Science.gov

Sample records for adverse toxic effects

  1. 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.

  2. 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

  3. [Antivaccine misinformation about rate of adverse effects and toxicity of vaccines].

    PubMed

    Mats, A N; Gol'dshteĭn, A V

    2010-01-01

    Two widely known antivaccine inventions are discussed: "vaccination is accompanied by adverse effects, which exceeded complications of respective infections on frequency and severity" and "vaccines represent appalling conglomerate of toxic substances, which is unnaturally to administer to children". Informational and psychological nature of dissemination of these inventions is analyzed. On the basis of recent literature data conclusion was made about the absence of real toxicity (including neurotoxicity), carcinogenicity, allergenicity and autopathogenicity of phenol, folmaldehyde, aluminium hydroxide, Twin 80, squalen (MF59) and ethylmercury in concentrations found in vaccines of national immunization schedule.

  4. Toxicity of macrolide antibiotics on isolated heart mitochondria: a justification for their cardiotoxic adverse effect.

    PubMed

    Salimi, Ahmad; Eybagi, Sadaf; Seydi, Enayatollah; Naserzadeh, Parvaneh; Kazerouni, Negar Panahi; Pourahmad, Jalal

    2016-01-01

    1. Macrolides belong to the polyketide class of natural products. These products are a group of drugs (typically antibiotics) which their activity stems from the presence of a macrolide ring. Antibiotic macrolides are used to treat infections caused by Gram-positive bacteria and Haemophilus influenzae infections such as respiratory tract and soft-tissue infections. Macrolides, mainly erythromycin and clarithromycin, rarely show QT prolongation, as their infamous adverse reaction which can lead to torsades de pointes. Electrophysiological studies showed that macrolides prolonging the QT interval inhibit the rapid component of the delayed rectifier K(+) current (IKr) through the block of potassium channels encoded by the human ether-a-go-go-related gene (HERG). Other studies suggest that increased ROS generation alters the kinetics of hERG K(+) conductance. 2. In our study, rat cardiomyocytes were isolated with collagen perfusion technique. Finally, mitochondria isolated from cardiomyocytes were exposed to erythromycin, azithromycin and clarithromycin for their probable toxicity effects. 3. Our results demonstrated that macrolides induced reactive oxygen species formation, mitochondrial membrane permeabilization and mitochondrial swelling and finally cytochrome c release in cardiomyocyte mitochondria. 4. These findings suggested that the toxicity of heart mitochondria is a starting point for cardiotoxic effects of macrolides including QT prolongation, torsades de pointes and arrhythmia.

  5. In Silico Models for Repeated-Dose Toxicity (RDT): Prediction of the No Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect Level (LOAEL) for Drugs.

    PubMed

    Pizzo, Fabiola; Benfenati, Emilio

    2016-01-01

    The preclinical stage in drug development requires the determination of repeated-dose toxicity (RDT) in animal models. The main outcome of RDT studies is the determination of the no observed adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL). NOAEL is important since it serves to calculate the maximum recommended starting dose (MRSD) which is the safe starting dose for clinical studies in human beings. Since in vivo RDT studies are expensive and time-consuming, in silico approaches could offer a valuable alternative. However, NOAEL and LOAEL modeling suffer some limitations since they do not refer to a single end point but to several different effects and the doses used in experimental studies strongly influence the final results. Few attempts to model NOAEL and LOAEL have been reported. The available database and models for the prediction of NOAEL and LOAEL are reviewed here. PMID:27311467

  6. 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

  7. 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

  8. 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

  9. Edaravone ameliorates the adverse effects of valproic acid toxicity in small intestine.

    PubMed

    Oktay, S; Alev, B; Tunali, S; Emekli-Alturfan, E; Tunali-Akbay, T; Koc-Ozturk, L; Yanardag, R; Yarat, A

    2015-06-01

    Valproic acid (VPA) is a drug used for the treatment of epilepsy, bipolar psychiatric disorders, and migraine. Previous studies have reported an increased generation of reactive oxygen species and oxidative stress in the toxic mechanism of VPA. Edaravone, a free radical scavenger for clinical use, can quench free radical reaction by trapping a variety of free radical species. In this study, effect of edaravone on some small intestine biochemical parameters in VPA-induced toxicity was investigated. Thirty seven Sprague Dawley female rats were randomly divided into four groups. The groups include control group, edaravone (30 mg(-1) kg(-1) day(-1)) given group, VPA (0.5 g(-1) kg(-1) day(-1)) given group, VPA + edaravone (in same dose) given group. Edaravone and VPA were given intraperitoneally for 7 days. Biochemical parameters such as malondialdehyde, as an index of lipid peroxidation(LPO), sialic acid (SA), glutathione levels and glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, catalase, myeloperoxidase, alkaline phosphatase (ALP), and tissue factor (TF) activities were determined in small intestine samples by colorimetric methods. Decreased small intestine antioxidant enzyme activities, increased LPO and SA levels, and increased activities of ALP and TF were detected in the VPA group. Based on our results edaravone may be suggested to reverse the oxidative stress and inflammation due to VPA-induced small intestine toxicity.

  10. 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...

  11. Can Adverse Effects of Acidity and Aluminum Toxicity Be Alleviated by Appropriate Rootstock Selection in Cucumber?

    PubMed

    Rouphael, Youssef; Rea, Elvira; Cardarelli, Mariateresa; Bitterlich, Michael; Schwarz, Dietmar; Colla, Giuseppe

    2016-01-01

    Low-pH and aluminum (Al) stresses are the major constraints that limit crop yield in acidic soils. Grafting vegetable elite cultivars onto appropriate rootstocks may represent an effective tool to improve crop tolerance to acidity and Al toxicity. Two greenhouse hydroponic experiments were performed to evaluate growth, yield, biomass production, chlorophyll index, electrolyte leakage, mineral composition, and assimilate partitioning in plant tissues of cucumber plants (Cucumis sativus L. "Ekron") either non-grafted or grafted onto "P360" (Cucurbita maxima Duchesne × Cucurbita moschata Duchesne; E/C) or figleaf gourd (Cucurbita ficifolia Bouché; E/F). Cucumber plants were cultured in pots and supplied with nutrient solutions having different pH and Al concentrations: pH 6, pH 3.5, pH 3.5 + 1.5 mM Al, and pH 3.5 + 3 mM Al (Experiment 1, 14 days) and pH 6, pH 3.5, and pH 3.5 + 0.75 mM Al (Experiment 2, 67 days). Significant depression in shoot and root biomass was observed in response to acidity and Al concentrations, with Al-stress being more phytotoxic than low pH treatment. Significant decrease in yield, shoot, and root biomass, leaf area, SPAD index, N, K, Ca, Mg, Mn, and B concentration in aerial parts (leaves and stems) in response to low pH with more detrimental effects at pH 3.5 + Al. Grafted E/C plants grown under low pH and Al had higher yield, shoot, and root biomass compared to E/F and non-grafted plants. This better crop performance of E/C plants in response to Al stress was related to (i) a reduced translocation of Al from roots to the shoot, (ii) a better shoot and root nutritional status in K, Ca, Mg, Mn, and Zn concentration, (iii) a higher chlorophyll synthesis, as well as (iv) the ability to maintain cell membrane stability and integrity (lower electrolyte leakage). Data provide insight into the role of grafting on Al stress tolerance in cucumber. PMID:27621740

  12. Can Adverse Effects of Acidity and Aluminum Toxicity Be Alleviated by Appropriate Rootstock Selection in Cucumber?

    PubMed Central

    Rouphael, Youssef; Rea, Elvira; Cardarelli, Mariateresa; Bitterlich, Michael; Schwarz, Dietmar; Colla, Giuseppe

    2016-01-01

    Low-pH and aluminum (Al) stresses are the major constraints that limit crop yield in acidic soils. Grafting vegetable elite cultivars onto appropriate rootstocks may represent an effective tool to improve crop tolerance to acidity and Al toxicity. Two greenhouse hydroponic experiments were performed to evaluate growth, yield, biomass production, chlorophyll index, electrolyte leakage, mineral composition, and assimilate partitioning in plant tissues of cucumber plants (Cucumis sativus L. “Ekron”) either non-grafted or grafted onto “P360” (Cucurbita maxima Duchesne × Cucurbita moschata Duchesne; E/C) or figleaf gourd (Cucurbita ficifolia Bouché; E/F). Cucumber plants were cultured in pots and supplied with nutrient solutions having different pH and Al concentrations: pH 6, pH 3.5, pH 3.5 + 1.5 mM Al, and pH 3.5 + 3 mM Al (Experiment 1, 14 days) and pH 6, pH 3.5, and pH 3.5 + 0.75 mM Al (Experiment 2, 67 days). Significant depression in shoot and root biomass was observed in response to acidity and Al concentrations, with Al-stress being more phytotoxic than low pH treatment. Significant decrease in yield, shoot, and root biomass, leaf area, SPAD index, N, K, Ca, Mg, Mn, and B concentration in aerial parts (leaves and stems) in response to low pH with more detrimental effects at pH 3.5 + Al. Grafted E/C plants grown under low pH and Al had higher yield, shoot, and root biomass compared to E/F and non-grafted plants. This better crop performance of E/C plants in response to Al stress was related to (i) a reduced translocation of Al from roots to the shoot, (ii) a better shoot and root nutritional status in K, Ca, Mg, Mn, and Zn concentration, (iii) a higher chlorophyll synthesis, as well as (iv) the ability to maintain cell membrane stability and integrity (lower electrolyte leakage). Data provide insight into the role of grafting on Al stress tolerance in cucumber. PMID:27621740

  13. Can Adverse Effects of Acidity and Aluminum Toxicity Be Alleviated by Appropriate Rootstock Selection in Cucumber?

    PubMed

    Rouphael, Youssef; Rea, Elvira; Cardarelli, Mariateresa; Bitterlich, Michael; Schwarz, Dietmar; Colla, Giuseppe

    2016-01-01

    Low-pH and aluminum (Al) stresses are the major constraints that limit crop yield in acidic soils. Grafting vegetable elite cultivars onto appropriate rootstocks may represent an effective tool to improve crop tolerance to acidity and Al toxicity. Two greenhouse hydroponic experiments were performed to evaluate growth, yield, biomass production, chlorophyll index, electrolyte leakage, mineral composition, and assimilate partitioning in plant tissues of cucumber plants (Cucumis sativus L. "Ekron") either non-grafted or grafted onto "P360" (Cucurbita maxima Duchesne × Cucurbita moschata Duchesne; E/C) or figleaf gourd (Cucurbita ficifolia Bouché; E/F). Cucumber plants were cultured in pots and supplied with nutrient solutions having different pH and Al concentrations: pH 6, pH 3.5, pH 3.5 + 1.5 mM Al, and pH 3.5 + 3 mM Al (Experiment 1, 14 days) and pH 6, pH 3.5, and pH 3.5 + 0.75 mM Al (Experiment 2, 67 days). Significant depression in shoot and root biomass was observed in response to acidity and Al concentrations, with Al-stress being more phytotoxic than low pH treatment. Significant decrease in yield, shoot, and root biomass, leaf area, SPAD index, N, K, Ca, Mg, Mn, and B concentration in aerial parts (leaves and stems) in response to low pH with more detrimental effects at pH 3.5 + Al. Grafted E/C plants grown under low pH and Al had higher yield, shoot, and root biomass compared to E/F and non-grafted plants. This better crop performance of E/C plants in response to Al stress was related to (i) a reduced translocation of Al from roots to the shoot, (ii) a better shoot and root nutritional status in K, Ca, Mg, Mn, and Zn concentration, (iii) a higher chlorophyll synthesis, as well as (iv) the ability to maintain cell membrane stability and integrity (lower electrolyte leakage). Data provide insight into the role of grafting on Al stress tolerance in cucumber.

  14. Can Adverse Effects of Acidity and Aluminum Toxicity Be Alleviated by Appropriate Rootstock Selection in Cucumber?

    PubMed Central

    Rouphael, Youssef; Rea, Elvira; Cardarelli, Mariateresa; Bitterlich, Michael; Schwarz, Dietmar; Colla, Giuseppe

    2016-01-01

    Low-pH and aluminum (Al) stresses are the major constraints that limit crop yield in acidic soils. Grafting vegetable elite cultivars onto appropriate rootstocks may represent an effective tool to improve crop tolerance to acidity and Al toxicity. Two greenhouse hydroponic experiments were performed to evaluate growth, yield, biomass production, chlorophyll index, electrolyte leakage, mineral composition, and assimilate partitioning in plant tissues of cucumber plants (Cucumis sativus L. “Ekron”) either non-grafted or grafted onto “P360” (Cucurbita maxima Duchesne × Cucurbita moschata Duchesne; E/C) or figleaf gourd (Cucurbita ficifolia Bouché; E/F). Cucumber plants were cultured in pots and supplied with nutrient solutions having different pH and Al concentrations: pH 6, pH 3.5, pH 3.5 + 1.5 mM Al, and pH 3.5 + 3 mM Al (Experiment 1, 14 days) and pH 6, pH 3.5, and pH 3.5 + 0.75 mM Al (Experiment 2, 67 days). Significant depression in shoot and root biomass was observed in response to acidity and Al concentrations, with Al-stress being more phytotoxic than low pH treatment. Significant decrease in yield, shoot, and root biomass, leaf area, SPAD index, N, K, Ca, Mg, Mn, and B concentration in aerial parts (leaves and stems) in response to low pH with more detrimental effects at pH 3.5 + Al. Grafted E/C plants grown under low pH and Al had higher yield, shoot, and root biomass compared to E/F and non-grafted plants. This better crop performance of E/C plants in response to Al stress was related to (i) a reduced translocation of Al from roots to the shoot, (ii) a better shoot and root nutritional status in K, Ca, Mg, Mn, and Zn concentration, (iii) a higher chlorophyll synthesis, as well as (iv) the ability to maintain cell membrane stability and integrity (lower electrolyte leakage). Data provide insight into the role of grafting on Al stress tolerance in cucumber.

  15. Laboratory toxicity and benthic invertebrate field colonization of Upper Columbia River sediments: finding adverse effects using multiple lines of evidence.

    PubMed

    Fairchild, J F; Kemble, N E; Allert, A L; Brumbaugh, W G; Ingersoll, C G; Dowling, B; Gruenenfelder, C; Roland, J L

    2012-07-01

    From 1930 to 1995, the Upper Columbia River (UCR) of northeast Washington State received approximately 12 million metric tons of smelter slag and associated effluents from a large smelter facility located in Trail, British Columbia, approximately 10 km north of the United States-Canadian border. Studies conducted during the past two decades have demonstrated the presence of toxic concentrations of heavy metals in slag-based sandy sediments, including cadmium, copper, zinc, and lead in the UCR area as well as the downstream reservoir portion of Lake Roosevelt. We conducted standardized whole-sediment toxicity tests with the amphipod Hyalella azteca (28-day) and the midge Chironomus dilutus (10-day) on 11 samples, including both UCR and study-specific reference sediments. Metal concentrations in sediments were modeled for potential toxicity using three approaches: (1) probable effects quotients (PEQs) based on total recoverable metals (TRMs) and simultaneously extracted metals (SEMs); (2) SEMs corrected for acid-volatile sulfides (AVS; i.e., ∑SEM - AVS); and (3) ∑SEM - AVS normalized to the fractional organic carbon (f(oc)) (i.e., ∑SEM - AVS/f(oc)). The most highly metal-contaminated sample (∑PEQ(TRM) = 132; ∑PEQ(SEM) = 54; ∑SEM - AVS = 323; and ∑SEM - AVS/(foc) = 64,600 umol/g) from the UCR was dominated by weathered slag sediment particles and resulted in 80% mortality and 94% decrease in biomass of amphipods; in addition, this sample significantly decreased growth of midge by 10%. The traditional ∑AVS - SEM, uncorrected for organic carbon, was the most accurate approach for estimating the effects of metals in the UCR. Treatment of the toxic slag sediment with 20% Resinex SIR-300 metal-chelating resin significantly decreased the toxicity of the sample. Samples ∑SEM - AVS > 244 was not toxic to amphipods or midge in laboratory testing, indicating that this value may be an approximate threshold for effects in the UCR. In situ benthic invertebrate

  16. Laboratory toxicity and benthic invertebrate field colonization of Upper Columbia River sediments: Finding adverse effects using multiple lines of evidence

    USGS Publications Warehouse

    Fairchild, J.F.; Kemble, N.E.; Allert, A.L.; Brumbaugh, W.G.; Ingersoll, C.G.; Dowling, B.; Gruenenfelder, C.; Roland, J.L.

    2012-01-01

    From 1930 to 1995, the Upper Columbia River (UCR) of northeast Washington State received approximately 12 million metric tons of smelter slag and associated effluents from a large smelter facility located in Trail, British Columbia, approximately 10 km north of the United States–Canadian border. Studies conducted during the past two decades have demonstrated the presence of toxic concentrations of heavy metals in slag-based sandy sediments, including cadmium, copper, zinc, and lead in the UCR area as well as the downstream reservoir portion of Lake Roosevelt. We conducted standardized whole-sediment toxicity tests with the amphipod Hyalella azteca (28-day) and the midge Chironomus dilutus (10-day) on 11 samples, including both UCR and study-specific reference sediments. Metal concentrations in sediments were modeled for potential toxicity using three approaches: (1) probable effects quotients (PEQs) based on total recoverable metals (TRMs) and simultaneously extracted metals (SEMs); (2) SEMs corrected for acid-volatile sulfides (AVS; i.e., ΣSEM - AVS); and (3) ΣSEM - AVS normalized to the fractional organic carbon (foc) (i.e., ΣSEM - AVS/foc). The most highly metal-contaminated sample (ΣPEQTRM = 132; ΣPEQSEM = 54; ΣSEM - AVS = 323; and ΣSEM - AVS/foc = 64,600 umol/g) from the UCR was dominated by weathered slag sediment particles and resulted in 80% mortality and 94% decrease in biomass of amphipods; in addition, this sample significantly decreased growth of midge by 10%. The traditional ΣAVS - SEM, uncorrected for organic carbon, was the most accurate approach for estimating the effects of metals in the UCR. Treatment of the toxic slag sediment with 20% Resinex SIR-300 metal-chelating resin significantly decreased the toxicity of the sample. Samples ΣSEM - AVS > 244 was not toxic to amphipods or midge in laboratory testing, indicating that this value may be an approximate threshold for effects in the UCR. In situ benthic invertebrate colonization

  17. PANCREATIC TOXICITY AS AN ADVERSE EFFECT INDUCED BY MEGLUMINE ANTIMONIATE THERAPY IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS

    PubMed Central

    LYRA, Marcelo Rosandiski; PASSOS, Sonia Regina Lambert; PIMENTEL, Maria Inês Fernandes; BEDOYA-PACHECO, Sandro Javier; VALETE-ROSALINO, Cláudia Maria; VASCONCELLOS, Erica Camargo Ferreira; ANTONIO, Liliane Fatima; SAHEKI, Mauricio Naoto; SALGUEIRO, Mariza Mattos; SANTOS, Ginelza Peres Lima; RIBEIRO, Madelon Noato; CONCEIÇÃO-SILVA, Fatima; MADEIRA, Maria Fatima; SILVA, Jorge Luiz Nunes; FAGUNDES, Aline; SCHUBACH, Armando Oliveria

    2016-01-01

    SUMMARY American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial. In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA). Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb5+)/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit. We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients. Patients treated with MA 20 mg Sb5+ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group. Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL. PMID:27680173

  18. Foliar application of brassinosteroids alleviates adverse effects of zinc toxicity in radish (Raphanus sativus L.) plants.

    PubMed

    Ramakrishna, Bellamkonda; Rao, S Seeta Ram

    2015-03-01

    Growth chamber experiments were conducted to investigate the comparative effect of 24-epibrassinolide (EBL) and 28-homobrassinolide (HBL) at 0.5, 1.0, or 2.0 μM concentrations by foliar application on radish plants growing under Zn(2+) stress. In radish plants exposed to excess Zn(2+), growth was substantially reduced in terms of shoot and root length, fresh and dry weight. However, foliar application of brassinosteroids (BRs) was able to alleviate Zn(2+)-induced stress and significantly improve the above growth traits. Zinc stress decreased chlorophyll a, b, and carotenoids levels in radish plants. However, follow-up treatment with BRs increased the photosynthetic pigments in stressed and stress-free plants. The treatment of BRs led to reduced levels of H2O2, lipid peroxidation and, electrolyte leakage (ELP) and improved the leaf relative water content (RWC) in stressed plants. Increased levels of carbonyls indicating enhanced protein oxidation under Zn(2+) stress was effectively countered by supplementation of BRs. Under Zn(2+) stress, the activities of catalase (CAT), ascorbate peroxidase (APX), and superoxidase dismutase (SOD) were increased but peroxidase (POD) and glutathione reductase (GR) decreased. Foliar spraying of BRs enhanced all these enzymatic activities in radish plants under Zn(2+) stress. The BRs application greatly enhanced contents of ascorbate (ASA), glutathione (GSH), and proline under Zn(2+) stress. The decrease in the activity of nitrate reductase (NR) caused by Zn(2+) stress was restored to the level of control by application of BRs. These results point out that BRs application elevated levels of antioxidative enzymes as well as antioxidants could have conferred resistance to radish plants against Zn(2+) stress resulting in improved plant growth, relative water content and photosynthetic attributes. Of the two BRs, EBL was most effective in amelioration of Zn(2+) stress.

  19. Adverse effects of cannabis.

    PubMed

    2011-01-01

    establish a causal relationship in either direction, because of these methodological limitations. In Australia, the marked increase in cannabis use has not been accompanied by an increased incidence of schizophrenia. On the basis of the available data, we cannot reach firm conclusions on whether or not cannabis use causes psychosis. It seems prudent to inform apparently vulnerable individuals that cannabis may cause acute psychotic decompensation, especially at high doses. Users can feel dependent on cannabis, but this dependence is usually psychological. Withdrawal symptoms tend to occur within 48 hours following cessation of regular cannabis use, and include increased irritability, anxiety, nervousness, restlessness, sleep difficulties and aggression. Symptoms subside within 2 to 12 weeks. Driving under the influence of cannabis doubles the risk of causing a fatal road accident. Alcohol consumption plays an even greater role. A few studies and a number of isolated reports suggest that cannabis has a role in the occurrence of cardiovascular adverse effects, especially in patients with coronary heart disease. Numerous case-control studies have investigated the role of cannabis in the incidence of some types of cancer. Its role has not been ruled out, but it is not possible to determine whether the risk is distinct from that of the tobacco with which it is often smoked. Studies that have examined the influence of cannabis use on the clinical course of hepatitis C are inconclusive. Alcohol remains the main toxic agent that hepatitis C patients should avoid. In practice, the adverse effects of low-level, recreational cannabis use are generally minor, although they can apparently be serious in vulnerable individuals. The adverse effects of cannabis appear overall to be less serious than those of alcohol, in terms of neuropsychological and somatic effects, accidents and violence.

  20. Adverse effects of cannabis.

    PubMed

    2011-01-01

    establish a causal relationship in either direction, because of these methodological limitations. In Australia, the marked increase in cannabis use has not been accompanied by an increased incidence of schizophrenia. On the basis of the available data, we cannot reach firm conclusions on whether or not cannabis use causes psychosis. It seems prudent to inform apparently vulnerable individuals that cannabis may cause acute psychotic decompensation, especially at high doses. Users can feel dependent on cannabis, but this dependence is usually psychological. Withdrawal symptoms tend to occur within 48 hours following cessation of regular cannabis use, and include increased irritability, anxiety, nervousness, restlessness, sleep difficulties and aggression. Symptoms subside within 2 to 12 weeks. Driving under the influence of cannabis doubles the risk of causing a fatal road accident. Alcohol consumption plays an even greater role. A few studies and a number of isolated reports suggest that cannabis has a role in the occurrence of cardiovascular adverse effects, especially in patients with coronary heart disease. Numerous case-control studies have investigated the role of cannabis in the incidence of some types of cancer. Its role has not been ruled out, but it is not possible to determine whether the risk is distinct from that of the tobacco with which it is often smoked. Studies that have examined the influence of cannabis use on the clinical course of hepatitis C are inconclusive. Alcohol remains the main toxic agent that hepatitis C patients should avoid. In practice, the adverse effects of low-level, recreational cannabis use are generally minor, although they can apparently be serious in vulnerable individuals. The adverse effects of cannabis appear overall to be less serious than those of alcohol, in terms of neuropsychological and somatic effects, accidents and violence. PMID:21462790

  1. 24-epibrassinolide mitigates the adverse effects of manganese induced toxicity through improved antioxidant system and photosynthetic attributes in Brassica juncea.

    PubMed

    Fariduddin, Qazi; Ahmed, Mumtaz; Mir, Bilal A; Yusuf, Mohammad; Khan, Tanveer A

    2015-08-01

    The objective of this study was to establish relationship between manganese-induced toxicity and antioxidant system response in Brassica juncea plants and also to investigate whether brassinosteroids activate antioxidant system to confer tolerance to the plants affected with manganese induced oxidative stress. Brassica juncea plants were administered with 3, 6, or 9 mM manganese at 10-day stage for 3 days. At 31-day stage, the seedlings were sprayed with deionized water (control) or 10(-8) M of 24-epibrassinolide, and plants were harvested at 45-day stage to assess growth, leaf gas-exchange traits, and biochemical parameters. The manganese treatments diminished growth along with photosynthetic attributes and carbonic anhydrase activity in the concentration-dependent manner, whereas it enhanced lipid peroxidation, electrolyte leakage, accumulation of H2O2 as well as proline, and various antioxidant enzymes in the leaves of Brassica juncea which were more pronounced at higher concentrations of manganese. However, the follow-up application of 24-epibrassinolide to the manganese stressed plants improved growth, water relations, and photosynthesis and further enhanced the various antioxidant enzymes viz. catalase, peroxidase, and superoxide dismutase and content of proline. The elevated level of antioxidant enzymes as well as proline could have conferred tolerance to the manganese-stressed plants resulting in improved growth and photosynthetic attributes.

  2. Comparing probabilistic and descriptive analyses of time-dose-toxicity relationship for determining no-observed-adverse-effect level in drug development.

    PubMed

    Glatard, Anaïs; Berges, Aliénor; Sahota, Tarjinder; Ambery, Claire; Osborne, Jan; Smith, Randall; Hénin, Emilie; Chen, Chao

    2015-10-15

    The no-observed-adverse-effect level (NOAEL) of a drug defined from animal studies is important for inferring a maximal safe dose in human. However, several issues are associated with its concept, determination and application. It is confined to the actual doses used in the study; becomes lower with increasing sample size or dose levels; and reflects the risk level seen in the experiment rather than what may be relevant for human. We explored a pharmacometric approach in an attempt to address these issues. We first used simulation to examine the behaviour of the NOAEL values as determined by current common practice; and then fitted the probability of toxicity as a function of treatment duration and dose to data collected from all applicable toxicology studies of a test compound. Our investigation was in the context of an irreversible toxicity that is detected at the end of the study. Simulations illustrated NOAEL's dependency on experimental factors such as dose and sample size, as well as the underlying uncertainty. Modelling the probability as a continuous function of treatment duration and dose simultaneously to data from multiple studies allowed the estimation of the dose, along with its confidence interval, for a maximal risk level that might be deemed as acceptable for human. The model-based data integration also reconciled between-study inconsistency and explicitly provided maximised estimation confidence. Such alternative NOAEL determination method should be explored for its more efficient data use, more quantifiable insight to toxic doses, and the potential for more relevant animal-to-human translation. PMID:26232187

  3. Gracilaria edulis exhibit antiproliferative activity against human lung adenocarcinoma cell line A549 without causing adverse toxic effect in vitro and in vivo.

    PubMed

    Sakthivel, Ravi; Muniasamy, Samuthirapandi; Archunan, Govindaraju; Devi, Kasi Pandima

    2016-02-01

    In the present study, the antiproliferative potential of various solvent extracts of Gracilaria edulis (GE) was tested against various cancer cell lines. In the A549 lung cancer cell line model, GE ethyl acetate extract (GEEA) (100 μg mL(-1)) treated group showed the maximum and significant (P < 0.05) growth inhibition at 48 h. The IC50 value was found to be 24.5 ± 19.1 μg mL(-1) at 48 h. Moreover, a low level of LDH release was observed at 48 h at various concentrations of (40, 60, 80 and 100 μg mL(-1)) GEEA extract-treated group compared to a control group. Changes in the cell morphology and echinoid spikes formation were observed at 48 h. Safety evaluation of GEEA in a non-cancerous liver cell line, PBMC and in Wistar rats positively revealed that the extract did not show any adverse toxic effects. The GEEA extract was partially purified by column chromatography and the active fraction was characterized through LC-MS analysis. Furthermore, HPLC and FT-IR analysis of the active fractions confirmed the presence of phytol, a diterpene compound with potent antiproliferative activity, which positively suggests that the red alga G. edulis contains a potent anticancer active principle.

  4. Adverse effects of general anaesthetics.

    PubMed

    Berthoud, M C; Reilly, C S

    1992-01-01

    This review deals with the adverse reactions associated with general anaesthetic agents in current use. These reactions fall into 2 categories; those which are more common, predictable and often closely related, and those which are rare, unpredictable and carry a high mortality. Both inhalational and intravenous anaesthetic agents affect the central nervous and cardio-respiratory systems in a dose-related manner. Neuronal inhibition results in decreasing levels of consciousness and depression of the medullary vital centres which can lead to cardiorespiratory failure. Both groups of agents have some depressant effect on the myocardium and vascular smooth muscle leading to a fall in cardiac output and hypotension. Centrally-mediated respiratory depression is common to both groups and the inhalational agents have a direct effect on lung physiology. The most important idiosyncratic reactions to the volatile agents are malignant hyperpyrexia and 'halothane hepatitis'. Malignant hyperpyrexia has an incidence of 1:12,000 with a mortality of about 24%. It is triggered most often by halothane together with suxamethonium. Post halothane hepatic necrosis is rare. Evidence points to 2 distinct syndromes; direct toxicity from the products of reductive metabolism, and a more serious illness, immunologically mediated via haptens formed by liver proteins and the products of oxidative metabolism. Prolonged nitrous oxide exposure can cause bone marrow depression and life-threatening pressure effects by expansion of air-filled spaces within the body. The idiosyncratic reactions to the intravenous agents include anaphylactoid reactions (which are rare) and triggering of acute porphyria. Etomidate is immunologically 'clean', but it inhibits cortisol synthesis. PMID:1418699

  5. The multisystem adverse effects of NSAID therapy.

    PubMed

    James, D S

    1999-11-01

    The clinical utility of nonsteroidal anti-inflammatory drugs (NSAIDs) to manage pain and inflammation is limited by adverse side effects. Although effective analgesic and anti-inflammatory agents, NSAIDs are associated with side effects that are a consequence of nonspecific inhibition of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). The primary adverse events associated with NSAID therapy are upper gastrointestinal (GI) ulceration, perforation, or bleeding, all of which involve mucosal damage of varying severity and can be asymptomatic and occur with little warning. Clinicians who prescribe NSAIDs should be able to identify patients who are at risk of an NSAID-induced GI adverse event and to detect and manage the event should one occur. The use of COX-2-specific inhibitors to manage pain and inflammation may minimize the risks of NSAID-associated toxicities.

  6. Adverse effects of anabolic steroids.

    PubMed

    Hickson, R C; Ball, K L; Falduto, M T

    1989-01-01

    Anabolic steroids are used therapeutically for various disorders and as ergogenic aids by athletes to augment strength, muscular development, and to enhance performance. There is a wide range of concomitant temporary and permanent adverse effects with steroid administration. Several well-documented adverse actions of these hormones may develop rapidly within several weeks or less (i.e. altered reproductive function) or require up to several years of steroid intake (i.e. liver carcinoma). More recent studies indicate that glucose intolerance, insulin resistance, increased cardiovascular disease risk profiles, cerebral dangers, musculoskeletal injuries, prostate cancer, psychosis and schizophrenic episodes, among others, accompany anabolic steroid intake. There is, at present, no evidence to support the claim that athletes are less susceptible to adverse effects than those individuals receiving hormone treatment in a clinical setting. Based on the available information which has accumulated primarily from cross-sectional, short term longitudinal, and case studies, there is a need: (a) to develop a comprehensive battery of specific and sensitive markers of adverse effects, particularly those that would be able to detect the onset of adverse actions; and (b) to conduct controlled long term longitudinal studies in order to fully understand the extensiveness and mechanisms involved in the occurrence of adverse effects.

  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.

  8. Correlation of blood Cr(III) and adverse health effects: Application of PBPK modeling to determine non-toxic blood concentrations.

    PubMed

    Monnot, Andrew D; Christian, Whitney V; Paustenbach, Dennis J; Finley, Brent L

    2014-08-01

    Chromium (Cr) (III) is a trace metal essential to human health and exposure typically occurs via the diet on a daily basis. Some groups of individuals, such as those consuming Cr(III) supplements or patients with Cr-containing implants, may have elevated blood Cr(III) concentrations. Although blood Cr(III) levels are thought to be an accurate metric of exposure, little is known about the relationship between these concentrations and possible adverse health risks. This study evaluated the various effects reported in animal and human epidemiological studies of Cr(III) exposure in an attempt to correlate them with blood Cr(III) concentrations. The target endpoints identified in this analysis included the hematological, hepatic, and renal systems. Animal and human physiological-based pharmacokinetic (PBPK) models were used to estimate steady state blood Cr(III) concentrations from a variety of dosing regimens. Based on the animal studies, our results suggest that blood Cr(III) concentrations as high as 480-580 μg/L are not associated with any responses. For each of the three health endpoints considered in this analysis (hematological, hepatic, and renal) no adverse effects were observed below 3,700 μg/L. Some hematological responses were observed at 3,700 μg/L, and adverse effects clearly occurred at 7,500 μg/L. These findings can be used to assess potential health risks to individuals with elevated blood Cr(III) concentrations.

  9. [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.

  10. [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

  11. 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

  12. Psychiatric adverse effects of pediatric corticosteroid use.

    PubMed

    Drozdowicz, Linda B; Bostwick, J Michael

    2014-06-01

    Corticosteroids, highly effective drugs for myriad disease states, have considerable neuropsychiatric adverse effects that can manifest in cognitive disorders, behavioral changes, and frank psychiatric disease. Recent reviews have summarized these effects in adults, but a comprehensive review on corticosteroid effects in children has not been published since 2005. Here, we systematically review articles published since then that, we find, naturally divide into 3 main areas: (1) chronic effects of acute prenatal and neonatal exposure associated with prematurity and congenital conditions; (2) immediate behavioral effects of acute exposure via oncological protocols; and (3) acute behavioral effects of sporadic use in children and adolescents with other conditions. PsycInfo, MEDLINE, Embase, and Scopus were queried to identify articles reporting psychiatric adverse effects of corticosteroids in pediatric patients. Search terms included corticosteroids, adrenal cortex hormones, steroid psychosis, substance-induced psychoses, glucocorticoids, dexamethasone, hydrocortisone, prednisone, adverse effects, mood disorders, mental disorders, psychosis, psychotic, psychoses, side effect, chemically induced, emotions, affective symptoms, toxicity, behavior, behavioral symptoms, infant, child, adolescent, pediatric, paediatric, neonatal, children, teen, and teenager. Following guidelines for systematic reviews from the Potsdam Consultation on Meta-Analysis, we have found it difficult to draw specific conclusions that are more than general impressions owing to the quality of the available studies. We find a mixed picture with neonates exposed to dexamethasone, with some articles reporting eventual deficits in neuropsychiatric functioning and others reporting no effect. In pediatric patients with acute lymphoblastic leukemia, corticosteroid use appears to correlate with negative psychiatric and behavioral effects. In children treated with corticosteroids for noncancer conditions

  13. Estimation of southern resident killer whale exposure to exhaust emissions from whale-watching vessels and potential adverse health effects and toxicity thresholds.

    PubMed

    Lachmuth, Cara L; Barrett-Lennard, Lance G; Steyn, D Q; Milsom, William K

    2011-04-01

    Southern resident killer whales in British Columbia and Washington are exposed to heavy vessel traffic. This study investigates their exposure to exhaust gases from whale-watching vessels by using a simple dispersion model incorporating data on whale and vessel behavior, atmospheric conditions, and output of airborne pollutants from the whale-watching fleet based on emissions data from regulatory agencies. Our findings suggest that current whale-watching guidelines are usually effective in limiting pollutant exposure to levels at or just below those at which measurable adverse health effects would be expected in killer whales. However, safe pollutant levels are exceeded under worst-case conditions and certain average-case conditions. To reduce killer whale exposure to exhaust we recommend: vessels position on the downwind side of whales, a maximum of 20 whale-watching vessels should be within 800 m at any given time, viewing periods should be limited, and current whale-watch guidelines and laws should be enforced.

  14. Adverse effects of antihypertensive drugs.

    PubMed

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  15. Home visiting and the biology of toxic stress: opportunities to address early childhood adversity.

    PubMed

    Garner, Andrew S

    2013-11-01

    Home visiting is an important mechanism for minimizing the lifelong effects of early childhood adversity. To do so, it must be informed by the biology of early brain and child development. Advances in neuroscience, epigenetics, and the physiology of stress are revealing the biological mechanisms underlying well-established associations between early childhood adversity and suboptimal life-course trajectories. Left unchecked, mediators of physiologic stress become toxic, alter both genome and brain, and lead to a vicious cycle of chronic stress. This so-called "toxic stress" results a wide array of behavioral attempts to blunt the stress response, a process known as "behavioral allostasis." Although behaviors like smoking, overeating, promiscuity, and substance abuse decrease stress transiently, over time they become maladaptive and result in the unhealthy lifestyles and noncommunicable diseases that are the leading causes of morbidity and mortality. The biology of toxic stress and the concept of behavioral allostasis shed new light on the developmental origins of lifelong disease and highlight opportunities for early intervention and prevention. Future efforts to minimize the effects of childhood adversity should focus on expanding the capacity of caregivers and communities to promote (1) the safe, stable, and nurturing relationships that buffer toxic stress, and (2) the rudimentary but foundational social-emotional, language, and cognitive skills needed to develop healthy, adaptive coping skills. Building these critical caregiver and community capacities will require a public health approach with unprecedented levels of collaboration and coordination between the healthcare, childcare, early education, early intervention, and home visiting sectors. PMID:24187125

  16. Prediction of drug-related cardiac adverse effects in humans--B: use of QSAR programs for early detection of drug-induced cardiac toxicities.

    PubMed

    Frid, Anna A; Matthews, Edwin J

    2010-04-01

    This report describes the use of three quantitative structure-activity relationship (QSAR) programs to predict drug-related cardiac adverse effects (AEs), BioEpisteme, MC4PC, and Leadscope Predictive Data Miner. QSAR models were constructed for 9 cardiac AE clusters affecting Purkinje nerve fibers (arrhythmia, bradycardia, conduction disorder, electrocardiogram, palpitations, QT prolongation, rate rhythm composite, tachycardia, and Torsades de pointes) and 5 clusters affecting the heart muscle (coronary artery disorders, heart failure, myocardial disorders, myocardial infarction, and valve disorders). The models were based on a database of post-marketing AEs linked to 1632 chemical structures, and identical training data sets were configured for three QSAR programs. Model performance was optimized and shown to be affected by the ratio of the number of active to inactive drugs. Results revealed that the three programs were complementary and predictive performances using any single positive, consensus two positives, or consensus three positives were as follows, respectively: 70.7%, 91.7%, and 98.0% specificity; 74.7%, 47.2%, and 21.0% sensitivity; and 138.2, 206.3, and 144.2 chi(2). In addition, a prospective study using AE data from the U.S. Food and Drug Administration's (FDA's) MedWatch Program showed 82.4% specificity and 94.3% sensitivity. Furthermore, an external validation study of 18 drugs with serious cardiotoxicity not considered in the models had 88.9% sensitivity. PMID:19941924

  17. [Cutaneous adverse effects of TNFalpha antagonists].

    PubMed

    Failla, V; Sabatiello, M; Lebas, E; de Schaetzen, V; Dezfoulian, B; Nikkels, A F

    2012-01-01

    The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

  18. Constructing, Quantifying, and Validating an Adverse Outcome Pathway for Vascular Developmental Toxicity

    EPA Science Inventory

    Constructing, Quantifying, and Validating an Adverse Outcome Pathway for Vascular Developmental Toxicity The adverse outcome pathway (AOP) for embryonic vascular disruption1 leading to a range of adverse prenatal outcomes was recently entered into the AOP wiki and accepted as par...

  19. The Yin: An adverse health perspective of nanoceria: uptake, distribution, accumulation, and mechanisms of its toxicity

    PubMed Central

    Yokel, Robert A.; Hussain, Salik; Garantziotis, Stavros; Demokritou, Philip; Castranova, Vincent; Cassee, Flemming R.

