Cyanotoxins: producing organisms, occurrence, toxicity, mechanism of action and human health toxicological risk evaluation.

PubMed

Buratti, Franca M; Manganelli, Maura; Vichi, Susanna; Stefanelli, Mara; Scardala, Simona; Testai, Emanuela; Funari, Enzo

2017-03-01

Cyanobacteria were present on the earth 3.5 billion years ago; since then they have colonized almost all terrestrial and aquatic ecosystems. They produce a high number of bioactive molecules, among which some are cyanotoxins. Cyanobacterial growth at high densities, forming blooms, is increasing in extension and frequency, following anthropogenic activities and climate changes, giving rise to some concern for human health and animal life exposed to cyanotoxins. Numerous cases of lethal poisonings have been associated with cyanotoxins ingestion in wild animal and livestock. In humans few episodes of lethal or severe human poisonings have been recorded after acute or short-term exposure, but the repeated/chronic exposure to low cyanotoxin levels remains a critical issue. The properties of the most frequently detected cyanotoxins (namely, microcystins, nodularins, cylindrospermopsin and neurotoxins) are here critically reviewed, describing for each toxin the available information on producing organisms, biosynthesis/genetic and occurrence, with a focus on the toxicological profile (including kinetics, acute systemic toxicity, mechanism and mode of action, local effects, repeated toxicity, genotoxicity, carcinogenicity, reproductive toxicity; human health effects and epidemiological studies; animal poisoning) with the derivation of health-based values and considerations on the risks for human health.

Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids.

PubMed

Gable, Robert S

2007-01-01

To extend previous reviews by assessing the acute systemic toxicity and psychological hazards of a dimethyltryptamine and beta-carboline brew (ayahuasca/hoasca) used in religious ceremonies. A systematic literature search, supplemented by interviews with ceremony participants. No laboratory animal models were located that tested the acute toxicity or the abuse potential of ayahuasca. Separate animal studies of the median lethal dose of dimethyltryptamine (DMT) and of several harmala alkaloids indicated that a lethal dose of these substances in humans is probably greater than 20 times the typical ceremonial dose. Adverse health effects may occur from casual use of ayahuasca, particularly when serotonergic substances are used in conjunction. DMT is capable of inducing aversive psychological reactions or transient psychotic episodes that resolve spontaneously in a few hours. There was no evidence that ayahuasca has substantial or persistent abuse potential. Long-term psychological benefits have been documented when ayahuasca is used in a well-established social context. A decoction of DMT and harmala alkaloids used in religious ceremonies has a safety margin comparable to codeine, mescaline or methadone. The dependence potential of oral DMT and the risk of sustained psychological disturbance are minimal.

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL)

PubMed Central

Abal, Paula; Louzao, M. Carmen; Antelo, Alvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R.; Botana, Luis M.

2017-01-01

Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard. PMID:28245573

Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge.

PubMed

Stanley, Daphne A; Honko, Anna N; Asiedu, Clement; Trefry, John C; Lau-Kilby, Annie W; Johnson, Joshua C; Hensley, Lisa; Ammendola, Virginia; Abbate, Adele; Grazioli, Fabiana; Foulds, Kathryn E; Cheng, Cheng; Wang, Lingshu; Donaldson, Mitzi M; Colloca, Stefano; Folgori, Antonella; Roederer, Mario; Nabel, Gary J; Mascola, John; Nicosia, Alfredo; Cortese, Riccardo; Koup, Richard A; Sullivan, Nancy J

2014-10-01

Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge.

Developmental toxicity and risk assessment of nonylphenol to the South American toad, Rhinella arenarum.

PubMed

Mariel, Aronzon Carolina; Alejandra, Babay Paola; Silvia, Pérez Coll Cristina

2014-09-01

The toxicity of Nonylphenol, an emerging pollutant, on the common South American toad Rhinella arenarum was stage and time dependent, thus Median Lethal Concentrations (LC50) for acute (96h), short-term chronic (168h) and chronic exposure (336h) were 1.06; 0.96 and 0.17mgNP/L from embryonic period (S.4), whereas for exposure from larvae (S.25), LC50 remained constant at 0.37mgNP/L from 96h to 168h, decreasing to 0.11mgNP/L at 336h. NOEC-168h for exposure from embryos was 0.025mgNP/L. The Teratogenic Potential (NOEC-lethality/NOEC-sublethal effects) was 23 times higher than the threshold value, indicating a high risk for embryos to be malformed in absence of significant lethality and representing a threat for the species conservation. By comparing with other amphibians, the early development of R. arenarum was very sensitive to NP. The results highlight the relevance of extending the exposure time and look for the most sensitive stage in order to perform the bioassays for conservation purposes. Copyright © 2014 Elsevier B.V. All rights reserved.

Mapping evaporative water loss in desert passerines reveals an expanding threat of lethal dehydration.

PubMed

Albright, Thomas P; Mutiibwa, Denis; Gerson, Alexander R; Smith, Eric Krabbe; Talbot, William A; O'Neill, Jacqueline J; McKechnie, Andrew E; Wolf, Blair O

2017-02-28

Extreme high environmental temperatures produce a variety of consequences for wildlife, including mass die-offs. Heat waves are increasing in frequency, intensity, and extent, and are projected to increase further under climate change. However, the spatial and temporal dynamics of die-off risk are poorly understood. Here, we examine the effects of heat waves on evaporative water loss (EWL) and survival in five desert passerine birds across the southwestern United States using a combination of physiological data, mechanistically informed models, and hourly geospatial temperature data. We ask how rates of EWL vary with temperature across species; how frequently, over what areas, and how rapidly lethal dehydration occurs; how EWL and die-off risk vary with body mass; and how die-off risk is affected by climate warming. We find that smaller-bodied passerines are subject to higher rates of mass-specific EWL than larger-bodied counterparts and thus encounter potentially lethal conditions much more frequently, over shorter daily intervals, and over larger geographic areas. Warming by 4 °C greatly expands the extent, frequency, and intensity of dehydration risk, and introduces new threats for larger passerine birds, particularly those with limited geographic ranges. Our models reveal that increasing air temperatures and heat wave occurrence will potentially have important impacts on the water balance, daily activity, and geographic distribution of arid-zone birds. Impacts may be exacerbated by chronic effects and interactions with other environmental changes. This work underscores the importance of acute risks of high temperatures, particularly for small-bodied species, and suggests conservation of thermal refugia and water sources.

