurodegenerative disorders. Epidemiological and a few animal studies have shown that chronic exposure of organophosphorus compounds (OPC) may cause neuronal injury and predispose to neuro- as well as psychotic disorders in conjunction with NI. However, in vivo studies are meager and do not represent the entire toxicologically diversified OPC. The present study aimed to investigate the result of non-observable adverse effect level dose of a highly toxic OPC, terbufos sulfone (TBS), on sub-chronic exposure on the status of proinflammatory cytokines; interleukin-1β, interleukin-6 and tumor necrosis factor-α in rats brain. In addition, lactate dehydrogenase, nitric oxide and reduced glutathione were also determined in brain. Red blood cell acetylcholinesterase was measured weekly. Total of four groups' saline control, diabetes control, non-diabetes TBS and diabetes treated with TBS were employed in the study. Control groups received saline and the experimental groups were injected with TBS intraperitonealy for fifteen days daily. Twenty four hours after the last injection, the animals were euthanized for collection of brain and serum samples. The study showed significant elevation of interleukin-6, tumor necrosis factor-α and lactate dehydrogenase in brain of TBS treated groups, while the presence of interleukin-1β was significantly greater in the non-diabetes TBS treated group when compared with saline control. The increase was observed to be independent of acetylcholinesterase level and diabetes condition. The change in reduced glutathione was modest as compared with control. Based on the findings, the study concludes that the non-observable adverse effect level dose of TBS has potential to cause NI and subsequent neurodegeneration, a remarkable sign of many chronic neuronal and psychotic disorders. Further studies with prolonged exposure and other neurodegenerative parameters are warranted. PMID

  9. Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial

    PubMed Central

    Florkowski, Christopher M; Chambers, Stephen T; Priest, Patricia C; Stewart, Alistair W; Jennings, Lance C; Livesey, John H; Camargo, Carlos A; Scragg, Robert; Murdoch, David R

    2014-01-01

    Objective To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Design Opportunistic addition to an established randomised double blind placebo controlled trial. Setting Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. Participants 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Intervention Participants were randomised to receive an oral dose of either 200 000 IU vitamin D3 monthly for two months then 100 000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. Main outcome measure This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of “psychological” adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. Results 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ2 P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ2 P=0.03). The number of psychological adverse events—such as fatigue, stress, anxiety, and insomnia

  10. Herbal Medicines and Epilepsy: The Potential for Benefit and Adverse Effects.

    PubMed

    Spinella, Marcello

    2001-12-01

    The widespread availability and use of herbal medicines raise the potential for adverse effects in the epilepsy population. Herbal sedatives (kava, valerian, chamomile, passionflower) may potentiate the effects of antiepileptic medications, increasing their sedative and cognitive effects. Despite some antiseizure effects in animal models, they should not be used in place of standard seizure medications because efficacy has not been established. Anecdotal, uncontrolled observations suggest that herbal stimulants containing ephedrine (ephedra or ma huang) and caffeine (cocoa, coffee, tea, maté, guarana, cola or kola) can exacerbate seizures in people with epilepsy, especially when taken in combination. Ginkgo and ginseng may also exacerbate seizures although the evidence for this is similarly anecdotal and uncertain. St. John's wort has the potential to alter medication pharmacokinetics and the seizure threshold. The essential oils of many plants contain epileptogenic compounds. There is mixed evidence for evening primrose and borage lowering the seizure threshold. Education of both health care providers and patients is the best way to avoid unintentional and unnecessary adverse reactions to herbal medicines. PMID:12609386

  11. Putative Kappa Opioid Heteromers As Targets for Developing Analgesics Free of Adverse Effects

    PubMed Central

    2015-01-01

    It is now generally recognized that upon activation by an agonist, β-arrestin associates with G protein-coupled receptors and acts as a scaffold in creating a diverse signaling network that could lead to adverse effects. As an approach to reducing side effects associated with κ opioid agonists, a series of β-naltrexamides 3–10 was synthesized in an effort to selectively target putative κ opioid heteromers without recruiting β-arrestin upon activation. The most potent derivative 3 (INTA) strongly activated KOR-DOR and KOR-MOR heteromers in HEK293 cells. In vivo studies revealed 3 to produce potent antinociception, which, when taken together with antagonism data, was consistent with the activation of both heteromers. 3 was devoid of tolerance, dependence, and showed no aversive effect in the conditioned place preference assay. As immunofluorescence studies indicated no recruitment of β-arrestin2 to membranes in coexpressed KOR-DOR cells, this study suggests that targeting of specific putative heteromers has the potential to identify leads for analgesics devoid of adverse effects. PMID:24978316

  12. Study of Adverse Effect Profile of Parenteral Zoledronic Acid in Female Patients with Osteoporosis

    PubMed Central

    Kotian, Prem; Sreenivasan, Sushanth

    2016-01-01

    Introduction Osteoporosis is still a under recognized entity in the population. Osteoporosis-related fractures can be prevented if people at risk can be screened, diagnosed and treated early. Bisphosphonates remain the mainstay of osteoporosis treatment as they have multimodal action. Oral bisphosphonate therapy has, significant gastrointestinal side effects leading to noncompliance. Of late parenteral Zoledronic Acid is being used as once or twice yearly infusion for the treatment of osteoporosis. Aim Our article studies the side effect profile and tolerability of parenteral Zoledronic Acid, one of the most potent bisphosphonate used in clinical practice in patients with osteoporosis. Materials and Methods This study was done in KMC hospitals where 49 patients diagnosed with osteoporosis were included for the study. After obtaining a written informed consent each patient received one infusion of 5 mg Zoledronic Acid as per standard treatment protocol. Patient was monitored for clinical improvement and development of any adverse effects. Conclusion In our study all subjects reported significant pain relief after infusion of Zoledronic Acid. Zoledronic Acid had very few serious adverse effects that can be prevented through pre-infusion screening, maintaining good hydration and careful patient monitoring. In our population the patients only experienced mild symptoms of pyrexia, arthralgia myalgia and influenza like symptoms which resolved with symptomatic treatment. PMID:26894105

  13. Psychiatric adverse effects of zonisamide in patients with epilepsy and mental disorder comorbidities.

    PubMed

    Cavanna, Andrea E; Seri, Stefano

    2013-11-01

    Over the last few years, zonisamide has been proposed as a potentially useful medication for patients with focal seizures, with or without secondary generalization. Since psychiatric adverse effects, including mania, psychosis, and suicidal ideation, have been associated with its use, it was suggested that the presence of antecedent psychiatric disorders is an important factor associated with the discontinuation of zonisamide therapy in patients with epilepsy. We, therefore, set out to assess the tolerability profile of zonisamide in a retrospective chart review of 23 patients with epilepsy and comorbid mental disorders, recruited from two specialist pediatric (n=11) and adult (n=12) neuropsychiatry clinics. All patients had a clinical diagnosis of treatment-refractory epilepsy after extensive neurophysiological and neuroimaging investigations. The vast majority of patients (n=22/23, 95.7%) had tried previous antiepileptic medications, and most adult patients (n=9/11, 81.8%) were on concomitant medication for epilepsy. In the majority of cases, the psychiatric adverse effects of zonisamide were not severe. Four patients (17.4%) discontinued zonisamide because of lack of efficacy, whereas only one patient (4.3%) discontinued it because of the severity of psychiatric adverse effects (major depressive disorder). The low discontinuation rate of zonisamide in a selected population of patients with epilepsy and neuropsychiatric comorbidity suggests that this medication is safe and reasonably well-tolerated for use in patients with treatment-refractory epilepsy. Given the limitations of the present study, including the relatively small sample size, further research is warranted to confirm this finding. PMID:24070880

  14. Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practitioners and Adverse Effects

    PubMed Central

    Chen, Qi; Espey, Michael Graham; Drisko, Jeanne; Levine, Mark

    2010-01-01

    Background Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM) practitioners. The scale of such use in the U.S. and associated side effects are unknown. Methods and Findings We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA's Adverse Events Database. Of 199 survey respondents (out of 550), 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25g/50ml vials) were 318,539 in 2006 and 354,647 in 2008. Manufacturers' yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study. Conclusions High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit. PMID:20628650

  15. Epigenetics and transcriptomics to detect adverse drug effects in model systems of human development.

    PubMed

    Balmer, Nina V; Leist, Marcel

    2014-07-01

    Prenatal exposure to environmental chemicals or drugs has been associated with functional or structural deficits and the development of diseases in later life. For example, developmental neurotoxicity (DNT) is triggered by lead, and this compound may predispose to neurodegenerative diseases in later life. The molecular memory for such late consequences of early exposure is not known, but epigenetic mechanisms (modification of the chromatin structure) could take this role. Examples and underlying mechanisms have been compiled here for the field of DNT. Moreover, we addressed the question as to what readout is suitable for addressing drug memory effects. We summarize how complex developmental processes can be modelled in vitro by using the differentiation of human stem cells. Although cellular models can never replicate the final human DNT phenotype, they can model the adverse effect that a chemical has on key biological processes essential for organ formation and function. Highly information-rich transcriptomics data may inform on these changes and form the bridge from in vitro models to human prediction. We compiled data showing that transcriptome analysis can indicate toxicity patterns of drugs. A crucial question to be answered in our systems is when and how transcriptome changes indicate adversity (as opposed to transient adaptive responses), and how drug-induced changes are perpetuated over time even after washout of the drug. We present evidence for the hypothesis that changes in the histone methylation pattern could represent the persistence detector of an early insult that is transformed to an adverse effect at later time-points in life. PMID:24476462

  16. Comparison of Pooled Risk Estimates for Adverse Effects from Different Observational Study Designs: Methodological Overview

    PubMed Central

    Golder, Su; Loke, Yoon K.; Bland, Martin

    2013-01-01

    Background A diverse range of study designs (e.g. case-control or cohort) are used in the evaluation of adverse effects. We aimed to ascertain whether the risk estimates from meta-analyses of case-control studies differ from that of other study designs. Methods Searches were carried out in 10 databases in addition to reference checking, contacting experts, and handsearching key journals and conference proceedings. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from case-control studies could be directly compared with the pooled estimate for the same adverse effect arising from other types of observational studies. Results We included 82 meta-analyses. Pooled estimates of harm from the different study designs had 95% confidence intervals that overlapped in 78/82 instances (95%). Of the 23 cases of discrepant findings (significant harm identified in meta-analysis of one type of study design, but not with the other study design), 16 (70%) stemmed from significantly elevated pooled estimates from case-control studies. There was associated evidence of funnel plot asymmetry consistent with higher risk estimates from case-control studies. On average, cohort or cross-sectional studies yielded pooled odds ratios 0.94 (95% CI 0.88–1.00) times lower than that from case-control studies. Interpretation Empirical evidence from this overview indicates that meta-analysis of case-control studies tend to give slightly higher estimates of harm as compared to meta-analyses of other observational studies. However it is impossible to rule out potential confounding from differences in drug dose, duration and populations when comparing between study designs. PMID:23977151

  17. Adverse effects of free fatty acid associated with increased oxidative stress in postischemic isolated rat hearts.

    PubMed

    Gambert, Ségolène; Vergely, Catherine; Filomenko, Rodolphe; Moreau, Daniel; Bettaieb, Ali; Opie, Lionel H; Rochette, Luc

    2006-02-01

    The mechanisms of the adverse effects of free fatty acids on the ischemic-reperfused myocardium are not fully understood. Long-chain fatty acids, including palmitate, uncouple oxidative phosphorylation and should therefore promote the formation of oxygen-derived free radicals, with consequent adverse effects. Conversely, the antianginal agent trimetazidine (TMZ), known to inhibit cardiac fatty acid oxidation, could hypothetically lessen the formation of reactive oxygen species (ROS) and thus improve reperfusion mechanical function. Isolated perfused rat hearts underwent 30 min of total global ischemia followed by 30 min of reperfusion. Hearts were perfused with glucose 5.5 mmol/l or palmitate 1.5 mmol/l with or without TMZ (100 micromol/l). Ascorbyl free radical (AFR) release during perfusion periods was measured by electron spin resonance as a marker of oxidative stress. Post-ischemic recovery in the palmitate group of heart was lower than in the glucose group with a marked rise in diastolic tension and reduction in left ventricular developed pressure (Glucose: 85 +/- 11 mmHg; Palmitate: 10 +/- 6 mmHg; p < 0.001). TMZ decreased diastolic tension in both glucose- and in palmitate-perfused hearts. Release of AFR within the first minute of reperfusion was greater in palmitate-perfused hearts and in hearts perfused with either substrate, this marker of oxidative stress was decreased by TMZ (expressed in arbitrary units/ml; respectively: 8.49 +/- 1.24 vs. 1.06 +/- 0.70 p < 0.05; 12.47 +/- 2.49 vs. 3.37 +/- 1.29 p < 0.05). Palmitate increased the formation of ROS and reperfusion contracture. TMZ, a potential inhibitor of palmitate-induced mitochondrial uncoupling, decreased the formation of free radicals and improved postischemic mechanical dysfunction. The novel conclusion is that adverse effects of fatty acids on ischemic-reperfusion injury may be mediated, at least in part, by oxygen-derived free radicals. PMID:16444597

  18. A longitudinal study of the interactive effects of perinatal complications and early family adversity on cognitive ability.