    2014-01-01

    This critical review evolved from a SNO Special Workshop on Nanoceria panel presentation addressing the toxicological risks of nanoceria: accumulation, target organs, and issues of clearance; how exposure dose/concentration, exposure route, and experimental preparation/model influence the different reported effects of nanoceria; and how can safer by design concepts be applied to nanoceria? It focuses on the most relevant routes of human nanoceria exposure and uptake, disposition, persistence, and resultant adverse effects. The pulmonary, oral, dermal, and topical ocular exposure routes are addressed as well as the intravenous route, as the latter provides a reference for the pharmacokinetic fate of nanoceria once introduced into blood. Nanoceria reaching the blood is primarily distributed to mononuclear phagocytic system organs. Available data suggest nanoceria’s distribution is not greatly affected by dose, shape, or dosing schedule. Significant attention has been paid to the inhalation exposure route. Nanoceria distribution from the lung to the rest of the body is less than 1% of the deposited dose, and from the gastrointestinal tract even less. Intracellular nanoceria and organ burdens persist for at least months, suggesting very slow clearance rates. The acute toxicity of nanoceria is very low. However, large/accumulated doses produce granuloma in the lung and liver, and fibrosis in the lung. Toxicity, including genotoxicity, increases with exposure time; the effects disappear slowly, possibly due to nanoceria’s biopersistence. Nanoceria may exert toxicity through oxidative stress. Adverse effects seen at sites distal to exposure may be due to nanoceria translocation or released biomolecules. An example is elevated oxidative stress indicators in the brain, in the absence of appreciable brain nanoceria. Nanoceria may change its nature in biological environments and cause changes in biological molecules. Increased toxicity has been related to greater surface

  20. Adverse effects of anabolic steroids in athletes.

    PubMed

    Kibble, M W; Ross, M B

    1987-09-01

    The effects of anabolic steroid use on athletic performance and the adverse effects associated with the use of anabolic steroids are reviewed. Anabolic steroids increase protein synthesis in skeletal muscles and reverse catabolic processes. Because of these properties, some athletes use anabolic steroids in an attempt to improve their athletic performance. However, studies indicate that increases in muscle mass and strength during anabolic steroid administration are observed only in athletes who already are weight-trained and who continue intensive training while maintaining high-protein, high-calorie diets. Adverse effects attributed to anabolic steroid use occur frequently. Serious adverse effects include hepatic and endocrine dysfunction; cardiovascular and behavioral changes also are reported. Some of the adverse effects associated with the use of these agents are irreversible, particularly in women. The use of anabolic steroids to improve athletic performance has become prevalent. However, the reported benefits are tempered by numerous adverse reactions.

  1. 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

  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. Adverse Outcome Pathways as Tools to Assess Drug-Induced Toxicity.

    PubMed

    Vinken, Mathieu

    2016-01-01

    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 toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of key events connected by key event relationships, and an adverse outcome. Development and evaluation of AOPs ideally complies with guidelines issued by the Organization for Economic Cooperation and Development. AOP frameworks have yet been proposed for major types of drug-induced injury, especially in the liver, including steatosis, fibrosis, and cholestasis. These newly postulated AOPs can serve a number of purposes pertinent to safety assessment of drugs, in particular the establishment of quantitative structure-activity relationships, the development of novel in vitro toxicity screening tests, and the elaboration of prioritization strategies. PMID:27311472

  4. Elucidation of Adverse Bioactivity Profiles as Predictors of Toxicity Potential

    EPA Science Inventory

    Toxicity testing in vitro remains a formidable challenge due to lack of understanding of key molecular targets and pathways underlying many pathological events. The combination of genome sequencing and widespread application of high-throughput screening tools have provided the me...

  5. Human Health Effects Associated with Exposure to Toxic Cyanobacteria

    EPA Science Inventory

    Reports of toxic cyanobacteria blooms are increasing worldwide. Warming and eutrophic surface water systems support the development of blooms. We examine the evidence for adverse human health effects associated with exposure to toxic blooms in drinking water, recreational water a...

  6. The radiology of adverse drug reactions and toxic hazards

    SciTech Connect

    Ansell, G.

    1985-01-01

    Dr. Ansell has produced a scholarly review of the radiology of drug reactions and toxic hazards in his latest book, which is based on over 1,200 articles in the world literature. About 800 of these articles are taken from outside the radiology literature, which indicates the need for this subject to be brought to the attention of the radiologist, particularly as concern about drug reactions and toxic hazards is always increasing. The book includes sections covering the chest, gastrointestinal tract, renal tract, skeletal system and soft tissues, and skull and central nervous system. Each section treats specific substances, such as steroids and heavy metals; specific radiologic signs, such as ureteric dilation; specific symptoms, such as dysphagia; industrial toxins; radiographic abnormalities are discussed; and numerous high-quality radiographs.

  7. Adverse Effects of Wheat Gluten.

    PubMed

    Koning, Frits

    2015-01-01

    Man began to consume cereals approximately 10,000 years ago when hunter-gatherers settled in the fertile golden crescent in the Middle East. Gluten has been an integral part of the Western type of diet ever since, and wheat consumption is also common in the Middle East, parts of India and China as well as Australia and Africa. In fact, the food supply in the world heavily depends on the availability of cereal-based food products, with wheat being one of the largest crops in the world. Part of this is due to the unique properties of wheat gluten, which has a high nutritional value and is crucial for the preparation of high-quality dough. In the last 10 years, however, wheat and gluten have received much negative attention. Many believe that it is inherently bad for our health and try to avoid consumption of gluten-containing cereals; a gluten-low lifestyle so to speak. This is fueled by a series of popular publications like Wheat Belly; Lose the Wheat, Lose the Weight, and Find Your Path Back to Health. However, in reality, there is only one condition where gluten is definitively the culprit: celiac disease (CD), affecting approximately 1% of the population in the Western world. Here, I describe the complexity of the cereals from which gluten is derived, the special properties of gluten which make it so widely used in the food industry, the basis for its toxicity in CD patients and the potential for the development of safe gluten and alternatives to the gluten-free diet.

  8. Adverse Effects of Wheat Gluten.

    PubMed

    Koning, Frits

    2015-01-01

    Man began to consume cereals approximately 10,000 years ago when hunter-gatherers settled in the fertile golden crescent in the Middle East. Gluten has been an integral part of the Western type of diet ever since, and wheat consumption is also common in the Middle East, parts of India and China as well as Australia and Africa. In fact, the food supply in the world heavily depends on the availability of cereal-based food products, with wheat being one of the largest crops in the world. Part of this is due to the unique properties of wheat gluten, which has a high nutritional value and is crucial for the preparation of high-quality dough. In the last 10 years, however, wheat and gluten have received much negative attention. Many believe that it is inherently bad for our health and try to avoid consumption of gluten-containing cereals; a gluten-low lifestyle so to speak. This is fueled by a series of popular publications like Wheat Belly; Lose the Wheat, Lose the Weight, and Find Your Path Back to Health. However, in reality, there is only one condition where gluten is definitively the culprit: celiac disease (CD), affecting approximately 1% of the population in the Western world. Here, I describe the complexity of the cereals from which gluten is derived, the special properties of gluten which make it so widely used in the food industry, the basis for its toxicity in CD patients and the potential for the development of safe gluten and alternatives to the gluten-free diet. PMID:26606684

  9. Encouraging spontaneous reporting of adverse effects.

    PubMed

    2015-02-01

    One priority when organising surveillance of health products is to remove barriers to reporting adverse effects. One way to encourage reporting is by providing regular feedback, as practised by the German drug bulletin arznei-telegramm, for example. PMID:25802925

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Adverse Effects of Common Drugs: Dietary Supplements.

    PubMed

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

    2015-09-01

    Dietary supplement-induced adverse effects often resolve quickly after discontinuation of the offending product, especially in younger patients. The potential for unwanted outcomes can be amplified in elderly patients or those taking multiple prescription drugs, especially where interactions exist with drugs metabolized by cytochrome P450 enzymes. Attributing injury or illness to a specific supplement can be challenging, especially in light of multi-ingredient products, product variability, and variability in reporting, as well as the vast underreporting of adverse drug reactions. Clinicians prescribing a new drug or evaluating a patient with a new symptom complex should inquire about use of herbal and dietary supplements as part of a comprehensive evaluation. Clinicians should report suspected supplement-related adverse effects to the local or state health department, as well as the Food and Drug Administration's MedWatch program (available at https://www.safetyreporting.hhs.gov). Clinicians should consider discussing suspected adverse effects involving drugs, herbal products, or dietary supplements with their community- and hospital-based pharmacists, and explore patient management options with medical or clinical toxicology subspecialists.

  16. Pharmacogenomics of statins: understanding susceptibility to adverse effects

    PubMed Central

    Kitzmiller, Joseph P; Mikulik, Eduard B; Dauki, Anees M; Murkherjee, Chandrama; Luzum, Jasmine A

    2016-01-01

    Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes), statin efficacy (eg, drug targets and pathways), and end-organ toxicity (eg, myopathy pathways) highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy. PMID:27757045

  17. Toxic effects of chromium and its compounds.

    PubMed

    Baruthio, F

    1992-01-01

    Chromium was discovered in 1797 by Vauquelin. Numerous industrial applications raised chromium to a very important economic element. At the same time, with the development of its uses, the adverse effects of chromium compounds in human health were being defined. Trivalent chromium is an essential trace element in humans and in animals. Chromium as pure metal has no adverse effect. Little toxic effect is attributed to trivalent chromium when present in very large quantities. Both acute and chronic toxicity of chromium are mainly caused by hexavalent compounds. The most important toxic effects, after contact, inhalation, or ingestion of hexavalent chromium compounds are the following: dermatitis, allergic and eczematous skin reactions, skin and mucous membrane ulcerations, perforation of the nasal septum, allergic asthmatic reactions, bronchial carcinomas, gastro-enteritis, hepatocellular deficiency, and renal oligo anuric deficiency. Prevention of occupational risks, biological monitoring of workers, and treatment of poisoning are also reported.

  18. 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.

  19. Linking Arsenic Metabolism and Toxic Effects

    EPA Science Inventory

    Although arsenic has been long recognized as a toxicant and a carcinogen, the molecular basis for few of its adverse effects are well understood. Like other metalloids, arsenic undergoes extensive metabolism involving oxidation state changes and formation of methyl-arsenic bonds ...

  20. 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.

  1. 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

  2. 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... sex. 4 Prenatal developmental toxicityReproduction and fertility Developmental neurotoxicity...

  3. 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.

  4. 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

  5. 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

  6. 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

  7. Immunomodulatory drugs: Oral and systemic adverse effects

    PubMed Central

    Mattila, Riikka; Gomez-Font, Rafael; Meurman, Jukka H.

    2014-01-01

    Objectives: The main objectives are to present the different adverses effects of the immunomodulatory drugs that can impair the quality of life of the immunosupressed patients and study the impact of immunomodualtion on oral diseases. Immunomodulatory drugs have changed the treatment protocols of many diseases where immune functions play a central role, such as rheumatic diseases. Their effect on oral health has not been systematically investigated, however. Study Design: We review current data on the new immunomodulatory drugs from the oral health perspective based on open literature search of the topic. Results: These target specific drugs appear to have less drug interactions than earlier immunomodulating medicines but have nevertheless potential side effects such as activating latent infections. There are some data showing that the new immunomodulatory drugs may also have a role in the treatment of certain oral diseases such as lichen planus or ameliorating symptoms in Sjögren´s syndrome, but the results have not been overly promising. Conclusions: In general, data are sparse of the effect of these new drugs vs. oral diseases and there are no properly powered randomized controlled trials published on this topic. Key words:Immunomodulatory drugs, oral diseases, adverse effects, therapeutic action. PMID:23986016

  8. Agomelatine: a review of adverse effects.

    PubMed

    2013-03-01

    More pharmacovigilance data on agomelatine became available in 2012. The main sources of information were surveillance data from the French national monitoring system, EU periodic safety update reports (PSURs), and the European pharmacovigilance database. The principal adverse effects of agomelatine consist of hepatic, pancreatic, neuropsychiatric, muscular and cutaneous disorders. The harms associated with agomelatine, which has no proven efficacy in depression, clearly outweigh the benefits. Until regulatory agencies decide to withdraw agomelatine from the market, it is up to healthcare professionals to protect patients from this unnecessarily dangerous drug.

  9. Adverse Effects of Psychotropic Medications: A Call to Action.

    PubMed

    Mago, Rajnish

    2016-09-01

    Adverse effects are common, bothersome, and a leading cause of discontinuation of treatment. The methodology for evaluating adverse effects of medications has been greatly neglected, however, especially in comparison to the methodology for assessment of efficacy of medications. Existing methods for assessment and reporting of adverse effects have important limitations leading to lack of much-needed data related to adverse effects. Lastly, there is little systematic research into management of most adverse effects. A series of recommendations are made in this article about how to improve identification, assessment, reporting, and management of adverse effects. PMID:27514294

  10. Adverse effects of differential parental attention1

    PubMed Central

    Sajwaj, Thomas E.; Pinkston, Susan; Cordua, Glenn; Jackson, Carolyn; Herbert, Emily W.; Pinkston, Elsie M.; Hayden, M. Loeman

    1973-01-01

    In two independent parent training projects (Kansas and Mississippi), mothers of deviant young children were observed to follow almost all child behaviors with attention. The mothers were then trained to use differential attention procedures to increase their child's appropriate behaviors and to decrease deviant behaviors. Contrary to expectations, the differential attention procedure produced substantial increases in deviant behavior for four of the children. This adverse effect was maintained over many sessions and was replicated in single organism, reversal designs. A fifth child showed no change. A sixth child showed some improvement. However, this effect was not recovered in a second application of differential attention, and the child became worse. The results underline the importance of subject generality in applied behavior analysis and strongly suggest that service programs using operant techniques must carefully evaluate their effects on behavior. PMID:16795386

  11. Limitations of toxicity characterization in life cycle assessment: Can adverse outcome pathways provide a new foundation?

    PubMed

    Gust, Kurt A; Collier, Zachary A; Mayo, Michael L; Stanley, Jacob K; Gong, Ping; Chappell, Mark A

    2016-07-01

    Life cycle assessment (LCA) has considerable merit for holistic evaluation of product planning, development, production, and disposal, with the inherent benefit of providing a forecast of potential health and environmental impacts. However, a technical review of current life cycle impact assessment (LCIA) methods revealed limitations within the biological effects assessment protocols, including: simplistic assessment approaches and models; an inability to integrate emerging types of toxicity data; a reliance on linear impact assessment models; a lack of methods to mitigate uncertainty; and no explicit consideration of effects in species of concern. The purpose of the current study is to demonstrate that a new concept in toxicological and regulatory assessment, the adverse outcome pathway (AOP), has many useful attributes of potential use to ameliorate many of these problems, to expand data utility and model robustness, and to enable more accurate and defensible biological effects assessments within LCIA. Background, context, and examples have been provided to demonstrate these potential benefits. We additionally propose that these benefits can be most effectively realized through development of quantitative AOPs (qAOPs) crafted to meet the needs of the LCIA framework. As a means to stimulate qAOP research and development in support of LCIA, we propose 3 conceptual classes of qAOP, each with unique inherent attributes for supporting LCIA: 1) mechanistic, including computational toxicology models; 2) probabilistic, including Bayesian networks and supervised machine learning models; and 3) weight of evidence, including models built using decision-analytic methods. Overall, we have highlighted a number of potential applications of qAOPs that can refine and add value to LCIA. As the AOP concept and support framework matures, we see the potential for qAOPs to serve a foundational role for next-generation effects characterization within LCIA. Integr Environ Assess Manag

  12. 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.

  13. 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

  14. Adverse skeletal effects of drugs - beyond Glucocorticoids.

    PubMed

    O'Sullivan, Susannah; Grey, Andrew

    2015-01-01

    Osteoporotic fractures are an important public health problem with significant individual and societal costs. In addition to the major risk factors for osteoporotic fracture, low bone mineral density (BMD), age, low body weight and history of fracture or falls, some drugs are now considered to be important secondary risk factor for bone loss and fracture, particularly amongst predisposed individuals. Currently available data are often generated from small observational clinical studies, making risk assessment and development of management guidelines difficult. In many cases, the exposed population has a low baseline risk for fracture and additional assessment and treatment may not be necessary. In this review, we focus on drugs other than glucocorticoids identified as potentially causing adverse skeletal effects, summarizing the existing evidence from preclinical and clinical studies, and suggest recommendations for patient management. PMID:25039381

  15. Persistent toxic substances: sources, fates and effects.

    PubMed

    Wong, Ming H; Armour, Margaret-Ann; Naidu, Ravi; Man, Ming

    2012-01-01

    Persistent toxic substances (PTS) include the Stockholm persistent organic pollutants, like dichlorodiphenyltrichloroethane, polychlorinated biphenyls, dioxin/furan, etc., and organometallic compounds, like organomercury, organotin, and organolead, which all share the same characteristics of being persistent, toxic, bioaccumulative, and able to travel long distances through different media. The adverse health effects of some of the emerging chemicals like pentabromodiphenyl ether, bisphenol A, and di(2-ethylhexyl)phthalate, which are widely used in daily appliances (e.g., TVs, computers, mobile phones, plastic baby bottles), have become a public health concern due to more evidence now available showing their adverse effects like disturbance of the endocrine system and cancer. This article is an attempt to review the current status of PTS in our environment, citing case studies in China and North America, and whether our existing drinking water treatment and wastewater treatment processes are adequate in removing them from water. Some management issues of these emerging chemicals of concern are also discussed.

  16. 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....

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a)...

  2. Identifying and managing adverse environmental health effects: 3. Lead exposure

    PubMed Central

    Sanborn, Margaret D.; Abelsohn, Alan; Campbell, Monica; Weir, Erica

    2002-01-01

    LEAD LEVELS IN NORTH AMERICAN CHILDREN AND ADULTS have declined in the past 3 decades, but lead persists in the environment in lead paint, old plumbing and contaminated soil. There are also a number of occupations and hobbies that carry a high risk of lead exposure. There is no evidence for a threshold below which lead has no adverse health effects. Blood lead levels previously considered safe are now known to cause subtle, chronic health effects. The health effects of lead exposure include developmental neurotoxicity, reproductive dysfunction and toxicity to the kidneys, blood and endocrine systems. Most lead exposures are preventable, and diagnosing lead poisoning is relatively simple compared with diagnosing health effects of exposures to other environmental toxins. Accurate assessment of lead poisoning requires specific knowledge of the sources, high-risk groups and relevant laboratory tests. In this article we review the multiple, systemic toxic effects of lead and provide current information on groups at risk, prevention, diagnosis and clinical treatment. We illustrate how the CH2OPD2 mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs) and specific screening questions are useful tools for physicians to quickly obtain an environmental exposure history and identify patients at high risk of lead exposure. By applying effective primary prevention, case-finding and treatment interventions for lead exposure, both the individual patient and the larger community reap the benefits of better health. PMID:12041847

  3. 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

  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.

  5. 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

  6. 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.

  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 the radioprotector WR2721

    SciTech Connect

    Cairnie, A.B.

    1983-04-01

    S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR2721) has radioprotective properties, but it is also toxic - in man it causes nausea and vomiting. Since radiation also causes nausea and vomiting it is important to know whether WR2721 would increase or decrease the likelihood of nausea and vomiting after radiation. This question was investigated in rats using the phenomenon of aversion to the taste of saccharin, which is readily inducible and is understood to be controlled in rats by the same pathways that control nausea and vomiting in man. The taste aversion was induced by giving 0.2 Gy /sup 60/Co ..gamma.. radiation 30 min after drinking 0.1% saccharin, or WR2721 immediately after the saccharin, or giving both radiation and WR2721. There were appropriate controls. In sham-irradiated rats, WR2721 (40 or 200 mg/kg, but not 8 mg/kg) produced a significant taste aversion. When WR2721 (40 or 200 mg/kg) was given immediately after the saccharin to irradiated rats it increased the taste aversion significantly, but it did not have any effect at 8 mg/kg. It was concluded that at doses which were optimal for radioprotection (approx.200 mg/kg) or lower, WR2721 increased in rats the taste aversion induced by radiation. By inference if conditioned taste aversion is an appropriate paradigm, WR2721 would increase nausea and vomiting in man induced by radiation.

  9. 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

  10. 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.

  11. ADVERSE HEALTH EFFECTS FROM ENVIRONMENTAL MANGANESE EXPOSURE.

    EPA Science Inventory

    The ubiquitous element, manganese (Mn), is an essential nutrient, but toxic at excessive exposure levels. Therefore, the US EPA set guideline levels for Mn exposure through inhalation (reference concentration-RfC=0.05 ?g/m3) and ingestion (reference dose-RfD=0.14 mg/kg/day (10 mg...

  12. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... CFR part 68) and applicable guidelines, to avoid adverse effects. (c) Consulting party review. If the... effects. Adverse effects on historic properties include, but are not limited to: (i) Physical destruction... (36 CFR part 68) and applicable guidelines; (iii) Removal of the property from its historic...

  13. 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

  14. Adverse effects of equine rabies immune gobulin.

    PubMed

    Wilde, H; Chomchey, P; Prakongsri, S; Puyaratabandhu, P; Chutivongse, S

    1989-02-01

    Following a recently published prospective study of 485 recipients of equine rabies immune globulin (ERIG) manufactured by Pasteur Vaccins (Paris), this paper reports a study of 323 postexposure rabies patients receiving ERIG manufactured by the Swiss Vaccine and Serum Institute (Berna). It is concluded that there may be significant differences in adverse reaction rates, reflecting differing manufacturing or purification processes and protein content. Further studies of different ERIG products and of different lots of the same product are needed while ERIG remains an essential component of postexposure rabies treatment in developing countries.

  15. 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...—(1) Resolution without the Council. (i) The agency official shall consult with the SHPO/THPO...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. THE ADVERSE-EFFECT POLICY FOR AGRICULTURAL LABOR.

    ERIC Educational Resources Information Center

    DELLON, HOWARD N.

    THE BASIC PHILOSOPHY UNDERLYING THE REGULATION OF FOREIGN WORKER IMPORTATIONS INTO THE UNITED STATES FOR AGRICULTURAL EMPLOYMENT IS THAT EMPLOYMENT OF SUCH WORKERS WILL NOT BE PERMITTED IF IT WILL HAVE AN ADVERSE EFFECT ON DOMESTIC WORKERS. THE "ADVERSE-EFFECT" POLICY HAS BEEN FOLLOWED SINCE THE ENACTMENT OF PUBLIC LAW 78 IN 1951 WHICH GOVERNED…

  2. [Toxic effect of benzalkonium chloride on animals and humans].

    PubMed

    Swiercz, Radosław; Hałatek, Tadeusz; Majcherek, Wanda; Grzelińiska, Zofia; Wasowicz, Wojciech

    2007-01-01

    Benzalkonium chloride (BAC) exerts toxic effects on microorganisms. This property has been utilized in the cosmetic industry and medicine, where it is used as effective germicide and preservative agents. Various BAC-containing preparations used by people may induce a number of adverse effects on the human body. Bearing in mind that BAC is widely used in different branches of the national economy, its toxic effect may cause a health problem of significant importance to humans. The authors describe BAC toxic effects exerted on humans and laboratory animals as well as relevant hazards resulting from the use of BAC-contained preparations. PMID:17926503

  3. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: I. Challenges and research needs in ecotoxicology.

    PubMed

    Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

    2015-02-01

    To elucidate the effects of chemicals on populations of different species in the environment, efficient testing and modeling approaches are needed that consider multiple stressors and allow reliable extrapolation of responses across species. An adverse outcome pathway (AOP) is a concept that provides a framework for organizing knowledge about the progression of toxicity events across scales of biological organization that lead to adverse outcomes relevant for risk assessment. In this paper, we focus on exploring how the AOP concept can be used to guide research aimed at improving both our understanding of chronic toxicity, including delayed toxicity as well as epigenetic and transgenerational effects of chemicals, and our ability to predict adverse outcomes. A better understanding of the influence of subtle toxicity on individual and population fitness would support a broader integration of sublethal endpoints into risk assessment frameworks. Detailed mechanistic knowledge would facilitate the development of alternative testing methods as well as help prioritize higher tier toxicity testing. We argue that targeted development of AOPs supports both of these aspects by promoting the elucidation of molecular mechanisms and their contribution to relevant toxicity outcomes across biological scales. We further discuss information requirements and challenges in application of AOPs for chemical- and site-specific risk assessment and for extrapolation across species. We provide recommendations for potential extension of the AOP framework to incorporate information on exposure, toxicokinetics and situation-specific ecological contexts, and discuss common interfaces that can be employed to couple AOPs with computational modeling approaches and with evolutionary life history theory. The extended AOP framework can serve as a venue for integration of knowledge derived from various sources, including empirical data as well as molecular, quantitative and evolutionary-based models

  4. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health.

    PubMed

    Garner, Andrew S; Shonkoff, Jack P

    2012-01-01

    Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span. PMID:22201148

  5. 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...

  6. Possible involvement of DEC1 on the adverse effects of quinolone antibiotics.

    PubMed

    Shi, Xiaohong; Zheng, Yan; Ma, Wanshan; Wang, Yunshan

    2010-04-30

    Quinolone antibacterial agents are widely used in the clinic because of their high antibacterial activity, broad spectra and favorable pharmacokinetics. However, the adverse effects induced by quinolones, such as tendon/articular toxicity, central nervous system toxicity, phototoxicity and dysglycemia, have greatly restricted their therapeutic use. Differentiated embryo-chondrocyte expressed gene 1 (DEC1), an important transcription factor that has a basic helix-loop-helix domain and is ubiquitously expressed in both human embryonic and adult tissues, has a pivotal function in various biological phenomena, including neurogenesis, neuroregulation, chondrogenesis, cell growth, oncogenesis, immune balance and circandian rhythm. Recently, DEC1 has received increasing attention for its role in maintaining the homeostasis of metabolism and energy. Research has shown that DEC1 may play a vital role in metabolic disease. Although the mechanism of the adverse reactions caused by quinolones has not been clarified, the distribution of these serious adverse effects in tissues and organs is consistent with the expression of DEC1 in corresponding normal tissues. In the present paper, we review evidence showing that DEC1 may take part in the adverse effects induced by quinolone antibiotics. The investigation of the molecular details of the toxicity caused by quinolones may help overcome the shortcomings of the antibiotics and reveal new, useful therapeutic functions besides their antimicrobial effect.

  7. [Adverse effects of antidepressive agents in hospitalized geriatric patients].

    PubMed

    Korínková, V; Kolibás, E; Králová, M; Novotný, V; Konceoj, V A; Pjatnickij, A N; Andrusenkova, M P

    1992-11-01

    The frequency, intensity and profile of adverse effects of antidepressants was studied in elderly patients. The series consisted of 102 patients with depression admitted to hospitals in Bratislava and Moscow. The adverse effects of amitriptyline (Amitriptylin Spofa) and maprotiline (Ludiomil Ciba-Geigy) were compared. The assessment done on days 0, 7, and 28 of treatment showed that xerostomia had the highest occurrence rate with both preparations studied. In patients treated with amitriptyline adverse effects were more severe and were recorded more frequently, requiring treatment withdrawal in 3 patients. The overall intensity of adverse effects was significantly higher with amitriptyline (p < 0.05). In the group of patients treated with amitriptyline the adverse effects were more marked in those with severe somatic pathology. The risk of amitriptyline treatment in elderly patients is being emphasized along with the need for monitoring and correcting adverse effects of the treatment. Although maprotiline exhibited a lower occurrence rate of adverse effects, cardiac functions should be regularly checked in patients with preexisting cardiac pathology. (Tab. 2, Fig. 3, Ref. 6.).

  8. 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

  9. Fewer adverse effects with doxycycline than with minocycline.

    PubMed

    2009-10-01

    (1) In mid-2008 the French National Pharmacovigilance Committee examined spontaneous reports of adverse effects observed during tetracycline therapy; (2) When sales figures are taken into account, reports were more frequent with minocycline than with doxycycline. The proportion of severe adverse effects was also higher with minocycline than with doxycycline; (3) Life-threatening hypersensitivity reactions and autoimmune adverse effects were more frequent with minocycline than with doxycycline; (4) In practice, minocycline has a less favourable risk-benefit balance than doxycycline, particularly in the treatment of acne.

  10. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

    PubMed Central

    Najam, Rahila; Mateen, Ahmed

    2013-01-01

    The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m2), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m2) after few treatment cycles. PMID:24187619

  11. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX.

    PubMed

    Bano, Nusrat; Najam, Rahila; Mateen, Ahmed

    2013-01-01

    The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m(2)), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m(2)) after few treatment cycles.

  12. Selenomethionine protects against adverse biological effects induced by space radiation.

    PubMed

    Kennedy, Ann R; Ware, Jeffrey H; Guan, Jun; Donahue, Jeremiah J; Biaglow, John E; Zhou, Zhaozong; Stewart, Jelena; Vazquez, Marcelo; Wan, X Steven

    2004-01-15

    Ionizing radiation-induced adverse biological effects impose serious challenges to astronauts during extended space travel. Of particular concern is the radiation from highly energetic, heavy, charged particles known as HZE particles. The objective of the present study was to characterize HZE particle radiation-induced adverse biological effects and evaluate the effect of D-selenomethionine (SeM) on the HZE particle radiation-induced adverse biological effects. The results showed that HZE particle radiation can increase oxidative stress, cytotoxicity, and cell transformation in vitro, and decrease the total antioxidant status in irradiated Sprague-Dawley rats. These adverse biological effects were all preventable by treatment with SeM, suggesting that SeM is potentially useful as a countermeasure against space radiation-induced adverse effects. Treatment with SeM was shown to enhance ATR and CHK2 gene expression in cultured human thyroid epithelial cells. As ionizing radiation is known to result in DNA damage and both ATR and CHK2 gene products are involved in DNA damage, it is possible that SeM may prevent HZE particle radiation-induced adverse biological effects by enhancing the DNA repair machinery in irradiated cells.

  13. Selenomethionine protects against adverse biological effects induced by space radiation.

    PubMed

    Kennedy, Ann R; Ware, Jeffrey H; Guan, Jun; Donahue, Jeremiah J; Biaglow, John E; Zhou, Zhaozong; Stewart, Jelena; Vazquez, Marcelo; Wan, X Steven

    2004-01-15

    Ionizing radiation-induced adverse biological effects impose serious challenges to astronauts during extended space travel. Of particular concern is the radiation from highly energetic, heavy, charged particles known as HZE particles. The objective of the present study was to characterize HZE particle radiation-induced adverse biological effects and evaluate the effect of D-selenomethionine (SeM) on the HZE particle radiation-induced adverse biological effects. The results showed that HZE particle radiation can increase oxidative stress, cytotoxicity, and cell transformation in vitro, and decrease the total antioxidant status in irradiated Sprague-Dawley rats. These adverse biological effects were all preventable by treatment with SeM, suggesting that SeM is potentially useful as a countermeasure against space radiation-induced adverse effects. Treatment with SeM was shown to enhance ATR and CHK2 gene expression in cultured human thyroid epithelial cells. As ionizing radiation is known to result in DNA damage and both ATR and CHK2 gene products are involved in DNA damage, it is possible that SeM may prevent HZE particle radiation-induced adverse biological effects by enhancing the DNA repair machinery in irradiated cells. PMID:14744637

  14. 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

  15. 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.

  16. 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.

  17. Adverse health effects of outdoor air pollutants.

    PubMed

    Curtis, Luke; Rea, William; Smith-Willis, Patricia; Fenyves, Ervin; Pan, Yaqin

    2006-08-01

    Much research on the health effects of outdoor air pollution has been published in the last decade. The goal of this review is to concisely summarize a wide range of the recent research on health effects of many types of outdoor air pollution. A review of the health effects of major outdoor air pollutants including particulates, carbon monoxide, sulfur and nitrogen oxides, acid gases, metals, volatile organics, solvents, pesticides, radiation and bioaerosols is presented. Numerous studies have linked atmospheric pollutants to many types of health problems of many body systems including the respiratory, cardiovascular, immunological, hematological, neurological and reproductive/ developmental systems. Some studies have found increases in respiratory and cardiovascular problems at outdoor pollutant levels well below standards set by such agencies as the US EPA and WHO. Air pollution is associated with large increases in medical expenses, morbidity and is estimated to cause about 800,000 annual premature deaths worldwide [Cohen, A.J., Ross Alexander, H., Ostro, B., Pandey, K.D., Kryzanowski, M., Kunzail, N., et al., 2005. The global burden of disease due to outdoor air pollution. J Toxicol Environ Health A. 68: 1-7.]. Further research on the health effects of air pollution and air pollutant abatement methods should be very helpful to physicians, public health officials, industrialists, politicians and the general public. PMID:16730796

  18. Scientific and Regulatory Policy Committee: Recommended ("Best") Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies.

    PubMed

    Kerlin, Roy; Bolon, Brad; Burkhardt, John; Francke, Sabine; Greaves, Peter; Meador, Vince; Popp, James

    2016-02-01

    Recommendations (best practices) are provided by the Society of Toxicologic Pathology's Adversity Working Group for making consistent interpretations of test article-related effects as "adverse" and assigning a "no observed adverse effect level" (NOAEL) in nonclinical toxicity studies. Adverse is a term indicating "harm" to the test animal, while nonadverse indicates lack of harm. Adverse findings in the study reports should be defined in relation to effects on the test species used and within the context of the given study. Test article-related effects should be described on their own merits, and decisions to consider them as adverse or nonadverse should be justified. Related effects may be discussed together; in particular, markers of toxicity that are not in and of themselves adverse ideally should be discussed in conjunction with the causal toxicity to determine adversity. Adverse findings should be identified in subreports (clinical data, pathology data, etc.) if sufficient information is available, and/or in the final study report as individual or grouped findings, but study NOAELs should be established at the level of the overall study report. Interpretations such as "not biologically relevant" or "not toxicologically important" should be avoided unless defined and supported by scientific rationale. Decisions defining adverse findings and the NOAEL in final study reports should combine the expertise of all contributing scientific disciplines. Where possible, use of NOAELs in data tables should be linked to explanatory text that places them in context. Ideally, in nonclinical summary documents, NOAELs from multiple studies are considered together in defining the most important adverse responses in the most sensitive species. These responses are then considered along with an understanding of their likely mechanisms, as well as other information such as variability in species sensitivity, comparative pathology, reversibility and progression, kinetics, and

  19. [Endocrinologic adverse effects of psychotropic drugs].

    PubMed

    Elenitza, Irene María

    2005-01-01

    Psychotropic drugs affect the regulatory mechanisms of different neuroendocrine axis. This chapter reviews the interactions between psychotropic drugs and prolactin, the hypothalamic-pituitary-thyroid axis and the hypothalamic-pituitary-gonadal axis. Hyperprolactinemia can cause galactorrhea, amenorrhea, sexual disfunction, impaired spermatogenesis and increased risk for osteoporosis and fractures. Atypical antipsychotics cause less hyperprolactinemia than conventional antipsychotics. Lithium has important effects on thyroid function. During lithium treatment, affectively ill patients show, in varying degrees and combinations, reduced levels of thyroid hormones and clinical evidence of subclinical hypothyroidism, overt hypothyroidism and goiter. Recent literature reports suggest that valproic acid, may be associated with polycistic ovarian syndrome. Until additional data is available, women starting valproate therapy should be warned about the possibility of endocrinology side effects.

  20. Aluminum toxicity. Hematological effects.

    PubMed

    Mahieu, S; del Carmen Contini, M; Gonzalez, M; Millen, N; Elias, M M

    2000-01-01

    Sequential effects of intoxication with aluminum hydroxide (Al) (80 mg/Kg body weight, i.p., three times a week), were studied on rats from weaning and up to 28 weeks. The study was carried out on hematological and iron metabolism-related parameters on peripheral blood, at the end of the 1st, 2nd, 3rd, 4th, 5th and 6th months of exposure. As it was described that hematotoxic effects of Al are mainly seen together with high levels of uremia, renal function was measured at the same periods. The animals treated developed a microcytosis and was accompanied by a decrease in mean corpuscular hemoglobin (MCH). Significantly lower red blood cell counts (RBC million/microl) were found in rats treated during the 1st month. These values matched those obtained for control rats during the 2nd month. From the 3rd month onwards, a significant increase was observed as compared to control groups, and the following values were obtained by the 6th month: (T) 10.0 +/- 0.3 versus (C) 8.7 +/- 0.2 (million/microl). Both MCH and mean corpuscular volume (MCV) were found to be significantly lower in groups treated from the 2nd month. At the end of the 6th month the following values were found: MCH (T) 13.3 +/- 0.1 versus (C) 16.9 +/- 0.3 (pg); MCV (T) 42.1 +/- 0.7 versus (C) 51.8 +/- 0.9 (fl). Al was found responsible for lower serum iron concentration levels and in the percentage of transferrin saturation. Thus, although microcytic anemia constitutes an evidence of chronic aluminum exposure, prolonged exposure could lead to a recovery of hematocrit and hemoglobin concentration values with an increase in red cell number. Nevertheless, both microcytosis and the decrease of MCH would persist. These modifications took place without changes being observed in the renal function during the observation period. PMID:10643868

  1. Aluminum toxicity. Hematological effects.

    PubMed

    Mahieu, S; del Carmen Contini, M; Gonzalez, M; Millen, N; Elias, M M

    2000-01-01

    Sequential effects of intoxication with aluminum hydroxide (Al) (80 mg/Kg body weight, i.p., three times a week), were studied on rats from weaning and up to 28 weeks. The study was carried out on hematological and iron metabolism-related parameters on peripheral blood, at the end of the 1st, 2nd, 3rd, 4th, 5th and 6th months of exposure. As it was described that hematotoxic effects of Al are mainly seen together with high levels of uremia, renal function was measured at the same periods. The animals treated developed a microcytosis and was accompanied by a decrease in mean corpuscular hemoglobin (MCH). Significantly lower red blood cell counts (RBC million/microl) were found in rats treated during the 1st month. These values matched those obtained for control rats during the 2nd month. From the 3rd month onwards, a significant increase was observed as compared to control groups, and the following values were obtained by the 6th month: (T) 10.0 +/- 0.3 versus (C) 8.7 +/- 0.2 (million/microl). Both MCH and mean corpuscular volume (MCV) were found to be significantly lower in groups treated from the 2nd month. At the end of the 6th month the following values were found: MCH (T) 13.3 +/- 0.1 versus (C) 16.9 +/- 0.3 (pg); MCV (T) 42.1 +/- 0.7 versus (C) 51.8 +/- 0.9 (fl). Al was found responsible for lower serum iron concentration levels and in the percentage of transferrin saturation. Thus, although microcytic anemia constitutes an evidence of chronic aluminum exposure, prolonged exposure could lead to a recovery of hematocrit and hemoglobin concentration values with an increase in red cell number. Nevertheless, both microcytosis and the decrease of MCH would persist. These modifications took place without changes being observed in the renal function during the observation period.

  2. Mirtazapine: pharmacology in relation to adverse effects.

    PubMed

    Nutt, D

    1997-01-01

    Mirtazapine is a new antidepressant that falls into the general class of receptor-blocking drugs rather than being an uptake or enzyme inhibitor. It can be described as a noradrenergic and specific serotonergic antidepressant (NaSSA). The unique pharmacology of mirtazapine means that it has a very different side effect profile from the tricyclic antidepressants, producing less alpha 1 adrenergic and muscarinic blockade, and the selective serotonin reuptake inhibitors (SSRIs) and the serotonin-noradrenaline reuptake inhibitors (SNRIs), causing much less nausea and sexual dysfunction by virtue of its blockade of 5-HT2 and 5-HT3 receptors. PMID:9265949

  3. Beneficial effect of sesame oil on heavy metal toxicity.

    PubMed

    Chandrasekaran, Victor Raj Mohan; Hsu, Dur-Zong; Liu, Ming-Yie

    2014-02-01

    Heavy metals become toxic when they are not metabolized by the body and accumulate in the soft tissue. Chelation therapy is mainly for the management of heavy metal-induced toxicity; however, it usually causes adverse effects or completely blocks the vital function of the particular metal chelated. Much attention has been paid to the development of chelating agents from natural sources to counteract lead- and iron-induced hepatic and renal damage. Sesame oil (a natural edible oil) and sesamol (an active antioxidant) are potently beneficial for treating lead- and iron-induced hepatic and renal toxicity and have no adverse effects. Sesame oil and sesamol significantly inhibit iron-induced lipid peroxidation by inhibiting the xanthine oxidase, nitric oxide, superoxide anion, and hydroxyl radical generation. In addition, sesame oil is a potent inhibitor of proinflammatory mediators, and it attenuates lead-induced hepatic damage by inhibiting nitric oxide, tumor necrosis factor-α, and interleukin-1β levels. Because metal chelating therapy is associated with adverse effects, treating heavy metal toxicity in addition with sesame oil and sesamol may be better alternatives. This review deals with the possible use and beneficial effects of sesame oil and sesamol during heavy metal toxicity treatment. PMID:23744838

  4. 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

  5. ToxAlerts: a Web server of structural alerts for toxic chemicals and compounds with potential adverse reactions.

    PubMed

    Sushko, Iurii; Salmina, Elena; Potemkin, Vladimir A; Poda, Gennadiy; Tetko, Igor V

    2012-08-27

    The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, http://ochem.eu). The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at http://ochem.eu/alerts, and it is constantly

  6. ToxAlerts: A Web Server of Structural Alerts for Toxic Chemicals and Compounds with Potential Adverse Reactions

    PubMed Central

    2012-01-01

    The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, http://ochem.eu). The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at http://ochem.eu/alerts, and it is constantly

  7. Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

    EPA Science Inventory

    There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

  8. Adverse effects of anabolic steroids in athletes. A constant threat.

    PubMed

    Maravelias, C; Dona, A; Stefanidou, M; Spiliopoulou, C

    2005-09-15

    Anabolic-androgenic steroids (AAS) are used as ergogenic aids by athletes and non-athletes to enhance performance by augmenting muscular development and strength. AAS administration is often associated with various adverse effects that are generally dose related. High and multi-doses of AAS used for athletic enhancement can lead to serious and irreversible organ damage. Among the most common adverse effects of AAS are some degree of reduced fertility and gynecomastia in males and masculinization in women and children. Other adverse effects include hypertension and atherosclerosis, blood clotting, jaundice, hepatic neoplasms and carcinoma, tendon damage, psychiatric and behavioral disorders. More specifically, this article reviews the reproductive, hepatic, cardiovascular, hematological, cerebrovascular, musculoskeletal, endocrine, renal, immunologic and psychologic effects. Drug-prevention counseling to athletes is highlighted and the use of anabolic steroids is must be avoided, emphasizing that sports goals may be met within the framework of honest competition, free of doping substances.