Mapping evaporative water loss in desert passerines reveals an expanding threat of lethal dehydration

PubMed Central

Mutiibwa, Denis; Gerson, Alexander. R.; Smith, Eric Krabbe; Talbot, William A.; O’Neill, Jacqueline J.; McKechnie, Andrew E.; Wolf, Blair O.

2017-01-01

Extreme high environmental temperatures produce a variety of consequences for wildlife, including mass die-offs. Heat waves are increasing in frequency, intensity, and extent, and are projected to increase further under climate change. However, the spatial and temporal dynamics of die-off risk are poorly understood. Here, we examine the effects of heat waves on evaporative water loss (EWL) and survival in five desert passerine birds across the southwestern United States using a combination of physiological data, mechanistically informed models, and hourly geospatial temperature data. We ask how rates of EWL vary with temperature across species; how frequently, over what areas, and how rapidly lethal dehydration occurs; how EWL and die-off risk vary with body mass; and how die-off risk is affected by climate warming. We find that smaller-bodied passerines are subject to higher rates of mass-specific EWL than larger-bodied counterparts and thus encounter potentially lethal conditions much more frequently, over shorter daily intervals, and over larger geographic areas. Warming by 4 °C greatly expands the extent, frequency, and intensity of dehydration risk, and introduces new threats for larger passerine birds, particularly those with limited geographic ranges. Our models reveal that increasing air temperatures and heat wave occurrence will potentially have important impacts on the water balance, daily activity, and geographic distribution of arid-zone birds. Impacts may be exacerbated by chronic effects and interactions with other environmental changes. This work underscores the importance of acute risks of high temperatures, particularly for small-bodied species, and suggests conservation of thermal refugia and water sources. PMID:28193891

Acute lethal toxicity, hyperkalemia associated with renal injury and hepatic damage after intravenous administration of cadmium nitrate in rats.

PubMed

Dote, Emi; Dote, Tomotaro; Shimizu, Hiroyasu; Shimbo, Yukari; Fujihara, Michiko; Kono, Koichi

2007-01-01

Cadmium nitrate Cd(NO(3))(2) (CdN) is commonly used in Ni-Cd battery factories. The possibility of accidental exposure to CdN is great. CdN is very soluble in water compared to other Cd compounds. Therefore, acute toxicity would be expected to be quick due to rapid absorption after exposure. However, the mechanisms of CdN toxicity have not been fully elucidated. We investigated the acute lethal toxicity and harmful systemic effects of acute exposure to large doses of CdN. The lethal dose and dose-response study of the liver and kidney were determined after intravenous administration of CdN in rats. The LD(50) of CdN was determined to be 5.5 mg/kg. Doses of 2.1, 4.2, 6.3 mg/kg were selected for the dose-response study. Liver injury was induced at doses greater than 4.2 mg/kg. Severe hepatic injury occurred in the 6.3 mg/kg group, which would have been caused by acute exposure to the high concentration of Cd that exceeded the critical concentration in hepatic tissue. A remarkable decrease in urine volume in the 6.3 mg/kg group indicated acute renal failure. A decrease in creatinine clearance suggested acute glomerular dysfunction at doses greater than 4.2 mg/kg. Increases in urinary N-acetyl-beta-D-glucosaminidase/creatinine, beta(2)-microglobulin and glucose in the 6.3 mg/kg group indicated proximal tubular injury. Secretion of K ion was also severely affected by proximal tubular injury and severe decreases in urine volume, and an increase in serum K ion was identified at doses greater than 4.2 mg/kg. Thus severe hyperkalemia might be associated with the cardiac-derived lethal toxicity of CdN.

Epidemiology of invasive pulmonary aspergillosis in patients with liver failure: Clinical presentation, risk factors, and outcomes.

PubMed

Zhang, Xuan; Yang, Meifang; Hu, Jianhua; Zhao, Hong; Li, Lanjuan

2018-02-01

Objective Invasive pulmonary aspergillosis (IPA) is a severe and often lethal infection. The possible risk factors, clinical presentation, and treatment of patients with simultaneous liver failure and IPA have received little attention in previous studies. The aim of this study was to investigate the epidemiology of IPA in patients with liver failure in an effort to reduce patient mortality. Methods The patients with liver failure (including acute liver failure , sub-acute liver failure , acute-on-chronic liver failure and chronic liver failure) were recruited from 2011 to 2016. The clinical data of these patients were retrieved for the study. Results In total, 1077 patients with liver failure were included in this study. Of the 1077 patients, 53 (4.9%) had IPA. Forty-four (83%) patients with IPA died. Independent risk factors for IPA were male sex (hazard ratio [HR] = 2.542), hepatorenal syndrome (HR = 2.463), antibiotic use (HR = 4.631), and steroid exposure (HR = 18.615). Conclusions IPA is a fatal complication in patients with liver failure. Male sex, hepatorenal syndrome, antibiotic use, and steroid exposure were independent risk factors for IPA. When patients with liver failure have these risk factors and symptoms of pneumonia such as cough or hemoptysis, clinicians should be cautious about the possibility of IPA.

Acetazolamide-related life-threatening hypophosphatemia in a glaucoma patient.