    PubMed

    Stanton, W R; McGee, R O; Silva, P A

    1989-06-01

    The effects of high, medium and low levels of perinatal complications and family adversity on intelligence quotient (IQ) scores were examined in a large sample of Dunedin children tested every second year in the age group 3-13 years. The aim was to test the hypothesis that favourable environmental circumstances attenuate the effects of perinatal complications on later cognitive ability. The results did not support this hypothesis but rather suggested that perinatal complications and family adversity have independent adverse effects on the development of children's cognitive ability. PMID:2764834

  19. Adverse Effects in the Pharmacologic Management of Bipolar Disorder During Pregnancy.

    PubMed

    Hogan, Charlotte S; Freeman, Marlene P

    2016-09-01

    Management of bipolar disorder during pregnancy often involves medications with potential adverse effects, including risks to the mother and fetus. Although some specifics are known, many medications continue to have incompletely characterized reproductive safety profiles. Women with bipolar disorder who are planning pregnancy face challenging decisions about their treatment; careful risk-benefit discussions are necessary. With the goal of further informing these discussions, this article reviews the data currently available regarding medication safety in the management of bipolar disorder during pregnancy, with specific attention to lithium, valproic acid, lamotrigine, carbamazepine, and antipsychotic medications. PMID:27514299

  20. Toxicological effect of MPA-CdSe QDs exposure on zebrafish embryo and larvae.

    PubMed

    Zhang, Wei; Lin, Kuangfei; Sun, Xue; Dong, Qiaoxiang; Huang, Changjiang; Wang, Huili; Guo, Meijin; Cui, Xinhong

    2012-09-01

    Cadmium selenium (CdSe) quantum dots (QDs) are semiconductor nanocrystals that hold wide range of applications and substantial production volumes. Due to unique composition and nanoscale properties, their potential toxicity to aquatic organisms has increasingly gained a great amount of interest. However, the impact of CdSe QDs exposure on zebrafish embryo and larvae remains almost unknown. Therefore, the lab study was performed to determine the developmental and behavioral toxicities to zebrafish under continuous exposure to low level CdSe QDs (0.05-31.25 mg L(-1)) coated with mercaptopropionic acid (MPA). The results showed MPA-CdSe exposure from embryo to larvae stage affected overall fitness. Our findings for the first time revealed that: (1) The 120 h LC(50) of MPA-CdSe for zebrafish was 1.98 mg L(-1); (2) embryos exposed to MPA-CdSe resulted in malformations incidence and lower hatch rate; (3) abnormal vascular of FLI-1 transgenic zebrafish larvae appeared after exposure to MPA-CdSe including vascular junction, bifurcation, crossing and particle appearance; (4) larvae behavior assessment showed during MPA-CdSe exposure a rapid transition from light-to-dark elicited a similar, brief burst and a higher basal swimming rate; (5) MPA-CdSe induced embryos cell apoptosis in the head and tail region. Results of the observations provide a basic understanding of MPA-CdSe toxicity to aquatic organisms and suggest the need for additional research to identify the toxicological mechanism. PMID:22595531

  1. Toxicological effects and recovery of the corneal epithelium in Cyprinus carpio communis Linn. exposed to monocrotophos: an scanning electron microscope study.

    PubMed

    Uppal, Ravneet Kaur; Johal, Mohinder Singh; Sharma, Madan Lal

    2015-05-01

    This study was conducted based on the evidence of fish habitats in North India being affected by organophosphate pesticides draining from agricultural fields into bodies of water, especially during the rainy season. Various tissues of fish such as scales, gills ovaries, kidney, and liver have been studied from the toxicological point of view, but the toxicological effects of aquatic pollutants on fish cornea have not been investigated to date. We conducted comparative toxicological studies on the cornea of Cyprinus carpio communis using two sublethal (0.038 and 0.126 ppm) concentrations of monocrotophos pesticide for 30 days. Corneas from all the groups were evaluated by a scanning electron microscope. The fish exposed to the monocrotophos pesticide developed corneal necrosis due to the formation of crystalloid-like structures, thinning and shrinkage of microridges on the corneal epithelium. After 30 days, fish from the monocrotophos-treated tank were transferred to normal environmental conditions. After 60 days under natural condition, epithelial cells did not fully recover. In conclusion, exposure to monocrotophos induces irreversible changes in the cornea of C. carpio communis. As fish and mammalian visual systems share many similarities, the reported finding may offer useful insights for further toxicological and ophthalmological studies in humans. PMID:24373492

  2. Tolazoline reversal of xylazine in bison (Bison bison): Mitigation of adverse effects

    USGS Publications Warehouse

    Roffe, Thomas J.; Sweeney, Steven J.

    2002-01-01

    Tolazoline is a mixed alpha-1 and -2 adrenergic antagonist used to reverse the sedative, analgesic and muscle-relaxing effects of xylazine, a potent alpha adrenergic agonist. Tolazoline has been used in cattle and is superior to yohimbine, another alpha adrenergic antagonist, in this species. In white-tailed deer, tolazoline shortened recovery times and reversed xylazine-induced bradycardia, respiratory depression, and bloat following xylazine-ketamine anesthesia (Kreeger et al. 1986). We have used it for a number of years in moose without any detected adverse reactions. Caulkett et al. (2000) used tolazoline in wood bison to reverse the xylazine-induced effects of xylazine-tiletamine/zolazepam anesthesia and did not report any ill effects. However, the reported side effects of tolazoline in horses (species for which the drug was developed and is labeled) include abdominal discomfort, gastrointestinal hypermotility, diarrhea, tachycardia, ventricular dysrhythmia, hypertension and apprehensiveness.

  3. Adverse health effects of Asian dust particles and heavy metals in Japan.

    PubMed

    Onishi, Kazunari; Otani, Shinji; Yoshida, Atsushi; Mu, Haosheng; Kurozawa, Youichi

    2015-03-01

    Asian dust events are now considered an environmental problem rather than a natural seasonal phenomenon. In this study, we evaluated the associations between daily adverse health effects and Asian dust events in Yonago, Japan. Participants included 54 healthy volunteers, who were distributed survey sheets on nasal, ocular, respiratory, and skin effects in February 2009. Moreover, we collected meteorological and air pollutant (nitric oxide, sulfur dioxide, suspended particulate matter) data and determined pollen and metallic element concentrations in total suspended particulates. Both soil-derived metals (Fe, Ca, Al) and contaminating metals (Pb, Cr, Mn, Ni, Zn) were significantly increased on Asian dust days. Multiple regression analyses showed that the score of the skin effect was significantly associated with the levels of suspended particulate matter and Ni. The results show that increased air pollutants on Asian dust days may have skin effects. PMID:22865718

  4. Longitudinal in vivo tracking of adverse effects following topical steroid treatment.

    PubMed

    Bower, Andrew J; Arp, Zane; Zhao, Youbo; Li, Joanne; Chaney, Eric J; Marjanovic, Marina; Hughes-Earle, Angela; Boppart, Stephen A

    2016-05-01

    Topical steroids are known for their anti-inflammatory properties and are commonly prescribed to treat many adverse skin conditions such as eczema and psoriasis. While these treatments are known to be effective, adverse effects including skin atrophy are common. In this study, the progression of these effects is investigated in an in vivo mouse model using multimodal optical microscopy. Utilizing a system capable of performing two-photon excitation fluorescence microscopy (TPEF) of reduced nicotinamide adenine dinucleotide (NADH) to visualize the epidermal cell layers and second harmonic generation (SHG) microscopy to identify collagen in the dermis, these processes can be studied at the cellular level. Fluorescence lifetime imaging microscopy (FLIM) is also utilized to image intracellular NADH levels to obtain molecular information regarding metabolic activity following steroid treatment. In this study, fluticasone propionate (FP)-treated, mometasone furoate (MF)-treated and untreated animals were imaged longitudinally using a custom-built multimodal optical microscope. Prolonged steroid treatment over the course of 21 days is shown to result in a significant increase in mean fluorescence lifetime of NADH, suggesting a faster rate of maturation of epidermal keratinocytes. Alterations to collagen organization and the structural microenvironment are also observed. These results give insight into the structural and biochemical processes of skin atrophy associated with prolonged steroid treatment. PMID:26739196

  5. Adverse effects of topical corticosteroids in paediatric eczema: Australasian consensus statement.

    PubMed

    Mooney, Emma; Rademaker, Marius; Dailey, Rebecca; Daniel, Ben S; Drummond, Catherine; Fischer, Gayle; Foster, Rachael; Grills, Claire; Halbert, Anne; Hill, Sarah; King, Emma; Leins, Elizabeth; Morgan, Vanessa; Phillips, Roderic J; Relic, John; Rodrigues, Michelle; Scardamaglia, Laura; Smith, Saxon; Su, John; Wargon, Orli; Orchard, David

    2015-11-01

    Atopic eczema is a chronic inflammatory disease affecting about 30% of Australian and New Zealand children. Severe eczema costs over AUD 6000/year per child in direct medical, hospital and treatment costs as well as time off work for caregivers and untold distress for the family unit. In addition, it has a negative impact on a child's sleep, education, development and self-esteem. The treatment of atopic eczema is complex and multifaceted but a core component of therapy is to manage the inflammation with topical corticosteroids (TCS). Despite this, TCS are often underutilised by many parents due to corticosteroid phobia and unfounded concerns about their adverse effects. This has led to extended and unnecessary exacerbations of eczema for children. Contrary to popular perceptions, (TCS) use in paediatric eczema does not cause atrophy, hypopigmentation, hypertrichosis, osteoporosis, purpura or telangiectasia when used appropriately as per guidelines. In rare cases, prolonged and excessive use of potent TCS has contributed to striae, short-term hypothalamic-pituitary-adrenal axis alteration and ophthalmological disease. TCS use can also exacerbate periorificial rosacea. TCS are very effective treatments for eczema. When they are used to treat active eczema and stopped once the active inflammation has resolved, adverse effects are minimal. TCS should be the cornerstone treatment of atopic eczema in children. PMID:25752907

  6. Psychiatric symptoms in adolescents: FKBP5 genotype--early life adversity interaction effects.

    PubMed

    Comasco, Erika; Gustafsson, Per A; Sydsjö, Gunilla; Agnafors, Sara; Aho, Nikolas; Svedin, Carl Göran

    2015-12-01

    Psychiatric disorders are multi-factorial and their symptoms overlap. Constitutional and environmental factors influence each other, and this contributes to risk and resilience in mental ill-health. We investigated functional genetic variation of stress responsiveness, assessed as FKBP5 genotype, in relation to early life adversity and mental health in two samples of adolescents. One population-based sample of 909 12-year-old adolescents was assessed using the Life Incidence of Traumatic Events scale and the Strengths and Difficulties Questionnaire. One sample of 398 17-year-old adolescents, enriched for poly-victimized individuals (USSS), was assessed using the Juvenile Victimization Questionnaire and the Trauma Symptom Checklist for Children (TSCC). The FKBP5 rs1360780 and rs3800373 polymorphisms were genotyped using a fluorescence-based competitive allele-specific PCR. Most prominently among poly-victimized older male adolescents, the least common alleles of the polymorphisms, in interaction with adverse life events, were associated with psychiatric symptoms, after controlling for ethno-socio-economic factors. The interaction effect between rs3800373 and adverse life events on the TSCC sub-scales-anxiety, depression, anger, and dissociation-and with the rs1360780 on dissociation in the USSS cohort remained significant after Bonferroni correction. This pattern of association is in line with the findings of clinical and neuroimaging studies, and implies interactive effects of FKBP5 polymorphisms and early life environment on several psychiatric symptoms. These correlates add up to provide constructs that are relevant to several psychiatric symptoms, and to identify early predictors of mental ill-health. PMID:26424511

  7. Adverse Effects of Daylight Saving Time on Adolescents' Sleep and Vigilance

    PubMed Central

    Medina, Diana; Ebben, Matthew; Milrad, Sara; Atkinson, Brianna; Krieger, Ana C.