  9. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone

    PubMed Central

    Dogra, Prerna; Suman, Saurav; Acharya, Saurav; Matta, Jyoti

    2016-01-01

    Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form. PMID:27672457

  10. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone.

    PubMed

    Paudel, Robin; Dogra, Prerna; Suman, Saurav; Acharya, Saurav; Matta, Jyoti

    2016-01-01

    Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form. PMID:27672457

  11. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone

    PubMed Central

    Dogra, Prerna; Suman, Saurav; Acharya, Saurav; Matta, Jyoti

    2016-01-01

    Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form.

  12. Neurological adverse effects of methylphenidate may be misdiagnosed as meningoencephalitis.

    PubMed

    Snell, Luke Blagdon; Bakshi, Dinkar

    2015-06-16

    We present a case of adverse neurological effects of methylphenidate therapy for attention deficit and hyperactivity disorder (ADHD). A 7-year-old boy presented to the emergency department (ED) having developed ataxic gait, orofacial dyskinesias and choreoathetosis of the limbs. The results of all blood investigations, EEG and CT scan of the head were unremarkable. Subsequently, a detailed history revealed he was being treated for ADHD, being started on methylphenidate in the past 3 months. Discontinuation of methylphenidate led to significant and rapid amelioration of neurological adverse effects.

  13. The Adverse Outcome Pathway: A conceptual framework to support toxicity testing in the 21st century

    EPA Science Inventory

    The field of regulatory toxicity testing is at a turning point. The U.S. National Research Council (NRC) envisioned a shift away from traditional toxicity testing and towards a focused effort to explore and understand pathways perturbed by biologically active substances or their ...

  14. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish.

    PubMed

    Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

    2015-02-01

    Adverse outcome pathways (AOPs) organize knowledge on the progression of toxicity through levels of biological organization. By determining the linkages between toxicity events at different levels, AOPs lay the foundation for mechanism-based alternative testing approaches to hazard assessment. Here, we focus on growth impairment in fish to illustrate the initial stages in the process of AOP development for chronic toxicity outcomes. Growth is an apical endpoint commonly assessed in chronic toxicity tests for which a replacement is desirable. Based on several criteria, we identified reduction in food intake to be a suitable key event for initiation of middle-out AOP development. To start exploring the upstream and downstream links of this key event, we developed three AOP case studies, for pyrethroids, selective serotonin reuptake inhibitors (SSRIs) and cadmium. Our analysis showed that the effect of pyrethroids and SSRIs on food intake is strongly linked to growth impairment, while cadmium causes a reduction in growth due to increased metabolic demands rather than changes in food intake. Locomotion impairment by pyrethroids is strongly linked to their effects on food intake and growth, while for SSRIs their direct influence on appetite may play a more important role. We further discuss which alternative tests could be used to inform on the predictive key events identified in the case studies. In conclusion, our work demonstrates how the AOP concept can be used in practice to assess critically the knowledge available for specific chronic toxicity cases and to identify existing knowledge gaps and potential alternative tests. PMID:25456049

  15. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish.

    PubMed

    Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

    2015-02-01

    Adverse outcome pathways (AOPs) organize knowledge on the progression of toxicity through levels of biological organization. By determining the linkages between toxicity events at different levels, AOPs lay the foundation for mechanism-based alternative testing approaches to hazard assessment. Here, we focus on growth impairment in fish to illustrate the initial stages in the process of AOP development for chronic toxicity outcomes. Growth is an apical endpoint commonly assessed in chronic toxicity tests for which a replacement is desirable. Based on several criteria, we identified reduction in food intake to be a suitable key event for initiation of middle-out AOP development. To start exploring the upstream and downstream links of this key event, we developed three AOP case studies, for pyrethroids, selective serotonin reuptake inhibitors (SSRIs) and cadmium. Our analysis showed that the effect of pyrethroids and SSRIs on food intake is strongly linked to growth impairment, while cadmium causes a reduction in growth due to increased metabolic demands rather than changes in food intake. Locomotion impairment by pyrethroids is strongly linked to their effects on food intake and growth, while for SSRIs their direct influence on appetite may play a more important role. We further discuss which alternative tests could be used to inform on the predictive key events identified in the case studies. In conclusion, our work demonstrates how the AOP concept can be used in practice to assess critically the knowledge available for specific chronic toxicity cases and to identify existing knowledge gaps and potential alternative tests.

  16. 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

  17. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... 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...

  18. 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....

  19. 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....

  20. [Study progress of adverse effects of arsenic on health].

    PubMed

    Kang, Jiaqi; Jin, Yinlong

    2004-05-01

    Adverse effects on health of high arsenic in drinking water and contaminated environment are currently of great concern. This review focuses on metabolism of arsenic and it's impairments to skin, blood circle system, nervous system, reproductive-and-urinary system, digestive system, respiratory system and immune system.

  1. Effects of micronutrients on metal toxicity.

    PubMed Central

    Peraza, M A; Ayala-Fierro, F; Barber, D S; Casarez, E; Rael, L T

    1998-01-01

    There is growing evidence that micronutrient intake has a significant effect on the toxicity and carcinogenesis caused by various chemicals. This paper examines the effect of micronutrient status on the toxicity of four nonessential metals: cadmium, lead, mercury, and arsenic. Unfortunately, few studies have directly examined the effect of dietary deficiency or supplementation on metal toxicity. More commonly, the effect of dietary alteration must be deduced from the results of mechanistic studies. We have chosen to separate the effect of micronutrients on toxic metals into three classes: interaction between essential micronutrients and toxic metals during uptake, binding, and excretion; influence of micronutrients on the metabolism of toxic metals; and effect of micronutrients on secondary toxic effects of metals. Based on data from mechanistic studies, the ability of micronutrients to modulate the toxicity of metals is indisputable. Micronutrients interact with toxic metals at several points in the body: absorption and excretion of toxic metals; transport of metals in the body; binding to target proteins; metabolism and sequestration of toxic metals; and finally, in secondary mechanisms of toxicity such as oxidative stress. Therefore, people eating a diet deficient in micronutrients will be predisposed to toxicity from nonessential metals. PMID:9539014

  2. 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

  3. Indoor air pollution: Acute adverse health effects and host susceptibility

    SciTech Connect

    Zummo, S.M.; Karol, M.H.

    1996-01-01

    Increased awareness of the poor quality of indoor air compared with outdoor air has resulted in a significant amount of research on the adverse health effects and mechanisms of action of indoor air pollutants. Common indoor air agents are identified, along with resultant adverse health effects, mechanisms of action, and likely susceptible populations. Indoor air pollutants range from biological agents (such as dust mites) to chemical irritants (such as nitrogen dioxide, carbon monoxide, sulfur dioxide, formaldehyde, and isocyanates). These agents may exert their effects through allergic as well as nonallergic mechanisms. While the public does not generally perceive poor indoor air quality as a significant health risk, increasing reports of illness related to indoor air and an expanding base of knowledge on the health effects of indoor air pollution are likely to continue pushing the issue to the forefront.

  4. 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.

  5. 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

  6. 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

  7. Optimising the retrieval of information on adverse drug effects.

    PubMed

    Golder, Su

    2013-12-01

    Pharmaceutical interventions have brought about many benefits to health, improving the population's well-being and life expectancy. However, these interventions are not without potential harmful side-effects and yet searching for the evidence on adverse effects is challenging. This article summarises a PhD whose main aim was to develop a better understanding of the implications of using different sources and approaches to identifying relevant data on adverse effects. The author is Su Golder, who has recently completed her PhD at the University of York and who has already published several articles on specific aspects of her research, including this journal. This article is the first in the Dissertations into Practice series to report on a PhD study, and it summarises her research in a way which emphasises the implications for practice.

  8. Energy Drink Consumption: Beneficial and Adverse Health Effects.

    PubMed

    Alsunni, Ahmed Abdulrahman

    2015-10-01

    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

  9. Ocular surface adverse effects of ambient levels of air pollution.

    PubMed

    Torricelli, André Augusto Miranda; Novaes, Priscila; Matsuda, Monique; Alves, Milton Ruiz; Monteiro, Mário Luiz Ribeiro

    2011-01-01

    It is widely recognized today that outdoor air pollution can affect human health. Various chemical components that are present in ambient pollution may have an irritant effect on the mucous membranes of the body, particularly those of the respiratory tract. Much less attention has been focused on the adverse effect on the ocular surface, despite the fact that this structure is even more exposed to air pollution than the respiratory mucosa since only a very thin tear film separates the corneal and conjunctival epithelia from the air pollutants. So far, clinical data are the more widespread tools used by ophthalmologists for assessing possible aggression to the ocular surface; however, clinical findings alone appears not to correlate properly with the complaints presented by the patients pointing out the need for further clinical and laboratory studies on the subject. The purpose of this study is to review signs and symptoms associated with chronic long-term exposure to environmental air pollutants on the ocular structures currently defined as the ocular surface and to review clinical and laboratory tests used to investigate the adverse effects of air pollutants on such structures. We also review previous studies that investigated the adverse effects of air pollution on the ocular surface and discuss the need for further investigation on the subject.

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

    PubMed

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

    2014-09-01

    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.

  11. Psychological adverse effects of cannabis smoking: a tentative classification.

    PubMed

    Nigrete, J C

    1973-01-20

    This paper stresses the need for an early definition and description of the "deviant" cannabis smoker in North America. Attention is called to the fact that on this continent heavy smokers have not yet been separated as "problem" users from other smokers.A comprehensive review of possible psychological adverse effects of the drug is made. The following classification is suggested: a) Severe intoxications, b) Pathological intoxications, c) Acute cannabis psychoses, d) Subacute and chronic cannabis psychoses and e) Residual conditions.

  12. Psychological adverse effects of cannabis smoking: a tentative classification.

    PubMed

    Nigrete, J C

    1973-01-20

    This paper stresses the need for an early definition and description of the "deviant" cannabis smoker in North America. Attention is called to the fact that on this continent heavy smokers have not yet been separated as "problem" users from other smokers.A comprehensive review of possible psychological adverse effects of the drug is made. The following classification is suggested: a) Severe intoxications, b) Pathological intoxications, c) Acute cannabis psychoses, d) Subacute and chronic cannabis psychoses and e) Residual conditions. PMID:4569453

  13. Systematic Review of Adverse Effects from Herbal Drugs Reported in Randomized Controlled Trials.

    PubMed

    Lee, Ji Young; Jun, Seung Ah; Hong, Sung Shin; Ahn, Yo Chan; Lee, Dong Soo; Son, Chang Gue

    2016-09-01

    Herbal drugs have become a popular form of healthcare, raising concerns about their safety. This study aimed to characterize the adverse effects of herbal drugs through a systematic review of results reported in randomized controlled trials (RCTs). Using eight electronic databases including PubMed, the Cochrane library and six Korean medical databases, the frequency of reported toxicity was recorded based on drug composition and indication. Among 4957 potentially relevant articles, 242 papers comprised of 244 studies met our inclusion criteria; these included 111 studies of a single herb and 133 of multiple herbs. These studies accounted for a total 15 441 participants (male = 5590; female = 9851; 7383 for single and 8058 for multiple herb studies). There were 480 cases (3.1%) of adverse events (344 for single, 136 for multiple herb studies; p < 0.01). A total of 259 cases reported blood test abnormalities, including five cases of abnormality in hepatic functional enzymes. The most frequently reported adverse event was digestive symptoms (44.3%), followed by nervous system symptoms (17.3%) and behaviors such as loss of appetite (16.3%). This is the first systematic review of adverse effects of herbal drugs among clinical studies, and the results indicate that herbal drugs are relatively safe. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27196988

  14. 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.

  15. Adverse effects of creatine supplementation: fact or fiction?

    PubMed

    Poortmans, J R; Francaux, M

    2000-09-01

    The consumption of oral creatine monohydrate has become increasingly common among professional and amateur athletes. Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. The objectives of this review are to identify the scientific facts and contrast them with reports in the news media, which have repeatedly emphasised the health risks of creatine supplementation and do not hesitate to draw broad conclusions from individual case reports. Exogenous creatine supplements are often consumed by athletes in amounts of up to 20 g/day for a few days, followed by 1 to 10 g/day for weeks, months and even years. Usually, consumers do not report any adverse effects, but body mass increases. There are few reports that creatine supplementation has protective effects in heart, muscle and neurological diseases. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals, but the effects are anecdotal. Liver and kidney dysfunction have also been suggested on the basis of small changes in markers of organ function and of occasional case reports, but well controlled studies on the adverse effects of exogenous creatine supplementation are almost nonexistent. We have investigated liver changes during medium term (4 weeks) creatine supplementation in young athletes. None showed any evidence of dysfunction on the basis of serum enzymes and urea production. Short term (5 days), medium term (9 weeks) and long term (up to 5 years) oral creatine supplementation has been studied in small cohorts of athletes whose kidney function was monitored by clearance methods and urine protein excretion rate. We did not find any adverse effects on renal function. The present review is not intended to reach conclusions on the effect of creatine supplementation on sport performance, but we believe that there is no evidence for deleterious effects

  16. Adverse outcome pathways linked to population models as a methodology for investigating effects of chemical stressors

    EPA Science Inventory

    In addressing the complexity and toxicity of chemical contaminants in Great Lakes ecosystems, we describe an approach to link chemically induced alterations in molecular and biochemical endpoints to adverse outcomes in whole organisms and populations. Analysis of population impac...

  17. Identification and characterization of adverse effects in 21st century toxicology.

    PubMed

    Keller, Douglas A; Juberg, Daland R; Catlin, Natasha; Farland, William H; Hess, Frederick G; Wolf, Douglas C; Doerrer, Nancy G

    2012-04-01

    The practice of toxicology is changing rapidly, as demonstrated by the response to the 2007 NRC report on "Toxicity Testing in the 21(st) Century." New assays are being developed to replace animal testing; yet the use of data from these assays in decision making is not clear. A Health and Environmental Sciences Institute committee held a May 2011 workshop to discuss approaches to identifying adverse effects in the context of the NRC report. Scientists from industry, government, academia, and NGOs discussed two case studies and explored how information from new, high data content assays developed for screening can be used to differentiate adverse effects from adaptive responses. The terms "adverse effect" and "adaptive response" were defined, as well as two new terms, the relevant pathways of toxicological concern (RPTCs) and relevant responses for regulation (RRRs). RPTCs are biochemical pathways associated with adverse events and need to be elucidated before they are used in regulatory decision making. RRRs are endpoints that are the basis for risk assessment and may or may not be at the level of pathways. Workshop participants discussed the criteria for determining whether, at the RPTC level, an effect is potentially adverse or potentially indicative of adaptability, and how the use of prototypical, data-rich compounds could lead to a greater understanding of RPTCs and their use as RRRs. Also discussed was the use of RPTCs in a weight-of-evidence approach to risk assessment. Inclusion of data at this level could decrease uncertainty in risk assessments but will require the use of detailed dosimetry and consideration of exposure context and the time and dose continuum to yield scientifically based decisions. The results of this project point to the need for an extensive effort to characterize RPTCs and their use in risk assessment to make the vision of the 2007 NRC report a reality.

  18. Synergetic toxic effect of an explosive material mixture in soil.

    PubMed

    Panz, Katarzyna; Miksch, Korneliusz; Sójka, Tadeusz

    2013-11-01

    Explosives materials are stable in soil and recalcitrant to biodegradation. Different authors report that TNT (2,4,6-trinitrotoluene), RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) and HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) are toxic, but most investigations have been performed in artificial soil with individual substances. The aim of the presented research was to assess the toxicity of forest soil contaminated with these substances both individually as well in combinations of these substances. TNT was the most toxic substance. Although RDX and HMX did not have adverse effects on plants, these compounds did cause earthworm mortality, which has not been reported in earlier research. Synergistic effects of explosives mixture were observed.

  19. Adverse effects of thalidomide administration in patients with neoplastic diseases.

    PubMed

    Dimopoulos, Meletios A; Eleutherakis-Papaiakovou, Vagelis

    2004-10-01

    Thalidomide, a glutamic acid derivative, was withdrawn from clinical use in 1962 due to its severe teratogenic effects. Its recent reinstitution in clinical practice was related to its benefits in leprosy and multiple myeloma. Moreover, the antiangiogenic and immunomodulatory properties of thalidomide have led to its evaluation in several malignant diseases, including myelofibrosis, renal cell cancer, prostate cancer, and Kaposi sarcoma. However, thalidomide use is associated with several side effects: somnolence and constipation are the most common, while deep vein thrombosis and peripheral neuropathy are the most serious. A combination of thalidomide with steroids or chemotherapy is being evaluated in several phase 2 studies. While it is not yet clear whether these combinations will enhance efficacy, they appear to increase the toxicity of thalidomide, and thalidomide analogs are being developed to minimize this toxicity. Ongoing studies will clarify the potential advantages of these agents in the treatment of neoplastic diseases.

  20. 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

  1. 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.

  2. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... signature: (1) “I have applied the criteria of 40 CFR 161.34 for flagging studies for potential adverse... criteria.” (2) “I have applied the criteria of 40 CFR 161.34 for flagging studies for potential adverse... this section when any criterion is met or exceeded. Table—Flagging Criteria Toxicity studies...

  3. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... signature: (1) “I have applied the criteria of 40 CFR 161.34 for flagging studies for potential adverse... criteria.” (2) “I have applied the criteria of 40 CFR 161.34 for flagging studies for potential adverse... this section when any criterion is met or exceeded. Table—Flagging Criteria Toxicity studies...

  4. 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.

  5. 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.

  6. 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

  7. Psychological adverse effects of cannabis smoking: a tentative classification

    PubMed Central

    Negrete, J. C.

    1973-01-01

    This paper stresses the need for an early definition and description of the “deviant” cannabis smoker in North America. Attention is called to the fact that on this continent heavy smokers have not yet been separated as “problem” users from other smokers. A comprehensive review of possible psychological adverse effects of the drug is made. The following classification is suggested: a) Severe intoxications, b) Pathological intoxications, c) Acute cannabis psychoses, d) Subacute and chronic cannabis psychoses and e) Residual conditions. PMID:4569453

  8. Adverse effects of bisphenol A on male reproductive function.

    PubMed

    Manfo, Faustin Pascal Tsagué; Jubendradass, Rajamanickam; Nantia, Edouard Akono; Moundipa, Paul Fewou; Mathur, Premendu Prakash

    2014-01-01

    BPA is a ubiquitous environmental contaminant, resulting mainly from manufacturing,use or disposal of plastics of which it is a component, and the degradation of industrial plastic-related wastes. Growing evidence from research on laboratory animals, wildlife, and humans supports the view that BPA produces an endocrine disrupting effect and adversely affects male reproductive function. To better understand the adverse effects caused by exposure to BPA, we performed an up-to-date literature review on the topic, with particular emphasis on in utero exposure, and associated effects on spermatogenesis, steroidogenesis, and accessory organs.BPA studies on experimental animals show that effects are generally more detrimental during in utero exposure, a critical developmental stage for the embryo. BPA has been found to produce several defects in the embryo, such as feminization of male fetuses, atrophy of the testes and epididymides, increased prostate size, shortening of AGD, disruption of BTB, and alteration of adult sperm parameters (e.g.,sperm count, motility, and density). BPA also affects embryo thyroid development.During the postnatal and pubertal periods and adulthood, BPA affects the hypothalamic-pituitary-testicular axis by modulating hormone (e.g., LH and FSH,androgen and estrogen) synthesis, expression and function of respective receptors(ER, AR). These effects alter sperm parameters. BPA also induces oxidative stress in the testis and epididymis, by inhibiting antioxidant enzymes and stimulating lipid peroxidation. This suggests that employing antioxidants may be a promising strategy to relieve BPA-induced disturbances.Epidemiological studies have also provided data indicating that BPA alters male reproductive function in humans. These investigations revealed that men occupationally exposed to BPA had high blood/urinary BPA levels, and abnormal semen parameters. BPA-exposed men also showed reduced libido and erectile ejaculatory difficulties; moreover, the

  9. 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

  10. 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

  11. 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

  12. 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

  13. Pharmacovigilance, risks and adverse effects of self-medication.

    PubMed

    Montastruc, Jean-Louis; Bondon-Guitton, Emmanuelle; Abadie, Delphine; Lacroix, Isabelle; Berreni, Aurélia; Pugnet, Grégory; Durrieu, Geneviève; Sailler, Laurent; Giroud, Jean-Paul; Damase-Michel, Christine; Montastruc, François

    2016-04-01

    Self-medication means resorting to one or more drugs in order to treat oneself without the help of a doctor. This phenomenon is developing fast. In this review, we will discuss the main definitions of self-medication; we will then present a few important characteristics of this therapeutic practice: prevalence, reasons, populations involved and drugs used. Whilst the theoretical risks of self-medication have been abundantly discussed in the literature (adverse effects, interactions, product, dosage or treatment duration errors, difficulty in self-diagnosis, risk of addiction or abuse…), there is in fact very little detailed pharmacovigilance data concerning the characteristics and the consequences of this usage in real life. This study therefore describes the all too rare data that is available: patients, clinical characteristics, "seriousness" and drugs involved in the adverse effects of self-medication. It also discusses leads to be followed in order to minimize medication risks, which are obviously not well known and clearly not sufficiently notified.

  14. Possible adverse effects of frying with vegetable oils.

    PubMed

    Dobarganes, Carmen; Márquez-Ruiz, Gloria

    2015-04-01

    The question of whether heated fats in the diet may be detrimental to health is nowadays of the upmost concern, but finding an answer is not easy and requires careful consideration of different aspects of lipid oxidation. This review is divided into two sections. The first part deals with the nature of the new compounds formed at high temperature in the frying process as well as their occurrence in the diet while the second part focuses on their possible nutritional and physiological effects. Oxidation products present in abused frying fats and oils are the compounds most suspected of impairing the nutritional properties of the oils or involving adverse physiological effects. The recent studies on their health implications include those related to their fate and those focused on their effects in metabolic pathways and the most prevalent diseases.

  15. Symptomatic sinus bradycardia: A rare adverse effect of intravenous ondansetron

    PubMed Central

    Moazzam, Md Shahnawaz; Nasreen, Farah; Bano, Shahjahan; Amir, Syed Hussain

    2011-01-01

    Ondansetron is a serotonin receptor antagonist which has been used frequently to reduce the incidence of post-operative nausea and vomiting in laparoscopic surgery. It has become very popular drug for the prevention of post-operative nausea and vomiting due to its superiority in-terms of efficacy as well as lack of side effects and drug interactions. Although cardiovascular adverse effects of this drug are rare, we found a case of symptomatic sinus bradycardia in a 43-year-old female patient, going for laparoscopic cholecystectomy, who developed the same after she was given intravenous ondansetron in operation theater during premedication. Hence, we report this case, as the rare possibility of encountering bradycardia effect after intravenous administration of ondansetron should be born in mind. PMID:21655029

  16. Clinical outcomes and adverse effect monitoring in allergic rhinitis.

    PubMed

    Juniper, Elizabeth F; Ståhl, Elisabeth; Doty, Richard L; Simons, F Estelle R; Allen, David B; Howarth, Peter H

    2005-03-01

    The subjective recording in diary cards of symptoms of itch, sneeze, nose running, and blockage, with the use of a rating scale to indicate the level of severity, is usual for clinical trials in allergic rhinitis. The primary outcome measure is usually a composite score that enables a single total symptoms score endpoint. It is appreciated, however, that rhinitis has a greater effect on the individual than is reflected purely by the recording of anterior nasal symptoms. Nasal obstruction is troublesome and may lead to sleep disturbance in addition to impaired daytime concentration and daytime sleepiness. These impairments affect school and work performance. Individuals with rhinitis find it socially embarrassing to be seen sneezing, sniffing, or blowing their nose. To capture these and other aspects of the disease-specific health-related quality of life, questionnaires such as the Rhinoconjunctivitis Quality of Life Questionnaire have been developed and validated for clinical trial use. The adoption of health-related quality of life questionnaires into clinical trials broadens the information obtained regarding the effect of the therapeutic intervention and helps focus on issues relevant to the individual patient. It must be appreciated that it is not only the disease that may adversely affect health-related quality of life; administered therapy, although intended to be beneficial, may also cause health impairment. Adverse-event monitoring is thus essential in clinical trials. The first-generation H 1 -histamines, because of their effect on central H 1 -receptors, are classically associated with central nervous system (CNS) effects such as sedation. Although this is not always perceived by the patient, it is clearly evident with objective performance testing, and positron emission tomography scanning has directly demonstrated the central H 1 -receptor occupancy. The second-generation H 1 -antihistamines have reduced central H 1 -receptor occupancy and considerably

  17. Adverse effects of low level heavy metal exposure on male reproductive function.

    PubMed

    Wirth, Julia J; Mijal, Renée S

    2010-04-01

    Lead, cadmium, mercury, and arsenic, often referred to as "heavy metals", are toxic for wildlife, experimental animals, and humans. While experimental animal and human occupational studies with high exposure levels generally support an adverse role for these metals in human reproductive outcomes, information on the effects of low, environmentally-realistic exposure levels of these metals on male reproductive outcomes is limited. We review the literature on effects of exposure to low levels of these metals on measures of male fertility (semen quality and reproductive hormone levels) and provide supporting evidence from experimental and occupational studies. Potentially modifying effects of genetic polymorphisms on these associations are discussed. A brief review of the literature on the effects of three trace metals, copper, manganese, and molybdenum, that are required for human health, yet may also cause adverse reproductive effects, follows. Overall, there were few studies examining the effects of exposure to low levels of these metals on male reproductive health. For all metals, there were several well-designed studies with sufficient populations appropriately adjusted for potential confounders and many of these reported harmful effects. However, many studies lacked sufficient numbers of participants to be able to detect differences in outcomes between exposed and non-exposed individuals, did not clearly identify the source and characteristics of the participants, and did not control for other exposures that could alter or contribute to the outcomes. The evidence for the effects of low exposure was strongest for cadmium, lead, and mercury and less certain for arsenic. The potential modifying effects of genetic polymorphisms has not been fully explored. Additional studies on the reproductive effects of these toxic ubiquitous metals on male reproduction are required to expand the knowledge base and to resolve inconsistencies.

  18. Neuromuscular adverse effects associated with systemic retinoid dermatotherapy: monitoring and treatment algorithm for clinicians.

    PubMed

    Chroni, Elisabeth; Monastirli, Alexandra; Tsambaos, Dionysios

    2010-01-01

    Although neuromuscular adverse effects represent significant clinical manifestations of hypervitaminosis A syndrome, surprisingly little attention has been paid to the potential neuromuscular toxicity of vitamin A derivatives (retinoids). Since isotretinoin and acitretin are currently the two most commonly used oral retinoids in systemic dermatotherapy, this review focuses exclusively on their neuromuscular adverse effects and proposes a neuromuscular algorithm for appropriate monitoring of patients treated with these two compounds. The most frequent CNS adverse effect associated with oral isotretinoin is headache, either as an independent adverse effect or as part of benign intracranial hypertension, which is additionally characterized by nausea and visual changes. Isolated cases of stiff-person-like syndrome, epileptic seizures and generalized muscle stiffness syndrome, possibly or probably related to oral treatment with isotretinoin, have also been reported. In addition, oral isotretinoin has reportedly been associated with muscular adverse effects that most frequently manifest as myalgia and stiffness and, in rare cases, as true myopathy or rhabdomyolysis. Creatine phosphokinase, a specific marker of muscle destruction, has been found to be elevated, occasionally by up to 100 times the normal value (with or without muscular symptoms and signs), in a variable percentage of patients receiving isotretinoin treatment and particularly in those undergoing vigorous physical exercise. Oral acitretin has been found to cause peripheral nerve dysfunction, particularly of sensory fibres, which in rare cases leads to clinically evident sensory disturbances. Less clear is the causal relationship between acitretin and benign intracranial hypertension or myopathy, whereas an isolated case of cranial nerve IV (oculomotor) palsy and a further case of thrombotic stroke during treatment with oral acitretin have been reported. Systemic diseases with involvement of nervous and

  19. European guidelines on managing adverse effects of medication for ADHD

    PubMed Central

    Banaschewski, T.; Buitelaar, J.; Coghill, D.; Danckaerts, M.; Dittmann, R. W.; Döpfner, M.; Hamilton, R.; Hollis, C.; Holtmann, M.; Hulpke-Wette, M.; Lecendreux, M.; Rosenthal, E.; Rothenberger, A.; Santosh, P.; Sergeant, J.; Simonoff, E.; Sonuga-Barke, E.; Wong, I. C. K.; Zuddas, A.; Steinhausen, H.-C.; Taylor, E.

    2010-01-01

    The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks. PMID:21042924

  20. 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

  1. Adverse effects of sucrose-rich diets on uraemic rats.

    PubMed

    Laouari, D; Kleinknecht, C; Burtin, M; Hinglais, N; Lacour, B; Landais, P; Broyer, M

    1990-01-01

    The nature of carbohydrate may affect the tolerance and progression of uraemia. The effects of three diets differing only in their carbohydrate source: namely corn starch (C), glucose (G) or sucrose (S) were examined. Study 1 examined the effects of the three carbohydrate diets on unilaterally nephrectomised control rats and severely uraemic rats. The three carbohydrates produced similar nutritional effects in uninephrectomised rats, whereas sucrose rapidly induced anorexia, stunting and slightly accelerated renal damage in uraemia. Study 2 examined the long-term effects of the three carbohydrates in moderate uraemia under conditions of high and identical carbohydrate intakes. Hyperphagic Zucker uraemic rats (F rats) received a daily allotment of each diet plus pure carbohydrate. Lean uraemic rats (L rats) received the same dietary allotment without the carbohydrate supplement. The F rats fed sucrose showed greater morbidity and mortality but little renal deterioration. Their plasma triglycerides increased dramatically. The L rats fed sucrose had the greatest urinary protein, the least creatinine clearance and the most severe renal damage. Thus, sucrose-rich but not glucose-rich diets have two adverse effects in uraemia: a deterioration in nutritional status, perhaps related to abnormal fructose utilisation, and a long-term effect on the kidney, resulting in accelerated renal deterioration.

  2. The dark side of the light: Phototherapy adverse effects.

    PubMed

    Valejo Coelho, Margarida Moura; Apetato, Margarida

    2016-01-01

    Phototherapy is a valuable therapeutic tool in Dermatology, but there may be drawbacks. Acute and long-term adverse effects, of variable severity, include skin erythema, xerosis, pruritus, blistering, altered pigmentation, photoaging, and photocarcinogenesis. Despite concerns over the carcinogenic potential of ultraviolet radiation, most studies have not found an increased risk of non-melanoma or melanoma skin cancer in patients treated with ultraviolet B (broadband and narrowband) and ultraviolet A1 phototherapy. These are therefore considered reasonably safe treatment modalities concerning the development of skin neoplasms, although caution and further investigation are warranted. Photoprotective measures, such as avoidance of concurrent sunlight exposure and covering skin areas not afflicted with disease, or more modern strategies, including phytochemical antioxidants and exogenous DNA repair enzymes, can minimize the hazards of phototherapy. Patients submitted to phototherapeutic regimens should undergo complete, careful dermatologic examination regularly and lifelong. PMID:27638433

  3. Potential Toxic Effects of Nano-Oxides

    NASA Astrophysics Data System (ADS)

    Xu, Mingsheng; Chen, Hongzheng; Shi, Minmin; Wu, Gang; Fujita, Daisuke; Hanagata, Nobutaka

    2013-09-01

    The increasing use of nanomaterials in industrial and consumer products has aroused global concern regarding their potential impact on environment and human health. A number of studies on the effects of nanomaterials in in vitro and in vivo systems have been shown that some nanomaterials are potentially toxic. We address the understanding of the link of physicochemical characteristics of some nano-oxides including SiO2, TiO2, and ZnO to the observed toxic effects. Understanding the contribution of physicochemical characteristics of nanomaterials to toxic effects would allow safety to be built into the design of nanomaterials and their applications, to allow their safe integration into products.

  4. Increasing the Benefits of Chemotherapy by Ameliorating the Adverse Effects

    PubMed Central

    Fernandez, L.A.

    1987-01-01

    When cancer is first diagnosed in most patients, it is usually incurable. Chemotherapy can cause remissions, prolonged disease-free survival, and prolonged survival in general, but it is associated with considerable toxicity to the physical and mental well-being of the patient. The number of side-effects increases when multiple drug combinations are used. In addition, financial and social problems add to the stress of coping with a fatal disease. Therefore both patients and physicians have asked whether survival (sometimes for extra months) with added side-effects of chemotherapy is worthwhile. The “soft” index of quality of life has been measured by many investigators, and a variety of interventions have been found to alleviate some distress. PMID:21263996

  5. 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

  6. A brief study of toxic effects of some medicinal herbs on kidney

    PubMed Central

    Asif, Mohammad

    2012-01-01

    Increased use of complementary and alternative herbal medicines in the treatment of various diseases.Some herbal therapies may be causes of potential toxicity that may be renal toxicity caused by the ingestion of herbs. The goal of this study is the toxic and beneficial effects of medicinal herbs on renal health by which evidence for benefit or toxicity has been found. Included are nephrotoxicity from aristolochic acid and other components within herbs, herb-drug interactions, heavy metal toxicity in herbs and adulterants during careless preparation of herbal medicine, resulting in adverse renal effects and renal toxicity from contaminants within the extracts. The review aims to provide knowledge and guide to encourage future toxicity studies on the kidney by medicinal herbs. PMID:23326775

  7. The problems of anticholinergic adverse effects in older patients.

    PubMed

    Feinberg, M

    1993-01-01

    concentration to frank delirium. Even mild effects can reduce function and increase dependency. At any level of care, the loss of independence increases the caregiver burden, costs, and most importantly, can negatively affect quality of life. Many age-related and disease-related conditions may predispose elderly patients to anticholinergic drug toxicity. Careful attention to anticholinergic effects when prescribing drugs, patient education, regular review of the entire drug regimen, and familiarity with the signs and symptoms of anticholinergic toxicity will help to reduce the risk of drug-induced problems. PMID:8369593

  8. 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.

  9. 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

  10. 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

  11. Core Concepts Involving Adverse Psychotropic Drug Effects: Assessment, Implications, and Management.

    PubMed

    Goldberg, Joseph F; Ernst, Carrie L

    2016-09-01

    Adverse effects from psychiatric drugs can profoundly influence treatment adherence and outcomes. Good care involves addressing adverse effects no differently than any other component of treatment. Knowledge about adverse effect assessment and management fosters a proper context that helps clinicians not sacrifice a drug's potential therapeutic benefits because of greater concerns about its tolerability. This article provides an overview of basic concepts related to the assessment and management of suspected adverse effects from psychotropic drugs. Key points are discussed regarding clinical, pharmacogenetic, pharmacokinetic, and pharmacodynamic risk factors for treatment-emergent adverse effects, alongside recommendations for their systematic assessment. PMID:27514295

  12. Environmental toxicant effects on neuroendocrine function.

    PubMed

    Gore, A C

    2001-03-01

    Exposure to environmental toxicants can have profound effects on normal growth and development. However, the mechanisms by which these toxicants exert these effects are not well understood. Many environmental toxicants alter reproductive function and have effects on the central nervous system and behavior, yet the link between these reproductive and neurologic phenomena has not been systematically investigated. The neuroendocrine (hypothalamic-pituitary-gonadal) axis, which integrates inputs to and outputs from the nervous and reproductive systems, is functionally and anatomically situated to mediate effects of environmental toxicants, particularly those that are endocrine-disrupting chemicals (EDCs), on developmental processes. This article reviews the current literature on EDC effects on the neuroendocrine system, particularly at the level of hypothalamic gonadotropin-releasing hormone (GnRH) neurons, the key cells involved in the regulation of reproductive function. The focus of this article is on two polychlorinated biphenyl mixtures (Aroclor 1221, Aroclor 1254) and two organochlorine pesticides (methoxychlor and chlorpyrifos). Some experimental data are presented for each of the four urban environmental toxicants on GnRH cells in vitro and in vivo. The results of in vitro experiments indicate that all four of the toxicants profoundly affect hypothalamic GnRH gene expression, cell survival, and neurite outgrowth, demonstrating direct effects of EDCs on a GnRH cell line. In in vivo experiments, three of the toxicants (Aroclor 1221, methoxychlor, and chlorpyrifos) caused significant alterations in GnRH mRNA levels in female rats. Both the in vitro and in vivo findings support the novel concept of chlorpyrifos as an EDC. The results, taken together with the literature, support the hypothesis that the neuroendocrine axis, and specifically GnRH neurons, are sensitive to urban environmental toxicants, and that reproductive and neurologic effects of EDCs may be

  13. Adverse respiratory effects of outdoor air pollution in the elderly.

    PubMed

    Bentayeb, M; Simoni, M; Baiz, N; Norback, D; Baldacci, S; Maio, S; Viegi, G; Annesi-Maesano, I

    2012-09-01

    Compared to the rest of the population, the elderly are potentially highly susceptible to the effects of outdoor air pollution due to normal and pathological ageing. The purpose of the present review was to gather data on the effects on respiratory health of outdoor air pollution in the elderly, on whom data are scarce. These show statistically significant short-term and chronic adverse effects of various outdoor air pollutants on cardiopulmonary morbidity and mortality in the elderly. When exposed to air pollution, the elderly experience more hospital admissions for asthma and chronic obstructive pulmonary disease (COPD) and higher COPD mortality than others. Previous studies also indicate that research on the health effects of air pollution in the elderly has been affected by methodological problems in terms of exposure and health effect assessments. Few pollutants have been considered, and exposure assessment has been based mostly on background air pollution and more rarely on objective measurements and modelling. Significant progress needs to be made through the development of 'hybrid' models utilising the strengths of information on exposure in various environments to several air pollutants, coupled with daily activity exposure patterns. Investigations of chronic effects of air pollution and of multi-pollutant mixtures are needed to better understand the role of air pollution in the elderly. Lastly, smoking, occupation, comorbidities, treatment and the neighbourhood context should be considered as confounders or modifiers of such a role. In this context, the underlying biological, physiological and toxicological mechanisms need to be explored to better understand the phenomenon through a multidisciplinary approach. PMID:22871325

  14. Mercury toxicity and neurodegenerative effects.

    PubMed

    Carocci, Alessia; Rovito, Nicola; Sinicropi, Maria Stefania; Genchi, Giuseppe

    2014-01-01

    Mercury is among the most toxic heavy metals and has no known physiological role in humans. Three forms of mercury exist: elemental, inorganic and organic. Mercury has been used by man since ancient times. Among the earliest were the Chinese and Romans, who employed cinnabar (mercury sulfide) as a red dye in ink (Clarkson et al. 2007). Mercury has also been used to purify gold and silver minerals by forming amalgams. This is a hazardous practice, but is still widespread in Brazil's Amazon basin, in Laos and in Venezuela, where tens of thousands of miners are engaged in local mining activities to find and purify gold or silver. Mercury compounds were long used to treat syphilis and the element is still used as an antiseptic,as a medicinal preservative and as a fungicide. Dental amalgams, which contain about 50% mercury, have been used to repair dental caries in the U.S. since 1856.Mercury still exists in many common household products around the world.Examples are: thermometers, barometers, batteries, and light bulbs (Swain et al.2007). In small amounts, some organo mercury-compounds (e.g., ethylmercury tiosalicylate(thimerosal) and phenylmercury nitrate) are used as preservatives in some medicines and vaccines (Ballet al. 2001).Each mercury form has its own toxicity profile. Exposure to Hg0 vapor and MeHg produce symptoms in CNS, whereas, the kidney is the target organ when exposures to the mono- and di-valent salts of mercury (Hg+ and Hg++, respectively)occur. Chronic exposure to inorganic mercury produces stomatitis, erethism and tremors. Chronic MeHg exposure induced symptoms similar to those observed in ALS, such as the early onset of hind limb weakness (Johnson and Atchison 2009).Among the organic mercury compounds, MeHg is the most biologically available and toxic (Scheuhammer et a!. 2007). MeHg is neurotoxic, reaching high levels of accumulation in the CNS; it can impair physiological function by disrupting endocrine glands (Tan et a!. 2009).The most

  15. Mercury toxicity and neurodegenerative effects.

    PubMed

    Carocci, Alessia; Rovito, Nicola; Sinicropi, Maria Stefania; Genchi, Giuseppe

    2014-01-01

    Mercury is among the most toxic heavy metals and has no known physiological role in humans. Three forms of mercury exist: elemental, inorganic and organic. Mercury has been used by man since ancient times. Among the earliest were the Chinese and Romans, who employed cinnabar (mercury sulfide) as a red dye in ink (Clarkson et al. 2007). Mercury has also been used to purify gold and silver minerals by forming amalgams. This is a hazardous practice, but is still widespread in Brazil's Amazon basin, in Laos and in Venezuela, where tens of thousands of miners are engaged in local mining activities to find and purify gold or silver. Mercury compounds were long used to treat syphilis and the element is still used as an antiseptic,as a medicinal preservative and as a fungicide. Dental amalgams, which contain about 50% mercury, have been used to repair dental caries in the U.S. since 1856.Mercury still exists in many common household products around the world.Examples are: thermometers, barometers, batteries, and light bulbs (Swain et al.2007). In small amounts, some organo mercury-compounds (e.g., ethylmercury tiosalicylate(thimerosal) and phenylmercury nitrate) are used as preservatives in some medicines and vaccines (Ballet al. 2001).Each mercury form has its own toxicity profile. Exposure to Hg0 vapor and MeHg produce symptoms in CNS, whereas, the kidney is the target organ when exposures to the mono- and di-valent salts of mercury (Hg+ and Hg++, respectively)occur. Chronic exposure to inorganic mercury produces stomatitis, erethism and tremors. Chronic MeHg exposure induced symptoms similar to those observed in ALS, such as the early onset of hind limb weakness (Johnson and Atchison 2009).Among the organic mercury compounds, MeHg is the most biologically available and toxic (Scheuhammer et a!. 2007). MeHg is neurotoxic, reaching high levels of accumulation in the CNS; it can impair physiological function by disrupting endocrine glands (Tan et a!. 2009).The most

  16. Adverse effects of perinatal nicotine exposure on reproductive outcomes.

    PubMed

    Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

    2015-12-01

    Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women.