PubMed

Hu, Ching-Yun; Lee, Bor-Jen; Cheng, Hsiang-Fan; Wang, Chen-Yu

2015-01-01

Acetazolamide-related hypophosphatemia leading to cardiac arrest is extremely rare. Herein we report a 78-year-old female glaucoma patient who developed general weakness and acute respiratory failure, followed by cardiac arrest 1 day after taking acetazolamide. The patient was successfully weaned from the ventilator after correction of hypophosphatemia and fully recovered. As acetazolamide was shown to have the potential to cause a lethal side effect in stable glaucoma, the risk of hypophosphatemia should be kept in mind by ophthalmologists. An examination of serum metabolic panels may be indicated in patients at risk of hypophosphatemia.

Acute toxicity of 353-nonylphenol and its metabolites for zebrafish embryos.

PubMed

Kammann, Ulrike; Vobach, Michael; Wosniok, Werner; Schäffer, Andreas; Telscher, Andreas

2009-03-01

Nonylphenol (NP) can be detected in the aquatic environment all over the world. It is applied as a technical mixture of isomers of which 353-NP is the most relevant both in terms of abundance (about 20% of total mass) and endocrine potential. 353-NP is metabolised in sewage sludge. The aims of the present study were to determine and to compare the acute toxicity of t-NP, 353-NP and its metabolites as well as to discuss if the toxicity of 353-NP changes during degradation. 353-NP and two of its metabolites were synthesised. The zebrafish embryo test was performed according to standard protocols. Several lethal and non-lethal endpoints during embryonal development were reported. NOEL, LOEL and EC50 were calculated. All tested compounds caused lethal as well as non-lethal malformations during embryo development. 353-NP showed a higher toxicity (EC50 for lethal endpoints 6.7 mg/L) compared to its metabolites 4-(3.5-dimethyl-3-heptyl)-2-nitrophenol (EC50 13.3 mg/L) and 4-(3,5-dimethyl-3-heptyl)-2-bromophenol (EC50 27.1 mg/L). In surface water, concentrations of NP are far below the NOEC identified by the zebrafish embryo test. However, in soils and sewage sludge, concentrations may reach or even exceed these concentrations. Therefore, sludge-treated sites close to surface waters should be analysed for NP and its metabolites in order to detect an unduly high contamination due to runoff events. The results of the present study point out that the toxicity of 353-NP probably declines during metabolisation in water, sediment and soil, but does not vanish since the major metabolites exhibit a clear toxic potential for zebrafish embryos. Metabolites of environmental pollutants should be included in the ecotoxicological test strategy for a proper risk assessment.

Calculating Hematopoietic-Mode-Lethality Risk Avoidance Associated with Radionuclide Decorporation Countermeasures Related to a Radiological Terrorism Incident

PubMed Central

Scott, Bobby R.

2009-01-01

This paper provides theoretical health-risk-assessment tools that are designed to facilitate planning for and managing radiological terrorism incidents that involve ingestion exposure to bone-seeking radionuclides (e.g., radiostrontium nuclides). The focus is on evaluating lethality risk avoidance (RAV; i.e., the decrease in risk) that is associated with radionuclide decorporation countermeasures employed to remove ingested bone-seeking beta and/or gamma-emitting radionuclides from the body. To illustrate the application of tools presented, hypothetical radiostrontium decorporation scenarios were considered that involved evaluating the hematopoietic-mode-lethality RAV. For evaluating the efficacy of specific decorporation countermeasures, the lethality risk avoidance proportion (RAP; which is the RAV divided by the total lethality risk in the absence of protective countermeasures) is introduced. The lethality RAP is expected to be a useful tool for designing optimal radionuclide decorporation schemes and for identifying green, yellow and red dose-rate zones. For the green zone, essentially all of the lethality risk is expected to be avoided (RAP = 1) as a consequence of the radionuclide decorporation scheme used. For the yellow zone, some but not all of the lethality risk is expected to be avoided. For the red zone, none of the lethality risk (which equals 1) is expected to be avoided. PMID:20011652

AP214, an analogue of α-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality

PubMed Central

Doi, Kent; Hu, Xuzhen; Yuen, Peter S.T.; Leelahavanichkul, Asada; Yasuda, Hideo; Kim, Soo Mi; Schnermann, Jürgen; Jonassen, Thomas E.N.; Frøkiær, Jørgen; Nielsen, Søren; Star, Robert A.

2008-01-01

Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. α-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new α-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 hr after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-α and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-κB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis. PMID:18354376

Clinical correlates of planned, more lethal suicide attempts in major depressive disorder.

PubMed

Nakagawa, Atsuo; Grunebaum, Michael F; Oquendo, Maria A; Burke, Ainsley K; Kashima, Haruo; Mann, J John

2009-01-01

Assessment of suicide plans is standard in acute psychiatric care, but there is a limited evidence base to guide this routine clinical practice. The purpose of this study was to investigate clinical correlates of suicide planning in depressed patients. 151 patients with major depressive disorder and a lifetime history of suicide attempt were studied. Subjects received a comprehensive evaluation including structured diagnostic interview for Axis I and II disorders, current symptoms, impulsivity, and systematic assessment of suicide planning prior to the most recent suicide attempt. Seriousness of suicide attempt planning correlated with lethality of suicidal acts. Comorbid anxiety disorder and anxiety correlated with less suicide planning. Specifically, this negative correlation was with comorbid panic disorder. Planning did not correlate with severity of depression or aggressive/impulsive traits. Cross-sectional design, retrospective recall of suicide planning data, limited applicability to completed suicide or other psychiatric disorders. In major depression, comorbid panic disorder appears protective against more carefully planned, higher lethality suicide attempts. Surprisingly, severity of depression and aggressive impulsive traits do not predict planning or lethality of suicide attempts. We have previously reported that anxiety severity protects against the probability of a suicide attempt and now extend that observation to show there is protection against lethality of a suicide attempt. Treatment of anxiety without directly treating major depression may place patients at greater risk of suicidal behavior.

Response to unfairness across the suicide risk spectrum.