    2015-01-01

    Study Objectives: Daylight saving time (DST) has been established with the intent to reduce energy expenditure, however unintentional effects on sleep and vigilance have not been consistently measured. The objective of this study was to test the hypothesis that DST adversely affects high school students' sleep and vigilance on the school days following its implementation. Methods: A natural experiment design was used to assess baseline and post-DST differences in objective and subjective measures of sleep and vigilance by actigraphy, sleep diary, sleepiness scale, and psychomotor vigilance testing (PVT). Students were tested during school days immediately preceding and following DST. Results: A total of 40 high school students were enrolled in this study; 35 completed the protocol. Sleep duration declined by an average of 32 minutes on the weeknights post-DST, reflecting a cumulative sleep loss of 2 h 42 min as compared to the baseline week (p = 0.001). This finding was confirmed by sleep diary analyses, reflecting an average sleep loss of 27 min/night (p = 0.004) post-DST. Vigilance significantly deteriorated, with a decline in PVT performance post-DST, resulting in longer reaction times (p < 0.001) and increased lapses (p < 0.001). Increased daytime sleepiness was also demonstrated (p < 0.001). Conclusions: The early March DST onset adversely affected sleep and vigilance in high school students resulting in increased daytime sleepiness. Larger scale evaluations of sleep impairments related to DST are needed to further quantify this problem in the population. If confirmed, measures to attenuate sleep loss post-DST should be implemented. Citation: Medina D, Ebben M, Milrad S, Atkinson B, Krieger AC. Adverse effects of daylight saving time on adolescents' sleep and vigilance. J Clin Sleep Med 2015;11(8):879–884. PMID:25979095

  8. Adverse and beneficial effects of plant extracts on skin and skin disorders.

    PubMed

    Mantle, D; Gok, M A; Lennard, T W

    2001-06-01

    Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively. Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for primary health care. Approximately one-third of all traditional medicines are for treatment of wounds or skin disorders, compared to only 1-3% of modern drugs. The use of such medicinal plant extracts for the treatment of skin disorders arguably has been based largely on historical/anecdotal evidence, since there has been relatively little data available in the scientific literature, particularly with regard to the efficacy of plant extracts in controlled clinical trials. In this article therefore, adverse and beneficial aspects of medicinal plants relating to skin and skin disorders have been reviewed, based on recently available information from the peer-reviewed scientific literature. Beneficial aspects of medicinal plants on skin include: healing of wounds and burn injuries (especially Aloe vera); antifungal, antiviral, antibacterial and acaricidal activity against skin infections such as acne, herpes and scabies (especially tea tree (Melaleuca alternifolia) oil); activity against inflammatory/immune disorders affecting skin (e.g. psoriasis); and anti-tumour promoting activity against skin cancer (identified using chemically-induced two-stage carcinogenesis in mice). Adverse effects of plants on skin reviewed include: irritant contact dermatitis caused mechanically (spines, irritant hairs) or by irritant chemicals in plant sap (especially members of the Ranunculaceae, Euphorbiaceae and Compositae plant families); phytophotodermatitis resulting from skin contamination by plants containing furocoumarins, and subsequent exposure to UV light (notably members of the Umbelliferae and Rutaceae plant families); and immediate (type I) or delayed hypersensitivity contact reactions mediated by the immune system in individuals sensitized to plants

  9. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation

    PubMed Central

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen

    2016-01-01

    Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  10. Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis

    PubMed Central

    Ryti, Niilo R.I.; Guo, Yuming; Jaakkola, Jouni J.K.

    2015-01-01

    Background There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. Objective We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Data sources and extraction Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. “Cold spell” was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Data synthesis Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0–64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Conclusions Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Citation Ryti NR, Guo Y, Jaakkola JJ. 2016. Global

  11. Nanotechnology: Toxicologic Pathology

    PubMed Central

    Hubbs, Ann F.; Sargent, Linda M.; Porter, Dale W.; Sager, Tina M.; Chen, Bean T.; Frazer, David G.; Castranova, Vincent; Sriram, Krishnan; Nurkiewicz, Timothy R.; Reynolds, Steven H.; Battelli, Lori A.; Schwegler-Berry, Diane; McKinney, Walter; Fluharty, Kara L.; Mercer, Robert R.

    2015-01-01

    Nanotechnology involves technology, science, and engineering in dimensions less than 100 nm. A virtually infinite number of potential nanoscale products can be produced from many different molecules and their combinations. The exponentially increasing number of nanoscale products will solve critical needs in engineering, science, and medicine. However, the virtually infinite number of potential nanotechnology products is a challenge for toxicologic pathologists. Because of their size, nanoparticulates can have therapeutic and toxic effects distinct from micron-sized particulates of the same composition. In the nanoscale, distinct intercellular and intracellular translocation pathways may provide a different distribution than that obtained by micron-sized particulates. Nanoparticulates interact with subcellular structures including microtubules, actin filaments, centrosomes, and chromatin; interactions that may be facilitated in the nanoscale. Features that distinguish nanoparticulates from fine particulates include increased surface area per unit mass and quantum effects. In addition, some nanotechnology products, including the fullerenes, have a novel and reactive surface. Augmented microscopic procedures including enhanced dark-field imaging, immunofluorescence, field-emission scanning electron microscopy, transmission electron microscopy, and confocal microscopy are useful when evaluating nanoparticulate toxicologic pathology. Thus, the pathology assessment is facilitated by understanding the unique features at the nanoscale and the tools that can assist in evaluating nanotoxicology studies. PMID:23389777

  12. A review of the adverse side effects associated with antipsychotics as related to their efficacy.

    PubMed

    Pakpoor, Jina; Agius, Mark

    2014-11-01

    Since the introduction of antipsychotic medication for the treatment of psychosis, a wide range of different types of antipsychotic drugs have been developed while their side effects have become evident. The side effects of both the typical and atypical generation of antipsychotics have important consequences for the quality of life of recipients, stigma experienced and also the level of care of patients. It is well acknowledged that the side effects of antipsychotics reduce compliance with the medication. In this review the data for an association between typical and atypical antipsychotics and the main side effects that are well-supported in the literature was explored: weight gain and associated metabolic effects; extrapyramidal symptoms and tardive dyskinesia; prolactin elevation and associated sexual effects; QTc elongation; and a group of miscellaneous side effects. It has been demonstrated that the production of adverse effects following the use of antipsychotic medication differs widely both between atypical and typical drugs but also within these subgroups. Considering the wide range of antipsychotics available amongst both groups and the differing effects they have on patients in terms of side effects, there is reason to believe that a more personalised approach to antipsychotic treatment should be considered. Additionally, screening for risk factors, screening for the appearance of side effects, as well as good communication with patients about the side effects and other options available are important tasks for clinicians in order to optimise concordance with medication. PMID:25413553

  13. Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation

    PubMed Central

    Mills, Nicholas L.; Miller, Mark R.; Lucking, Andrew J.; Beveridge, Jon; Flint, Laura; Boere, A. John F.; Fokkens, Paul H.; Boon, Nicholas A.; Sandstrom, Thomas; Blomberg, Anders; Duffin, Rodger; Donaldson, Ken; Hadoke, Patrick W.F.; Cassee, Flemming R.; Newby, David E.

    2011-01-01

    Aim Exposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution. Methods and results To determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 ± 4 vs. 133 ± 3 mmHg, P< 0.05) and attenuated vasodilatation to bradykinin (P= 0.005), acetylcholine (P= 0.008), and sodium nitroprusside (P< 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n= 6–9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P< 0.001) and sodium-nitroprusside (P= 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate. Conclusion Combustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions. PMID:21753226

  14. Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

    PubMed Central

    2013-01-01

    Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised

  15. Potential Adverse Effects of Amphetamine Treatment on Brain and Behavior: A Review

    PubMed Central

    Berman, Steven M.; Kuczenski, Ronald; McCracken, James T.; London, Edythe D.

    2009-01-01

    Rationale Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority 1. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Findings Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several-fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central

  16. Efficacy and adverse effects of medical marijuana for chronic noncancer pain

    PubMed Central

    Deshpande, Amol; Mailis-Gagnon, Angela; Zoheiry, Nivan; Lakha, Shehnaz Fatima

    2015-01-01

    Abstract Objective To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. Data sources In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. Study selection An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. Conclusion There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical

  17. [Antibodies, human leukocyte antigens, and biomodulators in transfusion-related acute adverse effects].

    PubMed

    Martínez Álvarez, Julio César

    2013-01-01

    With the onset of the AIDS epidemic, major changes occurred in blood banking and transfusion medicine. These changes occurred mainly in donor selection and screening tests for infectious diseases, blood centers modified their organizational philosophy regarding quality. Transfusion of blood products are procedures that allow us to correct the haematology deficiencies for which was indicated. But today, despite the strict controls that precede transfusion,recipients may have undesirable effects, which are known as adverse effects or adverse reactions to transfusion. Antibodies and antigens of the HLA system plays a role in a series of events related to transfusion, such as immunological platelet refractoriness, febrile non-haemolytic transfusion reactions, transfusion related acute lung injury (TRALI) and transfusion-associated graft-versus-host disease. The determination of anti-HLA antibodies is evidence that in most developed countries is used on a daily basis in the regular assessment of patients multitransfused or waiting lists for organs from deceased donors. The biomodulators are able to modify biological responses which act in sequence to lead to the differentiation of T lymphocytes. These agents may subcategorizes those which facilitate a normal immune response, those stimulates the immune response, those are capable of inducing immunosuppression not cytotoxic, and those enhancing the ability of the host to tolerate damage by cytotoxic treatment (transfusion or transplant). PMID:23435079

  18. Noise monitoring and adverse health effects in residents in different functional areas of Luzhou, China.

    PubMed

    Han, Zhi-Xia; Lei, Zhang-Heng; Zhang, Chun-Lian; Xiong, Wei; Gan, Zhong-Lin; Hu, Ping; Zhang, Qing-Bi

    2015-03-01

    The purpose of the study was to investigate the noise pollution situation and the resulting adverse effect on residents' health in Luzhou, China, to provide data for noise pollution prevention policies and interventions. Four different functional areas (commercial, construction, residential, and transportation hub areas) were chosen to monitor noise level for 3 months. The survey was performed by questionnaire on the spot on randomly selected individuals; it collected data on the impact of noise on residents' health (quality of sleep, high blood pressure, subjective feeling of nervous system damage, and attention) as well as the knowledge of noise-induced health damage, the degree of adaptation to noise, and their solutions. The noise levels of residential, commercial, transportation, and construction areas exceeded the national standards (P < .001). Sleep quality, prevalence of hypertension, and attention in transportation hub areas were significantly different from those in the other 3 areas (P < .05); only 24.46% of people knew the health hazards associated with noise; 64.57% of residents have adapted to the current noise environment. Most of them have to close the doors and windows to reduce noise. The noise pollution situation in Luzhou, China, is serious, especially the traffic noise pollution. Residents pay less attention to it and adopt single measures to reduce the noise. We should work toward the prevention and control of traffic noise and improve the residents' awareness to reduce the adverse health effects of noise. PMID:25504115

  19. Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane.

    PubMed

    Macdonald, James B; Macdonald, Brooke; Golitz, Loren E; LoRusso, Patricia; Sekulic, Aleksandar

    2015-02-01

    There has been a rapid emergence of numerous targeted agents in the oncology community in the last decade. This exciting paradigm shift in drug development lends promise for the future of individualized medicine. Given the pace of development and clinical deployment of targeted agents with novel mechanisms of action, dermatology providers may not be familiar with the full spectrum of associated skin-related toxicities. Cutaneous adverse effects are among the most frequently observed toxicities with many targeted agents, and their intensity can be dose-limiting or lead to therapy discontinuation. In light of the often life-saving nature of emerging oncotherapeutics, it is critical that dermatologists both understand the mechanisms and recognize clinical signs and symptoms of such toxicities in order to provide effective clinical management. Part I of this continuing medical education article will review in detail the potential skin-related adverse sequelae, the frequency of occurrence, and the implications associated with on- and off-target cutaneous toxicities of inhibitors acting at the cell membrane level, chiefly inhibitors of epidermal growth factor receptor, KIT, and BCR-ABL, angiogenesis, and multikinase inhibitors. PMID:25592338

  20. HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

    PubMed

    Nicol, Alcina F; de Andrade, Cecilia V; Russomano, Fabio B; Rodrigues, Luana S L; Oliveira, Nathalia S; Provance, David William; Nuovo, Gerard J

    2015-12-01

    The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings. PMID:26321154

  1. Imipenem and meropenem: Comparison of in vitro activity, pharmacokinetics, clinical trials and adverse effects

    PubMed Central

    Zhanel, George G; Simor, Andrew E; Vercaigne, Lavern; Mandell, Lionell

    1998-01-01

    OBJECTIVE: To compare and contrast imipenem and meropenem in terms of in vitro activity, pharmacokinetics, clinical efficacy and adverse effects. DATA SELECTION: MEDLINE search from 1975 to 1997 and follow-up of references. DATA EXTRACTION: Clinical trials comparing imipenem with meropenem, or either imipenem or meropenem with standard therapy in the treatment of serious infections were selected. DATA SYNTHESIS: Imipenem, the first carbapenem, was first marketed in 1987; meropenem was introduced to the market in 1996. In general, imipenem is more active against Gram-positive cocci while meropenem is more active against Gram-negative bacilli. The agents display similar pharmacokinetics. Clinical studies in patients with serious infections (intra-abdominal infection, respiratory infection, septicemia, febrile neutropenia) report similar bacteriological and clinical cure rates with imipenem and meropenem. Meropenem is approved for the treatment of bacterial meningitis, whereas imipenem is not. Adverse effects are similar. CONCLUSIONS: Current literature supports the use of imipenem at a dose of 500 mg every 6 h and meropenem at 1 g every 8 h for the treatment of severe infections. For the treatment of serious infections, imipenem (500 mg every 6 h or 2 g/day [$98/day]) is more economical than meropenem (1 g every 8 h or 3 g/day [$142/day]) based on acquisition cost. PMID:22346545

  2. Registered Nurses' Knowledge about Adverse Effects of Analgesics when Treating Postoperative Pain in Patients with Dementia.