  17. 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

  18. Adverse effects induced by ecgonine methyl ester to the zebra mussel: a comparison with the benzoylecgonine.

    PubMed

    Parolini, Marco; Binelli, Andrea

    2013-11-01

    Cocaine and its metabolites are the prevalent psychotropic substances in aquatic environment. However, to date the knowledge on their adverse effects to non-target organisms is inadequate. The aims of this study were to investigate sub-lethal effects induced by the ecgonine methyl ester (EME) to the freshwater bivalve Dreissena polymorpha and to compare its toxicity to that by benzoylecgonine (BE), the other main cocaine metabolite. EME sub-lethal effects were investigated by 14 days in-vivo exposures and a multi-biomarker approach. Slight variations in biomarker responses were found at 0.15 μg/L treatment. 0.5 μg/L EME treatment induced destabilization of lysosome membranes, an overall inactivation of defense enzymes, increases in lipid peroxidation, protein carbonylation and DNA fragmentation, but no variations in fixed genetic damage. The use of a biomarker response index (BRI) showed that at 0.5 μg/L both cocaine metabolites had the same toxicity to zebra mussels specimens. PMID:23974167

  19. Second-generation antipsychotics and extrapyramidal adverse effects.

    PubMed

    Divac, Nevena; Prostran, Milica; Jakovcevski, Igor; Cerovac, Natasa

    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

  20. Enzymes approved for human therapy: indications, mechanisms and adverse effects.

    PubMed

    Baldo, Brian A

    2015-02-01

    Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented. PMID:25648140

  1. Lowest adverse effects concentrations (LOAECs) for formaldehyde exposure.

    PubMed

    Gelbke, Heinz-Peter; Gröters, Sibylle; Morfeld, Peter

    2014-10-01

    In 2012 the Committee for Risk Assessment (RAC) of the European Chemicals Agency concluded that 2ppm formaldehyde represent a Lowest Observed Adverse Effect Concentration (LOAEC) for polypoid adenomas, histopathological lesions and cell proliferation. An analysis of all data shows that a LOAEC of 2ppm it is not justified for cell proliferation and polypoid adenomas. Higher values are also supported by a new statistical analysis. For histopathological lesions a NOAEC of 1ppm may be defined but the lesions at 2ppm cannot be regarded as pre-stages for tumour development. One major uncertainty exists: the description of polypoid adenomas and the lesions at 2ppm often is insufficient and diagnostic uncertainties can only be resolved by a re-evaluation according to modern histomorphological standards. Although the discrepancy between our assessment and that of RAC may seem rather small we feel the LOAECs proposed by RAC must be challenged taking into consideration the broad data base for formaldehyde and the potential impact of any published RAC opinion on the present discussions about appropriate occupational and indoor exposure limits.

  2. Enzymes approved for human therapy: indications, mechanisms and adverse effects.

    PubMed

    Baldo, Brian A

    2015-02-01

    Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.

  3. Iron deficiency anemia: adverse effects on infant psychomotor development.

    PubMed

    Walter, T; De Andraca, I; Chadud, P; Perales, C G

    1989-07-01

    In a double-blind, placebo-control prospective cohort study of 196 infants from birth to 15 months of age, assessment was made at 12 months of age of the relationship between iron status and psychomotor development, the effect of a short-term (10-day) trial of oral iron vs placebo, and the effect of long-term (3 months) oral iron therapy. Development was assessed with the mental and psychomotor indices and the infant behavior record of the Bayley Scales of Infant Development in 39 anemic, 30 control, and 127 nonanemic iron-deficient children. Anemic infants had significantly lower Mental and Psychomotor Developmental Index scores than control infants or nonanemic iron-deficient infants (one-way analysis of variance, P less than .0001). Control infants and nonanemic iron-deficient infants performed comparably. No difference was noted between the effect of oral administration of iron or placebo after 10 days or after 3 months of iron therapy. Among anemic infants a hemoglobin concentration less than 10.5 g/dL and duration of anemia of greater than 3 months were correlated with significantly lower motor and mental scores (P less than .05). Anemic infants failed specifically in language capabilities and body balance-coordination skills when compared with controls. These results, in a design in which intervening variables were closely controlled, suggest that when iron deficiency progresses to anemia, but not before, adverse influences in the performance of developmental tests appear and persist for at least 3 months despite correction of anemia with iron therapy. If these impairments prove to be long standing, prevention of iron deficiency anemia in early infancy becomes the only way to avoid them.

  4. 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

  5. Ziconotide: new drug. Limited analgesic efficacy, too many adverse effects.

    PubMed

    2008-10-01

    (1) When oral morphine does not relieve severe pain and when there is no specific treatment for the underlying cause, the first option is to try subcutaneous or intravenous administration. If this standard treatment fails or is poorly tolerated, intrathecal injection is usually preferred as the direct route to the central nervous system. However, one-quarter to one-half of patients still do not achieve adequate pain relief, and adverse effects are relatively frequent; (2) Ziconotide is not an opiate and is not related to the usual classes of drugs that interfere with nervous transmission in the posterior horn of the spinal cord. Marketing authorization has been granted for "severe, chronic pain in patients who require intrathecal analgesia". The Summary of Product Characteristics (SPC) recommends continuous infusion via an intrathecal catheter connected to a pump; (3) Clinical evaluation of ziconotide does not include any trials versus morphine in patients with nociceptive pain, or any trials versus tricyclic or antiepileptic drugs in patients with neurogenic pain; (4) In a trial in 220 patients in whom systemic morphine had failed, the mean pain score on a 100-mm visual analogue scale was 69.8 mm after three weeks on ziconotide, compared to 75.8 mm with placebo. This difference, although statistically significant, is clinically irrelevant. The proportion of "responders" (reduction of at least 30% in the initial pain score) was respectively 16.1% and 12.0% (no statistically significant difference); (5) The two other placebo-controlled trials included 112 patients with pain linked to cancer or HIV infection, and 257 patients with non-cancer pain. After a titration phase lasting 5 to 6 days, a combined analysis of the two trials showed that the mean pain score was 48.8 mm with ziconotide and 68.4 mm with placebo (statistically significant difference). However, many patients did not complete the titration phase. Efficacy also appeared to differ according to the type

  6. 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

  7. Use of Adverse Outcome Pathways for Assessing Effects of the Fungicide Propiconazole on Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOP) are used to describe the linkage of biological events from a molecular initiating point, to individual-level-endpoints relevant to risk assessment. This study was done to assess toxicity outcomes for the conazole fungicide propiconazole based on a p...

  8. Toxic effect onset and evaluations of medicinal drugs--horizon for Darwinian toxicological thought.

    PubMed

    Horii, Ikuo

    2010-08-01

    The theory of Darwinian Medicine linked to an extension of Darwin's evolutionary theory is based on the approach from the aspect of "why we become ill?".This theory enables us to understand the relationship between humans and diseases by thinking from evolutional perspective, shows an important help for preventive medicine, and is meaningful to consider the future human healthcare. Toxicology has been defined as a research of adverse effect of xenobiotic substances backed up by diverse-sciences. Toxic effects are basically responses to xenobiotic substances, and expressed as triggering or additional accelerating adverse effects toward abnormal condition. Toxic effects, biological adverse responses, are interpreted as protective responses of living body, and the adverse effects caused by drugs are also considered to be protective responses. This logic can be translated as "Darwinian Toxicology" corresponding to "Darwinian Medicine", replying to "why we get into toxic condition by xenobiotics exposure". This paper refers to the meaning of toxic effects based on mechanisms underlying and comprehensive drug safety evaluation from Darwinian Medicine perspectives.

  9. Toxic effects of Karenia mikimotoi extracts on mammalian cells

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Yan, Tian; Yu, Rencheng; Zhou, Mingjiang

    2011-07-01

    Karenia is one of the most harmful and representative red tide genus in a temperate zone. Blooms caused by this genus have resulted in massive fish death in the South China Sea and the East China Sea. However, the potential effects of this dinoflagellate on human health through the transfer of toxins via marine food webs, and the mechanisms of toxicity, are still unknown. Therefore, we examined the toxic effects of a strain of K. mikimotoi (isolated from the South China Sea) on the proliferation and morphology of four mammalian cell lines (two normal cell lines and two cancer cell lines). In addition, we carried out a preliminary investigation on the mechanism of toxicity of the alga. The results show that the polar lipid-soluble component of K. mikimotoi significantly inhibited proliferation of the four cell lines, and resulted in the cells becoming spherical, swollen and damaged. The result of Annexin V and PI double-staining confirmed that cell membranes were disrupted. The malonaldehyde (MDA) contents in the medium of the four cell lines treated with the polar-lipid extracts all increased significantly, which indicates that the polar-lipid toxins produced by K. mikimotoi could adversely affect mammalian cells by inducing lipid peroxidation. We conclude that K. mikimotoi is a potential threat to human health, and the comprehensive effect of this dinoflagellate and its mechanisms should be investigated further.

  10. Methods for estimating cleaning effectiveness, dispersion, and toxicity of shoreline cleaning agents at oil spills

    SciTech Connect

    Stransky, B.C.; Clayton, J.R. Jr.; Schwartz, M.J.; Snyder, B.J.; Lees, D.C.; Adkins, A.C.; Reilly, T.J.; Michel, J.

    1995-12-31

    Chemical shoreline cleaning agents (SCAs) are designed to enhance removal of stranded oil from shoreline surfaces. However, difficulties associated with estimating cleaning effectiveness and toxicity of SCAs for site-specific conditions make it desirable to perform measurements in the field with onsite oil, substrates, and resident or otherwise appropriate test organisms. Information for onsite testing should address the following questions: (1) does use of an SCA promote removal of oil from substate surfaces; (2) does use of an SCA increase the amount of dispersed oil in the water column; (3) does toxicity for resident organisms indicate a likelihood for adverse effects; (4) does toxicity with a portable test organism indicate a likelihood for adverse effects? Methodologies are described for use in a portable kit to estimate quantitative and qualitative information for cleaning effectiveness, dispersion of oil, and toxicity of SCAs in the field. Toxicity methodologies for resident organisms include echinoderm fertilization, byssal thread attachment for mussels, and righting/water-escaping ability for periwinkle snails. Microtox{trademark} is used for toxicity measurements as a portable test organism/assay. Use of portable methodologies for assessing cleaning effectiveness, dispersion of oil, and toxicity of SCAs in the field can assist onsite evaluations for cleaning performance and relative risk to biological resources, which are important for supporting use-no use decisions for SCAs.

  11. Fluoroquinolone-induced serious, persistent, multisymptom adverse effects.

    PubMed

    Golomb, Beatrice Alexandra; Koslik, Hayley Jean; Redd, Alan J

    2015-10-05

    We present a case series of four previously healthy, employed adults without significant prior medical history in each of whom symptoms developed while on fluoroquinolones (FQs), with progression that continued following discontinuation evolving to a severe, disabling multisymptom profile variably involving tendinopathy, muscle weakness, peripheral neuropathy, autonomic dysfunction, sleep disorder, cognitive dysfunction and psychiatric disturbance. Physicians and patients should be alert to the potential for FQ-induced severe disabling multisymptom pathology that may persist and progress following FQ use. Known induction by FQs of delayed mitochondrial toxicity provides a compatible mechanism, with symptom profiles (and documented mechanisms of FQ toxicity) compatible with the hypothesis of an exposure-induced mitochondrial neurogastrointestinal encephalomyopathy.

  12. 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

  13. Adverse effects of serotonin depletion in developing zebrafish.

    PubMed

    Airhart, Mark J; Lee, Deborah H; Wilson, Tracy D; Miller, Barney E; Miller, Merry N; Skalko, Richard G; Monaco, Paul J

    2012-01-01

    remained unaffected in brain, they were decreased in spinal cord. Five days subsequent to pCPA rescue, 5HT(1A) transcript concentrations remained decreased in brain while SERT transcript levels were elevated in both regions. These findings suggest that reduction of 5HT during early zebrafish development may have an adverse effect on body length, notochordal morphology, locomotor behavior, and serotonin message-related expression.

  14. Effect of thyroid hormone status and concomitant medication on statin induced adverse effects in hyperlipidemic patients.

    PubMed

    Berta, E; Harangi, M; Zsíros, N; Nagy, E V; Paragh, G; Bodor, M

    2014-06-01

    Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP

  15. International monitoring of adverse health effects associated with herbal medicines.

    PubMed

    Farah, M H; Edwards, R; Lindquist, M; Leon, C; Shaw, D

    2000-03-01

    Herbal medicines are used in health care around the world and may increase in importance. There is much uncertainty, however, with regard to their composition, efficacy and safety. There is substantial evidence that herbal medicines can cause serious adverse reactions, but more data are needed as regard their nature, frequency and preventability. In this respect the Uppsala Monitoring Centre of the World Health Organization can play a crucial role. Better reporting of adverse reactions to herbal medicines is needed, in particular with regard to the precise identity and composition of these products. A consistent use by producers, regulators and reporters of the international Latin binomial nomenclature and the use of the new Herbal Anatomical Therapeutic Chemical (ATC) classification are recommended. Copyright (c) 2000 John Wiley & Sons, Ltd. PMID:19025809

  16. Adverse effects of larkspur (Delphinium spp.) on cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are numerous species of larkspurs (Delphinium spp.) in North America. The larkspurs are a major cause of cattle losses on western ranges in the USA, especially on foothill and mountain rangelands. The toxicity of larkspur species is due to various norditerpenoid alkaloids. In this article, we ...

  17. 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

    toxicity and adverse psychological effects during late adulthood and senescence of adults who receive prolonged courses of amphetamine treatment are warranted. Finally, identification of the biological factors that confer risk and those that offer protection are also needed to better specify the parameters of safe, long-term, therapeutic administration of amphetamines to adults. PMID:18698321

  18. 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…

  19. Arrhythmogenic adverse effects of cardiac glycosides are mediated by redox modification of ryanodine receptors

    PubMed Central

    Ho, Hsiang-Ting; Stevens, Sarah C W; Terentyeva, Radmila; Carnes, Cynthia A; Terentyev, Dmitry; Györke, Sandor

    2011-01-01

    Abstract The therapeutic use of cardiac glycosides (CGs), agents commonly used in treating heart failure (HF), is limited by arrhythmic toxicity. The adverse effects of CGs have been attributed to excessive accumulation of intracellular Ca2+ resulting from inhibition of Na+/K+-ATPase ion transport activity. However, CGs are also known to increase intracellular reactive oxygen species (ROS), which could contribute to arrhythmogenesis through redox modification of cardiac ryanodine receptors (RyR2s). Here we sought to determine whether modification of RyR2s by ROS contributes to CG-dependent arrhythmogenesis and examine the relevant sources of ROS. In isolated rat ventricular myocytes, the CG digitoxin (DGT) increased the incidence of arrhythmogenic spontaneous Ca2+ waves, decreased the sarcoplasmic reticulum (SR) Ca2+ load, and increased both ROS and RyR2 thiol oxidation. Additionally, pretreatment with DGT increased spark frequency in permeabilized myocytes. These effects on Ca2+ waves and sparks were prevented by the antioxidant N-(2-mercaptopropionyl) glycine (MPG). The CG-dependent increases in ROS, RyR2 oxidation and arrhythmogenic propensity were reversed by inhibitors of NADPH oxidase, mitochondrial ATP-dependent K+ channels (mito-KATP) or permeability transition pore (PTP), but not by inhibition of xanthine oxidase. These results suggest that the arrhythmogenic adverse effects of CGs involve alterations in RyR2 function caused by oxidative changes in the channel structure by ROS. These CG-dependent effects probably involve release of ROS from mitochondria possibly mediated by NADPH oxidase. PMID:21807619

  20. Adverse Effects of Methylmercury: Environmental Health Research Implications

    PubMed Central

    Grandjean, Philippe; Satoh, Hiroshi; Murata, Katsuyuki; Eto, Komyo

    2010-01-01

    Background The scientific discoveries of health risks resulting from methylmercury exposure began in 1865 describing ataxia, dysarthria, constriction of visual fields, impaired hearing, and sensory disturbance as symptoms of fatal methylmercury poisoning. Objective Our aim was to examine how knowledge and consensus on methylmercury toxicity have developed in order to identify problems of wider concern in research. Data sources and extraction We tracked key publications that reflected new insights into human methylmercury toxicity. From this evidence, we identified possible caveats of potential significance for environmental health research in general. Synthesis At first, methylmercury research was impaired by inappropriate attention to narrow case definitions and uncertain chemical speciation. It also ignored the link between ecotoxicity and human toxicity. As a result, serious delays affected the recognition of methylmercury as a cause of serious human poisonings in Minamata, Japan. Developmental neurotoxicity was first reported in 1952, but despite accumulating evidence, the vulnerability of the developing nervous system was not taken into account in risk assessment internationally until approximately 50 years later. Imprecision in exposure assessment and other forms of uncertainty tended to cause an underestimation of methylmercury toxicity and repeatedly led to calls for more research rather than prevention. Conclusions Coupled with legal and political rigidity that demanded convincing documentation before considering prevention and compensation, types of uncertainty that are common in environmental research delayed the scientific consensus and were used as an excuse for deferring corrective action. Symptoms of methylmercury toxicity, such as tunnel vision, forgetfulness, and lack of coordination, also seemed to affect environmental health research and its interpretation. PMID:20529764

  1. Doping with anabolic androgenic steroids (AAS): Adverse effects on non-reproductive organs and functions.

    PubMed

    Nieschlag, Eberhard; Vorona, Elena

    2015-09-01

    Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17α-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms.

  2. Doping with anabolic androgenic steroids (AAS): Adverse effects on non-reproductive organs and functions.

    PubMed

    Nieschlag, Eberhard; Vorona, Elena

    2015-09-01

    Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17α-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms. PMID:26373946

  3. Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats

    PubMed Central

    Mossa, Abdel-Tawab H.; Ibrahim, Faten M.; Mohafrash, Samia M. M.; Abou Baker, Doha H.; El Gengaihi, Souad

    2015-01-01

    The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg−1 body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg−1 body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity. PMID:26265923

  4. 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

  5. Novel biopesticide based on a spider venom peptide shows no adverse effects on honeybees.

    PubMed

    Nakasu, Erich Y T; Williamson, Sally M; Edwards, Martin G; Fitches, Elaine C; Gatehouse, John A; Wright, Geraldine A; Gatehouse, Angharad M R

    2014-07-22

    Evidence is accumulating that commonly used pesticides are linked to decline of pollinator populations; adverse effects of three neonicotinoids on bees have led to bans on their use across the European Union. Developing insecticides that pose negligible risks to beneficial organisms such as honeybees is desirable and timely. One strategy is to use recombinant fusion proteins containing neuroactive peptides/proteins linked to a 'carrier' protein that confers oral toxicity. Hv1a/GNA (Galanthus nivalis agglutinin), containing an insect-specific spider venom calcium channel blocker (ω-hexatoxin-Hv1a) linked to snowdrop lectin (GNA) as a 'carrier', is an effective oral biopesticide towards various insect pests. Effects of Hv1a/GNA towards a non-target species, Apis mellifera, were assessed through a thorough early-tier risk assessment. Following feeding, honeybees internalized Hv1a/GNA, which reached the brain within 1 h after exposure. However, survival was only slightly affected by ingestion (LD50>100 µg bee(-1)) or injection of fusion protein. Bees fed acute (100 µg bee(-1)) or chronic (0.35 mg ml(-1)) doses of Hv1a/GNA and trained in an olfactory learning task had similar rates of learning and memory to no-pesticide controls. Larvae were unaffected, being able to degrade Hv1a/GNA. These tests suggest that Hv1a/GNA is unlikely to cause detrimental effects on honeybees, indicating that atracotoxins targeting calcium channels are potential alternatives to conventional pesticides.

  6. Adverse effects of the model environmental estrogen diethylstilbestrol are transmitted to subsequent generations.

    PubMed

    Newbold, Retha R; Padilla-Banks, Elizabeth; Jefferson, Wendy N

    2006-06-01

    The synthetic estrogen diethylstilbestrol (DES) is a potent perinatal endocrine disruptor. In humans and experimental animals, exposure to DES during critical periods of reproductive tract differentiation permanently alters estrogen target tissues and results in long-term abnormalities such as uterine neoplasia that are not manifested until later in life. Using the developmentally exposed DES mouse, multiple mechanisms have been identified that play a role in its carcinogenic and toxic effects. Analysis of the DES murine uterus reveals altered gene expression pathways that include an estrogen-regulated component. Thus, perinatal DES exposure, especially at low doses, offers the opportunity to study effects caused by weaker environmental estrogens and provides an example of the emerging scientific field termed the developmental origin of adult disease. As a model endocrine disruptor, it is of particular interest that even low doses of DES increase uterine tumor incidence. Additional studies have verified that DES is not unique; when other environmental estrogens are tested at equal estrogenic doses, developmental exposure results in increased incidence of uterine neoplasia similar to that caused by DES. Interestingly, our data suggest that this increased susceptibility for tumors is passed on from the maternal lineage to subsequent generations of male and female descendants; the mechanisms involved in these transgenerational events include genetic and epigenetic events. Together, our data point out the unique sensitivity of the developing organism to endocrine-disrupting chemicals, the occurrence of long-term effects after developmental exposure, and the possibility for adverse effects to be transmitted to subsequent generations. PMID:16690809

  7. [Dealing with adverse effects in phase I trials].

    PubMed

    Heger-Mahn, D; Mahler, M; Hermann, R; Nowak, H; Weber, W; Seibert-Grafe, M

    1995-03-01

    A questionnaire was completed by members of the Association for Applied Human Pharmacology (AGAH) in Germany with the aim of assessing the present situation regarding management of adverse events (AEs). A recommendation for documentation and evaluation of AEs was to be presented after discussion within the AGAH. The questionnaire referred to general questions, documentation of AEs, intensity and causality, coding and serious adverse events (SAE). Percentage return of answered questionnaires was 54.5%. Of the people contacted, 9.1% said they did not carry out phase I trials, and 36.4% did not reply. The survey in the 24 institutes convers an estimated 11200 volunteers who are included in clinical trials each year. The discussion about commencement of AEs documentation and its duration was contentious. Of the respondents, 38.5% AEs only after application of the trial substance, while 61.5% also make a documentation during the pre-trial phase (recruitment, pre-examination, supervision before application). 13.6% document only up to the post-examination and half of those questioned until AE symptoms have disappeared. 22.7% document until disappearance of symptoms only when AEs are definitely associated with the trial substance. A 3-point scale is used by most people questioned for evaluation of the intensity of an AE. Evaluation of causality, mostly undertaken by the examining physician and the director of the clinical trial, is not carried out homogeneously. There are several categories, but four classifications are most commonly used. 62.5% of codings of AEs are carried out according to the WHO Adverse Reaction Terminology.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  9. 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

  10. Low concentrations of metal mixture exposures have adverse effects on selected biomarkers of Xenopus laevis tadpoles.

    PubMed

    Yologlu, Ertan; Ozmen, Murat

    2015-11-01

    Polluted ecosystems may contain mixtures of metals, such that the combinations of metals, even in low concentrations, may cause adverse effects. In the present study, we focused on toxic effects of mixtures of selected metals, the LC50 values, and also their safety limit in aquatic systems imposed by the European legislation using a model organism. Xenopus laevis tadpoles were used as test organisms. They were exposed to metals or their combinations due to 96-h LC50 values. Glutathione S-transferase (GST), glutathione reductase (GR), acetylcholinesterase (AChE), carboxylesterase (CaE), glutathione peroxidase (GPx), and catalase (CAT) levels were evaluated. Metallothionein concentrations were also determined. The LC50s for Cd, Pb, and Cu were calculated as 5.81mg AI/L, 123.05mg AI/L, and 0.85mg AI/L, respectively. Low lethality ratios were observed with unary exposure of each metal in lower concentrations. Double or triple combinations of LC50 and LC50/2 concentrations caused 100% lethality with Cd+Cu and Pb+Cd+Cu mixtures, while the Pb+Cu mixture also caused high lethal ratios. The selected enzyme activities were significantly affected by metals or mixtures, and dose-related effects were determined. The metallothionein levels generally increased as related to concentration in unary metals and mixtures. Acceptable limit values of unary metals and mixtures did not significantly change metallothionein levels. The results suggest that oxidative stress-related mechanisms are involved in the toxicity induced by selected metals with combinations of very low concentrations.

  11. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  12. 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.

  13. 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

  14. Pharmacology, toxicology, clinical efficacy, and adverse effects of calcium polycarbophil, an enteral hydrosorptive agent.

    PubMed

    Danhof, I E

    1982-01-01

    Calcium polycarbophil is the calcium salt of polyacrylic acid crosslinked with divinyl glycol. It is chemically and physiologically inert. In dilute alkali it possesses marked hydrophilic capacity (60 to 100 times its weight), which is the basis for its therapeutic use. In daily dosages of 4 to 5 g in adults, it appears to be quite safe, is non-toxic, does not interfere with digestion or absorption, and does not cause gastrointestinal irritation. It appears to be effective in the treatment of both constipation and diarrhea due to functional or organic causes. Several days of continuous use are necessary before effectiveness becomes apparent. Clinical studies, of which there are relatively few, range from uncontrolled, unblinded evaluations of an almost anecdotal nature to well controlled, double-blind, crossover studies. Additional carefully controlled studies on dietary influences, exercise, and patient compliance would be helpful. Adverse effects, which are minimal, include epigastric fullness or heaviness, abdominal distention and bloating, and flatulence. As with all bulk-forming agents, calcium polycarbophil should not be used by persons who have stenotic lesions of the gastrointestinal tract.

  15. 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

  16. CNS Adverse Effects: From Functional Observation Battery/Irwin Tests to Electrophysiology.

    PubMed

    Fonck, Carlos; Easter, Alison; Pietras, Mark R; Bialecki, Russell A

    2015-01-01

    This chapter describes various approaches for the preclinical assessment of drug-induced central nervous system (CNS) adverse effects. Traditionally, methods to evaluate CNS effects have consisted of observing and scoring behavioral responses of animals after drug is administered. Among several behavioral testing paradigms, the Irwin and the functional observational battery (FOB) are the most commonly used assays for the assessment of CNS effects. The Irwin and FOB are considered good first-tier assays to satisfy the ICH S7A guidance for the preclinical evaluation of new chemical entities (NCE) intended for humans. However, experts have expressed concern about the subjectivity and lack of quantitation that is derived from behavioral testing. More importantly, it is difficult to gain insight into potential mechanisms of toxicity by assessing behavioral outcomes. As a complement to behavioral testing, we propose using electrophysiology-based assays, both in vivo and in vitro, such as electroencephalograms and brain slice field-potential recordings. To better illustrate these approaches, we discuss the implementation of electrophysiology-based techniques in drug-induced assessment of seizure risk, sleep disruption, and cognitive impairment.

  17. Toxic effects of air freshener emissions.

    PubMed

    Anderson, R C; Anderson, J H

    1997-01-01

    To evaluate whether emissions of a commercial air freshener produced acute toxic effects in a mammalian species, the authors allowed male Swiss-Webster mice to breathe the emissions of one commercial-brand solid air freshener for 1 h. Sensory irritation and pulmonary irritation were evaluated with the ASTM-E-981 test. A computerized version of this test measured the duration of the break at the end of inspiration and the duration of the pause at the end of expiration--two parameters subject to alteration via respiratory effects of airborne toxins. Measurements of expiratory flow velocity indicated changes in airflow limitation. The authors then subjected mice to a functional observational battery, the purpose of which was to probe for changes in nervous system function. Emissions of this air freshener at several concentrations (including concentrations to which many individuals are actually exposed) caused increases in sensory and pulmonary irritation, decreases in airflow velocity, and abnormalities of behavior measured by the functional observational battery score. The test atmosphere was subjected to gas chromatography/mass spectroscopy, and the authors noted the presence of chemicals with known irritant and neurotoxic properties. The Material Safety Data Sheet for the air freshener indicated that there was a potential for toxic effects in humans. The air freshener used in the study did not diminish the effect of other pollutants tested in combination. The results demonstrated that the air freshener may have actually exacerbated indoor air pollution via addition of toxic chemicals to the atmosphere.

  18. Toxic effects of chromium on tannery workers at Sialkot (Pakistan).

    PubMed

    Khan, Dilshad Ahmed; Mushtaq, Shahida; Khan, Farooq Ahmad; Khan, Muhammad Qaiser Alam

    2013-03-01

    Chromium is widely used in the leather industry, and tannery workers are under constant threat of adverse health effects due to its excessive exposure. Our objective was to find out the toxic effects of chromium on tannery workers at Sialkot, Pakistan. A total of 240 males consisting of 120 workers from tanneries at Sialkot and equal number of controls were included. Blood complete counts, high-sensitive C-reactive protein, malondialdehyde and routine biochemical tests were carried out by routine procedures. Chromium levels in blood (BCr) and urine were analyzed using graphite furnace atomic absorption spectrophotometer Perkin Elmer analyst-200. Results revealed that all the workers were male with average age of 33 years and 15 (13%) had skin rashes, 14 (12%) had chronic bronchitis, 10 (8%) had gastritis and 4 (3%) conjunctivitis. The tannery workers had significantly raised median (interquartile range) of BCr 569 (377-726) nmol/L as compared to 318 (245-397) nmol/L in the control (p < 0.001). Sixty-five (54%) workers had BCr levels above the upper limit set by Agency for Toxic Substance and Drug Registry. The urinary chromium excretion was significantly high in workers 131 (46-312) nmol/L as compared to 13 (3-26) nmol/L in controls (p < 0.01). The workers had hematological, hepatic and renal function impairment because of oxidative stress on body systems. It is concluded that about half of the workers had excessive exposure to chromium in the tanneries at Sialkot. They had significantly raised chromium levels in their biological fluids and adverse health effects due to enhanced oxidative stress and inflammatory changes.

  19. Potential adverse effects of applying phosphate amendments to immobilize soil contaminants.

    PubMed

    Majs, Frantisek

    2011-01-01

    Seven-day batch equilibrium experiments were conducted to measure the efficacy of four phosphate amendments (trisodium trimetaphosphate [TP3], dodecasodium phytate [Na-IP6], precipitated calcium phytate [Ca-IP6], and hydroxyapatite [HA]) for immobilizing Ni and U in organic-rich sediment. Using the eight-step modified Miller's sequential extraction procedure and the USEPA's Toxicity Characteristic Leaching Procedure, the effect of these amendments on the distribution of Ni and U was assessed. Relative to unamended controls, equilibrium aqueous-phase U concentrations were lower following HA and Ca-IP6 additions but higher following TP3 and Na-IP6 amendments, whereas aqueous Ni concentrations were not decreased only in the Na-IP6 amended treatment relative to the control. The poor rates of contaminant immobilization following TP3 and Na-IP6 amendments correlate with the dispersion of organic matter and organo-mineral colloids, which probably contain sorbed U and Ni. While all amendments shifted the U distribution toward more recalcitrant soil fractions, Ni was redistributed to more labile soil fractions. This study cautions that the addition of orthophosphates and organophosphates as contaminant immobilizing amendments may in fact have adverse effects, especially in high-organic soils. Particular attention is warranted at sites with mixed contaminants with varying geochemical behaviors.

  20. The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors

    PubMed Central

    Rizzo, Paola; Mele, Donato; Caliceti, Cristiana; Pannella, Micaela; Fortini, Cinzia; Clementz, Anthony George; Morelli, Marco Bruno; Aquila, Giorgio; Ameri, Pietro; Ferrari, Roberto

    2015-01-01

    Targeting the Notch pathway is a new promising therapeutic approach for cancer patients. Inhibition of Notch is effective in the oncology setting because it causes a reduction of highly proliferative tumor cells and it inhibits survival of cancer stem cells, which are considered responsible for tumor recurrence and metastasis. Additionally, since Delta-like ligand 4 (Dll4)-activated Notch signaling is a major modulator of angiogenesis, anti-Dll4 agents are being investigated to reduce vascularization of the tumor. Notch plays a major role in the heart during the development and, after birth, in response to cardiac damage. Therefore, agents used to inhibit Notch in the tumors (gamma secretase inhibitors and anti-Dll4 agents) could potentially affect myocardial repair. The past experience with trastuzumab and other tyrosine kinase inhibitors used for cancer therapy demonstrates that the possible cardiotoxicity of agents targeting shared pathways between cancer and heart and the vasculature should be considered. To date, Notch inhibition in cancer patients has resulted only in mild gastrointestinal toxicity. Little is known about the potential long-term cardiotoxicity associated to Notch inhibition in cancer patients. In this review, we will focus on mechanisms through which inhibition of Notch signaling could lead to cardiomyocytes and endothelial dysfunctions. These adverse effects could contrast with the benefits of therapeutic responses in cancer cells during times of increased cardiac stress and/or in the presence of cardiovascular risk factor. PMID:25629006

  1. Potential adverse effects of applying phosphate amendments to immobilize soil contaminants.

    PubMed

    Majs, Frantisek

    2011-01-01

    Seven-day batch equilibrium experiments were conducted to measure the efficacy of four phosphate amendments (trisodium trimetaphosphate [TP3], dodecasodium phytate [Na-IP6], precipitated calcium phytate [Ca-IP6], and hydroxyapatite [HA]) for immobilizing Ni and U in organic-rich sediment. Using the eight-step modified Miller's sequential extraction procedure and the USEPA's Toxicity Characteristic Leaching Procedure, the effect of these amendments on the distribution of Ni and U was assessed. Relative to unamended controls, equilibrium aqueous-phase U concentrations were lower following HA and Ca-IP6 additions but higher following TP3 and Na-IP6 amendments, whereas aqueous Ni concentrations were not decreased only in the Na-IP6 amended treatment relative to the control. The poor rates of contaminant immobilization following TP3 and Na-IP6 amendments correlate with the dispersion of organic matter and organo-mineral colloids, which probably contain sorbed U and Ni. While all amendments shifted the U distribution toward more recalcitrant soil fractions, Ni was redistributed to more labile soil fractions. This study cautions that the addition of orthophosphates and organophosphates as contaminant immobilizing amendments may in fact have adverse effects, especially in high-organic soils. Particular attention is warranted at sites with mixed contaminants with varying geochemical behaviors. PMID:21712583

  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. Toxic effects of silica nanoparticles on zebrafish embryos and larvae.

    PubMed

    Duan, Junchao; Yu, Yongbo; Shi, Huiqin; Tian, Linwei; Guo, Caixia; Huang, Peili; Zhou, Xianqing; Peng, Shuangqing; Sun, Zhiwei

    2013-01-01

    Silica nanoparticles (SiNPs) have been widely used in biomedical and biotechnological applications. Environmental exposure to nanomaterials is inevitable as they become part of our daily life. Therefore, it is necessary to investigate the possible toxic effects of SiNPs exposure. In this study, zebrafish embryos were treated with SiNPs (25, 50, 100, 200 µg/mL) during 4-96 hours post fertilization (hpf). Mortality, hatching rate, malformation and whole-embryo cellular death were detected. We also measured the larval behavior to analyze whether SiNPs had adverse effects on larvae locomotor activity. The results showed that as the exposure dosages increasing, the hatching rate of zebrafish embryos was decreased while the mortality and cell death were increased. Exposure to SiNPs caused embryonic malformations, including pericardial edema, yolk sac edema, tail and head malformation. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lower dose (25 and 50 µg/mL SiNPs) produced substantial hyperactivity while the higher doses (100 and 200 µg/mL SiNPs) elicited remarkably hypoactivity in dark periods. In summary, our data indicated that SiNPs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior. PMID:24058598

  4. Toxic effects of mercury, lead and gadolinium on vascular reactivity.

    PubMed

    Vassallo, D V; Simões, M R; Furieri, L B; Fioresi, M; Fiorim, J; Almeida, E A S; Angeli, J K; Wiggers, G A; Peçanha, F M; Salaices, M

    2011-09-01

    Heavy metals have been used in a wide variety of human activities that have significantly increased both professional and environmental exposure. Unfortunately, disasters have highlighted the toxic effects of metals on different organs and systems. Over the last 50 years, the adverse effects of chronic lead, mercury and gadolinium exposure have been underscored. Mercury and lead induce hypertension in humans and animals, affecting endothelial function in addition to their other effects. Increased cardiovascular risk after exposure to metals has been reported, but the underlying mechanisms, mainly for short periods of time and at low concentrations, have not been well explored. The presence of other metals such as gadolinium has raised concerns about contrast-induced nephropathy and, interestingly, despite this negative action, gadolinium has not been defined as a toxic agent. The main actions of these metals, demonstrated in animal and human studies, are an increase of free radical production and oxidative stress and stimulation of angiotensin I-converting enzyme activity, among others. Increased vascular reactivity, highlighted in the present review, resulting from these actions might be an important mechanism underlying increased cardiovascular risk. Finally, the results described in this review suggest that mercury, lead and gadolinium, even at low doses or concentrations, affect vascular reactivity. Acting via the endothelium, by continuous exposure followed by their absorption, they can increase the production of free radicals and of angiotensin II, representing a hazard for cardiovascular function. In addition, the actual reference values, considered to pose no risk, need to be reduced.

  5. Transient Adverse Side Effects During Neurofeedback Training: A Randomized, Sham-Controlled, Double Blind Study.

    PubMed

    Rogel, Ainat; Guez, Jonathan; Getter, Nir; Keha, Eldad; Cohen, Tzlil; Amor, Tali; Todder, Doron

    2015-09-01

    The benefits of clinical neurofeedback training are well known, however, its adverse side-effects are less studied. This research focuses on the transient adverse side effects of neurofeedback training via a double-blind, sham/controlled methodology. Thirty healthy undergraduate students volunteers were randomly divided into three treatment groups: increasing a modified Sensory Motor Rhythm, increasing Upper Alpha, and Sham/control group who receive a random reward. The training sessions were administered for a total of ten sessions. Questionnaires of transient adverse side effects were completed by all volunteers before each session. The results suggest that similar to most medical treatments, neurofeedback can cause transient adverse side effects. Moreover, most participants reported experiencing some side effects. The side effects can be divided into non-specific side effect, associated with the neurofeedback training in general and specific ones associated with the particular protocol. Sensory Motor Rhythm protocol seems to be the most sensitive to side effects.