PubMed

Carbajal, Jessica M; Gamboa, Jorge L; Moore, Jordan; Smith, Favrin; Ann Eads, Lou; Clothier, Jeffrey L; Cáceda, Ricardo

2017-12-01

Suicidal behavior is frequently triggered by social crises, such as familial, romantic, social or work-related conflict. A variety of cognitive and social functioning impairments has been associated with suicidal thoughts and acts. One of the precipitating and perpetuating factors of social conflict is the desire for retribution after a perceived offense, even at one's own detriment. We utilized the Ultimatum Game-a behavioral economic task which examines the behavioral response to perceived unfairness-in order to characterize the response to unfairness across the acute suicide risk spectrum. We examined five groups of adult individuals of both genders (n = 204): High- and Low-Lethality recent Suicide Attempters, Suicidal Ideators, Non-Suicidal Depressed Patients; and Healthy Controls. We also measured demographic and clinical variables. Even though all depressed groups showed similar rejection rates in the Ultimatum Game, there was a higher likelihood of rejecting offers in the low stakes condition in all acutely suicidal groups compared with healthy controls. Stake size, offer, education, and gender of the proposer were significantly associated with rejection rates. Acutely suicidal patients may be more vulnerable to adverse interpersonal interactions. Further characterization of social behavior may provide targets for secondary and tertiary prevention for high-risk individuals. Published by Elsevier B.V.

Acute liver injury following Garcinia cambogia weight-loss supplementation: case series and literature review.

PubMed

Crescioli, Giada; Lombardi, Niccolò; Bettiol, Alessandra; Marconi, Ettore; Risaliti, Filippo; Bertoni, Michele; Menniti Ippolito, Francesca; Maggini, Valentina; Gallo, Eugenia; Firenzuoli, Fabio; Vannacci, Alfredo

2018-05-25

Herbal weight-loss supplements are sold as self-medication products, and are often used under the misconception that their natural origin guarantees their safety. Food supplements are not required to provide any benefit/risk profile evaluation before marketing; however, possible risks associated with use of herbal extracts in food supplements are becoming more and more documented in the literature. Some herbs are listed as the leading cause of herb-induced liver injury, with a severe or potentially lethal clinical course, and unpredictable herb-drug interactions. Garcinia cambogia (GC) extract and GC-containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we present four cases of acute liver failure in women taking GC extract for weight loss, and a literature review of clinical evidences about hepatic toxicity in patients taking dietary supplements containing GC extract.

Toxicity assessment of chlorpyrifos-degrading fungal bio-composites and their environmental risks.

PubMed

Liu, Jie; Zhang, Xiaoying; Yang, Mengran; Hu, Meiying; Zhong, Guohua

2018-02-01

Bioremediation techniques coupling with functional microorganisms have emerged as the most promising approaches for in-situ elimination of pesticide residue. However, the environmental safety of bio-products based on microorganisms or engineered enzymes was rarely known. Here, we described the toxicity assessment of two previously fabricated fungal bio-composites which were used for the biodegradation of chlorpyrifos, to clarify their potential risks on the environment and non-target organisms. Firstly, the acute and chronic toxicity of prepared bio-composites were evaluated using mice and rabbits, indicating neither acute nor chronic effect was induced via short-term or continuous exposure. Then, the acute mortality on zebrafish was investigated, which implied the application of fungal bio-composites had no lethal risk on aquatic organisms. Meanwhile, the assessment on soil organic matters suggested that no threat was posed to soil quality. Finally, by monitoring, the germination of cabbage was not affected by the exposure to two bio-products. Therefore, the application of fungal bio-composites for chlorpyrifos elimination cannot induce toxic risk to the environment and non-target organisms, which insured the safety of these engineered bio-products for realistic management of pesticide residue, and provided new insights for further development of bioremediation techniques based on functional microorganisms.

Benzodiazepines and antipsychotic medications for treatment of acute cocaine toxicity in animal models--a systematic review and meta-analysis.

PubMed

Heard, Kennon; Cleveland, Nathan R; Krier, Shay

2011-11-01

There are no controlled human studies to determine the efficacy of benzodiazepines or antipsychotic medications for prevention or treatment of acute cocaine toxicity. The only available controlled data are from animal models and these studies have reported inconsistent benefits. The objective of this study was to quantify the reported efficacy of benzodiazepines and antipsychotic medication for the prevention of mortality due to cocaine poisoning. We conducted a systematic review to identify English language articles describing experiments that compared a benzodiazepine or antipsychotic medication to placebo for the prevention of acute cocaine toxicity in an animal model. We then used these articles in a meta-analysis with a random-effects model to quantify the absolute risk reduction observed in these experiments. We found 10 articles evaluating antipsychotic medications and 15 articles evaluating benzodiazepines. Antipsychotic medications reduced the risk of death by 27% (95% CI, 15.2%-38.7%) compared to placebo and benzodiazepines reduced the risk of death by 52% (42.8%-60.7%) compared to placebo. Both treatments showed evidence of a dose-response effect, and no experiment found a statistically significant increase in risk of death. We conclude that both benzodiazepines and antipsychotic medications are effective for the prevention of lethality from cocaine toxicity in animal models.

Japanese quail acute exposure to methamidophos: experimental design, lethal, sub-lethal effects and cholinesterase biochemical and histochemical expression.