    PubMed

    Rantala, Maija; Hartikainen, Sirpa; Kvist, Tarja; Kankkunen, Päivi

    2015-08-01

    Registered nurses (RNs) play a pivotal role in treating pain and preventing and recognizing the adverse effects (AEs) of analgesics in patients with dementia. The purpose of this study was to determine RNs' knowledge of potentially clinically relevant AEs of analgesics. A descriptive, cross-sectional study design was used. In all, 267 RNs treating orthopedic patients, including patients with dementia, in 7 university hospitals and 10 central hospitals in Finland, completed a questionnaire. Analgesics were defined according to the Anatomic Therapeutic Classification as strong opioids, weak opioids, nonsteroidal anti-inflammatory analgesics (NSAIDs), and paracetamol. Definitions of AEs were based on the literature. Logistic regression analysis was applied to analyze which variables predicted nurses' knowledge. The RNs had a clear understanding of the AEs of paracetamol and strong opioids. However, the AEs of NSAIDs, especially renal and cardiovascular AEs, were less well known. The median percentage of correct answers was 87% when asked about strong opioids, 73% for weak opioids, and 60% for NSAIDs. Younger RNs had better knowledge of opioid-related AEs (odds ratio [OR] per 1-year increase, 0.97; 95% confidence interval [CI], 0.94-1.00) and weak opioids (OR, 0.96; 95% CI, 0.93-0.99). This study provides evidence of a deficiency in RNs' knowledge, especially regarding the adverse renal and cardiovascular effects of NSAIDs. Such lack of knowledge indicates that hospitals may need to update the knowledge of older RNs, especially those who treat vulnerable patients with dementia. PMID:26047589

  3. Could cancer and infection be adverse effects of mesenchymal stromal cell therapy?

    PubMed Central

    Arango-Rodriguez, Martha L; Ezquer, Fernando; Ezquer, Marcelo; Conget, Paulette

    2015-01-01

    Multipotent mesenchymal stromal cells [also referred to as mesenchymal stem cells (MSCs)] are a heterogeneous subset of stromal cells. They can be isolated from bone marrow and many other types of tissue. MSCs are currently being tested for therapeutic purposes (i.e., improving hematopoietic stem cell engraftment, managing inflammatory diseases and regenerating damaged organs). Their tropism for tumors and inflamed sites and their context-dependent potential for producing trophic and immunomodulatory factors raises the question as to whether MSCs promote cancer and/or infection. This article reviews the effect of MSCs on tumor establishment, growth and metastasis and also susceptibility to infection and its progression. Data published to date shows a paradoxical effect regarding MSCs, which seems to depend on isolation and expansion, cells source and dose and the route and timing of administration. Cancer and infection may thus be adverse or therapeutic effects arising form MSC administration. PMID:25815124

  4. Gratitude buffers the adverse effect of viewing the thin ideal on body dissatisfaction.

    PubMed

    Homan, Kristin J; Sedlak, Brittany L; Boyd, Elizabeth A

    2014-06-01

    Gratitude has robust associations with multiple aspects of well-being. However, little research has explored whether the psychological benefits of gratitude extend to body image. We used a repeated measures experimental design to test whether a brief period of grateful reflection would buffer the adverse effect of exposure to thin-ideal media. Female undergraduates (N=67) completed three sessions one week apart. The conditions were specifically designed to isolate (a) the effects of viewing thin models on body dissatisfaction and (b) the moderating effect of grateful contemplation. Results showed that body dissatisfaction scores were lower for women who engaged in a brief period of grateful contemplation before viewing photographs of thin models than for women who reflected upon life hassles before viewing the same photographs. The magnitude of this decrease depended on BMI. Gratitude offers an innovative direction for future research directed toward helping women to accept their bodies. PMID:24958659

  5. DETERMINING THE CAUSES OF ADVERSE EFFECTS IN NEAR COASTAL ECOSYSTEMS: FROM TOXICITY IDENTIFICATION EVALUATIONS TO WATERSHED DIAGNOTICS

    EPA Science Inventory

    Several approaches are available for evaluating adverse effects in near coastal ecosystems. These range from performing toxicity tests with individual organisms on water column and sediment samples to conducting macrofaunal compositional analyses on pelagic and benthic communiti...

  6. DOSE-RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY I. CHARACTERIZATION OF DATABASE AND DETERMINATION OF NO OBSERVED ADVERSE EFFECT LEVELS

    EPA Science Inventory

    Developmental toxicity risk assessment currently relies on the estimation of reference doses or reference concentrations based on no observed adverse effect levels (NOAELS) and uncertainty factors. he benchmark dose (BMD) has been proposed as an alternative basis for reference va...

  7. Eco-toxicological effects of two kinds of lead compounds on forest tree seed in alkaline soil.

    PubMed

    Yang, Nan; Zhou, Fu-Rong; Wang, Jin-Xin

    2016-03-01

    In order to compare the different eco-toxicological effects of lead nitrate and lead acetate on forest tree seed, a biological incubation experiment was conducted to testify the inhibition effects of two lead compounds on rates of seed germination, root and stem elongation, and seedling fresh weight for six plants (Amaorpha fruticosa L., Robinia psedoacacia L., Pinus tabuliformis Carr., Platycladus orientalis L., Koelreuteria paniculata Laxm., Hippophae rhamnoides L.) in soil. The results indicate that the inhibition effects of the two lead compounds on the rates of root elongation of plants were greater than other indices; root elongation can possibly be used as indices to investigate the relationship between lead toxicity and plant response. The response of trees to lead toxicity varied significantly, and the order of tolerance to lead pollution was as follows: Amaorpha fruticosa L. > Platycladus orientalis L. > Koelreuteria paniculata Laxm. > Robinia psedoacacia L. > Pinus tabuliformis Carr. > Hippophae rhamnoides L. Therefore, we suggest that Amaorpha fruticosa L. and Platycladus orientalis L. be used as tolerant plants for soil phytoremediation and Hippophae rhamnoides L. as an indicative plant to diagnose the toxicity of lead pollution on soil quality. Lead nitrate and lead acetate differentially restrain seeds, with seeds being more sensitive to lead nitrate than lead acetate in the soil. Thus, the characteristics of lead compounds should be taken into full consideration to appraise its impact on the environment. PMID:26927657

  8. Proteomic and metabolomic analysis on the toxicological effects of Benzo[a]pyrene in pearl oyster Pinctada martensii.

    PubMed

    Chen, Hao; Song, Qinqin; Diao, Xiaoping; Zhou, Hailong

    2016-06-01

    Benzo[a]pyrene (BaP) is one of the typical toxic polycyclic aromatic hydrocarbons (PAHs) that are widely present in marine environment. BaP has diverse toxic effects, including teratogenic, carcinogenic, mutagenic effects and so on, in various organisms. In this work, we focused on the differential proteomic and metabolomic responses in the digestive gland of pearl oyster Pinctada martensii exposed to two doses of BaP (1 and 10μg/L). Metabolic responses revealed that the high dose of BaP (10μg/L) mainly caused disturbances in osmotic regulation and energy metabolism in the digestive gland. Proteomic responses indicated that both doses of BaP induced disturbances in energy metabolism, cytoskeleton, cell injury, oxidative stress and signal transduction based on the differential proteomic biomarkers. Overall, these results demonstrated a number of potential biomarkers that were characterized by an integrated proteomic and metabolomic approach and provided a useful insight into the toxicological effects on pearl oyster P. martensii. PMID:26999675

  9. Economic Adversity and Children’s Sleep Problems: Multiple Indicators and Moderation of Effects

    PubMed Central

    El-Sheikh, Mona; Bagley, Erika J.; Keiley, Margaret; Elmore-Staton, Lori; Chen, Edith; Buckhalt, Joseph A.

    2014-01-01

    Objective Toward explicating relations between economic adversity and children’s sleep, we examined associations between multiple indicators of socioeconomic status (SES)/adversity and children’s objectively and subjectively derived sleep parameters; ethnicity was examined as potential moderator. Methods Participants were 276 third- and fourth-grade children and their families (133 girls; M age = 9.44 years; SD = .71): 66% European American (EA) and 34% African American (AA). Four SES indicators were used: income-to-needs ratio, perceived economic well-being, maternal education, and community poverty. Children wore actigraphs for 7 nights and completed a self-report measure to assess sleep problems. Results Objectively and subjectively assessed sleep parameters were related to different SES indicators, and overall worse sleep was evident for children from lower SES homes. Specifically, children from homes with lower income-to-needs ratios had higher levels of reported sleep/wake problems. Parental perceived economic well-being was associated with shorter sleep minutes and greater variability in sleep onset for children. Lower mother’s education was associated with lower sleep efficiency. Children who attended Title 1 schools had shorter sleep minutes. Ethnicity was a significant moderator of effects in the link between some SES indicators and children’s sleep. AA children’s sleep was more negatively affected by income-to-needs ratio and mother’s education than was the sleep of EA children. Conclusions The results advocate for the importance of specifying particular SES and sleep variables used because they may affect the ability to detect associations between sleep and economic adversity. PMID:23148451

  10. Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.

    PubMed

    Mathiesen, O; Wetterslev, J; Kontinen, V K; Pommergaard, H-C; Nikolajsen, L; Rosenberg, J; Hansen, M S; Hamunen, K; Kjer, J J; Dahl, J B

    2014-11-01

    Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation. PMID:25116762

  11. Characterization of the adverse effects of nicotine on placental development: in vivo and in vitro studies

    PubMed Central

    Holloway, A. C.; Salomon, A.; Soares, M. J.; Garnier, V.; Raha, S.; Sergent, F.; Nicholson, C. J.; Feige, J. J.; Benharouga, M.

    2013-01-01

    In utero exposure to nicotine is associated with increased risk of numerous adverse fetal and neonatal outcomes, which suggests that it acts directly to affect placental development and the establishment of the fetomaternal circulation (FC). This study used both in vivo [Wistar rats treated with 1 mg/kg nicotine from 2 wk prior to mating until gestational day (GD) 15] and in vitro (RCHO-1 cell line; treated with 10−9 to 10−3M nicotine) models to examine the effects of nicotine on these pathways. At GD 15, control and treated placentas were examined for the impact of nicotine on 1) trophoblast invasion, proliferation, and degree of hypoxia, 2) labyrinth vascularization, 3) expression of key genes of placental development, and 4) expression of placental angiogenic factors. The RCHO-1 cell line was used to determine the direct effects of nicotine on trophoblast differentiation. Our in vivo experiments show that nicotine inhibits trophoblast interstitial invasion, increases placental hypoxia, downregulates labyrinth vascularization as well as key transcription factors Hand1 and GCM1, and decreases local and circulating EG-VEGF, a key placental angiogenic factor. The in vitro experiments confirmed the inhibitory effects of nicotine on the trophoblast migration, invasion, and differentiation processes and demonstrated that those effects are most likely due to a dysregulation in the expression of nicotine receptors and a decrease in MMP9 activity. Taken together, these data suggest that adverse effects of maternal smoking on pregnancy outcome are due in part to direct and endocrine effects of nicotine on the main processes of placental development and establishment of FC. PMID:24368670

  12. Conditional pharmacology/toxicology V: ambivalent effects of thiocyanate upon the development and the inhibition of experimental arthritis in rats by aurothiomalate (Myocrysin®) and metallic silver.