  6. 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...

  7. 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…

  8. 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:…

  9. The basic science of dermal fillers: past and present Part II: adverse effects.

    PubMed

    Gilbert, Erin; Hui, Andrea; Meehan, Shane; Waldorf, Heidi A

    2012-09-01

    The ideal dermal filler should offer long-lasting aesthetic improvement with a minimal side-effect profile. It should be biocompatible and stable within the injection site, with the risk of only transient undesirable effects from injection alone. However, all dermal fillers can induce serious and potentially long-lasting adverse effects. In Part II of this paper, we review the most common adverse effects related to dermal filler use.

  10. Ethanol: its adverse effects upon the hypothalamic-pituitary-gonadal axis.

    PubMed

    Gavaler, J S; Urso, T; Van Thiel, D H

    1983-01-01

    Considerable evidence has accrued over the preceding two decades to establish that ethanol is a gonadal toxin. In the male such toxicity is both direct, being expressed at the level of the hypothalamus and/or pituitary. Moreover, such toxicity is due in part to direct ethanol exposure and also in part to the consequences of ethanol metabolism (e.g., acetaldehyde generation, redox changes and alterations in enzyme levels and activities). Thus as a result of studies performed both in man and in animals, it has been shown conclusively that ethanol abuse per se, and not the associated liver disease that occurs with alcohol abuse, is responsible for the impotence, loss of libido, and testicular atrophy which are seen commonly in chronic alcoholic men. With prolonged alcohol abstinence, recent studies have suggested that spontaneous recovery of normal sexual function is possible in some chronic alcoholic men if testicular atrophy has not yet occurred and if their responses to clomiphene and/or luteinizing hormone releasing factor stimulation are normal. In contrast, abstinent alcoholic men with either overt testicular atrophy or inadequate responses to such pharmacologic challenges fail to recover despite continued alcoholic abstinence. Such men will require either a penile prosthesis or long-term oral androgen therapy to achieve "acceptable" sexual functioning. Considerably less information is available concerning the adverse effects of ethanol and alcohol abuse in women. The available data however, suggests that women, like men, develop gonadal injury as a consequence of alcohol abuse and that such injury occurs both at the level of the ovary and at the level of the hypothalamus and pituitary.

  11. 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

  12. 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.

  13. [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.

  14. Use and reported adverse effects of new chemical entities.

    PubMed

    Kennedy, D L; Goetsch, R A; Dreis, M W

    1989-03-01

    Reports submitted to the FDA through 1987 of adverse drug reactions (ADRs) to new chemical entities (NCEs) approved after 1983 are described, and estimates of each NCE's proportionate use in hospitals and within its therapeutic class are reported. This review was limited to those domestic spontaneous ADR reports submitted to the FDA by healthcare professionals. NCEs accounted for approximately 20% of the total number of domestic spontaneous ADR reports received in 1987, 22% of the reports of serious ADRs, and 24% of the reports that listed death as an outcome. Data on the use of these NCEs were obtained through the U.S. Pharmaceutical Market--Drugstores and Hospitals and the National Prescription Audit. Of the 93 drugs designated as NCEs in 1987, 65 had measurable use, with 41% of those used principally in hospitals. Most hospital-use NCEs were injectable antimicrobial agents, surgical drugs, and radioactive diagnostic agents. Because NCEs account for a disproportionate share of the ADRs reported to the FDA, and because of the high use of NCEs in hospitals, hospital pharmacists should be aware of the importance of monitoring and reporting serious ADRs associated with NCEs. PMID:2719041

  15. 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

  16. 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

  17. Manual therapy for the cervical spine and reported adverse effects: a survey of Irish manipulative physiotherapists.

    PubMed

    Sweeney, Aoife; Doody, Catherine

    2010-02-01

    The purpose of this study was to determine the use of manipulation and mobilisation by the Chartered Physiotherapists (CMPT) in Manipulative Therapy Ireland and to describe adverse effects associated with the use of these techniques. A 44 item postal survey was sent to all 259 members of the CPMT (response rate 49%, n=127). All 127 respondents used non-High Velocity Thrust Techniques (HVTT) and 27% (n=34) used HVTT. Nine percent (n=12) used HVTT on the upper cervical spine. Twenty six percent (n=33) reported an adverse effect in the previous 2 years. The adverse effects were associated with the use of HVTT (4%, n=5), non-HVTT (20%, n=26) and cervical traction (2%, n=2). The most serious adverse effects were associated with non-HVTT and included 1 drop attack, 1 fainting episode and 1 Transient Ischemic Attack (TIA) 4 days post treatment. Fifty three percent (n=18) of HVTT users and 40% (n=44) of non-HVTT users reported carrying out a vertebrobasilar insufficiency (VBI) assessment. The study shows that VBI assessment may not detect every patient at risk of adverse effects. Large scale studies to investigate the risk of serious adverse reactions are needed. A system of reporting adverse effects on a routine basis could be considered.

  18. Adverse effects on sexual development in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides.

    PubMed

    Hass, Ulla; Boberg, Julie; Christiansen, Sofie; Jacobsen, Pernille Rosenskjold; Vinggaard, Anne Marie; Taxvig, Camilla; Poulsen, Mette Erecius; Herrmann, Susan Strange; Jensen, Bodil Hamborg; Petersen, Annette; Clemmensen, Line Harder; Axelstad, Marta

    2012-09-01

    The present study investigated whether a mixture of low doses of five environmentally relevant endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, would cause adverse developmental toxicity effects in rats. In rat dams, a significant increase in gestation length was seen, while in male offspring increased nipple retention and increased incidence and severity of genital malformations were observed. Severe mixture effects on gestation length, nipple retention and genital malformations were seen at dose levels where the individual pesticides caused no or smaller effects when given alone. Generally, the mixture effect predictions based on dose-additivity were in good agreement with the observed effects. The results indicate that there is a need for modification of risk assessment procedures for pesticides, in order to take account of the mixture effects and cumulative intake, because of the potentially serious impact of mixed exposure on development and reproduction in humans. PMID:22659286

  19. A rare but important adverse effect of tacrolimus in a heart transplant recipient: diabetic ketoacidosis.

    PubMed

    Öztürk, Zeynelabidin; Gönç, E Nazlı; Akcan, Leman; Kesici, Selman; Ertuğrul, İlker; Bayrakçı, Benan

    2015-01-01

    Heart transplantation indications in pediatric population include congenital heart diseases, cardiomyopathies and retransplants. Cardiomyopathy is the primary indication for 11 to 17 years of age. The surveillance after transplantation is a very important issue because of both the rejection risk and the adverse effects due to medications after transplantation. Immunosuppressive agents that are commonly used after heart transplantations have several toxicities. Here we present an adolescent patient diagnosed with dilated cardiomyopathy, performed heart transplantation, treated with tacrolimus and suffered from diabetic ketoacidosis due to tacrolimus. After the diagnosis was made the appropriate fluid and insulin therapy was started immediately and ketoacidosis resolved in the first 24 hours of the therapy. The diagnosis revised as new onset diabetes mellitus after transplantation and the tacrolimus dosage titrated to therapeutic level. After glycemic control the patient discharged with rapid acting insulin, three times daily, before meals; and long acting insulin once daily at night. In ten month follow up time the insulin dosages were progressively reduced. PMID:27411426

  20. Factors Associated with Anti-Tuberculosis Medication Adverse Effects: A Case-Control Study in Lima, Peru

    PubMed Central

    Chung-Delgado, Kocfa; Revilla-Montag, Alejandro; Guillen-Bravo, Sonia; Velez-Segovia, Eduardo; Soria-Montoya, Andrea; Nuñez-Garbin, Alexandra; Silva-Caso, Wilmer; Bernabe-Ortiz, Antonio

    2011-01-01

    Background Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use. Methodology and Results A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005–2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65–9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17–3.89), anemia (OR = 2.10; IC95%: 1.13–3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29–19.6), and smoking (OR = 2.00; 95%CI: 1.03–3.87) were independently associated with adverse drug reactions. Conclusions Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients. PMID:22110689

  1. Impact of effects of acid precipitation on toxicity of metals.

    PubMed

    Nordberg, G F; Goyer, R A; Clarkson, T W

    1985-11-01

    Acid precipitation may increase human exposure to several potentially toxic metals by increasing metal concentrations in major pathways to man, particularly food and water, and in some instances by enhancing the conversion of metal species to more toxic forms. Human exposures to methylmercury are almost entirely by way of consumption of fish and seafood. In some countries, intakes by this route may approach the levels that can give rise to adverse health effects for population groups with a high consumption of these food items. A possible increase in methylmercury concentrations in fish from lakes affected by acid precipitation may thus be of concern to selected population groups. Human exposures to lead reach levels that are near those associated with adverse health effects in certain sensitive segments of the general population in several countries. The possibility exists that increased exposures to lead may be caused by acid precipitation through a mobilization of lead from soils into crops. A route of exposure to lead that may possibly be influenced by acid precipitation is an increased deterioration of surface materials containing lead and a subsequent ingestion by small children. A similar situation with regard to uptake from food exists for cadmium (at least in some countries). Human metal exposures via drinking water may be increased by acid precipitation. Decreasing pH increases corrosiveness of water enhancing the mobilization of metal salts from soil; metallic compounds may be mobilized from minerals, which may eventually reach drinking water. Also, the dissolution of metals (Pb, Cd, Cu) from piping systems for drinking water by soft acidic waters of high corrosivity may increase metal concentrations in drinking water. Exposures have occasionally reached concentrations which are in the range where adverse health effects may be expected in otherwise healthy persons. Dissolution from piping systems can be prevented by neutralizing the water before

  2. Adverse effects of meditation: a preliminary investigation of long-term meditators.

    PubMed

    Shapiro, D H

    1992-01-01

    Adverse effects of meditation were assessed in twenty-seven long term meditators (average 4.27 years) both retrospectively (time one) and prospectively at one month (time two) and six months (time three) following a meditation retreat. At both time one and time three subjects reported significantly more positive effects than negative from meditation. However, of the twenty-seven subjects, seventeen (62.9%) reported at least one adverse effect, and two (7.4%) suffered profound adverse effects. When subjects at time one were divided into three groups based on length of practice (16.7 months; 47.1 months; 105 months) there were no significant differences in adverse effects. How the data should be interpreted, and their implications both for the clinical and psychotherapeutic use of meditation as a relaxation/self-control strategy, and as a technique for facilitating personal and spiritual growth, are discussed. Limitations of the study and suggestions for future research are also offered.

  3. 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

  4. Potential adverse health effects of genetically modified crops.

    PubMed

    Bakshi, Anita

    2003-01-01

    Genetically modified crops have the potential to eliminate hunger and starvation in millions of people, especially in developing countries because the genetic modification can produce large amounts of foods that are more nutritious. Large quantities are produced because genetically modified crops are more resistant to pests and drought. They also contain greater amounts of nutrients, such as proteins and vitamins. However, there are concerns about the safety of genetically modified crops. The concerns are that they may contain allergenic substances due to introduction of new genes into crops. Another concern is that genetic engineering often involves the use of antibiotic-resistance genes as "selectable markers" and this could lead to production of antibiotic-resistant bacterial strains that are resistant to available antibiotics. This would create a serious public health problem. The genetically modified crops might contain other toxic substances (such as enhanced amounts of heavy metals) and the crops might not be "substantially equivalent" in genome, proteome, and metabolome compared with unmodified crops. Another concern is that genetically modified crops may be less nutritious; for example, they might contain lower amounts of phytoestrogens, which protect against heart disease and cancer. The review of available literature indicates that the genetically modified crops available in the market that are intended for human consumption are generally safe; their consumption is not associated with serious health problems. However, because of potential for exposure of a large segment of human population to genetically modified foods, more research is needed to ensure that the genetically modified foods are safe for human consumption.

  5. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under...

  6. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under...

  7. 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

  8. 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

  9. Novel biopesticide based on a spider venom peptide shows no adverse effects on honeybees

    PubMed Central

    Nakasu, Erich Y. T.; Williamson, Sally M.; Edwards, Martin G.; Fitches, Elaine C.; Gatehouse, John A.; Wright, Geraldine A.; Gatehouse, Angharad M. R.

    2014-01-01

    Evidence is accumulating that commonly used pesticides are linked to decline of pollinator populations; adverse effects of three neonicotinoids on bees have led to bans on their use across the European Union. Developing insecticides that pose negligible risks to beneficial organisms such as honeybees is desirable and timely. One strategy is to use recombinant fusion proteins containing neuroactive peptides/proteins linked to a ‘carrier’ protein that confers oral toxicity. Hv1a/GNA (Galanthus nivalis agglutinin), containing an insect-specific spider venom calcium channel blocker (ω-hexatoxin-Hv1a) linked to snowdrop lectin (GNA) as a ‘carrier’, is an effective oral biopesticide towards various insect pests. Effects of Hv1a/GNA towards a non-target species, Apis mellifera, were assessed through a thorough early-tier risk assessment. Following feeding, honeybees internalized Hv1a/GNA, which reached the brain within 1 h after exposure. However, survival was only slightly affected by ingestion (LD50 > 100 µg bee−1) or injection of fusion protein. Bees fed acute (100 µg bee−1) or chronic (0.35 mg ml−1) doses of Hv1a/GNA and trained in an olfactory learning task had similar rates of learning and memory to no-pesticide controls. Larvae were unaffected, being able to degrade Hv1a/GNA. These tests suggest that Hv1a/GNA is unlikely to cause detrimental effects on honeybees, indicating that atracotoxins targeting calcium channels are potential alternatives to conventional pesticides. PMID:24898372

  10. Medical marijuana patient counseling points for health care professionals based on trends in the medical uses, efficacy, and adverse effects of cannabis-based pharmaceutical drugs.

    PubMed

    Parmar, Jayesh R; Forrest, Benjamin D; Freeman, Robert A

    2016-01-01

    The purpose of this report is to present a review of the medical uses, efficacy, and adverse effects of the three approved cannabis-based medications and ingested marijuana. A literature review was conducted utilizing key search terms: dronabinol, nabilone, nabiximols, cannabis, marijuana, smoke, efficacy, toxicity, cancer, multiple sclerosis, nausea, vomiting, appetite, pain, glaucoma, and side effects. Abstracts of the included literature were reviewed, analyzed, and organized to identify the strength of evidence in medical use, efficacy, and adverse effects of the approved cannabis-based medications and medical marijuana. A total of 68 abstracts were included for review. Dronabinol's (Marinol) most common medical uses include weight gain, chemotherapy-induced nausea and vomiting (CINV), and neuropathic pain. Nabiximol's (Sativex) most common medical uses include spasticity in multiple sclerosis (MS) and neuropathic pain. Nabilone's (Cesamet) most common medical uses include CINV and neuropathic pain. Smoked marijuana's most common medical uses include neuropathic pain and glaucoma. Orally ingested marijuana's most common medical uses include improving sleep, reducing neuropathic pain, and seizure control in MS. In general, all of these agents share similar medical uses. The reported adverse effects of the three cannabis-based medications and marijuana show a major trend in central nervous system (CNS)-related adverse effects along with cardiovascular and respiratory related adverse effects. Marijuana shares similar medical uses with the approved cannabis-based medications dronabinol (Marinol), nabiximols (Sativex), and nabilone (Cesamet), but the efficacy of marijuana for these medical uses has not been fully determined due to limited and conflicting literature. Medical marijuana also has similar adverse effects as the FDA-approved cannabis-based medications mainly consisting of CNS related adverse effects but also including cardiovascular and respiratory

  11. Medical marijuana patient counseling points for health care professionals based on trends in the medical uses, efficacy, and adverse effects of cannabis-based pharmaceutical drugs.

    PubMed

    Parmar, Jayesh R; Forrest, Benjamin D; Freeman, Robert A

    2016-01-01

    The purpose of this report is to present a review of the medical uses, efficacy, and adverse effects of the three approved cannabis-based medications and ingested marijuana. A literature review was conducted utilizing key search terms: dronabinol, nabilone, nabiximols, cannabis, marijuana, smoke, efficacy, toxicity, cancer, multiple sclerosis, nausea, vomiting, appetite, pain, glaucoma, and side effects. Abstracts of the included literature were reviewed, analyzed, and organized to identify the strength of evidence in medical use, efficacy, and adverse effects of the approved cannabis-based medications and medical marijuana. A total of 68 abstracts were included for review. Dronabinol's (Marinol) most common medical uses include weight gain, chemotherapy-induced nausea and vomiting (CINV), and neuropathic pain. Nabiximol's (Sativex) most common medical uses include spasticity in multiple sclerosis (MS) and neuropathic pain. Nabilone's (Cesamet) most common medical uses include CINV and neuropathic pain. Smoked marijuana's most common medical uses include neuropathic pain and glaucoma. Orally ingested marijuana's most common medical uses include improving sleep, reducing neuropathic pain, and seizure control in MS. In general, all of these agents share similar medical uses. The reported adverse effects of the three cannabis-based medications and marijuana show a major trend in central nervous system (CNS)-related adverse effects along with cardiovascular and respiratory related adverse effects. Marijuana shares similar medical uses with the approved cannabis-based medications dronabinol (Marinol), nabiximols (Sativex), and nabilone (Cesamet), but the efficacy of marijuana for these medical uses has not been fully determined due to limited and conflicting literature. Medical marijuana also has similar adverse effects as the FDA-approved cannabis-based medications mainly consisting of CNS related adverse effects but also including cardiovascular and respiratory

  12. [THE ADVERSE EFFECTS OF SMOKING ON THE HANDS].

    PubMed

    Dreyfuss, Daniel; Calif, Edward; Stahl, Shalom

    2015-05-01

    Cigarette smoking is known to cause a multitude of harmful effects throughout the body. There are only a few accounts in the literature of these effects as related to the hands. This is a review of the literature, demonstrating the collected knowledge of decreased hand vascularity due to tobacco use and assessing the evidence connecting smoking and supposed resultant maladies, including Raynaud's phenomenon, hand-arm vibration syndrome, Buerger's disease, Dupuytren's contracture, carpal tunnel syndrome, effects on skin and fingernails, decreased skin and bone healing, complications of digit replantation and complex regional pain syndrome. Also presented is the possible increased risk of congenital hand malformations as related to maternal smoking. PMID:26168646

  13. Adverse human health effects associated with molds in the indoor environment.

    PubMed

    Hardin, Bryan D; Kelman, Bruce J; Saxon, Andrew

    2003-05-01

    inhalation exposure to fungi, bacteria, and other organic matter, usually in industrial or agricultural settings. Molds growing indoors are believed by some to cause building-related symptoms. Despite a voluminous literature on the subject, the causal association remains weak and unproven, particularly with respect to causation by mycotoxins. One mold in particular, Stachybotrys chartarum, is blamed for a diverse array of maladies when it is found indoors. Despite its well-known ability to produce mycotoxins under appropriate growth conditions, years of intensive study have failed to establish exposure to S. chartarum in home, school, or office environments as a cause of adverse human health effects. Levels of exposure in the indoor environment, dose-response data in animals, and dose-rate considerations suggest that delivery by the inhalation route of a toxic dose of mycotoxins in the indoor environment is highly unlikely at best, even for the hypothetically most vulnerable subpopulations. Mold spores are present in all indoor environments and cannot be eliminated from them. Normal building materials and furnishings provide ample nutrition for many species of molds, but they can grow and amplify indoors only when there is an adequate supply of moisture. Where mold grows indoors there is an inappropriate source of water that must be corrected before remediation of the mold colonization can succeed. Mold growth in the home, school, or office environment should not be tolerated because mold physically destroys the building materials on which it grows, mold growth is unsightly and may produce offensive odors, and mold is likely to sensitize and produce allergic responses in allergic individuals. Except for persons with severely impaired immune systems, indoor mold is not a source of fungal infections. Current scientific evidence does not support the proposition that human health has been adversely affected by inhaled mycotoxins in home, school, or office environments.

  14. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide

    EPA Science Inventory

    Identification of toxicity pathways linked to chemical -exposure is critical for a better understanding of biological effects of the exposure, toxic mechanisms, and for enhancement of the prediction of chemical toxicity and adverse health outcomes. To identify toxicity pathways a...

  15. Dose-Dependent Adverse Effects of Salinomycin on Male Reproductive Organs and Fertility in Mice

    PubMed Central

    Ojo, Olajumoke Omolara; Bhadauria, Smrati; Rath, Srikanta Kumar

    2013-01-01

    Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis

  16. Curcumin Inhibits The Adverse Effects of Sodium Arsenite in Mouse Epididymal Sperm

    PubMed Central

    Momeni, Hamid Reza; Eskandari, Najmeh

    2016-01-01

    Background The aim of this study was to investigate the effects of curcumin on epididy- mal sperm parameters in adult male Navel Medical Research Institute (NMRI) mice ex- posed to sodium arsenite. Materials and Methods In this experimental study, we divided the animals into four groups: control, sodium arsenite (5 mg/kg), curcumin (100 mg/kg) and curcumin+sodium arsenite. Exposures were performed by intraperitoneal injections for a 5-week period. After the exposure period, we recorded the animals’ body and left testes weights. The left caudal epididymis was used to count the sperm number and analyze motility, viability, morphological abnormalities, acrosome reaction, DNA integrity, and histone-protamine replacement in the spermatozoa. One-way analysis of variance (ANOVA) followed by the Tukey’s test was used to assess the statistical significance of the data with SPSS 16.0. P<0.05 was considered significant. Results Mice exposed to sodium arsenite showed a significant decrease in the num- ber, motility, viability, normal sperm morphology and acrosome integrity of spermato- zoa compared to the control group. In the curcumin+sodium arsenite group, curcumin significantly reversed these adverse effects to the point where they approximated the control. In addition, the application of curcumin alone had no significant difference in these parameters compared to the control and curcumin+sodium arsenite groups. However, we observed no significant differences in the body and the testis weight as well as the DNA integrity and histone-protamine replacement in the spermatozoa of the four groups. Conclusion Curcumin compensated for the toxic effects of sodium arsenite on a number of sperm parameters in adult mice. PMID:27441059

  17. 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

  18. 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

  19. Identifying and managing adverse environmental health effects: 4. Pesticides

    PubMed Central

    Sanborn, Margaret D.; Cole, Donald; Abelsohn, Alan; Weir, Erica

    2002-01-01

    PESTICIDE EXPOSURE CAN CAUSE MANY DIFFERENT HEALTH EFFECTS, from acute problems such as dermatitis and asthma exacerbation to chronic problems such as chronic obstructive pulmonary disease and cancer. The resulting clinical presentations are undifferentiated, and specific knowledge of the links to environmental exposures is often required for effective diagnosis. In this article we illustrate the use of the CH2OPD2 mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Drugs and Diet), a history-taking tool that assists physicians in quickly identifying possible environmental exposures. We also provide clinical information on the epidemiology, clinical presentations, treatment and prevention of pesticide exposures. PMID:12054413

  20. Volatile oils of Chinese crude medicines exhibit antiparasitic activity against human Demodex with no adverse effects in vivo

    PubMed Central

    LIU, JI-XIN; SUN, YAN-HONG; LI, CHAO-PIN

    2015-01-01

    Demodex is a type of permanent obligatory parasite, which can be found on the human body surface. Currently, drugs targeting Demodex usually result in adverse effects and have a poor therapeutic effect. Thus, the aim of the present study was to investigate the use of Chinese crude medicine volatile oils for targeting and inhibiting Demodex in vitro. The volatile oils of six Chinese crude medicines were investigated, including clove, orange fruit, Manchurian wildginger, cinnamon bark, Rhizome Alpiniae Officinarum and pricklyash peel, which were extracted using a distillation method. The exercise status of Demodex folliculorum and Demodex brevis and the antiparasitic effects of the volatile oils against the two species were observed using microscopy. A skin irritation test was used to examine the irritation intensity of the volatile oils. In addition, an acute toxicity test was utilized to observe the toxicity effects of the volatile oils on the skin. Xin Fumanling ointment was employed as a positive control to identify the therapeutic effects of the volatile oils. The results indicated that all six volatile oils were able to kill Demodex efficiently. In particular, the clove volatile oil was effective in inducing optimized anti-Demodex activity. The lethal times of the volatile oils were significantly decreased compared with the Xin Fumanling ointment (P<0.05). Furthermore, the skin irritation test results indicated that the clove volatile oil did not trigger any irritation (0.2 and 0.3 points for intact and scratched skin, respectively), and had a safety equal to that of distilled water. There were not any adverse effects observed following application of the clove volatile oil on the intact or scratched skin. In conclusion, the volatile oils of Chinese crude medicines, particularly that of clove, demonstrated an evident anti-Demodex activity and were able to kill Demodex effectively and safely in vivo. PMID:25780426

  1. Selenium toxicity: cause and effects in aquatic birds

    USGS Publications Warehouse

    Spallholz, J.E.; Hoffman, D.J.

    2002-01-01

    There are several manners in which selenium may express its toxicity: (1) an important mechanism appears to involve the formation of CH3Se- which either enters a redox cycle and generates superoxide and oxidative stress, or forms free radicals that bind to and inhibit important enzymes and proteins. (2) Excess selenium as selenocysteine results in inhibition of selenium methylation metabolism. As a consequence, concentrations of hydrogen selenide, an intermediate metabolite, accumulate in animals and are hepatotoxic, possibly causing other selenium-related adverse effects. (3) It is also possible that the presence of excess selenium analogs of sulfur-containing enzymes and structural proteins play a role in avian teratogenesis. l-selenomethionine is the most likely major dietary form of selenium encountered by aquatic birds, with lesser amounts of l-selenocysteine ingested from aquatic animal foods. The literature is suggestive that l-selenomethionine is not any more toxic to adult birds than other animals. l-Selenomethionine accumulates in tissue protein of adult birds and in the protein of egg white as would be expected to occur in animals. There is no suggestion from the literature that the levels of l-selenomethionine that would be expected to accumulate in eggs in the absence of environmental concentration of selenium pose harm to the developing embryo. For several species of aquatic birds, levels of Se as selenomethionine in the egg above 3 ppm on a wet weight basis result in reduced hatchability and deformed embryos. The toxicity of l-selenomethionine injected directly into eggs is greater than that found from the entry of l-selenomethionine into the egg from the normal adult diet. This suggests that there is unusual if not abnormal metabolism of l-selenomethionine in the embryo not seen when l-selenomethionine is present in egg white protein where it likely serves as a source of selenium for glutathione peroxidase synthesis in the developing aquatic chick.

  2. Nickel species: analysis and toxic effects.

    PubMed

    Schaumlöffel, Dirk

    2012-01-01

    This review gives an overview on the analysis of inorganic nickel species and their toxic effects. Based on the analytical procedure applied inorganic nickel species are usually classified in soluble, sulfidic, metallic and oxidic nickel fractions. Only few works were attempting a chemical characterization of the different nickel compounds in each fraction. This general classification in four nickel species groups is widely used in toxicological studies dealing with nickel particulate matter in workplace air. Compared to the general population, occupationally exposed people have a higher risk of respiratory tract cancer due to inhalation of nickel at their workplace in the nickel-producing or using industries. High cancer risk is related to less soluble oxidic and especially sulfidic nickel species in refinery dust. In contrast, within the general population the most harmful health effect related to nickel exposure is allergic contact dermatitis due to prolonged skin contact with nickel. Absorption processes of nickel species and molecular mechanisms of nickel toxicity are briefly outlined. PMID:22366237

  3. Environmental mercury and its toxic effects.

    PubMed

    Rice, Kevin M; Walker, Ernest M; Wu, Miaozong; Gillette, Chris; Blough, Eric R

    2014-03-01

    Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects. PMID:24744824

  4. Environmental Mercury and Its Toxic Effects

    PubMed Central

    Rice, Kevin M.; Walker, Ernest M.; Wu, Miaozong; Gillette, Chris

    2014-01-01

    Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects. PMID:24744824

  5. Environmental mercury and its toxic effects.

    PubMed

    Rice, Kevin M; Walker, Ernest M; Wu, Miaozong; Gillette, Chris; Blough, Eric R

    2014-03-01

    Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects.

  6. 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

  7. 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…

  8. 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.

  9. Potential toxic effects of glyphosate and its commercial formulations below regulatory limits.

    PubMed

    Mesnage, R; Defarge, N; Spiroux de Vendômois, J; Séralini, G E

    2015-10-01

    Glyphosate-based herbicides (GlyBH), including Roundup, are the most widely used pesticides worldwide. Their uses have increased exponentially since their introduction on the market. Residue levels in food or water, as well as human exposures, are escalating. We have reviewed the toxic effects of GlyBH measured below regulatory limits by evaluating the published literature and regulatory reports. We reveal a coherent body of evidence indicating that GlyBH could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects. It includes teratogenic, tumorigenic and hepatorenal effects. They could be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time. Some effects were detected in the range of the recommended acceptable daily intake. Toxic effects of commercial formulations can also be explained by GlyBH adjuvants, which have their own toxicity, but also enhance glyphosate toxicity. These challenge the assumption of safety of GlyBH at the levels at which they contaminate food and the environment, albeit these levels may fall below regulatory thresholds. Neurodevelopmental, reproductive, and transgenerational effects of GlyBH must be revisited, since a growing body of knowledge suggests the predominance of endocrine disrupting mechanisms caused by environmentally relevant levels of exposure.

  10. Potential toxic effects of glyphosate and its commercial formulations below regulatory limits.

    PubMed

    Mesnage, R; Defarge, N; Spiroux de Vendômois, J; Séralini, G E

    2015-10-01

    Glyphosate-based herbicides (GlyBH), including Roundup, are the most widely used pesticides worldwide. Their uses have increased exponentially since their introduction on the market. Residue levels in food or water, as well as human exposures, are escalating. We have reviewed the toxic effects of GlyBH measured below regulatory limits by evaluating the published literature and regulatory reports. We reveal a coherent body of evidence indicating that GlyBH could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects. It includes teratogenic, tumorigenic and hepatorenal effects. They could be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time. Some effects were detected in the range of the recommended acceptable daily intake. Toxic effects of commercial formulations can also be explained by GlyBH adjuvants, which have their own toxicity, but also enhance glyphosate toxicity. These challenge the assumption of safety of GlyBH at the levels at which they contaminate food and the environment, albeit these levels may fall below regulatory thresholds. Neurodevelopmental, reproductive, and transgenerational effects of GlyBH must be revisited, since a growing body of knowledge suggests the predominance of endocrine disrupting mechanisms caused by environmentally relevant levels of exposure. PMID:26282372

  11. Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models

    SciTech Connect

    Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

    2011-07-15

    Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds.

  12. Adverse effects of coal combustion related fine particulate matter (PM2.5) on nematode Caenorhabditis elegans.

    PubMed

    Sun, Lingmei; Lin, Zhiqing; Liao, Kai; Xi, Zhuge; Wang, Dayong

    2015-04-15

    The toxic effects of coal combustion related fine particulate matter (PM2.5), collected from Datong, Shanxi province, China, on nematode Caenorhabditis elegans were investigated. Exposure to PM2.5 resulted in deficits in development, reproduction, locomotion behavior, and lifespan, and induction of intestinal autofluorescence or reactive oxygen species (ROS) production. Prolonged exposure to PM2.5 led to more severe toxicity on nematodes than acute exposure. In addition, exposure to PM2.5 induced altered expression patterns of genes required for the control of oxidative stress. Reduction in mean defecation cycle length and developmental deficits in AVL and DVB neurons, which are involved in the control of defecation behavior, were also triggered by PM2.5 exposure. Thus, oxidative stress and abnormal defecation behavior may contribute greatly to the toxicity of coal combustion related PM2.5 in nematodes. The results also imply that the long-term adverse effects of coal combustion related PM2.5 on environmental organisms should be carefully considered.

  13. Effect of soil properties on the toxicity of Pb: assessment of the appropriateness of guideline values.

    PubMed

    Romero-Freire, A; Martin Peinado, F J; van Gestel, C A M

    2015-05-30

    Soil contamination with lead is a worldwide problem. Pb can cause adverse effects, but its mobility and availability in the terrestrial environment are strongly controlled by soil properties. The present study investigated the influence of different soil properties on the solubility of lead in laboratory spiked soils, and its toxicity in three bioassays, including Lactuca sativa root elongation and Vibrio fischeri illumination tests applied to aqueous extracts and basal soil respiration assays. Final aim was to compare soil-dependent toxicity with guideline values. The L. sativa bioassay proved to be more sensitive to Pb toxicity than the V. fischeri and soil respiration tests. Toxicity was significantly correlated with soil properties, with soil pH, carbonate and organic carbon content being the most important factors. Therefore, these variables should be considered when defining guideline values. PMID:25704434

  14. 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

  15. Adverse effects and bioconcentration of chromium in two freshwater rotifer species.

    PubMed

    Hernández-Ruiz, Esmeralda; Alvarado-Flores, Jesús; Rubio-Franchini, Isidoro; Ventura-Juárez, Javier; Rico-Martínez, Roberto

    2016-09-01

    Bioaccumulation of trivalent (CrIII) and hexavalent chromium (CrVI), and its adverse effects were studied in two rotifer species: Brachionus calyciflorus (two different strains), and Lecane quadridentata. Median Lethal Concentration (LC50) at 24 h of both species showed that CrVI is highly toxic: LC50 ranges from 4.7 × 10(-5) to 4 × 10(-6) mg L(-1)), compared with CrIII: LC50 ranges from 0.64 to 1.279 mg L(-1). Using the LC50 as an exposure concentration, and using atomic absorption, the bioconcentration factor (BCF) was obtained and BCFs of rotifers exposed to CrIII are four orders of magnitude lower than BCFs of rotifers exposed to CrVI. The effect of Cr on the elemental composition of the two species of rotifers in their structures by X-ray microanalysis by energy dispersion showed that Cr is found in intoxicated rotifers, but not in control rotifers. The basal immunoreactivity to metallothioneins is greater in B. calyciflorus than L. quadridentata. The immunoreactivity to metallothioneins decreases in B. calyciflorus when is exposed to CrIII, in contrast in L. quadridentata the immunoreactivity to metallothioneins increase when is exposed to CrIII, and the immunoreactivity to CrVI in L. quadridentata decrease. A mechanism is proposed in which the harder lorica of L. quadridentata acts as a barrier and accumulator of CrVI, and allows for attenuating responses like metallothionein production in L. quadridentata. Instead, in B. calyciflorus the lack of a harder lorica allows for deeper penetration of CrVI, and no time to produce attenuating measures. PMID:27258901

  16. Adverse effects and bioconcentration of chromium in two freshwater rotifer species.

    PubMed

    Hernández-Ruiz, Esmeralda; Alvarado-Flores, Jesús; Rubio-Franchini, Isidoro; Ventura-Juárez, Javier; Rico-Martínez, Roberto

    2016-09-01

    Bioaccumulation of trivalent (CrIII) and hexavalent chromium (CrVI), and its adverse effects were studied in two rotifer species: Brachionus calyciflorus (two different strains), and Lecane quadridentata. Median Lethal Concentration (LC50) at 24 h of both species showed that CrVI is highly toxic: LC50 ranges from 4.7 × 10(-5) to 4 × 10(-6) mg L(-1)), compared with CrIII: LC50 ranges from 0.64 to 1.279 mg L(-1). Using the LC50 as an exposure concentration, and using atomic absorption, the bioconcentration factor (BCF) was obtained and BCFs of rotifers exposed to CrIII are four orders of magnitude lower than BCFs of rotifers exposed to CrVI. The effect of Cr on the elemental composition of the two species of rotifers in their structures by X-ray microanalysis by energy dispersion showed that Cr is found in intoxicated rotifers, but not in control rotifers. The basal immunoreactivity to metallothioneins is greater in B. calyciflorus than L. quadridentata. The immunoreactivity to metallothioneins decreases in B. calyciflorus when is exposed to CrIII, in contrast in L. quadridentata the immunoreactivity to metallothioneins increase when is exposed to CrIII, and the immunoreactivity to CrVI in L. quadridentata decrease. A mechanism is proposed in which the harder lorica of L. quadridentata acts as a barrier and accumulator of CrVI, and allows for attenuating responses like metallothionein production in L. quadridentata. Instead, in B. calyciflorus the lack of a harder lorica allows for deeper penetration of CrVI, and no time to produce attenuating measures.

  17. 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)...

  18. 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)...

  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, 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)...

  1. 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

    ... 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)...

  2. The Adverse Effects of Alcohol on Vitamin A Metabolism

    PubMed Central

    Clugston, Robin D.; Blaner, William S.

    2012-01-01

    The objective of this review is to explore the relationship between alcohol and the metabolism of the essential micronutrient, vitamin A; as well as the impact this interaction has on alcohol-induced disease in adults. Depleted hepatic vitamin A content has been reported in human alcoholics, an observation that has been confirmed in animal models of chronic alcohol consumption. Indeed, alcohol consumption has been associated with declines in hepatic levels of retinol (vitamin A), as well as retinyl ester and retinoic acid; collectively referred to as retinoids. Through the use of animal models, the complex interplay between alcohol metabolism and vitamin A homeostasis has been studied; the reviewed research supports the notion that chronic alcohol consumption precipitates a decline in hepatic retinoid levels through increased breakdown, as well as increased export to extra-hepatic tissues. While the precise biochemical mechanisms governing alcohol’s effect remain to be elucidated, its profound effect on hepatic retinoid status is irrefutable. In addition to a review of the literature related to studies on tissue retinoid levels and the metabolic interactions between alcohol and retinoids, the significance of altered hepatic retinoid metabolism in the context of alcoholic liver disease is also considered. PMID:22690322

  3. The effectiveness and adverse effects profile of "burst" ketamine in refractory cancer pain: The VCOG PM 1-00 study.

    PubMed

    Jackson, Kate; Ashby, Michael; Howell, Deb; Petersen, Jennifer; Brumley, David; Good, Phillip; Pisasale, Maria; Wein, Simon; Woodruff, Roger

    2010-01-01

    This multi-centre study of adjuvant "burst" ketamine in palliative care in-patients documents its effectiveness, duration of pain relief, and adverse effects (AE) profile. Patients received a three-to-five day continuous subcutaneous infusion (CSCI) of ketamine escalated from 100 to 300 to 500 mg/24 hours if required. When the effective or maximum tolerated dose was attained, the infusion was continued for three days and each patient assessed as a responder or non-responder using strict criteria. The response rate was 22/44 (50 percent), with 4 (9 percent) becoming pain-free. Pain relief lasting two or more weeks was documented in 50 percent of responders. AEs were documented daily using the National Cancer Institute (NCI) Common Toxicity Criteria 0-4 scales. There were 11 grade 3 and 4 neurological AEs. However, no responders elected to cease treatment early due to neurological AEs. We concluded that this protocol in the controlled environment of an in-patient PC unit is relatively safe and simple with reasonable effectiveness.

  4. Unexpected adverse effects of Freon 11 and Freon 12 as medication propellants.

    PubMed

    Oenbrink, R J

    1993-06-01

    Metered-dose inhalers are frequently used in treating pulmonary diseases associated with bronchoconstriction, chiefly asthma and chronic bronchitis. These aerosolized medications are not without the potential for adverse effects. The author describes two patients who likely had adverse reactions to the Freon propellants used in the inhalers. These reactions are reported in order to alert physicians to their possible occurrence and to suggest a rational treatment approach. PMID:8349485

  5. 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.

  6. Acute toxic effects of fragrance products.

    PubMed

    Anderson, R C; Anderson, J H

    1998-01-01

    To evaluate whether fragrance products can produce acute toxic effects in mammals, we allowed groups of male Swiss-Webster mice to breathe the emissions of five commercial colognes or toilet water for 1 h. We used the ASTM-E-981 test method to evaluate sensory irritation and pulmonary irritation. We used a computerized version of this test to measure the duration of the break at the end of inspiration and the duration of the pause at the end of expiration. Decreases in expiratory flow velocity indicated airflow limitation. We subjected the mice to a functional observational battery to probe for changes in nervous system function. The emissions of these fragrance products caused various combinations of sensory irritation, pulmonary irritation, decreases in expiratory airflow velocity, as well as alterations of the functional observational battery indicative of neurotoxicity. Neurotoxicity was more severe after mice were repeatedly exposed to the fragrance products. Evaluation of one of the test atmospheres with gas chromatography/mass spectrometry revealed the presence of chemicals for which irritant and neurotoxic properties had been documented previously. In summary, some fragrance products emitted chemicals that caused a variety of acute toxicities in mice.