PubMed

Foudoulakis, Manousos; Balaskas, Christos; Csato, Attila; Szentes, Csaba; Arapis, Gerassimos

2013-04-15

We exposed the Japanese quail (Coturnix coturnix japonica) to the organophosphate methamidophos using acute oral test. Mortality and sub-lethal effects were recorded in accordance to internationally accepted protocols. In addition cholinesterases were biochemically estimated in tissues of the quail: brain, liver and plasma. Furthermore, brain, liver and duodenum cryostat sections were processed for cholinesterase histochemistry using various substrates and inhibitors. Mortalities occurred mainly in the first 1-2h following application. Sub-lethal effects, such as ataxia, ruffled feathers, tremor, salivation and reduced or no reaction to external stimuli were observed. Biochemical analysis in the brain, liver and plasma indicates a strong cholinesterase dependent inhibition with respect to mortality and sub-lethal effects of the quail. The histochemical staining also indicated a strong cholinesterase inhibition in the organs examined and the analysis of the stained sections allowed for an estimation and interpretation of the intoxication effects of methamidophos, in combination with tissue morphology visible by Haematoxylin and Eosin staining. We conclude that the use of biochemistry and histochemistry for the biomarker cholinesterase, may constitute a significantly novel approach for understanding the results obtained by the acute oral test employed in order to assess the effects of methamidophos and other chemicals known to inhibit this very important nervous system enzyme. Copyright © 2012 Elsevier B.V. All rights reserved.

Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

PubMed

Albright, Frederick S; Stephenson, Robert A; Agarwal, Neeraj; Cannon-Albright, Lisa A

2017-01-01

There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents.

PubMed

Albuquerque, Edson X; Pereira, Edna F R; Aracava, Yasco; Fawcett, William P; Oliveira, Maristela; Randall, William R; Hamilton, Tracey A; Kan, Robert K; Romano, James A; Adler, Michael

2006-08-29

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer's disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents

PubMed Central

Albuquerque, Edson X.; Pereira, Edna F. R.; Aracava, Yasco; Fawcett, William P.; Oliveira, Maristela; Randall, William R.; Hamilton, Tracey A.; Kan, Robert K.; Romano, James A.; Adler, Michael

2006-01-01

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer’s disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning. PMID:16914529

Choline intake and risk of lethal prostate cancer: incidence and survival123

PubMed Central

Richman, Erin L; Kenfield, Stacey A; Stampfer, Meir J; Giovannucci, Edward L; Zeisel, Steven H; Willett, Walter C; Chan, June M

2012-01-01

Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer. PMID:22952174

Are High-Lethality Suicide Attempters With Bipolar Disorder a Distinct Phenotype?

PubMed Central

Oquendo, Maria A.; Carballo, Juan Jose; Rajouria, Namita; Currier, Dianne; Tin, Adrienne; Merville, Jessica; Galfalvy, Hanga C.; Sher, Leo; Grunebaum, Michael F.; Burke, Ainsley K.; Mann, J. John

2013-01-01

Because Bipolar Disorder (BD) individuals making highly lethal suicide attempts have greater injury burden and risk for suicide, early identification is critical. BD patients were classified as high- or low-lethality attempters. High-lethality attempts required inpatient medical treatment. Mixed effects logistic regression models and permutation analyses examined correlations between lethality, number, and order of attempts. High-lethality attempters reported greater suicidal intent and more previous attempts. Multiple attempters showed no pattern of incremental lethality increase with subsequent attempts, but individuals with early high-lethality attempts more often made high-lethality attempts later. A subset of high-lethality attempters make only high-lethality attempts. However, presence of previous low-lethality attempts does not indicate that risk for more lethal, possibly successful, attempts is reduced. PMID:19590998

Acute Toxicities of the Saxitoxin Congeners Gonyautoxin 5, Gonyautoxin 6, Decarbamoyl Gonyautoxin 2&3, Decarbamoyl Neosaxitoxin, C-1&2 and C-3&4 to Mice by Various Routes of Administration

PubMed Central

Selwood, Andrew I.; Waugh, Craig; Harwood, David T.; Rhodes, Lesley L.; Reeve, John; Sim, Jim; Munday, Rex

2017-01-01

Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required. These are expressed as “Toxicity Equivalence Factors” (TEFs). At present, TEFs are largely based on relative specific activities following intraperitoneal injection in a mouse bioassay rather than on acute toxicity determinations. A more relevant parameter for comparison would be median lethal doses via oral administration, since this is the route through which humans are exposed to PSTs. In the present study, the median lethal doses of gonyautoxin 5, gonyautoxin 6, decarbamoyl neosaxitoxin and of equilibrium mixtures of decarbamoyl gonyautoxins 2&3, C1&2 and C3&4 by oral administration to mice have been determined and compared with toxicities via intraperitoneal injection. The results indicate that the TEFs of several of these substances require revision in order to more accurately reflect the risk these toxins present to human health. PMID:28230783

Acute toxicity, histopathology, and coagulopathy in American kestrels (Falco sparverius) following administration of the rodenticie diphacinone

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Meteyer, Carol U.; Voler, Steven F.; Eisemann, John D.; Johnston, John J.

2011-01-01

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 d of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell?s viper venom time at 48 and 96 h postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.

Impact of acute alcohol consumption on lethality of suicide methods.

PubMed

Park, C Hyung Keun; Yoo, Seong Ho; Lee, Jaewon; Cho, Sung Joon; Shin, Min-Sup; Kim, Eun Young; Kim, Se Hyun; Ham, Keunsoo; Ahn, Yong Min

2017-05-01

The influence of acute alcohol consumption on the factors related to suicide remains understudied. Thus, the present study investigated the relationship between blood alcohol content (BAC) and the lethality of suicide methods. Autopsy data on 315 South Korean suicide completers with a positive BAC were collected from a nationwide pool between May 2015 and November 2015, and the methods were dichotomised as suicide methods of low lethality (SMLL; drug/chemical overdose and sharp objects, n=67) and suicide methods of high lethality (SMHL; everything else, n=243). BAC at the time of autopsy and various suicide-related factors of these two groups were compared with logistic regression analyses. Compared to suicide completers with a BAC in the lowest range of 0.011-0.049%, suicide completers with a BAC in the range of 0.150-0.199% were more likely to use SMHL (odds ratio [OR]: 3.644, 95% confidence interval [CI]: 1.221-10.874). Additionally, the adoption of SMHL was significantly associated with the absence of a psychiatric illness (OR: 0.433, 95% CI: 0.222-0.843) and a younger age; the OR for high BAC among subjects in their 40s was 0.266 (95% CI: 0.083-0.856); in their 50s, 0.183 (95% CI: 0.055-0.615); and in their 60s, 0.057 (95% CI: 0.015-0.216). The relationship between BAC and suicide method lethality was represented by a bell-shaped pattern in which suicide methods of high lethality were more likely to be used by suicide completers with mid-range BAC levels. The increased impulsivity and impairments in particular executive functions, including planning and organization, associated with acute alcohol use may influence the selection of a particular suicide method based on its lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

A NOVEL SCORING SYSTEM: PREDICTING SEPTIC SHOCK AT DIAGNOSIS EASILY IN ACUTE COMPLICATED PYELONEPHRITIS PATIENTS.