    PubMed

    Whitehouse, Michael; Butters, Desley; Vernon-Roberts, Barrie

    2013-08-01

    This article discusses the bizarre and contrary effects of thiocyanate, the major detoxication product of hydrogen cyanide inhaled from tobacco smoke or liberated from cyanogenic foods, e.g. cassava. Thiocyanate both (1) promotes inflammatory disease in rats and (2) facilitates the anti-inflammatory action of historic metal therapies based on gold (Au) or silver (Ag) in three models of chronic polyarthritis in rats. Low doses of nanoparticulate metallic silver (NMS) preparations, i.e. zerovalent silver (Ag°) administered orally, suppressed the mycobacterial ('adjuvant')-induced arthritis (MIA) in rats. Similar doses of cationic silver, Ag(I), administered orally as silver oxide or soluble silver salts were inactive. By contrast, NMS only inhibited the development of the collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rats when thiocyanate was also co-administered in drinking water. These (a) arthritis-selective and (b) thiocyanate-inducible effects of Ag° were also observed in some previous, and now extended, studies with the classic anti-arthritic drug, sodium aurothiomalate (ATM, Myocrisin(®)) and its silver analogue (STM), administered subcutaneously to rats developing the same three forms of polyarthritis. In the absence of either Ag° or ATM, thiocyanate considerably increased the severity of the MIA, CIA and PIA, i.e. acting as a pro-pathogen. Hitherto, thiocyanate was considered relatively harmless. This may not be true in rats/people with immuno-inflammatory stress and concomitant leukocyte activation. Collectively, these findings show how the drug action of a xenobiotic might be determined by the nature (and severity) of the experimental inflammation, as an example of conditional pharmacology. They also suggest that an incipient toxicity, even of normobiotics such as thiocyanate, might likewise be modulated beneficially by well-chosen xenobiotics (drugs, nutritional supplements, etc.), i.e. conditional toxicology (Powanda 1995

  13. Pathophysiological Progression Model for Selected Toxicological Endpoints

    EPA Science Inventory

    The existing continuum paradigms are effective models to organize toxicological data associated with endpoints used in human health assessments. A compendium of endpoints characterized along a pathophysiological continuum would serve to: weigh the relative importance of effects o...

  14. EFFECTS OF SELECTED ORGANIC DRINKING WATER CONTAMINANTS ON MALE REPRODUCTION

    EPA Science Inventory

    Because of the recent increase in exposure of individuals to potentially harmful chemicals, it has become increasingly important to test the potential of environmental chemicals to cause adverse reproductive effects. The Division of Toxicology within the Department of Pharmacolog...

  15. Kinetics of Betamethasone and Fetal Cardiovascular Adverse Effects in Pregnant Sheep After Different Doses

    PubMed Central

    Schwab, Matthias; Coksaygan, Turhan; Samtani, Mahesh N.; Jusko, William J.; Nathanielsz, Peter W.

    2014-01-01

    OBJECTIVE To study the pharmacokinetics of different betamethasone doses and preparations used to enhance fetal lung maturation in the maternal and fetal circulation of sheep and the adverse effects on fetal blood pressure. METHODS Doses of 170 (n = 6) and 110 µg/kg (n = 6) betamethasone phosphate equivalent to 12 or 8mg, respectively, administered to a 70kg pregnant woman or 170 µg/kg (n = 6) of a depot formulation (50% betamethasone phosphate and 50% betamethasone acetate) were injected intramuscularly to chronically instrumented pregnant sheep. RESULTS Both betamethasone preparations produced highest maternal concentrations after 15 min followed by an exponential decline with a t1/2 of about 3 hours. The drug fell below the limit of detection at 8 to 12 hours. Betamethasone was first detectable in the fetal circulation at 1 hour, peaked at 3 hours, and decreased below the limit of detection at 8 hours independently of the dose or preparation. Maternal and fetal betamethasone concentrations achieved with the phosphate and acetate formulation were one half of those obtained with betamethasone phosphate, suggesting that very little betamethasone is released from the acetate within the first 8 hours when the effect on lung maturation is needed. Betamethasone led to a maximal increase of mean fetal blood pressure from 42 ± 1 to 51 ± 1 mm Hg (P<.05) and did not differ between the doses and preparations, although plasma concentrations showed a clear dose–concentration relationship. CONCLUSION The doses of betamethasone used in obstetrics are supramaximal in terms of cardiovascular effects in sheep. Risk-benefit studies are needed to find the effective steroid dose with the least adverse effects. PMID:16946223

  16. Toxicological evaluation of the effects of waste-to-energy ash-concrete on two marine species

    SciTech Connect

    Hamilton, K.L.; Nelson, W.G.; Curley, J.L. )

    1993-10-01

    The toxicological effects of waste-to-energy ash-concrete on survivorship, growth, and fecundity (end-point parameters) of Mysidopsis bahia and on survivorship and growth of Menidia beryllina were evaluated with the 7-d static-renewal toxicity test. Leachate and elutriate solutions were prepared from experimental ash-concrete test cylinders constructed from concrete with additions of either bottom ash (mix BA), mixed bottom ash and scrubber residue, or mixed bottom ash and fly ash (60:40%, mix BA:FA). Control experiments with concrete (without ash) and pH (7-9.5) were conducted to assess any toxic effects of the stabilization process. pH did not affect end-point parameters of Mysidopsis bahia or Menidia beryllina. However, the 100% elutriate solution made from concrete reduced survivorship of Mysidopsis bahia. For experiments with ash-concrete test cylinders with the BA mixture, 10-d leachate solution reduced survivorship of Mysidopsis bahia and the 100% elutriate solutions reduced survivorship of Mysidopsis bahia and Manidia beryllina. With the BA:SR mixture, the 100 and 50% elutriate solutions reduced survivorship of Menidia beryllina. The BA:FA 10- and 5-d leachate solutions and the 100, 50, and 25% elutriate solutions reduced survivorship of Menidia beryllina. The BA:FA 10- and 5-d leachate solutions and the 100, 50, 25% elutriate solutions reduced survivorship of Mysidopsis bahia.

  17. Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro Combined Toxicological Effects

    PubMed Central

    Smith, Marie-Caroline; Madec, Stéphanie; Coton, Emmanuel; Hymery, Nolwenn

    2016-01-01

    Some foods and feeds are often contaminated by numerous mycotoxins, but most studies have focused on the occurrence and toxicology of a single mycotoxin. Regulations throughout the world do not consider the combined effects of mycotoxins. However, several surveys have reported the natural co-occurrence of mycotoxins from all over the world. Most of the published data has concerned the major mycotoxins aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEA), fumonisins (FUM) and trichothecenes (TCTs), especially deoxynivalenol (DON). Concerning cereals and derived cereal product samples, among the 127 mycotoxin combinations described in the literature, AFs+FUM, DON+ZEA, AFs+OTA, and FUM+ZEA are the most observed. However, only a few studies specified the number of co-occurring mycotoxins with the percentage of the co-contaminated samples, as well as the main combinations found. Studies of mycotoxin combination toxicity showed antagonist, additive or synergic effects depending on the tested species, cell model or mixture, and were not necessarily time- or dose-dependent. This review summarizes the findings on mycotoxins and their co-occurrence in various foods and feeds from all over the world as well as in vitro experimental data on their combined toxicity. PMID:27023609

  18. Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro Combined Toxicological Effects.

    PubMed

    Smith, Marie-Caroline; Madec, Stéphanie; Coton, Emmanuel; Hymery, Nolwenn

    2016-04-01

    Some foods and feeds are often contaminated by numerous mycotoxins, but most studies have focused on the occurrence and toxicology of a single mycotoxin. Regulations throughout the world do not consider the combined effects of mycotoxins. However, several surveys have reported the natural co-occurrence of mycotoxins from all over the world. Most of the published data has concerned the major mycotoxins aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEA), fumonisins (FUM) and trichothecenes (TCTs), especially deoxynivalenol (DON). Concerning cereals and derived cereal product samples, among the 127 mycotoxin combinations described in the literature, AFs+FUM, DON+ZEA, AFs+OTA, and FUM+ZEA are the most observed. However, only a few studies specified the number of co-occurring mycotoxins with the percentage of the co-contaminated samples, as well as the main combinations found. Studies of mycotoxin combination toxicity showed antagonist, additive or synergic effects depending on the tested species, cell model or mixture, and were not necessarily time- or dose-dependent. This review summarizes the findings on mycotoxins and their co-occurrence in various foods and feeds from all over the world as well as in vitro experimental data on their combined toxicity. PMID:27023609

  19. Proteomic and metabolomic analysis on the toxicological effects of As (III) and As (V) in juvenile mussel Mytilus galloprovincialis.

    PubMed

    Yu, Deliang; Ji, Chenglong; Zhao, Jianmin; Wu, Huifeng

    2016-05-01

    Inorganic arsenic (As) is a known pollutant including two chemical forms (arsenite (As III) and arsenate (As V)), in marine and coastal environment. Marine mussel Mytilus galloprovincialis is an important environmental monitoring species around the world. In this study, we focused on valence-specific responses of As in juvenile mussel M. galloprovincialis using a combined proteomic and metabolomic approach. Metabolic responses indicated that As (III) mainly caused disturbance in osmotic regulation in juvenile mussels. As (V) caused disturbances in both osmotic regulation and energy metabolism marked by different metabolic responses, including betaine, taurine, glucose and glycogen. Proteomic responses exhibited that As (III) had a significant negative effect on cytoskeleton and cell structure (actin and collagen alpha-6(VI) chain). As (V) affected some key enzymes involved in energy metabolism (cytosolic malate dehydrogenase, cMDH) and cell development (ornithine aminotransferase and astacin). Overall, all these results confirmed the valence-specific responses in juvenile mussels to As exposures. These findings demonstrate that a combined metabolomic and proteomic approach could provide an important insight into the toxicological effects of environmental pollutants in organisms. PMID:26901476

  20. Te Inclusions in CZT Detectors: New Method for Correcting Their Adverse Effects

    SciTech Connect

    Bolotnikov, A.E.; Babalola, S.; Camarda, G.S.; Cui, Y.; Egarievwe, S.U.; Hawrami, R.; Hossain, A.; Yang, G.; James, R.B.

    2009-10-25

    Both Te inclusions and point defects can trap the charge carriers generated by ionizing particles in CdZnTe (CZT) detectors. The amount of charge trapped by point defects is proportional to the carriers’ drift time and can be corrected electronically. In the case of Te inclusions, the charge loss depends upon their random locations with respect to the electron cloud. Consequently, inclusions introduce fluctuations in the charge signals, which cannot be easily corrected. In this paper, we describe direct measurements of the cumulative effect of Te inclusions and its influence on the response of CZT detectors of different thicknesses and different sizes and concentrations of Te inclusions. We also discuss a means of partially correcting their adverse effects.

  1. Whole body vibration may have immediate adverse effects on the postural sway of stroke patients

    PubMed Central

    Hwang, Ki Jin; Ryu, Young Uk

    2016-01-01

    [Purpose] This study applied whole body vibration (WBV) at different vibration frequencies to chronic stroke patients and examined its immediate effect on their postural sway. [Subjects and Methods] A total of 14 (5 males, 9 females) stroke patients participated. The subjects were randomly assigned to one of the two vibration frequency groups (10 Hz and 40 Hz). Right before and after the application of WBV, the subjects performed quiet standing for 30 seconds, and COP parameters (range, total distance, and mean velocity) were analyzed. [Results] The 10 Hz WBV did not affect the postural sway of stroke patients. The 40 Hz WBV increased postural sway in the ML direction. [Conclusion] The results suggest that WBV application to stroke patients in the clinical field may have adverse effects and therefore caution is necessary. PMID:27064678

  2. Whole body vibration may have immediate adverse effects on the postural sway of stroke patients.

    PubMed

    Hwang, Ki Jin; Ryu, Young Uk

    2016-01-01

    [Purpose] This study applied whole body vibration (WBV) at different vibration frequencies to chronic stroke patients and examined its immediate effect on their postural sway. [Subjects and Methods] A total of 14 (5 males, 9 females) stroke patients participated. The subjects were randomly assigned to one of the two vibration frequency groups (10 Hz and 40 Hz). Right before and after the application of WBV, the subjects performed quiet standing for 30 seconds, and COP parameters (range, total distance, and mean velocity) were analyzed. [Results] The 10 Hz WBV did not affect the postural sway of stroke patients. The 40 Hz WBV increased postural sway in the ML direction. [Conclusion] The results suggest that WBV application to stroke patients in the clinical field may have adverse effects and therefore caution is necessary. PMID:27064678

  3. Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms

    PubMed Central

    Liu, Yonggang; Goodson, Jamie M.; Zhang, Bo; Chin, Michael T.