  7. 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

  8. Adversity in preschool-aged children: Effects on salivary interleukin-1β.

    PubMed

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

    2015-05-01

    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 interleukin (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. 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. The 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. Postchallenge IL-1β displayed positive associations with each adversity variable, but these were not significant. CRP was not significantly associated with any of the adversity variables. Given the evidence suggesting the involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

  9. Toxic Epidermal Necrolysis During Dronedarone Treatment: First Report of a Severe Serious Adverse Event Of A New Antiarrhythmic Drug.

    PubMed

    Gecks, Thomas; Prochnau, Dirk; Franz, Marcus; Jung, Christian; Kühnert, Helmut; Schliemann, Sibylle; Figulla, Hans Rainer

    2015-10-01

    A 77-year-old female patient with symptomatic atrial fibrillation with fast ventricular rate despite conventional antiarrhythmic therapy was treated with dronedarone. Five days later, she developed a maculopapulous exanthema and small flaccid blisters, which spread over the common integument predominantly located on the dorsal trunk. Over few days, the patient showed a severe epidermal necrolysis of approximately 30 % of the body area and ultimately died in multiorgan failure. Here, we report a rare case of toxic epidermal necrolysis during treatment with dronedarone leading to patient death.

  10. Effect of zeolite on toxicity of ammonia in freshwater sediments: Implications for toxicity identification evaluation procedures

    SciTech Connect

    Besser, J.M.; Ingersoll, C.G.; Leonard, E.N.; Mount, D.R.

    1998-11-01

    Techniques for reducing ammonia toxicity in freshwater sediments were investigated as part of a project to develop toxicity identification and evaluation (TIE) procedures for whole sediments. Although ammonia is a natural constituent of freshwater sediments, pollution can lead to ammonia concentrations that are toxic to benthic invertebrates, and ammonia can also contribute to the toxicity of sediments that contain more persistent contaminants. The authors investigated the use of amendments of a natural zeolite mineral, clinoptilolite, to reduce concentrations of ammonia in sediment pore water. Zeolites have been widely used for removal of ammonia in water treatment and in aqueous TIE procedures. The addition of granulated zeolite to ammonia-spiked sediments reduced pore-water ammonia concentrations and reduced ammonia toxicity to invertebrates. Amendments of 20% zeolite (v/v) reduced ammonia concentrations in pore water by {ge}70% in spiked sediments with ammonia concentrations typical of contaminated freshwater sediments. Zeolite amendments reduced toxicity of ammonia-spiked sediments to three taxa of benthic invertebrates (Hyalella azteca, Lumbriculus variegatus, and Chironomus tentans), despite their widely differing sensitivity to ammonia toxicity. In contrast, zeolite amendments did not reduce acute toxicity of sediments containing high concentrations of cadmium or copper or reduce concentrations of these metals in pore waters. These studies suggest that zeolite amendments, used in conjunction with toxicity tests with sensitive taxa such as H. azteca, may be an effective technique for selective reduction of ammonia toxicity in freshwater sediments.

  11. Effect of zeolite on toxicity of ammonia in freshwater sediments: Implications for toxicity identification evaluation procedures

    USGS Publications Warehouse

    Besser, J.M.; Ingersoll, C.G.; Leonard, E.N.; Mount, D.R.

    1998-01-01

    Techniques for reducing ammonia toxicity in freshwater sediments were investigated as part of a project to develop toxicity identification and evaluation (TIE) procedures for whole sediments. Although ammonia is a natural constituent of freshwater sediments, pollution can lead to ammonia concentrations that are toxic to benthic invertebrates, and ammonia can also contribute to the toxicity of sediments that contain more persistent contaminants. We investigated the use of amendments of a natural zeolite mineral, clinoptilolite, to reduce concentrations of ammonia in sediment pore water. Zeolites have been widely used for removal of ammonia in water treatment and in aqueous TIE procedures. The addition of granulated zeolite to ammonia-spiked sediments reduced pore-water ammonia concentrations and reduced ammonia toxicity to invertebrates. Amendments of 20% zeolite (v/v) reduced ammonia concentrations in pore water by ???70% in spiked sediments with ammonia concentrations typical of contaminated freshwater sediments. Zeolite amendments reduced toxicity of ammonia-spiked sediments to three taxa of benthic invertebrates (Hyalella azteca, Lumbriculus variegatus, and Chironomus tentans), despite their widely differing sensitivity to ammonia toxicity. In contrast, zeolite amendments did not reduce acute toxicity of sediments containing high concentrations of cadmium or copper or reduce concentrations of these metals in pore waters. These studies suggest that zeolite amendments, used in conjunction with toxicity tests with sensitive taxa such as H. azteca, may be an effective technique for selective reduction of ammonia toxicity in freshwater sediments.

  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.

  13. Adverse effects of psychological therapy: An exploratory study of practitioners' experiences from child and adolescent psychiatry.

    PubMed

    Jonsson, Ulf; Johanson, Josefin; Nilsson, Elin; Lindblad, Frank

    2016-07-01

    The scientific knowledge about adverse effects of psychological therapies and how such effects should be detected is limited. It is possible that children and adolescents are particularly vulnerable and need specific support in order to express adverse effects. In this exploratory study, we used a qualitative approach to explore practitioners' experiences of this phenomenon. Fourteen practitioners providing psychological therapy within the Child and Adolescent Psychiatric Service were interviewed. Qualitative content analysis was applied to the data. Four overarching categories brought up by the practitioners were identified: vagueness of the concept (reflecting that the concept was novel and hard to define), psychotherapist-client interaction (encompassing aspects of the interaction possibly related to adverse effects), consequences for the young person (including a range of emotional, behavioural and social consequences) and family effects (e.g. professional complications and decreased autonomy for the parent). Professional discussions on these issues could improve psychological therapy for children and adolescents. Based on our findings and previous research, we propose three basic aspects to consider when adverse effects are detected and managed in this context: typology (form, severity and duration), aetiology (hypothesis about the causes) and perspective (adverse effects seen from the points of view of different interested parties).

  14. 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

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

    PubMed

    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

  16. 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

  17. Association between Environmental Dioxin-Related Toxicants Exposure and Adverse Pregnancy Outcome: Systematic Review and Meta-Analysis.

    PubMed

    Pan, Xinjuan; Liu, Xiaozhuan; Li, Xing; Niu, Nannan; Yin, Xinjuan; Li, Ning; Yu, Zengli

    2015-01-01

    Dioxin-related compounds are associated with teratogenic and mutagenic risks in laboratory animals, and result in adverse pregnancy outcomes. However, there were inconsistent results in epidemiology studies. In view of this difference, we conducted a systematic review and meta-analysis to examine this association and to assess the heterogeneity among studies. Comprehensive literature searches were performed to search for relevant articles published in English up to 15 May 2012. In total, we identified 15 studies which included 9 cohort and 6 case control studies. The Cochrane Q test and index of heterogeneity (I(2)) were used to evaluate heterogeneity. In either cohort studies (I(2)=0.89, p<0.0001) or case control studies (I(2)=0.69, p=0.02), significant heterogeneity of risk estimates were observed. Subgroup analyses found no significant increased risk of adverse pregnancy outcome with air dioxin-related compounds exposure (RR=0.99, 95% CI:0.85-1.16), no significant increased risk of spontaneous abortion (SAB) with exposure to food dioxin-related compounds (RR=1.05, 95% CI:0.80-1.37), higher significant risks of low birth weight (LBW) with exposure to food dioxin-related compounds (RR=1.55, 95% CI:1.24-1.94), and higher significant risks of birth defects with maternal solid contaminants dioxin exposure (OR=1.24, 95% CI:1.19-1.29). In conclusion, more evidences are needed to confirm the association between environmental dioxin-related compounds exposure and pregnancy outcome. PMID:25780516

  18. Association between Environmental Dioxin-Related Toxicants Exposure and Adverse Pregnancy Outcome: Systematic Review and Meta-Analysis

    PubMed Central

    Pan, Xinjuan; Liu, Xiaozhuan; Li, Xing; Niu, Nannan; Yin, Xinjuan; Li, Ning; Yu, Zengli

    2015-01-01

    Dioxin-related compounds are associated with teratogenic and mutagenic risks in laboratory animals, and result in adverse pregnancy outcomes. However, there were inconsistent results in epidemiology studies. In view of this difference, we conducted a systematic review and meta-analysis to examine this association and to assess the heterogeneity among studies. Comprehensive literature searches were performed to search for relevant articles published in English up to 15 May 2012. In total, we identified 15 studies which included 9 cohort and 6 case control studies. The Cochrane Q test and index of heterogeneity (I2) were used to evaluate heterogeneity. In either cohort studies (I2=0.89, p<0.0001) or case control studies (I2=0.69, p=0.02), significant heterogeneity of risk estimates were observed. Subgroup analyses found no significant increased risk of adverse pregnancy outcome with air dioxin-related compounds exposure (RR=0.99, 95% CI:0.85–1.16), no significant increased risk of spontaneous abortion (SAB) with exposure to food dioxin-related compounds (RR=1.05, 95% CI:0.80–1.37), higher significant risks of low birth weight (LBW) with exposure to food dioxin-related compounds (RR=1.55, 95% CI:1.24–1.94), and higher significant risks of birth defects with maternal solid contaminants dioxin exposure (OR=1.24, 95% CI:1.19–1.29). In conclusion, more evidences are needed to confirm the association between environmental dioxin-related compounds exposure and pregnancy outcome. PMID:25780516

  19. Potential adverse effects of omega-3 Fatty acids in dogs and cats.

    PubMed

    Lenox, C E; Bauer, J E

    2013-01-01

    Fish oil omega-3 fatty acids, mainly eicosapentaenoic acid and docosahexaenoic acid, are used in the management of several diseases in companion animal medicine, many of which are inflammatory in nature. This review describes metabolic differences among omega-3 fatty acids and outlines potential adverse effects that may occur with their supplementation in dogs and cats with a special focus on omega-3 fatty acids from fish oil. Important potential adverse effects of omega-3 fatty acid supplementation include altered platelet function, gastrointestinal adverse effects, detrimental effects on wound healing, lipid peroxidation, potential for nutrient excess and toxin exposure, weight gain, altered immune function, effects on glycemic control and insulin sensitivity, and nutrient-drug interactions.

  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. Updated weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection by-products.

    PubMed

    Tardiff, Robert G; Carson, M Leigh; Ginevan, Michael E

    2006-07-01

    Disinfection by-products (DBP) are produced when water is treated with chemical disinfectants. Some toxicological and epidemiological studies suggest an association between DBP exposure and adverse reproductive and developmental effects. In a previous critical review, [Graves, C.G., Matanoski, G.M., Tardiff, R.G., 2001. Weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection by-products: a critical review. Regul. Toxicol. Pharmacol. 34, (2) 103-124] evaluated the weight of evidence for this exposure and these effects. This investigation updates the previous evaluation and considers all toxicological and epidemiological evidence since the earlier review and reassesses the weight-of-evidence for all of the data on the various effects, outcome by outcome. The updated toxicity weight of evidence found little indication of previously unreported reproductive or developmental toxicity. In particular, the recently published findings of an exceptionally well conducted cohort study of broad scope found no impact of chlorination by-products on the highly controversial outcome of spontaneous abortion, unlike predecessor studies of more limited methodology, leading the authors to recommend no further epidemiologic pursuit for this hypothesis since the cohort was scrutinized very closely and dispelled any concern of such an association. The updated epidemiologic weight of evidence demonstrated that no association with DBP exposure exists for over a dozen outcomes including low and very low birth weight, preterm delivery, some specific congenital anomalies, and neonatal death. The analysis found inconsistent or very weak results for all congenital anomalies/birth defects, all central nervous system anomalies, neural tube defects, and spontaneous abortion. As in the previous article, the updated weight of evidence suggested a positive association with DBP exposure and some measure of growth retardation such as

  2. Protective effects of phyllanthus emblica leaf extract on sodium arsenite-mediated adverse effects in mice.

    PubMed

    Sayed, Sadia; Ahsan, Nazmul; Kato, Masashi; Ohgami, Nobutaka; Rashid, Abdur; Akhand, Anwarul Azim

    2015-02-01

    Groundwater contamination of arsenic is the major cause of a serious health hazard in Bangladesh. No specific treatment is yet available to manage the large number of individuals exposed to arsenic. In this study, we evaluated the protective effects of Phyllanthus emblica (Indian gooseberry or Amla) leaf extract (PLE) on arsenic-mediated toxicity in experimental mice. Male Swiss albino mice were divided into three different groups (n=6/group). 'Control' mice received arsenic free water together with normal feed. Mice in the remaining two groups designated 'SA' and 'SA+PLE' were exposed to sodium arsenite (SA, 10 µg/g body weight/day) through drinking water in addition to receiving normal feed and PLE-supplemented feed, respectively. The weight gain of SA-exposed mice was decreased compared with the controls; however, this decrease in body weight gain was prevented when the feed was supplemented with PLE. A secondary effect of arsenic was enlargement of the liver, kidney and spleen of SA-group mice. Deposition of arsenic in those organs was demonstrated by ICP-MS. When PLE was supplemented in the feed the enlargement of the organs was minimized; however, the deposition of arsenic was not significantly reduced. These results indicated that PLE may not block arsenic deposition in tissue directly but rather may play a protective role to reduce arsenic-induced toxicity. Therefore, co-administration of PLE in arsenic-exposed animals might have a future therapeutic application for protecting against arsenic-mediated toxicity.

  3. Combined Transcriptomics Analysis for Classification of Adverse Effects As a Potential End Point in Effect Based Screening.

    PubMed

    de Boer, Tjalf E; Janssens, Thierry K S; Legler, Juliette; van Straalen, Nico M; Roelofs, Dick

    2015-12-15

    Environmental risk assessment relies on the use of bioassays to assess the environmental impact of chemicals. Gene expression is gaining acceptance as a valuable mechanistic end point in bioassays and effect-based screening. Data analysis and its results, however, are complex and often not directly applicable in risk assessment. Classifier analysis is a promising method to turn complex gene expression analysis results into answers suitable for risk assessment. We have assembled a large gene expression data set assembled from multiple studies and experiments in the springtail Folsomia candida, with the aim of selecting a set of genes that can be trained to classify general toxic stress. By performing differential expression analysis prior to classifier training, we were able to select a set of 135 genes which was enriched in stress related processes. Classifier models from this set were used to classify two test sets comprised of chemical spiked, polluted, and clean soils and compared to another, more traditional classifier feature selection. The gene set presented here outperformed the more traditionally selected gene set. This gene set has the potential to be used as a biomarker to test for adverse effects caused by chemicals in springtails to provide end points in environmental risk assessment. PMID:26523736

  4. The Effect of Lifetime Cumulative Adversity and Depressive Symptoms on Functional Status

    PubMed Central

    Litwin, Howard

    2014-01-01

    Objectives. The study aimed to examine whether lifetime cumulative adversity (LCA) and depressive symptoms moderate time-related trajectories of functional status. Method. A total of 15,073 older adults (mean age = 63.91 at Wave 1) who participated in the first four waves of the Survey of Health, Ageing and Retirement in Europe reported on exposure to negative life events, depressive symptoms and three measures of functional status—difficulty in performing daily and instrumental activities, and functional limitation. Results. Growth–curve models showed that time-related increase in disability and functional limitation was steeper among those exposed to higher levels of lifetime adversity. Moreover, a three-way interaction between time, lifetime adversity, and depressive symptoms emerged across measures of functional status, so that when exposure to lifetime adversity was accompanied by high level of depressive symptoms, the time-related increase in disability and functional limitation was the steepest. Discussion. LCA is associated with a hastening of the disablement process, especially under conditions of high distress. Although the overall modest effects imply that resilience to lifetime adversity is widespread among older adults, prevention and intervention programs should consider that distressed older adults previously exposed to high levels of lifetime adversity are at risk for more rapid impairment in functional status. PMID:24898028

  5. Redox nanoparticle therapeutics to cancer--increase in therapeutic effect of doxorubicin, suppressing its adverse effect.

    PubMed

    Yoshitomi, Toru; Ozaki, Yuki; Thangavel, Sindhu; Nagasaki, Yukio

    2013-11-28

    The ultimate goal of cancer chemotherapy is to achieve a cure without causing any adverse effects. We have developed a pH-sensitive redox nanoparticle (RNP(N)), which disintegrates under acidic conditions and exposes nitroxide radicals, leading to strongly scavenging reactive oxygen species (ROS). After intravenous administration of RNP(N) to tumor bearing mice, it effectively accumulated in tumors due to the leaky neovascular and immature lymphatic system and scavenged ROS, resulting in suppression of inflammation and activation of NF-кB, after disintegration of RNP(N) in the tumors. Pre-administration of RNP(N) prior to treatments with anticancer agents, doxorubicin, to tumor-bearing mice significantly suppressed the progression of tumor size, compared to low-molecular weight 4-hydroxy-TEMPO. Interestingly, the administration of RNP(N) suppressed adverse effects of doxorubicin to normal organs due to the scavenging ROS and suppression of inflammation, which was confirmed by reduction in lactate dehydrogenase and creatine phosphokinase activities in plasma. RNP(N) is thus anticipated as a novel and ideal adjuvant for cancer chemotherapy.

  6. 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

  7. 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.

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

    NASA Astrophysics Data System (ADS)

    Herrera, Higmar; Yañez, Elvia; Deras, Diana C.; Reyes, Francianella

    2010-12-01

    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).

  9. 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

  10. 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

  11. Antiangiogenic agents and the skin: cutaneous adverse effects of sorafenib, sunitinib, and bevacizumab.

    PubMed

    Ara, M; Pastushenko, E

    2014-12-01

    As new antiangiogenic therapies have been introduced and added to the therapeutic arsenal against various types of cancer, previously unknown adverse effects have been detected. These effects negatively impact patients' quality of life and can even make it necessary to suspend treatment. Adverse skin reactions occur in 90% of patients treated with angiogenesis inhibitors. In some cases, a correlation has been observed between the severity of reactions and treatment efficacy and tumor response. It is therefore extremely important that dermatologists be able to recognize and manage these reactions. Moreover, in order to avoid the unjustified withdrawal of potentially life-extending treatments, dermatologists must be able to differentiate between non-life-threatening reactions and life-threatening reactions that necessitate the suspension of treatment. In this review article, we analyze the main cutaneous adverse effects of the most common antiangiogenic agents. PMID:24766821

  12. 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).

  13. Acute adverse effects of radiation therapy on HIV-positive patients in Japan: study of 31 cases at Tokyo Metropolitan Komagome Hospital.

    PubMed

    Kaminuma, Takuya; Karasawa, Katsuyuki; Hanyu, Nahoko; Chang, Ta-Chen; Kuga, Gencho; Okano, Naoko; Kubo, Nobuteru; Okuma, Yusuke; Nagata, Yasunobu; Maeda, Yoshiharu; Ajisawa, Atsushi

    2010-01-01

    Recently, the number of human immunodeficiency virus (HIV) -positive patients has increased in Japan. HIV-positive patients are at a higher risk of cancer than the general population. This paper retrospectively reports the acute adverse effects of radiation therapy on HIV-positive patients who were treated at Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital (TMCICK). Thirty-one cases involving 24 HIV-positive cancer patients who were treated at TMCICK from January 1997 to March 2009 were included in this study. All acute adverse effects of radiation therapy were examined during, and one month after, the last radiation therapy session. Acute adverse effects were classified according to the site of radiation therapy treatment and analyzed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 3 acute adverse effects were seen in 17% of cases, and Grade 2 toxicities were found in 23% of patients. Damage to the skin and mucosa, including stomatitis or diarrhea, tended to occur after low-dose radiation therapy; however, no severe acute adverse effects were seen in other organs, such as the brain, lung, and bone. Acute adverse effects tended to occur earlier in HIV-positive patients and became severe more frequently than in the general population. In particular, disorders of the mucosa, such as those of the oral cavity, pharynx, and intestine, tended to occur rapidly. It was shown that radiation therapy is safe when treatment is performed carefully and that it is a very useful treatment for cancer in HIV-positive patients.

  14. 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

  15. 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 ...

  16. Mice fed on a diet enriched with genetically engineered multivitamin corn show no sub-acute toxic effects and no sub-chronic toxicity.

    PubMed

    Arjó, Gemma; Capell, Teresa; Matias-Guiu, Xavier; Zhu, Changfu; Christou, Paul; Piñol, Carme

    2012-12-01

    Multivitamin corn is a novel genetically engineered variety that simultaneously produces high levels of β-carotene, ascorbate and folate, and therefore has the potential to address simultaneously multiple micronutrient deficiencies caused by the lack of vitamins A, B9 and C in developing country populations. As part of the development process for genetically engineered crops and following European Food Safety Authority (EFSA) recommendations, multivitamin corn must be tested in whole food/feed sub-chronic animal feeding studies to ensure there are no adverse effects, and potential allergens must be identified. We carried out a 28-day toxicity assessment in mice, which showed no short-term sub-acute evidence of diet-related adverse health effects and no difference in clinical markers (food consumption, body weight, organ/tissue weight, haematological and biochemical blood parameters and histopathology) compared to mice fed on a control diet. A subsequent 90-day sub-chronic feeding study again showed no indications of toxicity compared to mice fed on control diets. Our data confirm that diets enriched with multivitamin corn have no adverse effects on mice, do not induce any clinical signs of toxicity and do not contain known allergens.

  17. Temporal and spatial scales of effects of toxic and non-toxic stressors

    SciTech Connect

    Lee, H. II; Specht, D.

    1995-12-31

    Estuarine ecosystems are potentially subjected to over 25 types of non-toxic stressors, including sedimentation, nutrients, exotic species, and habitat loss. Many non-toxic stressors operate over entire estuaries. For example, spread of exotics such as Spartina in Willapa Bay, WA may impact much of the intertidal area. Alterations due to toxic pollutants tend to be localized near their inputs. However, trophic transport can spread DDT and PCBs throughout a much wider area. Toxic pollutants are often introduced into the environment rapidly through discharges and spills, and then affect organisms fairly rapidly (within minutes to over a life cycle). The time course for non-toxic stressors is more variable. Some non-toxic alterations are very rapid, such as physical manipulation of habitats (e.g., filling). Alterations to habitats or watershed inputs are gradual, and thus difficult to detect in standard studies. For example, a slight increase in segmentation is difficult to quantify over a few years, but over decades could have major effects on estuarine ecosystems. The duration of effects of toxic pollutants depends upon their dilution, degradation and burial rates, and range from minutes for rapidly diluted soluble pollutants to decades or centuries for recalcitrant pollutants such as DDT. Duration of effects for non-toxic stressors are often ``permanent`` over ecological time for two reasons. Firstly, many non-toxic alterations are due to changes in watersheds, which recover slowly if logged or not at all if native habitat is transformed for development or farming. Secondly, several of the non-toxic stressors, such as invasions of exotics, result in a new, ``stable`` ecological system, so there is no recovery in the sense that pollutants degrade.

  18. 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

  19. Proposed actions for the US Food and Drug Administration to implement to minimize adverse effects associated with energy drink consumption.

    PubMed

    Thorlton, Janet; Colby, David A; Devine, Paige

    2014-07-01

    Energy drink sales are expected to reach $52 billion by 2016. These products, often sold as dietary supplements, typically contain stimulants. The Dietary Supplement Protection Act claims an exemplary public health safety record. However, in 2011 the number of emergency department visits related to consumption of energy drinks exceeded 20,000. Nearly half of these visits involved adverse effects occurring from product misuse. Political, social, economic, practical, and legal factors shape the landscape surrounding this issue. In this policy analysis, we examine 3 options: capping energy drink caffeine levels, creating a public education campaign, and increasing regulatory scrutiny regarding the manufacture and labeling of energy drinks. Increased regulatory scrutiny may be in order, especially in light of wrongful death lawsuits related to caffeine toxicity resulting from energy drink consumption.

  20. Proposed Actions for the US Food and Drug Administration to Implement to Minimize Adverse Effects Associated With Energy Drink Consumption

    PubMed Central

    Colby, David A.; Devine, Paige

    2014-01-01

    Energy drink sales are expected to reach $52 billion by 2016. These products, often sold as dietary supplements, typically contain stimulants. The Dietary Supplement Protection Act claims an exemplary public health safety record. However, in 2011 the number of emergency department visits related to consumption of energy drinks exceeded 20 000. Nearly half of these visits involved adverse effects occurring from product misuse. Political, social, economic, practical, and legal factors shape the landscape surrounding this issue. In this policy analysis, we examine 3 options: capping energy drink caffeine levels, creating a public education campaign, and increasing regulatory scrutiny regarding the manufacture and labeling of energy drinks. Increased regulatory scrutiny may be in order, especially in light of wrongful death lawsuits related to caffeine toxicity resulting from energy drink consumption. PMID:24832439

  1. Toxicity and Neuropharmacological Effects of Elenine

    PubMed Central

    Navarro, Eduardo; Alonso, S. J.; Navarro, R.

    2011-01-01

    Elenine is the aglycone of elenoside, a cytotoxic arylnaphthalene lignan (NSC 644013-W/1) derived from Justicia hyssopifolia. (Family: Acanthaceae). Elenoside is a β-D-glucoside, with a similar chemical structure to etoposide, exhibiting central depressant activity. In the present study, elenine was given to mice and rats at doses of 10, 20, and 40 mg/kg. Acute toxicity (24 h) and general behaviour in mice was studied as well as its effects on muscular relaxant activity, locomotor activity (Varimex test), and the open-field test and were compared with 10 mg/kg of chlorpromazine. Elenine produced a reduction in the permanence time in muscular relaxant activity (traction test). Spontaneous activity was lower in the Varimex test. The ambulation and rearing were lower compared with the control group, and an increase in boluses was observed in the open-field test. Thus, it can be concluded that elenine has central sedative effects at lower doses than those used with elenoside and has a possible application in conditions of anxiety. PMID:21716687

  2. Sublethal toxicant effects with dynamic energy budget theory: model formulation.

    PubMed

    Muller, Erik B; Nisbet, Roger M; Berkley, Heather A

    2010-01-01

    We develop and test a general modeling framework to describe the sublethal effects of pollutants by adding toxicity modules to an established dynamic energy budget (DEB) model. The DEB model describes the rates of energy acquisition and expenditure by individual organisms; the toxicity modules describe how toxicants affect these rates by changing the value of one or more DEB parameters, notably the parameters quantifying the rates of feeding and maintenance. We investigate four toxicity modules that assume: (1) effects on feeding only; (2) effects on maintenance only; (3) effects on feeding and maintenance with similar values for the toxicity parameters; and (4) effects on feeding and maintenance with different values for the toxicity parameters. We test the toxicity modules by fitting each to published data on feeding, respiration, growth and reproduction. Among the pollutants tested are metals (mercury and copper) and various organic compounds (chlorophenols, toluene, polycyclic aromatic hydrocarbons, tetradifon and pyridine); organisms include mussels, oysters, earthworms, water fleas and zebrafish. In most cases, the data sets could be adequately described with any of the toxicity modules, and no single module gave superior fits to all data sets. We therefore propose that for many applications, it is reasonable to use the most general and parameter sparse module, i.e. module 3 that assumes similar effects on feeding and maintenance, as a default. For one example (water fleas), we use parameter estimates to calculate the impact of food availability and toxicant levels on the long term population growth rate. PMID:19633955

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

    PubMed Central

    2012-01-01

    and related adverse effects. PMID:22998971

  4. Health effects and toxicity mechanisms of rare earth elements-Knowledge gaps and research prospects.

    PubMed

    Pagano, Giovanni; Guida, Marco; Tommasi, Franca; Oral, Rahime

    2015-05-01

    In the recent decades, rare earth elements (REE) have undergone a steady spread in several industrial and medical applications, and in agriculture. Relatively scarce information has been acquired to date on REE-associated biological effects, from studies of bioaccumulation and of bioassays on animal, plant and models; a few case reports have focused on human health effects following occupational REE exposures, in the present lack of epidemiological studies of occupationally exposed groups. The literature is mostly confined to reports on few REE, namely cerium and lanthanum, whereas substantial information gaps persist on the health effects of other REE. An established action mechanism in REE-associated health effects relates to modulating oxidative stress, analogous to the recognized redox mechanisms observed for other transition elements. Adverse outcomes of REE exposures include a number of endpoints, such as growth inhibition, cytogenetic effects, and organ-specific toxicity. An apparent controversy regarding REE-associated health effects relates to opposed data pointing to either favorable or adverse effects of REE exposures. Several studies have demonstrated that REE, like a number of other xenobiotics, follow hormetic concentration-related trends, implying stimulatory or protective effects at low levels, then adverse effects at higher concentrations. Another major role for REE-associated effects should be focused on pH-dependent REE speciation and hence toxicity. Few reports have demonstrated that environmental acidification enhances REE toxicity; these data may assume particular relevance in REE-polluted acidic soils and in REE mining areas characterized by concomitant REE and acid pollution. The likely environmental threats arising from REE exposures deserve a new line of research efforts.

  5. The Air Toxics Health Effects Database (ATHED)

    SciTech Connect

    Woodall, George M. Smith, Roy L.

    2008-11-15

    The Air Toxics Health Effects Database (ATHED) is currently used by the EPA's Office of Air Quality Planning and Standards (OAQPS) to support risk assessments for the Residual Risk Program. An assessment of the residual risk is required to be performed at a specified time (typically 8years) following the promulgation of a technology-based Maximum Achievable Control Technologies (MACT) standard. The goal of the Residual Risk Program is to assure that the risk that remains after MACT standards are implemented (i.e., the 'residual risk') is acceptable, and if not, to propose additional regulations to mitigate those risks. ATHED maintains all available reference values for each chemical as separate data records, and includes values for all exposure durations (acute, short-term, subchronic and chronic). These values are used as benchmarks to determine acceptable exposure levels to the hazardous air pollutants (HAPs) listed in Section 112 of the Clean Air Act. ATHED also provides useful background information on the uncertainty and/or modifying factors that were applied in the derivation of each reference value, as well as the point of departure and the critical study/studies. To facilitate comparisons across durations for a specific chemical, ATHED data can be graphically presented.

  6. Methylprednisolone pharmacokinetics, cortisol response, and adverse effects in black and white renal transplant recipients.

    PubMed

    Tornatore, K M; Biocevich, D M; Reed, K; Tousley, K; Singh, J P; Venuto, R C

    1995-03-15

    It is generally assumed that chronic glucocorticoid therapy is similar pharmacologically when administered to either black or white renal transplant recipients, resulting in adrenal suppression, low circulating plasma cortisol concentrations, and a similar degree of drug exposure and toxicity. To examine this theory and to investigate the relationship of glucocorticoid metabolism to steroid-induced adverse effects among specific ethnic groups of renal transplant recipients, 9 black and 9 white male patients chronically receiving methylprednisolone were enrolled. All patients had stable renal function and were matched for age, weight, and time since transplant. Standard pharmacokinetic parameters for methylprednisolone were determined and cortisol responses were characterized by total cortisol area under the concentration curve (AUC), return cortisol AUC, and cortisol suppression half-life. All patients received their daily oral dose of methylprednisolone (mean daily dose = 11 mg for blacks and 11 mg for whites) as an intravenous infusion with serial plasma samples obtained over 24 h. The patients were assessed for the presence of specific cushingoid manifestations (buffalo hump, moon facies) and steroid-associated diabetes. Methylprednisolone and cortisol were analyzed via HPLC. In the black patients, the mean clearance of methylprednisolone (206 +/- 70 ml/hr/kg) was significantly slower with a smaller volume of distribution (0.95 +/- 0.32 L/kg) when compared with the white group (327 +/- 129 ml/hr/kg, P = 0.03; volume of distribution = 1.33 +/- 0.27 L/kg, P = 0.015). Despite chronic methylprednisolone therapy, a definite 24-hr cortisol response pattern was noted in 15 of the 18 patients with a mean total cortisol AUC of 732 +/- 443 ng.hr/ml in blacks and 539 +/- 361 ng.hr/ml in whites (P = 0.17, black vs. white). The mean cortisol suppression half-life was 4.31 +/- 1.54 hr in black recipients and 4.11 +/- 1.49 hr in whites (P = 0.48). The mean return cortisol AUC

  7. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 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...

  8. 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...

  9. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 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...

  10. 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…

  11. 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...

  12. 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...

  13. 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...

  14. Effects of brine addition on effluent toxicity and marine toxicity identification evaluation (TIE) manipulations

    SciTech Connect

    Ho, K.T.; Burgess, R.M. ); Mitchell, K. . Biology Dept.); Zappala, M. )

    1995-02-01

    Little information is available concerning the effect of salinity adjustment on effluent storage and toxicity identification evaluation (TIE) performance. These factors are important for accurate assessments of potential toxicity to marine organisms. The objective of this study was to determine (a) the effect of salinity adjustment using hypersaline brine on the toxicity of effluents stored up to 40 d, and (b) to determine the effect of salinity adjustment on TIE manipulations. Changes in effluent toxicity over time were examined by using a municipal and an industrial effluent. A toxicity time series was performed for 16 d for the industrial effluent and 40 d for the municipal effluent. Toxicity was measured with modified 48-h acute Mysidopsis bahia and Menidia beryllina tests. Results indicate that, compared to day 0 test results, effluent stored with brine had fewer significant changes in toxicity than did effluent stored without brine. To determine the effects of brine addition on TIE manipulations, the authors conducted a series of manipulations in which one aliquot of an effluent had brine added prior to the TIE manipulations and the other aliquot had brine added after the TIE manipulation. The manipulations conducted were EDTA addition, sodium thiosulfate addition, C[sub 18] extraction, aeration, filtration, and graduated pH manipulations. Toxicity was measured with the modified 48-h acute mysid test. Addition of brine had no effect on the outcome of TIE manipulations. They have concluded that it is operationally easier to add brine as soon as possible after sampling and that effluent tests should be conducted as soon as practical.

  15. Guidance on health effects of toxic chemicals. Safety Analysis Report Update Program

    SciTech Connect

    Foust, C.B.; Griffin, G.D.; Munro, N.B.; Socolof, M.L.

    1994-02-01

    Martin Marietta Energy Systems, Inc. (MMES), and Martin Marietta Utility Services, Inc. (MMUS), are engaged in phased programs to update the safety documentation for the existing US Department of Energy (DOE)-owned facilities. The safety analysis of potential toxic hazards requires a methodology for evaluating human health effects of predicted toxic exposures. This report provides a consistent set of health effects and documents toxicity estimates corresponding to these health effects for some of the more important chemicals found within MMES and MMUS. The estimates are based on published toxicity information and apply to acute exposures for an ``average`` individual. The health effects (toxicological endpoints) used in this report are (1) the detection threshold; (2) the no-observed adverse effect level; (3) the onset of irritation/reversible effects; (4) the onset of irreversible effects; and (5) a lethal exposure, defined to be the 50% lethal level. An irreversible effect is defined as a significant effect on a person`s quality of life, e.g., serious injury. Predicted consequences are evaluated on the basis of concentration and exposure time.

  16. Trophic status of a community can alter the bioavailability and toxic effects of contaminants

    SciTech Connect

    McCarthy, J.F.; Bartell, S.M.

    1986-01-01

    Binding of hydrophobic organic and metal contaminants to particulate and dissolved organic matter (POM and DOM) in aquatic systems affects the availability of contaminants and their subsequent dose to biota. Eutrophic systems that contain high levels of organic sorbents will have lower concentrations of freely dissolved, readily available toxicant, thus reducing the exposure of the biota. In more oligotrophic systems with lower levels of sorbents, toxic exposure may be greater. These interactions suggest a relationship between the trophic state of an ecosystem and its susceptibility to toxic effects. Studies on the binding of organic contaminants to POM and DOM and its effects on toxicant accumulation are reviewed. The role of system productivity on adverse effects is explored by computer simulations, using a combined fate and effects model to evaluate the impacts of naphthalene on the production dynamics and contaminant body burden in different model populations when the concentration of POM varied from 0 to 10 mg C/L. Higher levels of POM decreased body burdens and moderated the reduction in productivity resulting from the exposure to naphthalene. Any interpretation of functional tests used to evaluate hazardous substances should consider the interaction between the trophic state of the system and the potential dose of toxicant available to biota.

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

    EPA Science Inventory

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

  18. Orlistat-associated adverse effects and drug interactions: a critical review.

    PubMed

    Filippatos, Theodosios D; Derdemezis, Christos S; Gazi, Irene F; Nakou, Eleni S; Mikhailidis, Dimitri P; Elisaf, Moses S

    2008-01-01

    Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.

  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. Association of acute adverse effects with high local SAR induced in the brain from prolonged RF head and neck hyperthermia.

    PubMed

    Adibzadeh, F; Verhaart, R F; Verduijn, G M; Fortunati, V; Rijnen, Z; Franckena, M; van Rhoon, G C; Paulides, M M

    2015-02-01

    To provide an adequate level of protection for humans from exposure to radio-frequency (RF) electromagnetic fields (EMF) and to assure that any adverse health effects are avoided. The basic restrictions in terms of the specific energy absorption rate (SAR) were prescribed by IEEE and ICNIRP. An example of a therapeutic application of non-ionizing EMF is hyperthermia (HT), in which intense RF energy is focused at a target region. Deep HT in the head and neck (H&N) region involves inducing energy at 434 MHz for 60 min on target. Still, stray exposure of the brain is considerable, but to date only very limited side-effects were observed. The objective of this study is to investigate the stringency of the current basic restrictions by relating the induced EM dose in the brain of patients treated with deep head and neck (H&N) HT to the scored acute health effects. We performed a simulation study to calculate the induced peak 10 g spatial-averaged SAR (psSAR₁₀g) in the brains of 16 selected H&N patients who received the highest SAR exposure in the brain, i.e. who had the minimum brain-target distance and received high forwarded power during treatment. The results show that the maximum induced SAR in the brain of the patients can exceed the current basic restrictions (IEEE and ICNIRP) on psSAR₁₀g for occupational environments by 14 times. Even considering the high local SAR in the brain, evaluation of acute effects by the common toxicity criteria (CTC) scores revealed no indication of a serious acute neurological effect. In addition, this study provides pioneering quantitative human data on the association between maximum brain SAR level and acute adverse effects when brains are exposed to prolonged RF EMF.

  1. Association of acute adverse effects with high local SAR induced in the brain from prolonged RF head and neck hyperthermia

    NASA Astrophysics Data System (ADS)

    Adibzadeh, F.; Verhaart, R. F.; Verduijn, G. M.; Fortunati, V.; Rijnen, Z.; Franckena, M.; van Rhoon, G. C.; Paulides, M. M.

    2015-02-01

    To provide an adequate level of protection for humans from exposure to radio-frequency (RF) electromagnetic fields (EMF) and to assure that any adverse health effects are avoided. The basic restrictions in terms of the specific energy absorption rate (SAR) were prescribed by IEEE and ICNIRP. An example of a therapeutic application of non-ionizing EMF is hyperthermia (HT), in which intense RF energy is focused at a target region. Deep HT in the head and neck (H&N) region involves inducing energy at 434 MHz for 60 min on target. Still, stray exposure of the brain is considerable, but to date only very limited side-effects were observed. The objective of this study is to investigate the stringency of the current basic restrictions by relating the induced EM dose in the brain of patients treated with deep head and neck (H&N) HT to the scored acute health effects. We performed a simulation study to calculate the induced peak 10 g spatial-averaged SAR (psSAR10g) in the brains of 16 selected H&N patients who received the highest SAR exposure in the brain, i.e. who had the minimum brain-target distance and received high forwarded power during treatment. The results show that the maximum induced SAR in the brain of the patients can exceed the current basic restrictions (IEEE and ICNIRP) on psSAR10g for occupational environments by 14 times. Even considering the high local SAR in the brain, evaluation of acute effects by the common toxicity criteria (CTC) scores revealed no indication of a serious acute neurological effect. In addition, this study provides pioneering quantitative human data on the association between maximum brain SAR level and acute adverse effects when brains are exposed to prolonged RF EMF.

  2. The another toxic effect of carbamate insecticides.

    PubMed

    Sobeková, Anna; Holovská, Katarína; Lenártová, Viera; Flesárová, Slávka; Javorský, P

    2009-03-01

    The activities of the antioxidant and detoxifying enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), glutathione reductase (GR), glutathione-S-transferase (GST), and the content of thiobarbituric acid reactive substances (TBARS) were determined in the liver and kidney of rabbits after exposure to bendiocarb. In the liver, the activities of SOD, CAT and GR were not affected by bendiocarb. The induction or inhibition of isoenzymes of SOD (mainly MnSOD) were observed in the experimental groups. The activities of GSHPx-cum and GSHPx-H2O2 significantly decreased on the days 3 and 10 of the experiment. The activity of GST significantly increased on the day 9 of the experiment. In the kidney, the activity of SOD was significantly increased and the new MnSOD isoenzymes were detected. The activities of CAT and GSHPx-H2O2 were significantly decreased in the experimental groups. The activity of GR significantly increased on days 3 and 10, and the activity of GST was significantly increased on days 3, 10, and 30. Exposure of rabbit to bendiocarb did not affect the content of TBARS in the kidney. In the liver, the content of TBARS was significantly increased in the experimental groups as compared to the control. Our results showed that the response of organs to bendiocarb is different and may depend on the specific organ damage and their protective abilities. The alterations in the activities of the antioxidant defence system, increased TBARS values, and changes in the SOD isoenzyme pattern showed that the toxic effect of bendiocarb is not only in the acetylcholine esterase inhibition, but also in ROS production.