PubMed

Kubota, Masashi; Kanno, Toru; Nishiyama, Ryuichi; Okada, Takashi; Higashi, Yoshihito; Yamada, Hitoshi

2016-01-01

(Objectives) Because acute complicated pyelonephritis can easily cause sepsis and concomitant shock status, it is a potentially lethal disease. However, the predictors for the severity of pyelonephritis is not well analyzed. In this study, we aimed at clarifying the clinical characteristic risk factors associated with septic shock in patients with acute complicated pyelonephritis. (Materials and methods) From May 2009 to March 2014, 267 patients with acute complicated pyelonephritis were treated at our institution. We investigated the characteristics of the patients associated with septic shock, and assessed risk factors in these patients. By using these risk factors, we established a novel scoring system to predict septic shock. (Results) 267 patients included 145 patients with ureteral calculi and 75 patients with stent-related pyelonephritis. Septic shock occurred in 35 patients (13%), and the mortality rate was 0.75%. Multivariate analysis revealed that (P): Performance Status ≥3 (p=0.0014), (U): Presence of Ureteral calculi (p=0.043), (S): Sex of female (p=0.023), and (H): the presence of Hydronephrosis (p=0.039) were independent risk factors for septic shock. P.U.S.H. scoring system (range 0-4), which consists of these 4 factors, were positively correlated with the rate of septic shock (score 0: 0%, 1: 5.3%, 2: 3.4%, 3: 25.0%, 4: 42.3%). Importantly, patients with 3-4 P.U.S.H. scores were statistically more likely to become septic shock than those with 0-2 score (p=0.00014). (Conclusions) These results suggest that P.U.S.H. scoring system using 4 clinical factors is useful to predict the status of septic shock in patients with acute complicated pyelonephritis.

Human radiation tolerance

NASA Technical Reports Server (NTRS)

Lushbaugh, C. C.

1974-01-01

The acute radiation syndrome in man is clinically bounded by death at high dose levels and by the prodromal syndrome of untoward physiological effects at minimal levels of clinically effective exposure. As in lower animals, man experiences principally three acute modes of death from radiation exposure (Bond et al., 1965). These are known collectively as the lethal radiation syndromes: central nervous system death, gastrointestinal death, and hematopoietic death. The effect of multiple exposure on lethality, the effect of multiple exposure on hematopoietic recovery, and quantitative aspects of cell and tissue repair are discussed.

Regular Aspirin Use and the Risk of Lethal Prostate Cancer in the Physicians' Health Study.

PubMed

Downer, Mary K; Allard, Christopher B; Preston, Mark A; Gaziano, J Michael; Stampfer, Meir J; Mucci, Lorelei A; Batista, Julie L

2017-11-01

Regular aspirin use probably protects against some malignancies including prostate cancer (PC), but its impact on lethal PC is particularly unclear. To investigate the association between regular aspirin and (1) the risk of lethal PC in a large prospective cohort and (2) survival after PC diagnosis. In 1981/82, the Physicians' Health Study randomized 22 071 healthy male physicians to aspirin, β-carotene, both, or placebo. After the trial ended in 1988, annual questionnaires have obtained data on aspirin use, cancer diagnoses, and outcomes up to 2009 for the whole cohort, and to 2015 for PC patients. We evaluated the relationship between regular aspirin (>3 tablets/week) and lethal PC (metastases or PC death). Cox proportional-hazards models estimated hazard ratios (HRs) for the risk of lethal PC in the whole cohort and postdiagnosis survival among men initially diagnosed with nonlethal PC. Risk analysis revealed that 502 men developed lethal PC by 2009. Current and past regular aspirin was associated with a lower risk of lethal PC (current: HR 0.68, 95% confidence interval [CI] 0.52-0.89; past: HR 0.54, 95% CI 0.40-0.74) compared to never users. In the survival analysis, 407/3277 men diagnosed with nonlethal PC developed lethal disease by 2015. Current postdiagnostic aspirin was associated with lower risks of lethal PC (HR 0.68, 95% CI 0.52-0.90) and overall mortality (HR 0.72, 95% CI 0.61-0.9). We could not assess aspirin dose, and inconsistencies were observed in some sensitivity analyses. Current regular aspirin use was associated with a lower risk of lethal PC among all participants. Current postdiagnostic use was associated with improved survival after diagnosis, consistent with a potential inhibitory effect of aspirin on PC progression. A randomized trial is warranted to confirm or refute these findings. We examined the potential effect of regular aspirin use on lethal prostate cancer. We found that taking aspirin was associated with a lower risk of lethal prostate cancer, and taking it after diagnosis may help to prevent prostate cancer from becoming fatal. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Lethal and Sub-lethal Effects of Four Insecticides on the Aphidophagous Coccinellid Adalia bipunctata (Coleoptera: Coccinellidae).