    2015-01-01

    Exposure to air pollution has long been known to trigger cardiovascular events, primarily through activation of local and systemic inflammatory pathways that affect the vasculature. Detrimental effects of air pollution exposure on heart failure and cardiac remodeling have also been described in human populations. Recent studies in both human subjects and animal models have provided insights into the basic physiological, cellular and molecular mechanisms that play a role in adverse cardiac remodeling. This review will give a brief overview of the relationship between air pollution and cardiovascular disease, describe the clinical effects of air pollution exposure on cardiac remodeling, describe the basic mechanisms that affect remodeling as described in human and animal systems and will discuss future areas of investigation. PMID:26042051

  4. An adverse effect of an injectable cosmetic procedure: a case of mistaken identities.

    PubMed

    Ahn, Christine S; Mateus, Rosa; Khan, Irfan; Rao, Babar K

    2013-12-01

    Minimally invasive cosmetic procedures are being performed at increasing rates. This is likely due to the combination of a growing aging population, an increased accessibility through non-physician providers, and a common association of "minimally invasive" with the concept of fewer side effects. Despite their overall successes, there are adverse effects associated with these procedures, which are most often related to injection location, amount, and technique. This case describes a patient who sought botulinum toxin injections to smooth the appearance of periorbital lines who presented 12 months later with chronic multiple palpable nodules in the injection sites. Histopathological evaluation demonstrated a foreign body reaction resembling the reaction against semi-permanent or permanent fillers such as poly-L-lactic acid or polymethylmethacralate. Knowledge of the biochemical properties and life cycles of dermal fillers guided the decision to surgically excise the nodules, with cosmetically satisfactory results. PMID:24301251

  5. Oculocutaneous albinism in sub-Saharan Africa: adverse sun-associated health effects and photoprotection.

    PubMed

    Wright, Caradee Y; Norval, Mary; Hertle, Richard W

    2015-01-01

    Oculocutaneous albinism (OCA) is a genetically inherited autosomal recessive condition. Individuals with OCA lack melanin and therefore are susceptible to the harmful effects of solar ultraviolet radiation, including extreme sun sensitivity, photophobia and skin cancer. OCA is a grave public health issue in sub-Saharan Africa with a prevalence as high as 1 in 1000 in some tribes. This article considers the characteristics and prevalence of OCA in sub-Saharan African countries. Sun-induced adverse health effects in the skin and eyes of OCA individuals are reviewed. Sun exposure behavior and the use of photoprotection for the skin and eyes are discussed to highlight the major challenges experienced by these at-risk individuals and how these might be best resolved. PMID:25298350

  6. Ketotifen treatment of adverse reactions to foods: clinical and immunological effects.

    PubMed

    Ciprandi, G; Scordamaglia, A; Ruffoni, S; Pizzorno, G; Canonica, G W

    1986-01-01

    Fifteen patients with cutaneous signs and symptoms caused by adverse reactions to foods were treated in an open trial with ketotifen for 4 to 6 weeks. Seven subjects were allergic and 8 had food intolerance. Each patient was treated with a single dose of ketotifen daily: 2 mg half an hour before going to sleep. Clinical improvement was achieved in 6 out of 7 allergic patients and in 6 out of 8 patients with food intolerance. Since several drugs have been demonstrated to have an influence on immune response, the in vitro effects of ketotifen on some immunological parameters were also studied. Ketotifen showed a significant inhibitory effect on autologous mixed lymphocyte reaction responsiveness. PMID:2949941

  7. Aerospace toxicology overview: aerial application and cabin air quality.

    PubMed

    Chaturvedi, Arvind K

    2011-01-01

    Aerospace toxicology is a rather recent development and is closely related to aerospace medicine. Aerospace toxicology can be defined as a field of study designed to address the adverse effects of medications, chemicals, and contaminants on humans who fly within or outside the atmosphere in aviation or on space flights. The environment extending above and beyond the surface of the Earth is referred to as aerospace. The term aviation is frequently used interchangeably with aerospace. The focus of the literature review performed to prepare this paper was on aerospace toxicology-related subject matters, aerial application and aircraft cabin air quality. Among the important topics addressed are the following: · Aerial applications of agricultural chemicals, pesticidal toxicity, and exposures to aerially applied mixtures of chemicals and their associated formulating solvents/surfactants The safety of aerially encountered chemicals and the bioanalytical methods used to monitor exposures to some of them · The presence of fumes and smoke, as well as other contaminants that may generally be present in aircraft/space vehicle cabin air · And importantly, the toxic effects of aerially encountered contaminants, with emphasis on the degradation products of oils, fluids, and lubricants used in aircraft, and finally · Analytical methods used for monitoring human exposure to CO and HCN are addressed in the review, as are the signs and symptoms associated with exposures to these combustion gases. Although many agricultural chemical monitoring studies have been published, few have dealt with the occurrence of such chemicals in aircraft cabin air. However, agricultural chemicals do appear in cabin air; indeed, attempts have been made to establish maximum allowable concentrations for several of the more potentially toxic ones that are found in aircraft cabin air. In this article, I emphasize the need for precautionary measures to be taken to minimize exposures to aerially

  8. The enduring effects of abuse and related adverse experiences in childhood

    PubMed Central

    Anda, Robert F.; Felitti, Vincent J.; Bremner, J. Douglas; Walker, John D.; Whitfield, Charles; Perry, Bruce D.; Dube, Shanta R.; Giles, Wayne H.

    2011-01-01

    Background Childhood maltreatment has been linked to a variety of changes in brain structure and function and stress-responsive neurobiological systems. Epidemiological studies have documented the impact of childhood maltreatment on health and emotional well-being. Methods After a brief review of the neurobiology of childhood trauma, we use the Adverse Childhood Experiences (ACE) Study as an epidemiological “case example” of the convergence between epidemiologic and neurobiological evidence of the effects of childhood trauma. The ACE Study included 17,337 adult HMO members and assessed 8 adverse childhood experiences (ACEs) including abuse, witnessing domestic violence, and serious household dysfunction. We used the number of ACEs (ACE score) as a measure of cumulative childhood stress and hypothesized a “dose-response” relationship of the ACE score to 18 selected outcomes and to the total number of these outcomes (comorbidity). Results Based upon logistic regression analysis, the risk of every outcome in the affective, somatic, substance abuse, memory, sexual, and aggression-related domains increased in a graded fashion as the ACE score increased (P < 0.001). The mean number of comorbid outcomes tripled across the range of the ACE score. Conclusions The graded relationship of the ACE score to 18 different outcomes in multiple domains theoretically parallels the cumulative exposure of the developing brain to the stress response with resulting impairment in multiple brain structures and functions. PMID:16311898

  9. Cutaneous adverse effects of targeted therapies: Part II: Inhibitors of intracellular molecular signaling pathways.

    PubMed

    Macdonald, James B; Macdonald, Brooke; Golitz, Loren E; LoRusso, Patricia; Sekulic, Aleksandar

    2015-02-01

    The last decade has spawned an exciting new era of oncotherapy in dermatology, including the development of targeted therapies for metastatic melanoma and basal cell carcinoma. Along with skin cancer, deregulation of the PI3K-AKT-mTOR and RAS-RAF-MEK-ERK intracellular signaling pathways contributes to tumorigenesis of a multitude of other cancers, and inhibitors of these pathways are being actively studied. Similar to other classes of targeted therapies, cutaneous adverse effects are among the most frequent toxicities observed with mitogen-activated protein kinase pathway inhibitors, PI3K-AKT-mTOR inhibitors, hedgehog signaling pathway inhibitors, and immunotherapies. Given the rapid expansion of these families of targeted treatments, dermatologists will be essential in offering dermatologic supportive care measures to cancer patients being treated with these agents. Part II of this continuing medical education article reviews skin-related adverse sequelae, including the frequency of occurrence and the implications associated with on- and off-target cutaneous toxicities of inhibitors of the RAS-RAF-MEK-ERK pathway, PI3K-AKT-mTOR pathway, hedgehog signaling pathway, and immunotherapies. PMID:25592339

  10. Evaluation of a procedure to assess the adverse effects of illicit drugs.

    PubMed

    van Amsterdam, J G C; Best, W; Opperhuizen, A; de Wolff, F A

    2004-02-01

    The assessment procedure of new synthetic illicit drugs that are not documented in the UN treaty on psychotropic drugs was evaluated using a modified Electre model. Drugs were evaluated by an expert panel via the open Delphi approach, where the written score was discussed on 16 items, covering medical, health, legal, and criminalistic issues of the drugs. After this face-to-face discussion the drugs were scored again. Taking the assessment of ketamine as an example, it appeared that each expert used its own scale to score, and that policymakers do not score deviant from experts trained in the medical-biological field. Of the five drugs evaluated by the panel, p-methoxy-metamphetamine (PMMA), gamma-hydroxybutyric acid (GHB), and 4-methylthio-amphetamine (MTA) were assessed as more adverse than ketamine and psilocine and psilocybine-containing mushrooms. Whereas some experts slightly adjusted during the assessment procedure their opinion on ketamine and PMMA, the opinion on mushrooms was not affected by the discussion held between the two scoring rounds. All experts rank the five drugs in a similar way on the adverse effect scale i.e., concordance scale of the Electre model, indicating unanimity in the expert panel with respect to the risk classification of these abused drugs. PMID:14746774

  11. Duration of Internet use and adverse psychosocial effects among European adolescents.

    PubMed

    Secades-Villa, Roberto; Calafat, Amador; Fernández-Hermida, José Ramón; Juan, Montse; Duch, Mariangels; Skärstrand, Eva; Becoña, Elisardo; Talic, Sanela

    2014-01-01

    Despite the significant contributions from previous studies about the prevalence of problematic Internet use (PIU) among adolescents in Europe, important questions remain regarding adverse consequences of PIU. This study aims to assess the relation between duration of Internet use and adverse psychosocial effects among adolescents from six European countries. The final sample included 7,351 adolescents (50.8% male and 49.2% female; mean age: 14.6±1.90) recruited from randomly selected schools within the six study sites. Results showed that 12.9% of adolescents used Internet more than 20 hours per week. There was a significant relationship between duration of Internet use and frequency of alcohol, tobacco, cannabis and other illegal drug use. Duration of Internet use is also significantly associated with school problems, with use of slot machines and with other psychosocial problems. These findings highlight the need to strengthen preventive efforts for reducing PIU and related consequences among adolescents. Key Words: Internet, adolescents, psychosocial problems. PMID:25314040

  12. Review for carrageenan-based pharmaceutical biomaterials: favourable physical features versus adverse biological effects.

    PubMed

    Liu, Jingjing; Zhan, Xiudan; Wan, Jianbo; Wang, Yitao; Wang, Chunming

    2015-05-01

    Carrageenan (CRG) is a family of natural polysaccharides derived from seaweeds and has widely been used as food additives. In the past decade, owing to its attractive physicochemical properties, CRG has been developed into versatile biomaterials vehicles for drug delivery. Nevertheless, studies also emerged to reveal its adverse effects on the biological system. In this review, we critically appraise the latest literature (two thirds since 2008) on the development of CRG-based pharmaceutical vehicles and the perspective of using CRG for broader biomedical applications. We focus on how current strategies exploit the unique gelling mechanisms, strong water absorption and abundant functional groups of the three major CRG varieties. Notably, CRG-based matrices are demonstrated to increase drug loading and drug solubility, enabling release of orally administrated drugs in zero-order or in a significantly prolonged period. Other amazing features, such as pH-sensitivity and adhesive property, of CRG-based formulations are also introduced. Finally, we discuss the adverse influence of CRG on the human body and then suggest some future directions for the development of CRG-based biomaterials for broader applications in biomedicine. PMID:25659668

  13. Mediators and Adverse Effects of Child Poverty in the United States.

    PubMed

    Pascoe, John M; Wood, David L; Duffee, James H; Kuo, Alice

    2016-04-01

    The link between poverty and children's health is well recognized. Even temporary poverty may have an adverse effect on children's health, and data consistently support the observation that poverty in childhood continues to have a negative effect on health into adulthood. In addition to childhood morbidity being related to child poverty, epidemiologic studies have documented a mortality gradient for children aged 1 to 15 years (and adults), with poor children experiencing a higher mortality rate than children from higher-income families. The global great recession is only now very slowly abating for millions of America's children and their families. At this difficult time in the history of our nation's families and immediately after the 50th anniversary year of President Lyndon Johnson's War on Poverty, it is particularly germane for the American Academy of Pediatrics, which is "dedicated to the health of all children," to publish a research-supported technical report that examines the mediators associated with the long-recognized adverse effects of child poverty on children and their families. This technical report draws on research from a number of disciplines, including physiology, sociology, psychology, economics, and epidemiology, to describe the present state of knowledge regarding poverty's negative impact on children's health and development. Children inherit not only their parents' genes but also the family ecology and its social milieu. Thus, parenting skills, housing, neighborhood, schools, and other factors (eg, medical care) all have complex relations to each other and influence how each child's genetic canvas is expressed. Accompanying this technical report is a policy statement that describes specific actions that pediatricians and other child advocates can take to attenuate the negative effects of the mediators identified in this technical report and improve the well-being of our nation's children and their families. PMID:26962239

  14. Microbiology & Toxicology: Space Environment

    NASA Video Gallery

    One key aspect in maintaining crew health and performance during spaceflight missions is the provision of a habitable environment with acceptably low concentrations of microbiological and toxicolog...