  3. On toxic effects of scientific journals.

    PubMed

    Molinie, Antoinette; Bodenhausen, Geoffrey

    2013-06-01

    The advent of online publishing greatly facilitates the dissemination of scientific results. This revolution might have led to the untimely death of many traditional publishing companies, since today’s scientists are perfectly capable of writing, formatting and uploading files to appropriate websites that can be consulted by colleagues and the general public alike. They also have the intellectual resources to criticize each other and organize an anonymous peer review system. The Open Access approach appears promising in this respect, but we cannot ignore that it is fraught with editorial and economic problems. A few powerful publishing companies not only managed to survive, but also rake up considerable profits. Moreover, they succeeded in becoming influential ‘trendsetters’ since they decide which papers deserve to be published. To make money, one must set novel trends, like Christian Dior or Levi’s in fashion, and open new markets, for example in Asia. In doing so, the publishers tend to supplant both national and transnational funding agencies in defining science policy. In many cases, these agencies tend simply to adopt the commercial criteria defined by the journals, forever eager to improve their impact factors. It is not obvious that the publishers of scientific journals, the editorial boards that they appoint, or the people who sift through the vast numbers of papers submitted to a handful of ‘top’ journals are endowed with sufficient insight to set the trends of future science. It seems even less obvious that funding agencies should blindly follow the fashion trends set by the publishers. The perverse relationships between private publishers and public funding agencies may have a toxic effect on science policy.

  4. 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.

  5. Barrage fishponds: Reduction of pesticide concentration peaks and associated risk of adverse ecological effects in headwater streams.

    PubMed

    Gaillard, Juliette; Thomas, Marielle; Iuretig, Alain; Pallez, Christelle; Feidt, Cyril; Dauchy, Xavier; Banas, Damien

    2016-03-15

    Constructed wetlands have been suggested as pesticide risk mitigation measures. Yet, in many agricultural areas, ponds or shallow lakes are already present and may contribute to the control of non-point source contamination by pesticides. In order to test this hypothesis, we investigated the influence of extensively managed barrage fishponds (n = 3) on the dissolved concentrations of 100 pesticides in headwater streams over the course of a year. Among the 100 pesticides, 50 different substances were detected upstream and 48 downstream. Highest measured concentration upstream was 26.5 μg/L (2-methyl-4-chlorophenoxyacetic acid, MCPA) and 5.19 μg/L (isoproturon) downstream. Fishponds were found to reduce peak exposure levels as high pesticide concentrations (defined here as ≥ 1 μg/L) generally decreased by more than 90% between upstream and downstream sampling sites. The measured concentrations in the investigated streams were compared to laboratory toxicity data for standard test organisms (algae, invertebrates and fish) using the toxic unit approach. When considering the threshold levels set by the European Union within the first tier risk assessment procedure for pesticide registration (commission regulation (EU) N° 546/2011), regulatory threshold exceedances were observed for 22 pesticides upstream from fishponds and for 9 pesticides downstream. Therefore, the investigated barrage fishponds contributed to the reduction of pesticide peak concentrations and potential risk of adverse effects for downstream ecosystems.

  6. Barrage fishponds: Reduction of pesticide concentration peaks and associated risk of adverse ecological effects in headwater streams.

    PubMed

    Gaillard, Juliette; Thomas, Marielle; Iuretig, Alain; Pallez, Christelle; Feidt, Cyril; Dauchy, Xavier; Banas, Damien

    2016-03-15

    Constructed wetlands have been suggested as pesticide risk mitigation measures. Yet, in many agricultural areas, ponds or shallow lakes are already present and may contribute to the control of non-point source contamination by pesticides. In order to test this hypothesis, we investigated the influence of extensively managed barrage fishponds (n = 3) on the dissolved concentrations of 100 pesticides in headwater streams over the course of a year. Among the 100 pesticides, 50 different substances were detected upstream and 48 downstream. Highest measured concentration upstream was 26.5 μg/L (2-methyl-4-chlorophenoxyacetic acid, MCPA) and 5.19 μg/L (isoproturon) downstream. Fishponds were found to reduce peak exposure levels as high pesticide concentrations (defined here as ≥ 1 μg/L) generally decreased by more than 90% between upstream and downstream sampling sites. The measured concentrations in the investigated streams were compared to laboratory toxicity data for standard test organisms (algae, invertebrates and fish) using the toxic unit approach. When considering the threshold levels set by the European Union within the first tier risk assessment procedure for pesticide registration (commission regulation (EU) N° 546/2011), regulatory threshold exceedances were observed for 22 pesticides upstream from fishponds and for 9 pesticides downstream. Therefore, the investigated barrage fishponds contributed to the reduction of pesticide peak concentrations and potential risk of adverse effects for downstream ecosystems. PMID:26773430

  7. Groundwater air stripping: Effect on water toxicity

    SciTech Connect

    Eldridge, R.B.; Simpson, C.W.; Elliott, D.J.

    1995-02-01

    An air stripping unit was designed to reduce groundwater hydrocarbon content and biotoxicity to acceptable levels. A pilot plant study was conducted to determine the water treatability and to optimize the commercial unit design conditions. A measurement of the pilot plant effluent toxicity was obtained from {open_quotes}Microtox{close_quotes} analysis and rigorous bio-assays. These results indicated that reduction of the water hydrocarbon content to permitted discharge limits was accompanied by the elimination of water toxicity. The Onda mass transfer model was used to prepare the commercial unit design. A post-installation evaluation indicated that the model gave a good representation of the commercial unit performance. Toxicity reductions observed in the pilot plant were also observed in the commercial unit. 3 refs., 5 figs., 3 tabs.

  8. Nutraceutical strategies for ameliorating the toxic effects of alcohol.

    PubMed

    McCarty, Mark F

    2013-04-01

    Rodent studies reveal that oxidative stress, much of it generated via induction/activation of NADPH oxidase, is a key mediator of a number of the pathogenic effects of chronic ethanol overconsumption. The highly reactive ethanol metabolite acetaldehyde is a key driver of this oxidative stress, and doubtless works in other ways to promote alcohol-induced pathology. Effective antioxidant measure may therefore be useful for mitigating the adverse health consequences of alcohol consumption; spirulina may have particular utility in this regard, as its chief phycochemical phycocyanobilin has recently been shown to function as an inhibitor of certain NADPH oxidase complexes, mimicking the physiological role of its chemical relatives biliverdin/bilirubin in this respect. Moreover, certain nutraceuticals, including taurine, pantethine, and lipoic acid, may have the potential to boost the activity of the mitochondrial isoform of aldehyde dehydrogenase, ALDH-2, accelerating conversion of acetaldehyde to acetate (which arguably has protective health effects). Little noticed clinical studies conducted nearly three decades ago reported that pre-ingestion of either taurine or pantethine could blunt the rise in blood acetaldehyde following ethanol consumption. Other evidence suggests that lipoic acid may function within mitochondria to maintain aldehyde dehydrogenase in a reduced active conformation; the impact of this agent on ethanol metabolism has however received little or no study. Studies evaluating the impact of nutracetical strategies on prevention of hangovers - which likely are mediated by acetaldehyde - may represent a quick, low-cost way to identify nutraceutical regimens that merit further attention for their potential impact on alcohol-induced pathology. Measures which boost or preserve ALDH-2 activity may also have important antioxidant potential, as this enzyme functions physiologically to protect cells from toxic aldehydes generated by oxidant stress. PMID

  9. 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

  10. Stereological study on the effect of vitamin C in preventing the adverse effects of bisphenol A on rat ovary

    PubMed Central

    Soleimani Mehranjani, Malek; Mansoori, Tayebeh

    2016-01-01

    Background: Bisphenol A (BPA), an environmental pollutant, can generate free radicals which damages the reproductive system. Vitamin C is an antioxidant which may prevent the adverse effects of free radicals. Objective: The aim was to investigate the effect of vitamin C on the ovary tissue in rats treated with BPA. Materials and Methods: In this experimental study, 24 female Wistar rats (200±20 gr) were randomly divided into 4 groups (n=6): control, BPA (60 µg/Kg/day), vitamin C (150 mg/Kg/day) and BPA + vitamin C and orally treated for 20 days. The left ovaries were taken out, fixed for tissue processing and studied using stereological methods. Data were analyzed with SPSS using one-way ANOVA, and the means were considered significantly different at (p<0.05). Results: The total volume of ovary and cortex (p<0.01), medulla (p<0.05), the volume of corpus luteum (p<0.001) and the mean number of antral follicles (p<0.001) significantly reduced in BPA group compared with control, while the number of atretic follicles increased (p<0.05). The volume of oocyte (p<0.01) and its nucleus (p<0.001) in the antral follicles and the thickness of zona pellucida (ZP) in the secondary (p<0.05) and antral (p<0.001) follicles significantly decreased in BPA group compared with controls. The above parameters in the BPA + vitamin C group were compensated to control level. Conclusion: Vitamin C can be used as a potential antioxidant in the case of BPA toxication PMID:27525324

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. Efficacy and adverse effects of memantine treatment for Alzheimer's disease from randomized controlled trials.

    PubMed

    Jiang, Jue; Jiang, Hong

    2015-09-01

    The role of memantine as a treatment for Alzheimer's disease (AD) has been controversial. In clinical trials, a high dropout rate and numerous adverse events associated with memantine have been observed. However, given the relative scarcity of effective treatments for AD it would seem prudent to re-examine existing evidence to determine whether or not memantine should be used. Eight databases were utilized for randomized controlled trials that were published prior to December 31, 2013 and were according with the inclusion criteria. Trial methods, clinical characteristics, outcomes, and adverse events were extracted and analyzed with Review Manager 5.2. We obtained 2293 studies and determined that 13 of those studies met the inclusion criteria. Memantine therapy showed significant benefits to cognition, mental state, activities of daily life, the clinician's global impression in term with MMSE, SIB, NPI, ADCS-ADL19, CIBIC-Plus, respectively. Memantine therapy did not significantly increase the incidence of total adverse events, serious adverse events, death but it did increase the risk for somnolence.

  17. TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations.

    PubMed

    Ekstrand-Hammarström, Barbro; Hong, Jaan; Davoodpour, Padideh; Sandholm, Kerstin; Ekdahl, Kristina N; Bucht, Anders; Nilsson, Bo

    2015-05-01

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity.

  18. TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations.

    PubMed

    Ekstrand-Hammarström, Barbro; Hong, Jaan; Davoodpour, Padideh; Sandholm, Kerstin; Ekdahl, Kristina N; Bucht, Anders; Nilsson, Bo

    2015-05-01

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. PMID:25770998

  19. [Is intravenous immunoglobulin effective in toxic epidermal necrolysis and Stevens-Johnson syndrome?].

    PubMed

    Navajas, Lucas; Rada, Gabriel

    2014-10-17

    Toxic epidermal necrolysis and Stevens-Johnson syndrome are severe cutaneous adverse drug reactions. Intravenous immunoglobulin is described as a therapeutic option, however its use is still controversial. Using Epistemonikos database, which is maintained by screening over 20 databases, we identified six systematic reviews, including 39 primary studies. We combined the evidence using tables for summary of findings, following the GRADE approach, and concluded there is uncertainty about the effects of intravenous immunoglobulin because the certainty of the evidence is very low; it probably leads to important adverse effects; and has high cost. Intravenous immunoglobulin should not be used outside the context of a clinical trial, or only in cases where other treatments have failed and there are no resource constraints.

  20. 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

  1. 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.

  2. 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

  3. Tannery wastewater characterization and toxicity effects on Daphnia spp.

    PubMed

    Cooman, K; Gajardo, M; Nieto, J; Bornhardt, C; Vidal, G

    2003-02-01

    Tannery wastewater contains large quantities of organic and inorganic compounds, including toxic substances such as sulfides and chromium salts. The evaluation of wastewater quality in Chile nowadays is based on chemical specific measurements and toxicity tests. The goal of this research was to characterize tannery wastewater and to relate its physical/chemical parameters with its acute toxicity effect on Daphnia pulex. To distinguish the most important toxic compounds, physical/chemical techniques were applied to a grab sample of a final effluent based on the Phase I toxicity identification evaluation (TIE) procedure. In addition, the toxicity of a beamhouse effluent after an activated sludge reactor treatment was investigated on Daphnia magna (introduced species) and D. pulex (native species). Effluent from different tannery processes (soaking, beamhouse, tanning and final) demonstrated high values of chemical organic demand (COD; 2840-27,600 mg L(-1)), chloride (1813-16,500 mg L(-1)), sulfate (230-35,200 mg L(-1)), and total solids (8600-87,100 mg L(-1)). All effluents showed extremely toxic effects on D. pulex, with 24-h mean lethal values (LC(50)) ranging from 0.36% to 3.61%. The Phase I TIE profile showed that toxicity was significantly reduced by air stripping, filtration, and a cationic exchange resin, with toxicity reductions ranging between 46% and 76%. The aerobically treated beamhouse effluent showed significantly less toxicity for both species (43%-74%). The chemical parameters demonstrated that the remaining toxicity of the treated beamhouse effluent was associated with its ammonia (120 mg N-NH(3) L(-1)) and chloride (11,300 mg Cl(-) L(-1)) contents.

  4. 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

  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.

  6. 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

  7. 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.

  8. 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

  9. Tooth-Bleaching: A Review of the Efficacy and Adverse Effects of Various Tooth Whitening Products.

    PubMed

    Majeed, Abdul; Farooq, Imran; Grobler, Sias R; Rossouw, R J

    2015-12-01

    Tooth bleaching (whitening) is one of the most common and inexpensive method for treating discolouration of teeth. Dental aesthetics, especially tooth colour, is of great importance to majority of the people; and discolouration of even a single tooth can negatively influence the quality of life. Therefore, a review of the literature was carried out (limited to aesthetic tooth-bleaching) to provide a broad overview of the efficacy and adverse effects of various tooth whitening products on soft and hard oral tissues.

  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. 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.

  12. Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.

    PubMed

    Matthews, Edwin J; Kruhlak, Naomi L; Weaver, James L; Benz, R Daniel; Contrera, Joseph F

    2004-12-01

    The FDA's Spontaneous Reporting System (SRS) database contains over 1.5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects. We have linked the trade names of the drugs to 1861 generic names and retrieved molecular structures for each chemical to obtain a set of 1515 organic chemicals that are suitable for modeling with commercially available QSAR software packages. ADR report data for 631 of these compounds were extracted and pooled for the first five years that each drug was marketed. Patient exposure was estimated during this period using pharmaceutical shipping units obtained from IMS Health. Significant drug effects were identified using a Reporting Index (RI), where RI = (# ADR reports / # shipping units) x 1,000,000. MCASE/MC4PC software was used to identify the optimal conditions for defining a significant adverse effect finding. Results suggest that a significant effect in our database is characterized by > or = 4 ADR reports and > or = 20,000 shipping units during five years of marketing, and an RI > or = 4.0. Furthermore, for a test chemical to be evaluated as active it must contain a statistically significant molecular structural alert, called a decision alert, in two or more toxicologically related endpoints. We also report the use of a composite module, which pools observations from two or more toxicologically related COSTAR term endpoints to provide signal enhancement for detecting adverse effects. PMID:16472241

  13. Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know.

    PubMed

    Thomas, Grace; Kloner, Robert A; Rezkalla, Shereif

    2014-01-01

    Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists be made aware of the potential for marijuana-associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency. In this report, the investigators focus on the known cardiovascular, cerebrovascular, and peripheral effects of marijuana inhalation. Temporal associations between marijuana use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis have been described. In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects.

  14. Effects of early adversity on young children's diurnal cortisol rhythms and externalizing behavior.

    PubMed

    Bernard, Kristin; Zwerling, Jordana; Dozier, Mary

    2015-12-01

    Early adversity is associated with biological and behavioral dysregulation in early childhood. We examined whether early adversity (i.e., poverty and involvement with child protective services [CPS]) had an indirect effect on externalizing behavior through HPA axis dysregulation, specifically blunted diurnal cortisol patterns. Participants included 94 children between the ages of 3.94 and 6.52 years old, who had a history of CPS involvement (n = 53) or no history of CPS involvement (n = 41). Cortisol samples were collected at wake-up and bedtime across 3 days, and parent-reported externalizing behavior was assessed using the Child Behavior Checklist. Results showed that history of CPS involvement and poverty were associated with blunted cortisol patterns, which in turn led to elevated externalizing behavior. The indirect effect of CPS involvement on externalizing behavior through blunted cortisol was significant, whereas the indirect effect of poverty on externalizing behavior was nonsignificant. Findings add to our understanding of neurobiological mechanisms linking early adversity to psychopathology. PMID:26289841

  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. 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.

  17. Possible adverse effect of chromium in occupational exposure of tannery workers.

    PubMed

    Kornhauser, Carlos; Wróbel, Katarzyna; Wróbel, Kazimierz; Malacara, Juan Manuel; Nava, Laura Eugenia; Gómez, Leobardo; González, Rita

    2002-04-01

    Our aim was to investigate the adverse effects of occupational exposure to trivalent chromium. We measured chromium and iron levels in serum and urine and hemoglobin levels in tannery workers and unexposed persons. We studied three groups of subjects. Group 1 included 15 non-smoking male tannery workers highly exposed to chromium from tanning and retanning departments. Group 2 included 14 non-smoking male tannery workers with moderate chromium exposure from dying, drying and finishing departments. Group 3 included 11 healthy, non-smoking male subjects without direct chromium exposure. Higher serum chromium levels were observed in groups 1 and 2 with respect to group 3 (mean values respectively: 0.43; 0.25 and 0.13 microg x l(-1)). Urine chromium levels in group 1 were higher than those in controls (mean values: 1.78 and 1.35 microg x l(-1)). In group 1 an inverse association was found between serum chromium and urine iron (-0.524), urine chromium and hemoglobin (-0.594) and between the urine chromium to iron ratio and hemoglobin (-0.693, p<0.05). The results suggest a chromium adverse effect on iron metabolism, possibly associated with excessive body chromium accumulation. In conclusion, chromium urine test could be recommended for diagnosis of chromium adverse effect on iron metabolism. Further studies are needed to quantify the relationship between urine chromium and hemoglobin metabolism.

  18. Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know.

    PubMed

    Thomas, Grace; Kloner, Robert A; Rezkalla, Shereif

    2014-01-01

    Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists be made aware of the potential for marijuana-associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency. In this report, the investigators focus on the known cardiovascular, cerebrovascular, and peripheral effects of marijuana inhalation. Temporal associations between marijuana use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis have been described. In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects. PMID:24176069

  19. A TOXICITY IDENTIFICATION EVALUATION OF SILTY MARINE HARBOR SEDIMENTS TO CHARACTERIZE PERSISTENT AND NON-PERSISTENT CONSTITUENTS

    EPA Science Inventory

    Sediment toxicity in silty marine harbor sediments is frequently dominated by ammonia or sulfide, leaving the adverse effects of persistent toxic substances unnoticed. To investigate the latter, we subjected interstitial water from three contaminated silty sediments to toxicity i...

  20. Alkaloids from Veratrum taliense Exert Cardiovascular Toxic Effects via Cardiac Sodium Channel Subtype 1.5

    PubMed Central

    Wang, Gan; Rong, Ming-Qiang; Li, Qiong; Liu, Ya-Ping; Long, Cheng-Bo; Meng, Ping; Yao, Hui-Ming; Lai, Ren; Luo, Xiao-Dong

    2015-01-01

    Several species of the genus Veratrum that produce steroid alkaloids are commonly used to treat pain and hypertension in China and Europe. However, Veratrum alkaloids (VAs) induce serious cardiovascular toxicity. In China, Veratrum treatment often leads to many side effects and even causes the death of patients, but the pathophysiological mechanisms under these adverse effects are not clear. Here, two solanidine-type VAs (isorubijervine and rubijervine) isolated from Veratrum taliense exhibited strong cardiovascular toxicity. A pathophysiological study indicated that these VAs blocked sodium channels NaV1.3–1.5 and exhibited the strongest ability to inhibit NaV1.5, which is specifically expressed in cardiac tissue and plays an essential role in cardiac physiological function. This result reveals that VAs exert their cardiovascular toxicity via the NaV1.5 channel. The effects of VAs on NaV1.3 and NaV1.4 may be related to their analgesic effect and skeletal muscle toxicity, respectively. PMID:26729167

  1. Assessment of toxic effects of triclosan on the terrestrial snail (Achatina fulica).

    PubMed

    Wang, Xiaonan; Liu, Zhengtao; Wang, Wanhua; Yan, Zhenguang; Zhang, Cong; Wang, Weili; Chen, Lihong

    2014-08-01

    Triclosan (TCS) is a broad-spectrum antimicrobial agent used in personal care products, and as a result, is widespread in the environment. Toxicity tests of TCS on aquatic organisms have been reported, but limited toxicity data on terrestrial species are available. In this study, the 28-d chronic toxicity of TCS on the biomass, shell diameter growth, and total food intake of the terrestrial snail Achatina fulica were tested. Moreover, biochemical responses, including changes in the activity of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and the content of malondialdehyde (MDA), were examined after 14-d and 28-d exposure. Results showed that TCS had toxic effects on the biomass, shell diameter growth, and total food intake of A. fulica with no observed effect concentration (NOEC) values of 24 mg kg(-1). As for the antioxidant enzymes, TCS caused significant oxidative stress even at the low concentration of 24 mg kg(-1). The CAT and POD activities at the high concentrations of 200 and 340 mg kg(-1), respectively, were significantly inhibited. The SOD and CAT activity in treatments below 118 mg kg(-1) and the MDA content in all treatments showed dose-effect relationships. This study demonstrated that TCS caused adverse effects on terrestrial invertebrates, and provided valuable information for the risk assessment imposed by TCS in the terrestrial environment.

  2. Silver nanoparticles: their potential toxic effects after oral exposure and underlying mechanisms--a review.

    PubMed

    Gaillet, Sylvie; Rouanet, Jean-Max

    2015-03-01

    Because of their antimicrobial properties, the use of silver nanoparticles (AgNPs) is increasing fast in industry, food, and medicine. In the food industry, nanoparticles are used in packaging to enable better conservation products such as sensors to track their lifetime, and as food additives, such as anti-caking agents and clarifying agents for fruit juices. Nanoemulsions, used to encapsulate, protect and deliver additives are also actively developed. Nanomaterials in foods will be ingested and passed through the digestive tract. Those incorporated in food packaging may also be released unintentionally into food, ending up in the gastrointestinal tract. It is therefore important to make a risk assessment of nanomaterials to the consumer. Thus, exposure to AgNPs is increasing in quantity and it is imperative to know their adverse effects in man. However, controversies still remain with respect to their toxic effects and their mechanisms. Understanding the toxic effects and the interactions of AgNPs with biological systems is necessary to handle these nanoparticles and their use. They usually generate reactive oxygen species resulting in increased pro-inflammatory reactions and oxidative stress via intracellular signalling pathways. Here, we mainly focus on the routes of exposure of AgNPs, toxic effects and the mechanisms underlying the induced toxicity.

  3. Biological markers in environmental sentinels to establish exposure to, and effects of, atmospheric toxicants

    SciTech Connect

    McCarthy, J.F.; Tschaplinski, T.J. )

    1989-01-01

    This paper will discuss an approach that can contribute to evaluating the exposure of organisms to airborne toxicants, and can be particularly valuable as a tool to evaluate the biological significance of that exposure (NRC 1987). The approach is based on biological monitoring of animals and plants in areas impacted by airborne toxicants, and, more specifically, on measurement of molecular, biochemical, and physiological biological markers (biomarkers) in target species. In this context, the measurement of body burdens of persistent compounds (or metabolites) and of biomarkers of exposure or effects, permit the animals and plants to serve as sentinels indicating the presence of bioavailable contaminants, as surrogates to estimate the possible exposure and risk to humans, and as short-term predictors of long-term adverse effects at a population or community level. 69 refs., 5 figs., 2 tabs.

  4. Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures

    SciTech Connect

    Monnet-Tschudi, Florianne Hazekamp, Arno; Perret, Nicolas; Zurich, Marie-Gabrielle; Mangin, Patrice; Giroud, Christian; Honegger, Paul

    2008-04-01

    Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 {mu}M in single treatment and of 1 {mu}M and 2 {mu}M in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated 48 h after the single treatment with 5 {mu}M of THC or JWH 015, whereas the expression of TNF-{alpha} remained unchanged. These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation.

  5. The effect of MMF dose and trough levels on adverse effects in pediatric heart transplant recipients.

    PubMed

    Siddiqi, Nida; Lamour, Jacqueline M; Hsu, Daphne T

    2015-09-01

    Limited pharmacokinetic and safety data exist for MMF in pediatric HTR. Previously targeted MPA-TL are 1.5-3.0 μg/mL. The objective of this study was to assess the outcomes targeting MPA-TL of 0.8-2.0 μg/mL in pediatric HTR. MPA-TL were retrospectively collected 2-12 months post-transplant. Acute rejection, infection, leukopenia, and GI complaints were then correlated with MPA-TL. A total of 355 MPA-TL from 22 HTR were included. Median age was 2.5 yr. Primary indication for transplant was dilated cardiomyopathy (64%). Mean MPA-TL was 1.7 ± 0.9 μg/mL. African American patients received significantly higher doses (702 ± 235 mg/m(2) ) compared with other races (p = 0.035). Leukopenia was less common in patients with SUB MPA vs. others (p = 0.01). MMF was discontinued for GI complaints in one patient and leukopenia in two patients. One SUB patient had acute rejection, and one SUP patient had infection. One-yr survival was 100%. Targeting a lower range for MPA-TL was not associated with significant rejection or infection. Despite lower MPA-TL, MMF was discontinued in 3/22 patients for adverse effects.

  6. Chemical and microbial exposures in a school building: adverse health effects in children.

    PubMed

    Putus, Tuula; Tuomainen, Anneli; Rautiala, Sirpa

    2004-04-01

    In this cross-sectional study, the authors examined the relationship between an unusual combination of indoor air contaminants in a school and adverse health effects among the attending children. A leaking roof and damp floors, together with gaseous leaks from the sewage system, led to a combined exposure of hydrocarbons, 2-ethylhexanol from plastic floor coverings, and moisture-associated microbes. The health status of 274 children in the school was assessed via repeated symptom questionnaires. Statistical analysis revealed a relationship between the indoor air contaminants and adverse health outcomes such as respiratory irritation, asthmatic symptoms, eye and general symptoms, and increased occurrence of common viral respiratory infections. No association was found between the exposures and doctor-diagnosed asthma, other allergic diseases, or bacterial respiratory infections. Chemical contaminants from the sewer system and damp construction materials were identified as the source of the problem. Remediation of the school building improved the indoor air quality and the health status of the children.

  7. Lack of toxic effect of technical azadirachtin during postnatal development of rats.

    PubMed

    Srivastava, M K; Raizada, R B

    2007-03-01

    Azadirachtin, a biopesticide has been evaluated for its possible toxic effects during postnatal development of rats over two generations. Rats were fed 100, 500 and 1000ppm technical azadirachtin through diet which is equivalent to 5, 25 and 50mg/kg body weight of rats. Technical azadirachtin has not produced any adverse effects on reproductive function and data were comparable to control animals over two generations. There were no toxicological effect in parent rats as evidenced by clinical signs of toxicity, enzymatic parameters like AST, ALT, ALP, S. bilirubin, S. cholesterol, total protein and histopathology of liver, brain, kidney and testes/ovary. The litters of F(1B) and F(2B) generations were devoid of any morphological, visceral and teratological changes. The percent cumulative loss and growth index of pups were also comparable to respective controls in successive growth period of 0, 4, 7, 14 and 21 days in two generations. There were no major malformations in fetuses while some insignificant minor skeletal variations like missing 5th sternebrae and bipartite thoracic centre found were not compound or dose related. No significant pathomorphological changes were observed in liver, kidney, brain and gonads of F(2B) pups. In conclusion rats fed technical azadirachtin showed no evidence of cumulative effects on postnatal development and reproductive performance over two generations. Absence of any major adverse reproductive effects in adults as well as in 21 days old pups of F(2B) generation suggest the safe use of technical azadirachtin as a biopesticide. PMID:17084955

  8. 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…

  9. Isolation of bacteria from toxic dinoflagellate Alexandrium minutum and their effects on algae toxicity.

    PubMed

    Lu, Y H; Chai, T J; Hwang, D F

    2000-11-01

    Attempts were made to isolate the bacteria from toxic dinoflagellate Alexandrium minutum T1 and to study the effect of these bacteria on the growth and toxicity of A. minutum T1. It was found that intracellular bacterial species including Pasteurella haemolytica, Pseudomonas vesicularis, and Sphingomonas sp., and extracellular bacterial species including Pasteurolla pneumotropica, Morganella wisconsensis, Flavobacterium oryzihabitans, Pseudomonas pseudomallei, and Sphingomonas sp. All of them were cultured and determined to have non-PSP-producing ability. The maximum cell number of A. minutum cultured without isolated bacteria was higher than that cultured with isolated bacteria. The total toxicity of A. minutum cultured with bacteria was similar to that of A. minutum T1 cultured without bacteria from lag phase to stationary phase, but it was lower after stationary phase. The growth of A. minutum T1 cultured without antibiotics was also better than that cultured with antibiotics. The total toxicity of A. minutum cultured without antibiotics was higher than that of A. minutum cultured with antibiotics. However, the cell toxicity of A. minutum did not decrease even if the culture medium was added with antibiotics.

  10. Isolation of bacteria from toxic dinoflagellate Alexandrium minutum and their effects on algae toxicity.

    PubMed

    Lu, Y H; Chai, T J; Hwang, D F

    2000-11-01

    Attempts were made to isolate the bacteria from toxic dinoflagellate Alexandrium minutum T1 and to study the effect of these bacteria on the growth and toxicity of A. minutum T1. It was found that intracellular bacterial species including Pasteurella haemolytica, Pseudomonas vesicularis, and Sphingomonas sp., and extracellular bacterial species including Pasteurolla pneumotropica, Morganella wisconsensis, Flavobacterium oryzihabitans, Pseudomonas pseudomallei, and Sphingomonas sp. All of them were cultured and determined to have non-PSP-producing ability. The maximum cell number of A. minutum cultured without isolated bacteria was higher than that cultured with isolated bacteria. The total toxicity of A. minutum cultured with bacteria was similar to that of A. minutum T1 cultured without bacteria from lag phase to stationary phase, but it was lower after stationary phase. The growth of A. minutum T1 cultured without antibiotics was also better than that cultured with antibiotics. The total toxicity of A. minutum cultured without antibiotics was higher than that of A. minutum cultured with antibiotics. However, the cell toxicity of A. minutum did not decrease even if the culture medium was added with antibiotics. PMID:11126517

  11. Toxic shock syndrome Staphylococcus aureus: effect of tampons on toxic shock syndrome toxin 1 production.

    PubMed

    Schlievert, P M; Blomster, D A; Kelly, J A

    1984-11-01

    Tampons were tested for effect on growth and production of toxic shock syndrome toxin 1 by Staphylococcus aureus. Under good growth conditions, regular absorbency tampons had little effect on bacterial growth and inhibited toxin production two- to fourfold. In contrast, higher absorbency tampons had three different effects: 1) some tampons had no effect on bacterial growth but inhibited toxin production; 2) many tampons inhibited both growth and toxin production; 3) one tampon inhibited growth but increased exotoxin per cell. These effects were independent of degree of saturation of the tampons and were observed at incubation times of six, 12, and 18 hours. In no instance was the production of toxic shock syndrome toxin 1 per milliliter increased in the presence of tampons when compared with control.

  12. 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

  13. 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.

  14. Adverse effects and tolerability of medications for the treatment of tobacco use and dependence.

    PubMed

    Hays, J Taylor; Ebbert, Jon O

    2010-12-24

    Tobacco use is the leading cause of preventable death and disability in the world. Although gradually declining in most developed countries, the prevalence of tobacco use has increased among developing countries. Treatment for tobacco use and dependence is effective, although long-term abstinence rates remain disappointingly low. In response, new treatments continue to be developed. In addition, many of the pharmacotherapies that have been available for years have found new applications with the use of medication combinations, higher doses and a longer duration of therapy for approved medications. There are now seven medications (nicotine patch, nicotine gum, nicotine lozenge, nicotine inhaler, nicotine nasal spray, bupropion sustained release and varenicline) approved for tobacco dependence treatment in most countries, and many national and professional society practice guidelines recommend their use. Although each of the medications used for tobacco dependence treatment has been rigorously tested for efficacy and safety, broader experience in clinical trials and in observational population-based studies suggests that adverse events associated with these medications are relatively common. Since 2008, two of the medications (varenicline and bupropion) have come under increasing scrutiny because of reports of unexplained serious adverse events (SAEs), including behaviour change, depression, self-injurious thoughts and suicidal behaviour. To date, this association has not been shown to be caused by these medications, but concerns about medication safety continue. Prescribers require a working knowledge of the common adverse effects for all of these medications as well as a more detailed knowledge of the SAE potential. Nicotine replacement therapy (NRT) has been rigorously tested in clinical trials for over 30 years. A number of adverse effects are commonly associated with NRT use, although SAEs are rare. The adverse effects associated with NRT are due to the

  15. Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review

    PubMed Central

    Hirshburg, Jason M.; Kelsey, Petra A.; Therrien, Chelsea A.; Gavino, A. Carlo; Reichenberg, Jason S.

    2016-01-01

    Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment. PMID:27672412

  16. Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review

    PubMed Central

    Hirshburg, Jason M.; Kelsey, Petra A.; Therrien, Chelsea A.; Gavino, A. Carlo; Reichenberg, Jason S.

    2016-01-01

    Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment.

  17. Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review.

    PubMed

    Hirshburg, Jason M; Kelsey, Petra A; Therrien, Chelsea A; Gavino, A Carlo; Reichenberg, Jason S

    2016-07-01

    Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment. PMID:27672412

  18. Particle-specific toxic effects of differently shaped zinc oxide nanoparticles to zebrafish embryos (Danio rerio).

    PubMed

    Hua, Jing; Vijver, Martina G; Richardson, Michael K; Ahmad, Farooq; Peijnenburg, Willie J G M

    2014-12-01

    A general approach is proposed that allows for quantifying the relative toxic contribution of ions released from metallic nanoparticles and of the particles themselves, as exemplified for the case of differently shaped zinc oxide (ZnO) nanoparticles (NPs) exposed to zebrafish embryos. First of all, the toxicity of suspensions of ZnO nanoparticles (NP(total))--nanospheres, nanosticks, cuboidal submicron particles (SMPs), and Zn(NO3)2--to the embryos was assessed. The observed toxicity of ZnO NP(total) is assumed to result from the combined effect of the particles present in the suspensions (NP(particle)) and of the dissolved Zn(2+) ions released from the particles (NP(ion)). Different addition models were used to explicitly account for the toxicity of NP(particle). The median lethal concentrations (LC50) of NP(particle) of nanospheres, nanosticks, and SMPs were found to range between 7.1 mg Zn/L and 11.9 mg Zn/L (i.e., to differ by a factor of 1.7). Behavioral performance showed no significant differences among all types of the NP(particle). The median effective concentrations (EC50) of the particles were found to range between 1.0 mg Zn/L and 2.2 mg Zn/L. At the LC50 of each particle suspension, the main contribution to lethality to zebrafish embryos was from the NP(particle) (52%-72%). For hatching inhibition, the NP(particle) was responsible for 38% to 83% of the adverse effects observed. The ZnO nanosticks were more toxic than any of the other NPs with regard to the endpoints mortality and hatching inhibition. The main contribution to toxicity to zebrafish embryos was from the NP(particle) at the LC50 and EC50 of each particle suspension.

  19. Transplacental Exposure to AZT Induces Adverse Neurochemical and Behavioral Effects in a Mouse Model: Protection by L-Acetylcarnitine

    PubMed Central

    Venerosi Pesciolini, Aldina; Tramutola, Antonella; Ajmone-Cat, Maria Antonietta; Cinque, Carlo; Alemà, Giovanni Sebastiano; Giovine, Angela; Peluso, Gianfranco; Minghetti, Luisa; Nicolai, Raffaella; Calamandrei, Gemma; Casolini, Paola

    2013-01-01

    Maternal-fetal HIV-1 transmission can be prevented by administration of AZT, alone or in combination with other antiretroviral drugs to pregnant HIV-1-infected women and their newborns. In spite of the benefits deriving from this life-saving prophylactic therapy, there is still considerable uncertainty on the potential long-term adverse effects of antiretroviral drugs on exposed children. Clinical and experimental studies have consistently shown the occurrence of mitochondrial dysfunction and increased oxidative stress following prenatal treatment with antiretroviral drugs, and clinical evidence suggests that the developing brain is one of the targets of the toxic action of these compounds possibly resulting in behavioral problems. We intended to verify the effects on brain and behavior of mice exposed during gestation to AZT, the backbone of antiretroviral therapy during human pregnancy. We hypothesized that glutamate, a neurotransmitter involved in excitotoxicity and behavioral plasticity, could be one of the major actors in AZT-induced neurochemical and behavioral alterations. We also assessed the antioxidant and neuroprotective effect of L-acetylcarnitine, a compound that improves mitochondrial function and is successfully used to treat antiretroviral-induced polyneuropathy in HIV-1 patients. We found that transplacental exposure to AZT given per os to pregnant mice from day 10 of pregnancy to delivery impaired in the adult offspring spatial learning and memory, enhanced corticosterone release in response to acute stress, increased brain oxidative stress also at birth and markedly reduced expression of mGluR1 and mGluR5 subtypes and GluR1 subunit of AMPA receptors in the hippocampus. Notably, administration during the entire pregnancy of L-acetylcarnitine was effective in preventing/ameliorating the neurochemical, neuroendocrine and behavioral adverse effects induced by AZT in the offspring. The present preclinical findings provide a mechanistic hypothesis for

  20. 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…

  1. 42 CFR 493.1808 - Adverse action on any type of CLIA certificate: Effect on Medicare approval.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Adverse action on any type of CLIA certificate... REQUIREMENTS Enforcement Procedures § 493.1808 Adverse action on any type of CLIA certificate: Effect on Medicare approval. (a) Suspension or revocation of any type of CLIA certificate. When CMS suspends...

  2. 42 CFR 493.1808 - Adverse action on any type of CLIA certificate: Effect on Medicare approval.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Adverse action on any type of CLIA certificate... REQUIREMENTS Enforcement Procedures § 493.1808 Adverse action on any type of CLIA certificate: Effect on Medicare approval. (a) Suspension or revocation of any type of CLIA certificate. When CMS suspends...

  3. 42 CFR 493.1808 - Adverse action on any type of CLIA certificate: Effect on Medicare approval.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Adverse action on any type of CLIA certificate... REQUIREMENTS Enforcement Procedures § 493.1808 Adverse action on any type of CLIA certificate: Effect on Medicare approval. (a) Suspension or revocation of any type of CLIA certificate. When CMS suspends...

  4. 42 CFR 493.1808 - Adverse action on any type of CLIA certificate: Effect on Medicare approval.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Adverse action on any type of CLIA certificate... REQUIREMENTS Enforcement Procedures § 493.1808 Adverse action on any type of CLIA certificate: Effect on Medicare approval. (a) Suspension or revocation of any type of CLIA certificate. When CMS suspends...

  5. 42 CFR 493.1808 - Adverse action on any type of CLIA certificate: Effect on Medicare approval.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Adverse action on any type of CLIA certificate... REQUIREMENTS Enforcement Procedures § 493.1808 Adverse action on any type of CLIA certificate: Effect on Medicare approval. (a) Suspension or revocation of any type of CLIA certificate. When CMS suspends...

  6. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus update.

    PubMed

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

    2013-12-01

    The Proceedings of a Canadian Working Group Consensus Conference, first published in 2011, provided a summary of statin-associated adverse effects and intolerance and management suggestions. In this update, new clinical studies identified since then that provide further insight into effects on muscle, cognition, cataracts, diabetes, kidney disease, and cancer are discussed. Of these, the arenas of greatest controversy pertain to purported effects on cognition and the emergence of diabetes during long-term therapy. Regarding cognition, the available evidence is not strongly supportive of a major adverse effect of statins. In contrast, the linkage between statin therapy and incident diabetes is more firm. However, this risk is more strongly associated with traditional risk factors for new-onset diabetes than with statin itself and any possible negative effect of new-onset diabetes during statin treatment is far outweighed by the cardiovascular risk reduction benefits. Additional studies are also discussed, which support the principle that systematic statin rechallenge, and lower or intermittent statin dosing strategies are the main methods for dealing with suspected statin intolerance at this time.