PubMed

Depalo, Laura; Lanzoni, Alberto; Masetti, Antonio; Pasqualini, Edison; Burgio, Giovanni

2017-12-05

Conventional insecticide assays, which measure the effects of insecticide exposure on short-term mortality, overlook important traits, including persistence of toxicity or sub-lethal effects. Therefore, such approaches are especially inadequate for prediction of the overall impact of insecticides on beneficial arthropods. In this study, the side effects of four modern insecticides (chlorantraniliprole, emamectin benzoate, spinosad, and spirotetramat) on Adalia bipunctata (L.) (Coleoptera: Coccinellidae) were evaluated under laboratory conditions by exposition on treated potted plants. In addition to investigation of acute toxicity and persistence of harmful activity in both larvae and adults of A. bipunctata, demographic parameters were evaluated, to provide a comprehensive picture of the nontarget effects of these products. Field doses of the four insecticides caused detrimental effects to A. bipunctata; but in different ways. Overall, spinosad showed the best toxicological profile among the products tested. Emamectin benzoate could be considered a low-risk insecticide, but had high persistence. Chlorantraniliprole exhibited lethal effects on early instar larvae and adults, along with a long-lasting activity, instead spirotetramat showed a low impact on larval and adult mortality and can be considered a short-lived insecticide. However, demographic analysis demonstrated that chlorantraniliprole and spirotetramat caused sub-lethal effects. Our findings highlight that sole assessment of mortality can lead to underestimation of the full impact of pesticides on nontarget insects. Demographic analysis was demonstrated to be a sensitive method for detection of the sub-lethal effects of insecticides on A. bipunctata, and this approach should be considered for evaluation of insecticide selectivity. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Utilization of ICU Data to Improve 30 and 60 Day Mortality Models

DTIC Science & Technology

2017-01-06

Acute Radiation Syndrome , Mortality, Burn Combined Injury, Lethality, Small Intestine, Ordinary Differential...short period of time (high dose rate) causes acute radiation syndrome (ARS). Depending on the radiation dose, an individual may experience the...hematopoietic acute radiation syndrome (H-ARS) or the gastrointestinal acute radiation syndrome (GI-ARS) (reviewed in Maciàă I Garau et al., 2011). For acute

Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida.

PubMed

Rico, Andreu; Sabater, Consuelo; Castillo, María-Ángeles

2016-05-01

The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure period of 2 days; and mortality, weight loss, enzymatic activities (cholinesterase, lactate dehydrogenase and alkaline phosphatase) and histopathological effects after an exposure period of 14 days. Carbendazim was found to be highly toxic to E. fetida (LC50=2mg/kg d.w.), significantly reducing earthworm weight and showing an avoidance response at soil concentrations that are close to those predicted in rice-fields and in surrounding ecosystems. The insecticide dimethoate showed a moderate acute toxicity (LC50=28mg/kg d.w.), whereas the rest of tested pesticides showed low toxicity potential (LC50 values above 100mg/kg d.w.). For these pesticides, however, weight loss was identified as a sensitive endpoint, with NOEC values approximately 2 times or lower than the calculated LC10 values. The investigated effects on the enzymatic activities of E. fetida and the observed histopathological alterations (longitudinal and circular muscle lesions, edematous tissues, endothelial degeneration and necrosis) proved to be sensitive biomarkers to monitor pesticide contamination and are proposed as alternative measures to evaluate pesticide risks on agro-ecosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute Toxicity and Efficacy of Current Medical Countermeasures against VM in Guinea Pigs: A Comparison to VX and VR

DTIC Science & Technology

2013-05-01

and diazepam with and without pretreatment with pyridostigmine bromide . The 24 hr median lethal dose (MLD) of VM was determined using a sequential... pyridostigmine bromide . The 24 hr median lethal dose (MLD) of VM was determined using a sequential stage approach. The efficacy of medical...with and without pyridostigmine bromide (PB) pretreatment against lethal intoxication with VM, VR or VX. Methods Animals: Adult male Hartley

[The alpha-fetoprotein in prognosis of survival of and functional rehabilitation of patients with ischemic stroke].

PubMed

Arkhipkin, A A; Liang, O V; Kochetov, A G

2014-10-01

The study was carried out to determine the prognostic value of alpha-fetoprotein in development of lethal outcome and degree of functional rehabilitation of patients with ischemic stroke. The sampling included 216 patients in acute period of ischemic stroke. At the first day of development of disease they were measured the level of human alpha-fetoprotein. At the second day of disease patients were evaluated the degree of functional rehabilitation and the rate of lethal outcomes was calculated. Previously, the reference interval for alpha-fetoprotein was calculated according the guidelines of the International federation of clinical chemistry and national standard. The reference interval amounted to 0.59-3.78 mE/l. The study results demonstrated that low level of alpha-fetoprotein is related to higher risk of lethal outcome (SE=1.7, p=0.012). The increasing of level of alpha-fetoprotein over mentioned threshold value statistically significant increases probability of survival of patients. The further increasing more than 2.28 mE/l is related to subsequent good functional rehabilitation according the modifies Rankine scale (SE=1.4, p=0.001) and Barthel index (SE=1.49, p<0.001).

Sensitivity of seven PCRs for early detection of koi herpesvirus in experimentally infected carp, Cyprinus carpio L., by lethal and non-lethal sampling methods.

PubMed

Monaghan, S J; Thompson, K D; Adams, A; Bergmann, S M

2015-03-01

Koi herpesvirus (KHV) causes an economically important, highly infectious disease in common carp and koi, Cyprinus carpio L. Since the occurrence of mass mortalities worldwide, highly specific and sensitive molecular diagnostic methods have been developed for KHV detection. The sensitivity and reliability of these assays have essentially focused at the detection of low viral DNA copy numbers during latent or persistent infections. However, the efficacy of these assays has not been investigated with regard to low-level viraemia during acute infection stages. This study was conducted to compare the sensitivity of seven different polymerase chain reaction (PCR) assays to detect KHV during the first hours and days post-infection (hpi; dpi), using lethal and non-lethal sampling methods. The results highlight the limitations of the assays for detecting virus during the first 4 dpi despite rapid mortality in experimentally infected carp. False-negative results were associated with time post-infection and the tissue sampled. Non-lethal sampling appears effective for KHV screening, with efficient detection in mucus samples obtained from external swabs during this early infection period (<5 dpi), while biopsies from gills and kidney were negative using the same PCR assays. Non-lethal sampling may improve the reliability of KHV detection in subclinical, acutely infected carp. © 2014 John Wiley & Sons Ltd.