  15. An in-flight simulation of approach and landing of a STOL transport with adverse ground effect

    NASA Technical Reports Server (NTRS)

    Ellis, D. R.

    1976-01-01

    The results of an in-flight simulation program undertaken to study the problems of landing a representative STOL transport in the presence of adverse ground effects are presented. Landings were performed with variations in ground effect magnitude, ground effect lag, and thrust response. Other variations covered the effects of augmented lift response, SAS-failures, turbulence, segmented approach, and flare warning. The basic STOL airplane required coordinated use of both stick and throttle for consistently acceptable landings, and the presence of adverse ground effects made the task significantly more difficult. Ground effect lag and good engine response gave noticeable improvement, as did augmented lift response.

  16. Ground experiments for finding principles and working out methods for preventing adverse effects of weightlessness on the human organism

    NASA Technical Reports Server (NTRS)

    Kakurin, L. I.; Gregoryev, A. I.; Mikhailov, V. M.; Tishler, V. A.

    1980-01-01

    A comparative assessment of the effectiveness of different prophylactic procedures to prevent the adverse effects of weightlessness is presented. It is concluded that: physical training is most effective but no single method by itself produces the full effect, and an adjustment of regimes to one another enhances the effect. The approved complex of prophylactic procedures affected basic changes occurring in hypokinesia: deficit of muscular activity, no or reduced BP hydrostatic component, reduced volume of blood circulation, reduced hydration level, and the application of various prophylactic complexes during 49 day antiorthostatic hypodynamia eliminated or reduced the adverse effects of weightlessness in simulation.

  17. Useful biomarkers for assessing the adverse health effects of PCBs in allergic children: pediatric molecular epidemiology.

    PubMed

    Tsuji, Mayumi

    2015-01-01

    The incidences of childhood allergies have been increasing in recent years in many parts of the world. The development of allergic disorders is attributed to a complex series of interactions between individuals' genetic backgrounds and their immune and psychoneurotic responses to environmental factors. Among the various possible environmental causes of childhood allergies, the early exposure of developing infants to air pollutants and the presence of persistent chemical pollutants such as pesticides have been suggested most frequently. Therefore, it is very important to obtain epidemiological evidence of direct associations between clearly defined adverse health effects and exposure to low levels of pollutants. However, there are no useful biomarkers for assessing such associations. Thus, we planned to establish reliable health-related biomarkers that could be used to investigate these relationships in children. The serum concentrations of several sub-types of polychlorinated biphenyl (PCB) congeners were found to be significantly correlated with interleukin (IL)-8 mRNA expression among asthmatic children. In addition, IL-22 mRNA expression was found to be particularly useful for detecting the effects of environmental pollutants, especially PCB congeners, in a sub-population of vulnerable children who exhibited positive immunoglobulin E (IgE) responses to milk or egg. Furthermore, we detected significant differences in IL-22 mRNA expression between the IgE-negative non-asthmatic subjects and the asthmatic children who exhibited positive IgE reactions toward egg or milk. In conclusion, IL-8 and IL-22 mRNA expressions could be useful biomarkers for detecting sub-populations of children who are particularly vulnerable to the adverse health effects of environmental pollutants, especially PCBs. PMID:25344634

  18. Surgical Correction of Scoliosis in Children with Spastic Quadriplegia: Benefits, Adverse Effects, and Patient Selection

    PubMed Central

    Legg, Julian; Davies, Evan; Raich, Annie L.; Dettori, Joseph R.; Sherry, Ned

    2014-01-01

    Study Rationale Cerebral palsy (CP) is a group of nonprogressive syndromes of posture and motor impairment associated with lesions of the immature brain. Spastic quadriplegia is the most severe form with a high incidence of scoliosis, back pain, respiratory compromise, pelvic obliquity, and poor sitting balance. Surgical stabilization of the spine is an effective technique for correcting deformity and restoring sitting posture. The decision to operate in this group of patients is challenging. Objectives The aim of this study is to determine the benefits of surgical correction of scoliosis in children with spastic quadriplegia, the adverse effects of this treatment, and what preoperative factors affect patient outcome after surgical correction. Materials and Methods A systematic review was undertaken to identify studies describing benefits and adverse effects of surgery in spastic quadriplegia. Factors affecting patient outcome following surgical correction of scoliosis were assessed. Studies involving adults and nonspastic quadriplegia were excluded. Results A total of 10 case series and 1 prospective and 3 retrospective cohort studies met inclusion criteria. There was significant variation in the overall risk of complications (range, 10.9−70.9%), mortality (range, 2.8−19%), respiratory/pulmonary complications (range, 26.9−57.1%), and infection (range, 2.5−56.8%). Factors associated with a worse outcome were a significant degree of thoracic kyphosis, days in the intensive care unit, and poor nutritional status. Conclusion Caregivers report a high degree of satisfaction with scoliosis surgery for children with spastic quadriplegia. There is limited evidence of preoperative factors that can predict patient outcome after scoliosis. There is a need for well-designed prospective studies of scoliosis surgery in spastic quadriplegia. PMID:24715871

  19. NATIONAL TOXICOLOGY PROGRAM (NTP) DATA

    EPA Science Inventory

    The National Toxicology Program (NTP) was established in 1978 by the Department of Health and Human Services (DHHS) to coordinate toxicological testing programs within the department, strengthen the science base in toxicology; develop and validate improved testing methods; and pr...

  20. Do shrubs reduce the adverse effects of grazing on soil properties?

    USGS Publications Warehouse

    Eldridge, David J.; Beecham, Genevieve; Grace, James B.

    2015-01-01

    Increases in the density of woody plants are a global phenomenon in drylands, and large aggregations of shrubs, in particular, are regarded as being indicative of dysfunctional ecosystems. There is increasing evidence that overgrazing by livestock reduces ecosystem functions in shrublands, but that shrubs may buffer the negative effects of increasing grazing. We examined changes in water infiltration and nutrient concentrations in soils under shrubs and in their interspaces in shrublands in eastern Australia that varied in the intensity of livestock grazing. We used structural equation modelling to test whether shrubs might reduce the negative effects of overgrazing on infiltration and soil carbon and nitrogen (henceforth ‘soil nutrients’). Soils under shrubs and subject to low levels of grazing were more stable and had greater levels of soil nutrients. Shrubs had a direct positive effect on soil nutrients; but, grazing negatively affected nutrients by increasing soil bulk density. Structural equation modelling showed that shrubs had a direct positive effect on water flow under ponded conditions but also enhanced water flow, indirectly, through increased litter cover. Any positive effects of shrubs on water flow under low levels of grazing waned at high levels of grazing. Our results indicate that shrubs may reduce the adverse effects of grazing on soil properties. Specifically, shrubs could restrict access to livestock and therefore protect soils and plants beneath their canopies. Low levels of grazing are likely to ensure the retention of soil water and soil carbon and nitrogen in shrubland soils.

  1. Adverse outcome pathway (AOP) development: Guiding principles and best practices

    EPA Science Inventory

    Adverse outcome pathways (AOPs) represent a conceptual framework that can support greater application of mechanistic data in regulatory decision-making. However, in order for the scientific community to collectively address the daunting challenge of describing relevant toxicologi...

  2. Adverse outcome pathway (AOP) development II: Best practices

    EPA Science Inventory

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including high throughput in vitro, high content omics and imaging, and biomarkers, in risk-based decision-making....

  3. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal

    PubMed Central

    2016-01-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012–2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  4. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal.

    PubMed

    Cooper, Ziva D

    2016-05-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012-2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  5. Propolis: a review of properties, applications, chemical composition, contact allergy, and other adverse effects.

    PubMed

    de Groot, Anton C

    2013-01-01

    Propolis (bee glue) is the resinous substance that bees collect from living plants for the construction and adaptation of their nests. It has antibacterial, antifungal, and antiviral properties and may have a wide range of other beneficial biological activities. Propolis is available as a dietary supplement, in products for the protection of health and prevention of diseases, in biopharmaceuticals, and as a constituent of (bio)cosmetics. In this article, the following aspects of propolis are reviewed: the nature and chemical composition, its biological properties and applications, contact allergy and allergic contact dermatitis (sensitizing potential, products causing contact allergy, clinical picture, frequency of sensitization, coreactivity and cross-reactivity, the allergens in propolis), and other adverse effects. PMID:24201459

  6. Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

    PubMed Central

    Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E.

    2015-01-01

    Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

  7. Diagnostic criteria for adverse health effects in the environs of wind turbines.

    PubMed

    McMurtry, Robert Y; Krogh, Carmen Me

    2014-10-01

    In an effort to address climate change, governments have pursued policies that seek to reduce greenhouse gases. Alternative energy, including wind power, has been proposed by some as the preferred approach. Few would debate the need to reduce air pollution, but the means of achieving this reduction is important not only for efficiency but also for health protection. The topic of adverse health effects in the environs of industrial wind turbines (AHE/IWT) has proven to be controversial and can present physicians with challenges regarding the management of an exposure to IWT. Rural physicians in particular must be aware of the possibility of people presenting to their practices with a variety of sometimes confusing complaints. An earlier version of the diagnostic criteria for AHE/IWT was published in August 2011. A revised case definition and a model for a study to establish a confirmed diagnosis is proposed. PMID:25383200

  8. Evidence for the adverse effect of starvation on bone quality: a review of the literature.

    PubMed

    Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

    2015-01-01

    Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

  9. Diagnostic criteria for adverse health effects in the environs of wind turbines

    PubMed Central

    Krogh, Carmen ME

    2014-01-01

    Summary In an effort to address climate change, governments have pursued policies that seek to reduce greenhouse gases. Alternative energy, including wind power, has been proposed by some as the preferred approach. Few would debate the need to reduce air pollution, but the means of achieving this reduction is important not only for efficiency but also for health protection. The topic of adverse health effects in the environs of industrial wind turbines (AHE/IWT) has proven to be controversial and can present physicians with challenges regarding the management of an exposure to IWT. Rural physicians in particular must be aware of the possibility of people presenting to their practices with a variety of sometimes confusing complaints. An earlier version of the diagnostic criteria for AHE/IWT was published in August 2011. A revised case definition and a model for a study to establish a confirmed diagnosis is proposed. PMID:25383200

  10. Glucagon like peptide-1 receptor agonists may ameliorate the metabolic adverse effect associated with antiretroviral therapy.

    PubMed

    Culha, Mehmet Gokhan; Inkaya, Ahmet Cagkan; Yildirim, Emre; Unal, Serhat; Serefoglu, Ege Can

    2016-09-01

    The number of people living with HIV and AIDS (PLWHA) reached to almost 40 million, half of which are under antiretroviral treatment (ART). Although the introduction of this therapy significantly improved the life span and quality of PLWHA, metabolic complications of these people remains to be an important issue. These metabolic complications include hyperlipidemia, abnormal fat redistribution and diabetes mellitus, which are defined as lipodystrophy syndrome. Glucagon-like peptide-1 (GLP-1) is a neuropeptide secreted from intestinal L cells and recently developed GLP-1 receptor agonists (GLP-1RAs) stimulate insulin secretion, improve weight control and reduce cardiovascular outcomes. This class of drugs may be a valuable medication in the treatment of HIV-associated metabolic adverse effects and extend the life expectancy of patients infected with HIV. PMID:27515222

  11. Metabolically normal obese people are protected from adverse effects following weight gain

    PubMed Central

    Fabbrini, Elisa; Yoshino, Jun; Yoshino, Mihoko; Magkos, Faidon; Tiemann Luecking, Courtney; Samovski, Dmitri; Fraterrigo, Gemma; Okunade, Adewole L.; Patterson, Bruce W.; Klein, Samuel

    2015-01-01

    BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as “metabolically normal obese” (MNO), but not those defined as “metabolically abnormal obese” (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain–induced metabolic dysfunction. TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170. FUNDING. This work was supported by NIH grants UL1 RR024992 (Clinical Translational Science Award), DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Center Grant), and UL1 TR000450 (KL2 Award); a Central Society for Clinical and Translational Research Early Career Development Award; and by grants from the Longer Life Foundation and the Kilo Foundation. PMID

  12. Metabolic and renal adverse effects of antiretroviral therapy in HIV-infected children and adolescents.

    PubMed

    Fortuny, Clàudia; Deyà-Martínez, Ángela; Chiappini, Elena; Galli, Luisa; de Martino, Maurizio; Noguera-Julian, Antoni