  7. 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

  8. Determination of an acute no-observed-adverse-effect level (NOAEL) for copper in water.

    PubMed

    Araya, M; McGoldrick, M C; Klevay, L M; Strain, J J; Robson, P; Nielsen, F; Olivares, M; Pizarro, F; Johnson, L A; Poirier, K A

    2001-10-01

    A prospective, double-blind controlled study was designed to determine the acute no-observed-adverse-effect level (NOAEL) of nausea in an apparently healthy population of 179 individuals who drank copper-containing water as the sulfate salt. Subjects were recruited at three different international sites and given a blind, randomly selected dose (0, 2, 4, 6, or 8 mg Cu/L) in a bolus of 200 ml (final total copper dose was equivalent to 0, 0.4, 0.8, 1.2, and 1.6 mg) once weekly over a consecutive 5-week period. Gastrointestinal (GI) symptoms of nausea, abdominal pain, vomiting, or diarrhea were screened for a period of up to 24 h. Nausea was the most frequently reported effect and was reported within the first 15 min of ingestion. For the combined trisite population (n=179), 8, 9, 14, 25, and 44 subjects responded positively to one or more GI symptoms at 0, 2, 4, 6, and 8 mg Cu/L, respectively. Analysis of the data demonstrated a clear dose response to the combined positive GI effects and to nausea alone. Statistically significant greater reporting of effects occurred at 6 and 8 mg Cu/L. Therefore, an acute NOAEL and lowest-observed-adverse-effect level of 4 and 6 mg Cu/L (0.8 and 1.2 mg Cu), respectively, were determined in drinking water for a combined international human population.

  9. 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.

  10. 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

  11. Mercury exposure from dental amalgam fillings: absorbed dose and the potential for adverse health effects.

    PubMed

    Mackert, J R; Berglund, A

    1997-01-01

    This review examines the question of whether adverse health effects are attributable to amalgam-derived mercury. The issue of absorbed dose of mercury from amalgam is addressed first. The use of intra-oral Hg vapor measurements to estimate daily uptake must take into account the differences between the collection volume and flow rate of the measuring instrument and the inspiratory volume and flow rate of air through the mouth during inhalation of a single breath. Failure to account for these differences will result in substantial overestimation of the absorbed dose. Other factors that must be considered when making estimates of Hg uptake from amalgam include the accurate measurement of baseline (unstimulated) mercury release rates and the greater stimulation of Hg release afforded by chewing gum relative to ordinary food. The measured levels of amalgam-derived mercury in brain, blood, and urine are shown to be consistent with low absorbed doses (1-3 micrograms/day). Published relationships between the number of amalgam surfaces and urine levels are used to estimate the number of amalgam surfaces that would be required to produce the 30 micrograms/g creatinine urine mercury level stated by WHO to be associated with the most subtle, pre-clinical effects in the most sensitive individuals. From 450 to 530 amalgam surfaces would be required to produce the 30 micrograms/g creatinine urine mercury level for people without any excessive gum-chewing habits. The potential for adverse health effects and for improvement in health following amalgam removal is also addressed. Finally, the issue of whether any material can ever be completely exonerated of claims of producing adverse health effects is considered.

  12. Effects of N-acetylcysteine on alcohol abstinence and alcohol-induced adverse effects in rats.

    PubMed

    Ferreira Seiva, Fábio Rodrigues; Amauchi, Juliana Fujihara; Ribeiro Rocha, Katiucha Karolina; Souza, Gisele Aparecida; Ebaid, Geovana Xavier; Burneiko, Regina Miranda; Novelli, Ethel Lourenzi Barbosa

    2009-03-01

    Alcoholism is rampant in modern society and some antioxidant compound could perhaps be useful to reduce the damage done by alcohol consumption and abstinence. The present study was undertaken to investigate the association of N-acetylcysteine (NAC) intake, alcoholism, and alcohol abstinence on lipid profile, in vivo low-density lipoprotein (LDL) oxidation, oxidative stress, and antioxidant status in serum and liver of rats. Initially, male Wistar 30 rats were divided into two groups: (C, N=6) given standard chow and water; (E, N=24) receiving standard chow and aqueous ethanol solution in semi-voluntary research. After 30 days of ethanol exposure, (E) group was divided into four subgroups (N=6/group): (E-E) continued drinking 30% ethanol solution; (E-NAC) drinking ethanol solution containing 2 g/L NAC; (AB) changed ethanol solution to water; (AB-NAC) changed ethanol to aqueous solution 2 g/L NAC. After 15 days of the E-group division, E-E rats had higher serum alanine transaminase, lower body weight, and surface area, despite higher energy intake than C. E-E rats had also lower feed efficiency, dyslipidemia with enhanced triacylglycerol, very low-density lipoprotein (VLDL), lipid hydroperoxide (LH) and in vivo oxidized-LDL (ox-LDL). AB, E-NAC, and AB-NAC rats ameliorated serum oxidative stress markers and normalized serum lipids. E-E rats had higher hepatic LH and lower reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio than C, indicating hepatic oxidative stress. AB and E-NAC rats normalized hepatic LH, GSSG, and the GSH/GSSG ratio, compared to E-E. AB-NAC rats had the lowest serum ox-LDL, hepatic LH levels, and the highest GSH reductase activity in hepatic tissue. In conclusion, the present study brought new insights into alcohol consumption, because ethanol exposure enhanced serum in vivo ox-LDL, as well as serum and hepatic oxidative stress. N-acetylcysteine offers promising therapeutic value to inhibit ethanol-induced adverse effects. Ethanol

  13. Toxic effects of colloidal nanosilver in zebrafish embryos.

    PubMed

    Olasagasti, Maider; Gatti, Antonietta M; Capitani, Federico; Barranco, Alejandro; Pardo, Miguel Angel; Escuredo, Kepa; Rainieri, Sandra

    2014-05-01

    A variety of consumer products containing silver nanoparticles (Ag NPs) are currently marketed. However, their safety for humans and for the environment has not yet been established and no standard method to assess their toxicity is currently available. The objective of this work was to develop an effective method to test Ag NP toxicity and to evaluate the effects of ion release and Ag NP size on a vertebrate model. To this aim, the zebrafish animal model was exposed to a solution of commercial nanosilver. While the exposure of embryos still surrounded by the chorion did not allow a definite estimation of the toxic effects exerted by the compound, the exposure for 48 h of 3-day-old zebrafish hatched embryos afforded a reliable evaluation of the effects of Ag NPs. The effects of the exposure were detected especially at molecular level; in fact, some selected genes expressed differentially after the exposure. The Ag NP toxic performance was due to the combined effect of Ag(+) ion release and Ag NP size. However, the effect of NP size was particularly detectable at the lowest concentration of nanosilver tested (0.01 mg l(-1)) and depended on the solubilization media. The results obtained indicate that in vivo toxicity studies of nanosilver should be performed with ad hoc methods (in this case using hatched embryos) that might be different depending on the type of nanosilver. Moreover, the addition of this compound to commercial products should take into consideration the Ag NP solubilization media.

  14. Overcoming toxicity and side-effects of lipid-lowering therapies.

    PubMed

    Wilkinson, Michael J; Laffin, Luke J; Davidson, Michael H

    2014-06-01

    Lowering serum lipid levels is part of the foundation of treating and preventing clinically significant cardiovascular disease. Recently, the American Heart Association/American College of Cardiology released cholesterol guidelines which advocate for high efficacy statins rather than LDL-c goals for five patient subgroups at high risk for cardiovascular disease. Therefore, it is critical that clinicians have an approach for managing side-effects of statin therapy. Statins are associated with myopathy, transaminase elevations, and an increased risk of incident diabetes mellitus among some patients; connections between statins and other processes, such as renal and neurologic function, have also been studied with mixed results. Statin-related adverse effects might be minimized by careful assessment of patient risk factors. Strategies to continue statin therapy despite adverse effects include switching to another statin at a lower dose and titrating up, giving intermittent doses of statins, and adding non-statin agents. Non-statin lipid-lowering drugs have their own unique limitations. Management strategies and algorithms for statin-associated toxicities are available to help guide clinicians. Clinical practice should emphasize tailoring therapy to address each individual's cholesterol goals and risk of developing adverse effects on lipid-lowering drugs.

  15. The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s).

    PubMed

    Dorato, Michael A; Engelhardt, Jeffery A

    2005-08-01

    The no-observed-adverse-effect-level (NOAEL) is an important part of the non-clinical risk assessment. It is a professional opinion based on the design of the study, indication of the drug, expected pharmacology, and spectrum of off-target effects. There is no consistent standard definition of NOAEL. This is based, in part, on the varied definitions of what constitutes an adverse effect. Toxicologists, either investigating or reviewing, have not been consistent in defining an effect as either adverse or acceptable. The common definition of NOAEL, "the highest experimental point that is without adverse effect," serves us well in general discussions. It does not, however, address the interpretation of risk based on toxicologically relevant effects, nor does it consider the progression of effect with respect to duration and/or dose. This paper will discuss the issues and application of a functional definition of the NOAEL in toxicology evaluations.

  16. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... female, pregnant? (J) Exposure data: amount of pesticide; duration of exposure; weight of victim. (K) Was... of systems supplied. (C) If finished water samples, water supply systems sampled. (D) If finished water samples, percent surface water source by specific surface water sources to water supply...

  17. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... female, pregnant? (J) Exposure data: amount of pesticide; duration of exposure; weight of victim. (K) Was... of systems supplied. (C) If finished water samples, water supply systems sampled. (D) If finished water samples, percent surface water source by specific surface water sources to water supply...

  18. 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... of systems supplied. (C) If finished water samples, water supply systems sampled. (D) If finished water samples, percent surface water source by specific surface water sources to water supply...

  19. 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... of systems supplied. (C) If finished water samples, water supply systems sampled. (D) If finished water samples, percent surface water source by specific surface water sources to water supply...

  20. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... female, pregnant? (J) Exposure data: amount of pesticide; duration of exposure; weight of victim. (K) Was... of systems supplied. (C) If finished water samples, water supply systems sampled. (D) If finished water samples, percent surface water source by specific surface water sources to water supply...

  1. ADVERSE EFFECTS OF ANTIANDROGENIC PESTICIDE AND TOXIC SUBSTANCES ON REPRODUCTIVE DEVELOPMENT IN THE MALE

    EPA Science Inventory

    Anthropogenic endocrine disrupting chemicals (EDCs) or chemical mixtures alter androgen-response tissues via a variety of mechanisms including mimicking or blocking the action of the natural ligand to the androgen receptor (AR), inhibiting steroid hormone synthesis or by acting a...

  2. 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

  3. 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

  4. Effect of 70-nm silica particles on the toxicity of acetaminophen, tetracycline, trazodone, and 5-aminosalicylic acid in mice.

    PubMed

    Li, X; Kondoh, M; Watari, A; Hasezaki, T; Isoda, K; Tsutsumi, Y; Yagi, K

    2011-04-01

    Exposure to nano-sized particles is increasing because they are used in a wide variety of industrial products, cosmetics, and pharmaceuticals. Some animal studies indicate that such nanomaterials may have some toxicity, but their synergistic actions on the adverse effects of drugs are not well understood. In this study, we investigated whether 70-nm silica particles (nSP70), which are widely used in cosmetics and drug delivery, affect the toxicity of a drug for inflammatory bowel disease (5-aminosalicylic acid), an antibiotic drug (tetracycline), an antidepressant drug (trazodone), and an antipyretic drug (acetaminophen) in mice. Co-administration of nSP70 with trazodone did not increase a biochemical marker of liver injury. In contrast, co-administration increased the hepatotoxicity of the other drugs. Co-administration of nSP70 and tetracycline was lethal. These findings indicate that evaluation of synergistic adverse effects is important for the application of nano-sized materials.

  5. 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

  6. 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

  7. Potato glycoalkaloids and adverse effects in humans: an ascending dose study.

    PubMed

    Mensinga, Tjeert T; Sips, Adrienne J A M; Rompelberg, Cathy J M; van Twillert, Klaas; Meulenbelt, Jan; van den Top, Hester J; van Egmond, Hans P

    2005-02-01

    Glycoalkaloids in potatoes may induce gastro-intestinal and systemic effects, by cell membrane disruption and acetylcholinesterase inhibition, respectively. The present single dose study was designed to evaluate the toxicity and pharmacokinetics of orally administered potato glycoalkaloids (alpha-chaconine and alpha-solanine). It is the first published human volunteer study were pharmacokinetic data were obtained for more than 24 h post-dose. Subjects (2-3 per treatment) received one of the following six treatments: (1-3) solutions with total glycoalkaloid (TGA) doses of 0.30, 0.50 or 0.70 mg/kg body weight (BW), or (4-6) mashed potatoes with TGA doses of 0.95, 1.10 or 1.25 mg/kg BW. The mashed potatoes had a TGA concentration of nearly 200 mg/kg fresh weight (the presently recognised upper limit of safety). None of these treatments induced acute systemic effects. One subject who received the highest dose of TGA (1.25 mg/kg BW) became nauseous and started vomiting about 4 h post-dose, possibly due to local glycoalkaloid toxicity (although the dosis is lower than generally reported in the literature to cause gastro-intestinal disturbances). Most relevant, the clearance of glycoalkaloids usually takes more than 24 h, which implicates that the toxicants may accumulate in case of daily consumption.

  8. 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

  9. [Herbal medicines and severe adverse effects: uvular angioedema caused by Echballium elaterium].

    PubMed

    Caiozzi, Gianella; Cabrera, Daniel; Mardónez, José Miguel; Saldías, Fernando

    2002-12-01

    Herbal medicine is a growing alternative for established medicine. Many plants and herbs are currently in use for a myriad of diseases and symptoms. However, there are many reports in the literature of life-threatening adverse effects of these drugs. We report a 39 years old male, that consulted for pain in the nostrils and severe nasal obstruction, that appeared two hours after instilling Ecballium elaterirum in the nostrils. On physical examination, uvular edema was observed. The patient was successfully managed with intravenous betametasone and chlorphenamine. PMID:12611242

  10. Tooth-Bleaching: A Review of the Efficacy and Adverse Effects of Various Tooth Whitening Products.

    PubMed

    Majeed, Abdul; Farooq, Imran; Grobler, Sias R; Rossouw, R J

    2015-12-01

    Tooth bleaching (whitening) is one of the most common and inexpensive method for treating discolouration of teeth. Dental aesthetics, especially tooth colour, is of great importance to majority of the people; and discolouration of even a single tooth can negatively influence the quality of life. Therefore, a review of the literature was carried out (limited to aesthetic tooth-bleaching) to provide a broad overview of the efficacy and adverse effects of various tooth whitening products on soft and hard oral tissues. PMID:26691365

  11. Toxic effects on survival and reproduction, a process oriented approach

    SciTech Connect

    Bedaux, J.J.M.; Kooijman, S.A.L.M.

    1995-12-31

    The authors present a new analysis of survival and reproduction data from toxicity tests. The analysis is based on the Dynamic Energy Budget theory for feeding, growth and reproduction, and a one-compartment kinetics for the toxic compound. The toxic effect size depends on the internal concentration. Effects on survival occur via the hazard rate, which is set equal to the killing rate times the internal concentration that exceeds a threshold value. Effects on reproduction depend on the mode of action of the toxicant: direct effects (mortality during oogenesis or energy costs per egg), or indirect effects (via growth, maintenance or assimilation). The effects on energetic parameters are quantified by the ratio between the internal concentration that exceeds a threshold value, and the tolerance concentration. The process-based models quantify effects as functions of exposure time and (external) concentration on a mechanistic basis. The parameters (no effect concentration, killing rate, tolerance concentration and elimination rate) are independent from the chosen exposure time of the toxicity test. The standard log-logistic models are purely descriptive, have more parameters and are sensitive to the chosen exposure time. The estimation of no-effect concentrations (NOEC`s as well as parametric NEC`S) in standard statistical analyses is problematic. Application to ring test data for chronic tests on Daphnia magna and other toxicity data reveals that these problems do not occur with the analysis, due to the absence of free gradient parameters. It is possible to obtain estimates for the standard model parameters from the new parameters, but not vice versa. The authors believe that the analysis provides a better basis for risk assessment and QSAR studies than the standard one.

  12. Cyproheptadine for prevention of neuropsychiatric adverse effects of efavirenz: a randomized clinical trial.

    PubMed

    Dabaghzadeh, Fatemeh; Ghaeli, Padideh; Khalili, Hossein; Alimadadi, Abbas; Jafari, Sirous; Akhondzadeh, Shahin; Khazaeipour, Zahra

    2013-03-01

    Cyproheptadine prevention of the neuropsychiatric adverse effects of an antiretroviral regimen including efavirenz has been evaluated in a randomized clinical trial. Twenty-five patients (16 males and 9 females with mean±SD ages of 36±9 years) in a cyproheptadine group, and 26 patients (17 males and 9 females with mean±SD ages of 34±7 years) in a control group completed the trial. Sexual contact and injection drug use were the main routs of HIV infection in both groups. The patients' neuropsychiatric adverse effects were evaluated based on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation, and Somatization Subscale of Symptom Checklist 90 at baseline and 4 weeks after treatment. Cyproheptadine significantly decreased the scores of Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation of the patients after 4 weeks in comparison with control group. All of the scores increased in control group following antiretroviral therapy. Although short duration of the patients' follow-up was a major limitation of the study, the results of the study showed that cyprohepradine is effective in prevention of depression, anxiety, hallucination, aggressive behaviors, emotional withdrawal, poor rapport, poor impulse control, active social avoidance, suicidal ideation, and improved sleep quality of HIV-positive patients after initiation of antiretroviral therapy including efavirenz.

  13. 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

  14. 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

  15. 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.

  16. XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility

    PubMed Central

    McNeill, Daniel R.; Lin, Ping-Chang; Miller, Marshall G.; Pistell, Paul J.; de Souza-Pinto, Nadja C.; Fishbein, Kenneth W.; Spencer, Richard G.; Liu, Yie; Pettan-Brewer, Christina; Ladiges, Warren C.; Wilson, David M.

    2011-01-01

    Oxidative DNA damage plays a role in disease development and the aging process. A prominent participant in orchestrating the repair of oxidative DNA damage, particularly single-strand breaks, is the scaffold protein XRCC1. A series of chronological and biological aging parameters in XRCC1 heterozygous (HZ) mice were examined. HZ and wild-type (WT) C57BL/6 mice exhibit a similar median lifespan of ~26 months and a nearly identical maximal life expectancy of ~37 months. However, a number of HZ animals (7 of 92) showed a propensity for abdominal organ rupture, which may stem from developmental abnormalities given the prominent role of XRCC1 in endoderm and mesoderm formation. For other end-points evaluated—weight, fat composition, blood chemistries, condition of major organs, tissues and relevant cell types, behavior, brain volume and function, and chromosome and telomere integrity—HZ mice exhibited by-and-large a normal phenotype. Treatment of animals with the alkylating agent azoxymethane resulted in both liver toxicity and an increased incidence of precancerous lesions in the colon of HZ mice. Our study indicates that XRCC1 haploinsufficiency in mammals has little effect on chronological longevity and many key biological markers of aging in the absence of environmental challenges, but may adversely affect normal animal development or increase disease susceptibility to a relevant genotoxic exposure. PMID:21737425

  17. 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

  18. 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.

  19. 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

  20. Effect of polymer grafting density on silica nanoparticle toxicity.

    PubMed

    Lin, I-Chun; Liang, Mingtao; Liu, Tzu-Yu; Jia, Zhongfan; Monteiro, Michael J; Toth, Istvan

    2012-12-01

    Nanoparticles are commonly engineered with a layer of polymers on the surface used to increase their stability and biocompatibility, as well as providing multifunctional properties. Formulating the nanoparticle size and surface properties with polymers directly affects the way these nanoparticles interact with a biological system. Many previous studies have emphasized the importance of nanoparticle size and surface charge in affecting their toxicity in cells. However, the potential weakness in many of these studies is that the polymer grafting densities on nanoparticles have been disregarded during toxicity evaluation. In the current study, we hypothesized that the density of polymers on nanoparticles will affect their toxicity to cells, especially for nanoparticle cores that are toxic themselves. To address this issue, we synthesized a range of RAFT (reversible addition fragmentation chain transfer) polymers bearing different surface charges and coated them onto silica nanoparticles (SiNPs) with different grafting densities. The in vitro cytotoxicity of these SiNPs was evaluated using the MTT (thiazolyl blue tetrazolium bromide) assay with Caco-2 cells. We found that neutral (biocompatible) polymers with a high grafting density on SiNPs were effective at protecting the cells from the toxicity of the silica core. High cellular toxicity was only observed for cationic polymer-SiNPs, while all other neutral and anionic polymer-SiNPs induced limited cellular toxicity. In contrast, the toxic effects induced by low density polymer-coated SiNPs were mostly attributed to the silica core, while the polymer coatings had a limited contribution. These findings are important indicators for the future evaluation of the toxicological profile of polymer-coated nanoparticles.

  1. Arsenic Toxicity: The Effects on Plant Metabolism

    PubMed Central

    Finnegan, Patrick M.; Chen, Weihua

    2012-01-01

    The two forms of inorganic arsenic, arsenate (AsV) and arsenite (AsIII), are easily taken up by the cells of the plant root. Once in the cell, AsV can be readily converted to AsIII, the more toxic of the two forms. AsV and AsIII both disrupt plant metabolism, but through distinct mechanisms. AsV is a chemical analog of phosphate that can disrupt at least some phosphate-dependent aspects of metabolism. AsV can be translocated across cellular membranes by phosphate transport proteins, leading to imbalances in phosphate supply. It can compete with phosphate during phosphorylation reactions, leading to the formation of AsV adducts that are often unstable and short-lived. As an example, the formation and rapid autohydrolysis of AsV-ADP sets in place a futile cycle that uncouples photophosphorylation and oxidative phosphorylation, decreasing the ability of cells to produce ATP and carry out normal metabolism. AsIII is a dithiol reactive compound that binds to and potentially inactivates enzymes containing closely spaced cysteine residues or dithiol co-factors. Arsenic exposure generally induces the production of reactive oxygen species that can lead to the production of antioxidant metabolites and numerous enzymes involved in antioxidant defense. Oxidative carbon metabolism, amino acid and protein relationships, and nitrogen and sulfur assimilation pathways are also impacted by As exposure. Readjustment of several metabolic pathways, such as glutathione production, has been shown to lead to increased arsenic tolerance in plants. Species- and cultivar-dependent variation in arsenic sensitivity and the remodeling of metabolite pools that occurs in response to As exposure gives hope that additional metabolic pathways associated with As tolerance will be identified. PMID:22685440

  2. 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

  3. Toxic effects of bisphenol A on sexual and asexual reproduction in Hydra oligactis.

    PubMed

    Fukuhori, N; Kitano, M; Kimura, H

    2005-05-01

    Hydra oligactis, an evolutionarily primitive invertebrate, produced eggs or testes (sexual reproduction) when starved at 10 degrees C, and produced buds (asexual reproduction) when fed at 20 degrees C. Bisphenol A (BPA) at 2-4 mg/L given to male or female hydra had adverse effects on both sexual and asexual reproduction. Despite the estrogenic nature of BPA, testis formation and egg formation were similarly affected. The doses causing these acute toxicities were comparable to those reported earlier in aquatic invertebrates and were much higher than environmentally detected doses, at which the disruption of the endocrine system has been reported in fishes. All these facts indicate that the adverse effects are the results of general toxicity and may not be due to the estrogenic function of the compound. On the other hand, we found that BPA at 1 mg/L (a dose still much higher than environmental doses) stimulated asexual reproduction. No such stimulation of sexual reproduction was seen. When male hydras were fed at 10 degrees C, they produced both buds and testes simultaneously. BPA at 0.5 and 1 mg/L under this condition also stimulated asexual reproduction, whereas it suppressed sexual reproduction more severely than BPA at 2-3 mg/L. There may be some interaction between processes involved in sexual and asexual reproduction under this condition, and the stimulation of asexual reproduction by BPA may cause suppression of sexual reproduction.

  4. 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

  5. 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

  6. 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.

  7. Organophosphate pesticides exposure among farmworkers: pathways and risk of adverse health effects.

    PubMed

    Suratman, Suratman; Edwards, John William; Babina, Kateryna

    2015-01-01

    Organophosphate (OP) compounds are the most widely used pesticides with more than 100 OP compounds in use around the world. The high-intensity use of OP pesticides contributes to morbidity and mortality in farmworkers and their families through acute or chronic pesticides-related illnesses. Many factors contributing to adverse health effects have been investigated by researchers to determine pathways of OP-pesticide exposure among farmers in developed and developing countries. Factors like wind/agricultural pesticide drift, mixing and spraying pesticides, use of personal protective equipment (PPE), knowledge, perceptions, washing hands, taking a shower, wearing contaminated clothes, eating, drinking, smoking, and hot weather are common in both groups of countries. Factors including low socioeconomic status areas, workplace conditions, duration of exposure, pesticide safety training, frequency of applying pesticides, spraying against the wind, and reuse of pesticide containers for storage are specific contributors in developing countries, whereas housing conditions, social contextual factors, and mechanical equipment were specific pathways in developed countries. This paper compares existing research in environmental and behavioural exposure modifying factors and biological monitoring between developing and developed countries. The main objective of this review is to explore the current depth of understanding of exposure pathways and factors increasing the risk of exposure potentially leading to adverse health effects specific to each group of countries.

  8. [Non-steroid anti-inflammatory drugs and adverse gastrointestinal effects. An unresolved problem].

    PubMed

    López, A

    1999-01-01

    Non-steroid anti-inflammatory drugs are a class of medicine widely used throughout the world. This is a pharmacological group in continuous growth, to which some new molecules have been added in recent years. The great drawback of non-steroid anti-inflammatory drugs are their adverse effects, outstanding of which due to their frequency and importance being those that occur in the gastrointestinal tract. By means of a search in Medline and other databases, this work reviews the latest data published on the incidence of dyspepsia, gastroduodenal lesions, gastrointestinal complications and mortality associated with consumption of non-steroid anti-inflammatory drugs. Similarly, a brief description is made of the mechanism of lesions to the stomach of the non-steroid anti-inflammatory drugs and the different risk factors that condition the appearance of adverse effects at the gastrointestinal level. Finally, an analysis is made of the preventive strategy and the different medicines that can be used to this end and a contrast is made of the evidence extracted from the different published studies and the reality of the use of the different "gastroprotectors". This review concludes with a series of questions that still remain unresolved concerning treatment with non-steroid anti-inflammatory drugs and their lesions to the stomach.

  9. 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.

  10. Physical basis of adverse and therapeutic effects of low intensity microwave radiation.

    PubMed

    Hyland, G J

    2008-05-01

    A physical basis of adverse and therapeutic effects of low intensity microwave radiation is presented based on the concept of oscillatory similitude between the frequency of an external microwave field (together with any lower frequency modulations thereof) and those of certain endogenous dipolar coherent excitations allied to aliveness, which play the role of 'tuned circuits' via which a living organism is electromagnetically sensitised in a non-linear way to external fields too weak to be able to cause heating. From this perspective, an external electromagnetic field affects a living system not as a toxin but rather by perturbing its endogenous electromagnetic activity. The possibility of adverse perturbation is illustrated by reference to the microwave fields used in mobile telecommunications whose signals interfere in a non-thermal way with biofunctionality--in particular, undermining the efficacy of processes that would otherwise afford natural protection against the development of pathology. Therapeutic modalities of microwave exposure, on the other hand, are illustrated using the example of microwave resonance therapy--which can be considered as an electromagnetic version of acupuncture, and as an example of 'quantum medicine'--whose normalising effect on a wide range of pathologies is striking, and which affords a novel alternative to conventional pharmacological interventions.

  11. Adverse environmental health effects of ultra-low relative humidity indoor air.

    PubMed

    Sato, Mikiya; Fukayo, Shingo; Yano, Eiji

    2003-03-01

    In Japan, relative humidity (RH) shows the lowest achievement rate among the various general air quality standards for work environment. It has been mainly contributed by airtight design of modern buildings and occurrence of dry outdoor air in winter. Furthermore, an ultra-dry air environment of nearly 0% RH is often required in sophisticated industries. In order to assess the adverse health effects of the ultra-dry air environment, using a self-reported questionnaire, we have undertaken a study of over 200 employees of a high-tech device developing laboratory having a room at 2.5% RH (ultra-dry room). Those who worked in the ultra-dry room were identified and the prevalence of symptoms was compared with the other workers. Analysis was performed by Wilcoxon's test and Fisher's exact test. In the ultra-dry room, all the twelve workers covered their skin with long-sleeve clothes, paper caps, paper masks and latex gloves. They reported skin symptoms more often (p<0.05) than the other workers (N=143). The prevalence of atopic dermatitis was also higher in the exposed workers (p<0.05). The complaints of workers in the ultra-dry environment were similar to preceding reports concerning moderately dry environmental exposures. The current precautions to protect the workers from the adverse effects of ultra-low RH appear to be insufficient, indicating that additional measures such as selection of appropriate clothing to mere skin coverage should be considered.

  12. 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

  13. 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

  14. Low incidence of severe adverse effects after mandibular ridge reconstruction using hydroxylapatite.

    PubMed

    Mercier, P; Bellavance, F

    1999-08-01

    The short and long term adverse effects after ridge reconstruction using hydroxylapatite (HA) are presented in this study. The HA was inserted using a modified tunnelling technique, followed by a lowering of the floor of the mouth and a vestibuloplasty using split thickness skin graft, 4-6 weeks later. The study comprised 637 patients followed for a period of 1 to 10 years (mean 6.0+/-2.6 years). Major loss of HA was seen in 17 patients (2.7%). Donor site visibility (skin graft) appeared to improve greatly over the years from 29.2% to 8.8% at the latest follow-up. Neurosurgery deficits also improved from 11.6% (paraesthesia and dysaesthesia) to 4.6%. Long term follow-up revealed a high percentage of patient satisfaction (97%), indicating that the low incidence of severe adverse effects of the procedure does play a significant role in the appreciation of the procedure and prosthetic care. PMID:10416894

  15. Investigating clandestine drug laboratories: adverse medical effects in law enforcement personnel.

    PubMed

    Burgess, J L; Barnhart, S; Checkoway, H

    1996-10-01

    A retrospective cohort study was conducted among an international group of 46 law enforcement chemists and 13 Washington State clandestine drug laboratory investigation team members with more than 2,800 combined investigations. Each participant completed a questionnaire concerning previous drug laboratory investigations and adverse health effects during response activities. Methamphetamine laboratories accounted for 81-97% of all responses. Total illness incident rates varied between 0.75-3.4% of responses. Most exposures were through inhalation, and many occurred in the years prior to use of personal protective equipment. Symptoms were primarily those of headache and respiratory, mucous membrane, and skin irritation. Most illness episodes occurred during the processing phase of laboratory responses, and none occurred during the entry phase. A majority of illness episodes occurred in laboratories with leak/spills, fire/explosion, or uncontrolled reactions. Responding to an active laboratory was associated with a 7 to 15-fold risk of becoming ill as compared with setup, in-transit, or former (equipment removed) laboratory responses. No other laboratories characteristics were consistently associated with a significantly elevated relative risk of adverse health effects. PMID:8892555

  16. [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).

  17. 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

  18. 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.

  19. Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose–volume histogram analysis

    PubMed Central

    Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

    2015-01-01

    Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose–volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5–V20, mean lung dose (MLD), and heart V30–V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer. PMID:25755255

  20. Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis.

    PubMed

    Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

    2015-05-01

    Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose-volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5-V20, mean lung dose (MLD), and heart V30-V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer.

  1. 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

  2. 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

  3. 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...

  4. The no-observed-adverse-effect level (NOAEL) of baby aloe powder (BAP) for nutraceutical application based upon toxicological evaluation.

    PubMed

    Kwack, Seung Jun; Do, Seon-Gil; Kim, Young Woo; Kim, Yeon-Joo; Gwak, Hyo-Min; Park, Hyun Jong; Roh, Taehyun; Shin, Min Kyung; Lim, Seong Kwang; Kim, Hyung Sik; Lee, Byung-Mu

    2014-01-01

    Aloe has been used in versatile herbal medications and nutraceuticals throughout history. Aloe is widely considered to be generally safe for humans and used globally. The effectiveness and pharmacological properties of aloe are dependent upon when the plant is collected. However, little is known about the toxicology of whole-body aloe collected within less than 1 yr. Based upon widespread exposure to aloe, it is important to determine a daily intake level of this chemical to ensure its safety for humans. To determine the no-observed-adverse-effect level (NOAEL) of baby aloe powder (BAP) for clinical application, Sprague-Dawley (SD) rats were treated orally for 4 wk with 4 different concentrations: 0, 0.125, 0.5, and 2 g/kg body weight (bw). In this study, no significant or dose-dependent toxicological effects of BAP were observed in biochemical or hematological parameters, urinalysis, clinical signs, body weight, and food and water consumption. There were changes in some biomarkers in certain treated groups compared to controls; however, all values were within their reference ranges and not dose-dependent. Based on these results, the NOAEL of BAP was estimated to be greater than 2 g/kg bw in male and 2 g/kg bw in female SD rats. Collectively, these data suggest that BAP used in this study did not produce any marked subacute toxic effects up to a maximum concentration of 2 g/kg bw, and thus use in nutraceuticals and in pharmaceutical and cosmetic applications at a concentration of >2 g/kg is warranted.

  5. Toxic effects of Cadmium on the garden snail (Helix aspersa)

    SciTech Connect

    Russell, L.K.; DeHaven, J.I.; Botts, R.P.

    1981-05-01

    Spreading treated municipal wastes on agricultural and forest lands is becoming an established method of disposal. However, there is concern about the deleterious effects of toxicants, particularly cadmium, in the sludges. Cadmium concentrations in sewage sludge have been reported as high as 1500 ppM. The work reported here is a part of a larger project to investigate the ecological effects of municipal wastes on forest lands. Snails, Helix aspersa, were chosen to examine the entrance of cadmium into terrestrial food chains. This experiment was designed to determine cadmium accumulation, acute toxicity, and behavioral, reproductive and growth responses with increasing levels of cadmium.

  6. Towards the standardization of nanoecotoxicity testing: Natural organic matter 'camouflages' the adverse effects of TiO2 and CeO2 nanoparticles on green microalgae.

    PubMed

    Cerrillo, Cristina; Barandika, Gotzone; Igartua, Amaya; Areitioaurtena, Olatz; Mendoza, Gemma

    2016-02-01

    In the last few years, the emission of CeO2 and TiO2 nanoparticles (NPs) into the environment has been raising concerns about their potential adverse effects on wildlife and human health. Aquatic organisms constitute one of the most important pathways for the entrance of these NPs and transfer throughout the food web, but divergences exist in the experimental data published on their aquatic toxicity. The pressing need for standardization of methods to analyze their ecotoxicity requires aquatic media representing realistic environmental conditions. The present study aimed to determine the usefulness of Suwannee River natural organic matter (SR-NOM) in the assessment of the agglomeration kinetics and ecotoxicity of CeO2 and TiO2 NPs towards green microalgae Pseudokirchneriella subcapitata. SR-NOM alleviated the adverse effects of NPs on algal growth, completely in the case of TiO2 NPs and partially in the case of CeO2 NPs, suggesting a 'camouflage' of toxicity. This behavior has been observed also for other algal species and types of natural organic matter in the literature. Furthermore, SR-NOM markedly increased the stability of the NPs in algal medium, which led to a better reproducibility of the toxicity test results, and provided an electrophoretic mobility similar to that previously reported in various river and groundwaters. Thus, SR-NOM can be a representative sample of what is found in many different ecosystems, and the observed 'camouflage' of the effects of CeO2 and TiO2 NPs on algal cells might be considered as a natural interaction occurring in their standardized ecotoxicological assessment. PMID:26580731

  7. Towards the standardization of nanoecotoxicity testing: Natural organic matter 'camouflages' the adverse effects of TiO2 and CeO2 nanoparticles on green microalgae.

    PubMed

    Cerrillo, Cristina; Barandika, Gotzone; Igartua, Amaya; Areitioaurtena, Olatz; Mendoza, Gemma

    2016-02-01

    In the last few years, the emission of CeO2 and TiO2 nanoparticles (NPs) into the environment has been raising concerns about their potential adverse effects on wildlife and human health. Aquatic organisms constitute one of the most important pathways for the entrance of these NPs and transfer throughout the food web, but divergences exist in the experimental data published on their aquatic toxicity. The pressing need for standardization of methods to analyze their ecotoxicity requires aquatic media representing realistic environmental conditions. The present study aimed to determine the usefulness of Suwannee River natural organic matter (SR-NOM) in the assessment of the agglomeration kinetics and ecotoxicity of CeO2 and TiO2 NPs towards green microalgae Pseudokirchneriella subcapitata. SR-NOM alleviated the adverse effects of NPs on algal growth, completely in the case of TiO2 NPs and partially in the case of CeO2 NPs, suggesting a 'camouflage' of toxicity. This behavior has been observed also for other algal species and types of natural organic matter in the literature. Furthermore, SR-NOM markedly increased the stability of the NPs in algal medium, which led to a better reproducibility of the toxicity test results, and provided an electrophoretic mobility similar to that previously reported in various river and groundwaters. Thus, SR-NOM can be a representative sample of what is found in many different ecosystems, and the observed 'camouflage' of the effects of CeO2 and TiO2 NPs on algal cells might be considered as a natural interaction occurring in their standardized ecotoxicological assessment.

  8. Minimization of Local and Systemic Adverse Effects of Topical Glucocorticoids by Nanoencapsulation: In Vivo Safety of Hydrocortisone-Hydroxytyrosol Loaded Chitosan Nanoparticles.

    PubMed

    Siddique, Muhammad Irfan; Katas, Haliza; Iqbal Mohd Amin, Mohd Cairul; Ng, Shiow-Fern; Zulfakar, Mohd Hanif; Buang, Fhataheya; Jamil, Adawiyah

    2015-12-01

    Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC-HT coloaded chitosan nanoparticles (HC-HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC-HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC-HT CSNPs exhibited LD50 > 125 mg/body surface area of active, which is 100-fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC-HT CSNPs did not cause skin irritation, as measured by Tewameter®, Mexameter®, and as observed visually. Moreover, no-observed-adverse-effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC-HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations.

  9. 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.

  10. Exercise in the heat: strategies to minimize the adverse effects on performance.

    PubMed

    Terrados, N; Maughan, R J

    1995-01-01

    Exercise in the heat is usually associated with reduced performance; both dehydration and hyperthermia adversely affect mental and physical performance. For athletes from temperate climates, the negative effects of heat had humidity can be attenuated by a period of acclimatization. This requires up to 10-14 days. Endurance-trained individuals already show some of the adaptations that accompany acclimatization, but further adaptation occurs with training in the heat. Prior dehydration has a negative effect even on exercise of short duration where sweat losses are small. The athlete must begin exercise fully hydrated and regular ingestion of fluids is beneficial where the exercise duration exceeds 40 min. Dilute carbohydrate-electrolyte (sodium) drinks are best for fluid replacement and also supply some substrate for the exercising muscles. Post-exercise rehydration requires electrolyte as well as volume replacement. In extreme conditions, neither acclimatization nor fluid replacement will allow hard exercise to be performed without some risk of heat illness.

  11. Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms.

    PubMed

    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.

  12. Addressing the potential adverse effects of school-based BMI assessments on children's wellbeing.

    PubMed

    Gibbs, Lisa; O'Connor, Thea; Waters, Elizabeth; Booth, Michael; Walsh, Orla; Green, Julie; Bartlett, Jenny; Swinburn, Boyd

    2008-01-01

    INTRODUCTION. Do child obesity prevention research and intervention measures have the potential to generate adverse concerns about body image by focussing on food, physical activity and body weight? Research findings now demonstrate the emergence of body image concerns in children as young as 5 years. In the context of a large school-community-based child health promotion and obesity prevention study, we aimed to address the potential negative effects of height and weight measures on child wellbeing by developing and implementing an evidence-informed protocol to protect and prevent body image concerns. fun 'n healthy in Moreland! is a cluster randomised controlled trial of a child health promotion and obesity prevention intervention in 23 primary schools in an inner urban area of Melbourne, Australia. Body image considerations were incorporated into the study philosophies, aims, methods, staff training, language, data collection and reporting procedures of this study. This was informed by the published literature, professional body image expertise, pilot testing and implementation in the conduct of baseline data collection and the intervention. This study is the first record of a body image protection protocol being an integral part of the research processes of a child obesity prevention study. Whilst we are yet to measure its impact and outcome, we have developed and tested a protocol based on the evidence and with support from stakeholders in order to minimise the adverse impact of study processes on child body image concerns.

  13. 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.

  14. 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.

  15. 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