    2015-05-01

    Worldwide, the benefits of combined antiretroviral (ARV) therapy in morbidity and mortality due to perinatally acquired human immunodeficiency virus infection are beyond question and outweigh the toxicity these drugs have been associated with in HIV-infected children and adolescents to date. In puberty, abnormal body fat distribution is stigmatizating and leads to low adherence to ARV treatment. The other metabolic comorbidities (mitochondrial toxicity, dyslipidemias, insulin resistance and low bone mineral density) and renal toxicity, albeit nonsymptomatic in most children, are increasingly being reported and potentially put this population at risk for early cardiovascular or cerebrovascular atherosclerotic disease, diabetes, pathologic fractures or premature renal failure in the third and fourth decades of life. Evidence from available studies is limited because of methodological limitations and also because of several HIV-unrelated factors influencing, to some degree, the development of these conditions. Current recommendations for the prevention, diagnosis, monitoring and treatment of metabolic and renal adverse effects in HIV-children and adolescents are based on adult studies, observational pediatric studies and experts' consensus. Healthy lifestyle habits (regarding diet, exercise and refraining from toxic substances) and wise use of ARV options are the only preventive tools for the majority of patients. Should abnormal findings arise, switches in one or more ARV drugs have proved useful. Specific therapies are also available for some of these comorbidities, although the experience in the pediatric age is still very scarce. We aim to summarize the epidemiological, clinical and therapeutic aspects of metabolic and renal adverse effects in vertically HIV-infected children and adolescents. PMID:25629891

  13. Home informatics in healthcare: assessment guidelines to keep up quality of care and avoid adverse effects.

    PubMed

    Roback, Kerstin; Herzog, Almut

    2003-01-01

    Due to an ageing population and improved treatment possibilities, a shortage in hospital beds is a fact in many countries. Home healthcare schemes using information technology (IT) are under development as a response to this and with the intention to produce a more cost-effective care. So far it has been shown that home healthcare is beneficial to certain patient groups. The trend is a widening of the criteria for admission to home healthcare, which means treatment in the home of more severe conditions that otherwise would require in-hospital care. Home informatics has the potential to become a means of providing good care at home. In this process, it is important to consider what new risks will be encountered when placing electronic equipment in the home care environment. Continuous assessment and guidance is important in order to achieve a safe and effective care. Based on a review of current knowledge this paper presents an inventory of risks and adverse events specific to this area. It was found that risks and adverse events could stem from technology in itself, from human-technology interaction conditions or from the environment in which the technology is placed. As a result from the risk inventory, this paper proposes guidelines for the planning and assessment of IT-based hospital-at-home schemes. These assessment guidelines are specifically aimed at performance improvement and thus to be considered a complement to the more general guidelines on telehomecare adopted by the American Telemedicine Association (ATA) in October 2002. PMID:12775936

  14. Adverse effects of pesticides residues on biochemical markers in pakistani tobacco farmers.

    PubMed

    Khan, Dilshad A; Bhatti, Mahwish M; Khan, Farooq A; Naqvi, Syed T; Karam, A

    2008-01-01

    Tobacco is an important cash crop of Pakistan and tremendous amount of irrational pesticides are being used to control insect growth. The frequency of plasma pesticide residues above acceptable daily intake (ADI) and its correlation with biochemical markers for assessment of adverse health effects in the tobacco farmers at district Sawabi, Pakistan was determined. Total 109 adult males consisting of 55 tobacco farmers exposed to pesticides and 54 controls were included. Pesticides residues in blood were analyzed on HPLC and GC-NPD. Plasma butyrylcholinesterase (BChE) was analyzed by Ellman's method. Biochemical markers including serum calcium, phosphorus, urea, creatinine, bilirubin and liver enzymes were measured on Selectra-E auto analyzer. The tobacco farmers had multiple pesticides residues above ADI in their blood consisting of 35 (63%) methomyl; 31 (56%) thiodicarb; 34(62%) cypermethrin; 27 (49%) Imidacloprid; 18 (32%) Methamidophos and 15 (27%) endosulfan. BChE activity was significantly decreased in the pesticides exposed farmers as compared to controls (P<0.001). Plasma biochemical markers including ALT, AST, CK, LDH and phosphate were significantly raised in the pesticides exposed farmers as compared to control group (P<0.001). Total pesticides residues revealed a significant positive correlation with AST (r=0.42), LDH(r= 0.47), ALT (r=0.20) and phosphorus (r=0.51). Excessive exposure to pesticide caused cytotoxic changes in the hepatic and renal biochemical markers which were positively correlated with pesticide residue. Hence these biomarkers might be used in addition to BChE activity for monitoring of adverse effects of pesticides on the health of farm workers. PMID:19079663

  15. Adverse Effects of Pesticides Residues on Biochemical Markers in Pakistani Tobacco Farmers

    PubMed Central

    Khan, Dilshad A; Bhatti, Mahwish M; Khan, Farooq A; Naqvi, Syed T; Karam, A

    2008-01-01

    Tobacco is an important cash crop of Pakistan and tremendous amount of irrational pesticides are being used to control insect growth. The frequency of plasma pesticide residues above acceptable daily intake (ADI) and its correlation with biochemical markers for assessment of adverse health effects in the tobacco farmers at district Sawabi, Pakistan was determined. Total 109 adult males consisting of 55 tobacco farmers exposed to pesticides and 54 controls were included. Pesticides residues in blood were analyzed on HPLC and GC-NPD. Plasma butyrylcholinesterase (BChE) was analyzed by Ellman's method. Biochemical markers including serum calcium, phosphorus, urea, creatinine, bilirubin and liver enzymes were measured on Selectra-E auto analyzer. The tobacco farmers had multiple pesticides residues above ADI in their blood consisting of 35 (63%) methomyl; 31 (56%) thiodicarb; 34(62%) cypermethrin; 27 (49%) Imidacloprid; 18 (32%) Methamidophos and 15 (27%) endosulfan. BChE activity was significantly decreased in the pesticides exposed farmers as compared to controls (P<0.001). Plasma biochemical markers including ALT, AST, CK, LDH and phosphate were significantly raised in the pesticides exposed farmers as compared to control group (P<0.001). Total pesticides residues revealed a significant positive correlation with AST (r=0.42), LDH(r= 0.47), ALT (r=0.20) and phosphorus (r=0.51). Excessive exposure to pesticide caused cytotoxic changes in the hepatic and renal biochemical markers which were positively correlated with pesticide residue. Hence these biomarkers might be used in addition to BChE activity for monitoring of adverse effects of pesticides on the health of farm workers. PMID:19079663

  16. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles.

    PubMed

    Krentz, A J; Fujioka, K; Hompesch, M

    2016-06-01

    Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs. PMID:26936802

  17. Adverse effects of testosterone replacement therapy: an update on the evidence and controversy

    PubMed Central

    Grech, Anthony; Breck, John

    2014-01-01

    Testosterone replacement therapy (TRT) has been used in millions of men worldwide to treat diminished libido and erectile dysfunction, and to improve strength and physical function. The estimated likelihood of adverse effects of long-term TRT is still essentially unknown, as overall high-quality evidence based upon prospective randomized trials to recommend for or against its use in most men with testosterone deficiency (TD) is lacking. Evidence to suggest that TRT increases cardiovascular morbidity and mortality risks is poor, as results vary across study populations and their baseline comorbidities. While TRT may increase serum prostate-specific antigen levels in some men, it often remains within clinically acceptable ranges, and has not been shown to increase the risk of prostate cancer. Current literature supports that TRT does not substantially worsen lower urinary tract symptoms, and may actually improve symptoms in some men. Limited evidence suggests that TRT may initially worsen obstructive sleep apnea in some men, but that this is not a longstanding effect. TRT may result in erythrocytosis in some men, however long-term studies have not reported significant adverse events (e.g. cerebrovascular accident, vascular occlusive events, venous thromboembolisms). Future research will require dedicated focus on evaluation of large, multiethnic cohorts of men through prospective trials to better elucidate both risk and hazard ratios of TRT as it relates to cardiovascular disease, prostate cancer, lower urinary tract symptoms, obstructive sleep apnea, erythrocytosis, and other to-be-determined theoretical risks in men both with and without cardiovascular risk equivalents. PMID:25360240

  18. Mitigating Adverse Effects of a Human Mission on Possible Martian Indigenous Ecosystems

    NASA Technical Reports Server (NTRS)

    Lupisella, M. L.

    2000-01-01

    Although human beings are, by most standards, the most capable agents to search for and detect extraterrestrial life, we are also potentially the most harmful. While there has been substantial work regarding forward contamination with respect to robotic missions, the issue of potential adverse effects on possible indigenous Martian ecosystems, such as biological contamination, due to a human mission has remained relatively unexplored and may require our attention now as this presentation will try to demonstrate by exploring some of the relevant scientific questions, mission planning challenges, and policy issues. An informal, high-level mission planning decision tree will be discussed and is included as the next page of this abstract. Some of the questions to be considered are: (1) To what extent could contamination due to a human presence compromise possible indigenous life forms? (2) To what extent can we control contamination? For example, will it be local or global? (3) What are the criteria for assessing the biological status of Mars, both regionally and globally? For example, can we adequately extrapolate from a few strategic missions such as sample return missions? (4) What should our policies be regarding our mission planning and possible interaction with what are likely to be microbial forms of extraterrestrial life? (5) Central to the science and mission planning issues is the role and applicability of terrestrial analogs, such as Lake Vostok for assessing drilling issues, and modeling techniques. Central to many of the policy aspects are scientific value, international law, public concern, and ethics. Exploring this overall issue responsibly requires an examination of all these aspects and how they interrelate. A chart is included, titled 'Mission Planning Decision Tree for Mitigating Adverse Effects to Possible Indigenous Martian Ecosystems due to a Human Mission'. It outlines what questions scientists should ask and answer before sending humans to Mars.

  19. Mitigating Adverse Effects of a Human Mission on Possible Martian Indigenous Ecosystems

    NASA Astrophysics Data System (ADS)

    Lupisella, M. L.

    2000-07-01

    Although human beings are, by most standards, the most capable agents to search for and detect extraterrestrial life, we are also potentially the most harmful. While there has been substantial work regarding forward contamination with respect to robotic missions, the issue of potential adverse effects on possible indigenous Martian ecosystems, such as biological contamination, due to a human mission has remained relatively unexplored and may require our attention now as this presentation will try to demonstrate by exploring some of the relevant scientific questions, mission planning challenges, and policy issues. An informal, high-level mission planning decision tree will be discussed and is included as the next page of this abstract. Some of the questions to be considered are: (1) To what extent could contamination due to a human presence compromise possible indigenous life forms? (2) To what extent can we control contamination? For example, will it be local or global? (3) What are the criteria for assessing the biological status of Mars, both regionally and globally? For example, can we adequately extrapolate from a few strategic missions such as sample return missions? (4) What should our policies be regarding our mission planning and possible interaction with what are likely to be microbial forms of extraterrestrial life? (5) Central to the science and mission planning issues is the role and applicability of terrestrial analogs, such as Lake Vostok for assessing drilling issues, and modeling techniques. Central to many of the policy aspects are scientific value, international law, public concern, and ethics. Exploring this overall issue responsibly requires an examination of all these aspects and how they interrelate. A chart is included, titled 'Mission Planning Decision Tree for Mitigating Adverse Effects to Possible Indigenous Martian Ecosystems due to a Human Mission'. It outlines what questions scientists should ask and answer before sending humans to Mars.

  20. Adverse effect of outdoor air pollution on cardiorespiratory fitness in Chinese children

    NASA Astrophysics Data System (ADS)

    Gao, Yang; Chan, Emily Y. Y.; Zhu, Yingjia; Wong, Tze Wai

    2013-01-01

    Little is known about the health impact of air pollution on children's cardiovascular health. A cross-sectional study was conducted and data was analysed in 2048 Chinese schoolchildren (aged 8-10 years) in three districts of Hong Kong to examine the association between exposure to outdoor air pollution and cardiorespiratory fitness. Annual means of ambient PM10, SO2, NO2 and O3 from 1996 to 2003 were used to estimate individual exposure of the subjects. Cardiorespiratory fitness was measured for maximal oxygen uptake (VO2max), predicted by the multistage fitness test (MFT). Height and weight were measured and other potential confounders were collected with questionnaires. Analysis of covariance was performed to estimate the impact of air pollution on complete speed in the MFT and predicted VO2max. The results showed that children in high-pollution district had significantly lower complete speed and predicted VO2max compared to those in low- and moderate-pollution districts. Complete speed and predicted VO2max was estimated to reduce 0.327 km h-1 and 1.53 ml kg-1 min-1 per 10 μg m-3 increase in PM10 annual mean respectively, with those in girls being greater than in boys. Being physically active could not significantly result in improved cardiorespiratory fitness in polluted districts. The adverse effect seems to be independent of short-term exposure to air pollution. We concluded that long-term exposure to higher outdoor air pollution levels was negatively associated with cardiorespiratory fitness in Chinese schoolchildren, especially for girls. PM10 is the most relevant pollutant of the adverse effect. Elevated cardiorespiratory fitness observed in physically activate children could be negated by increased amount of inhaled pollutants during exercise.