Adverse Effects of Plasma Transfusion

PubMed Central

Pandey, Suchitra; Vyas, Girish N.

2012-01-01

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

Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Won, Young-Suk; Song, Ji-Won; Lim, Jong-Hwan

Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels ofmore » malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [{sup 14}C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects. - Highlights: • ob/ob mice are resistant to lethal doses of thioacetamide, compared to ob/+ mice. • ob/ob mice show reduced oxidative stress and enhanced antioxidant enzyme activity. • ob/ob mice exhibit diminished bioactivation of thioacetamide.« less

A comprehensive evaluation of CHEK2 germline mutations in men with prostate cancer.

PubMed

Wu, Yishuo; Yu, Hongjie; Zheng, S Lilly; Na, Rong; Mamawala, Mufaddal; Landis, Tricia; Wiley, Kathleen; Petkewicz, Jacqueline; Shah, Sameep; Shi, Zhuqing; Novakovic, Kristian; McGuire, Michael; Brendler, Charles B; Ding, Qiang; Helfand, Brian T; Carter, H Ballentine; Cooney, Kathleen A; Isaacs, William B; Xu, Jianfeng

2018-06-01

Germline mutations in CHEK2 have been associated with prostate cancer (PCa) risk. Our objective is to examine whether germline pathogenic CHEK2 mutations can differentiate risk of lethal from indolent PCa. A case-case study of 703 lethal PCa patients and 1455 patients with low-risk localized PCa of European, African, and Chinese origin was performed. Germline DNA samples from these patients were sequenced for CHEK2. Mutation carrier rates and their association with lethal PCa were analyzed using the Fisher exact test and Kaplan-Meier survival analysis. In the entire study population, 40 (1.85%) patients were identified as carrying one of 15 different germline CHEK2 pathogenic or likely pathogenic mutations. CHEK2 mutations were detected in 16 (2.28%) of 703 lethal PCa patients compared with 24 (1.65%) of 1455 low-risk PCa patients (P = 0.31). No association was found between CHEK2 mutation status and early-diagnosis or PCa-specific survival time. However, the most common mutation in CHEK2, c.1100delC (p.T367 fs), had a significantly higher carrier rate (1.28%) in lethal PCa patients than low-risk PCa patients of European American origin (0.16%), P = 0.0038. The estimated Odds Ratio of this mutation for lethal PCa was 7.86. The carrier rate in lethal PCa was also significantly higher than that (0.46%) in 32 461 non-Finnish European subjects from the Exome Aggregation Consortium (ExAC) (P = 0.01). While overall CHEK2 mutations were not significantly more common in men with lethal compared to low-risk PCa, the specific CHEK2 mutation, c.1100delC, appears to contribute to an increased risk of lethal PCa in European American men. © 2018 Wiley Periodicals, Inc.

Utilization of ICU Data to Improve 30 and 60 Day HENRE Mortality Models, Revision 1

DTIC Science & Technology

2017-05-12

Acute Radiation Syndrome , Mortality, Burn Combined Injury, Lethality, Small Intestine, Ordinary...a large dose of radiation in a short period of time (high dose rate) causes acute radiation syndrome (ARS). Depending on the radiation dose, an...individual may experience the hematopoietic acute radiation syndrome (H-ARS) or the gastrointestinal acute radiation syndrome (GI-ARS) (reviewed in

Cytotoxicity assays with fish cells as an alternative to the acute lethality test with fish.

PubMed

Segner, Helmut

2004-10-01

In ecotoxicology, in vitro assays with fish cells are currently applied for mechanistic studies, bioanalytical purposes and toxicity screening. This paper discusses the potential of cytotoxicity assays with fish cells to reduce, refine or replace acute lethality tests using fish. Basal cytotoxicity data obtained with fish cell lines or fish primary cell cultures show a reasonable to good correlation with lethality data from acute toxicity tests, with the exception of compounds that exert a specific mode of toxic action. Basal cytotoxicity data from fish cell lines also correlate well with cytotoxicity data from mammalian cell lines. However, both the piscine and mammalian in vitro assays are clearly less sensitive than the fish test. Therefore, in vivo LC50 values (concentrations of the test compounds that are lethal to 50% of the fish in the experiment within 96 hours) currently cannot be predicted from in vitro values. This in vitro-in vivo difference in sensitivity appears to be true for both fish cell lines and mammalian cell lines. Given the good in vitro-in vivo correlation in toxicity ranking, together with the clear-cut difference in sensitivity, the role of cytotoxicity assays in a tiered alternative testing strategy could be in priority setting in relation to toxic hazard and in the toxicity classification of chemicals and environmental samples.

The use of Ampelisca abdita growth rate as an indicator of sediment quality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weston, D.P.; Thompson, B.

1995-12-31

Acute lethal bioassays with amphipod crustaceans are routinely used to assess toxicity of bulk sediments. A study within the San Francisco Bay Regional Monitoring Program (RMP) is in progress to develop a chronic bioassay with the amphipod Ampelisca abdita, measuring both survivorship and growth rates. This approach is attractive because depression of growth rate is likely to be a more sensitive indicator of toxic effects than acute lethality, and natural populations of A. abdita exist throughout the Bay. Spiked sediment bioassays, using cadmium and crude oil, were used to demonstrate the relative sensitivity of the standard 10-day lethal test vs.more » the 30-day growth test. Sediments were also collected from 9 sites throughout the Bay, ranging from areas adjacent to municipal wastewater discharges to areas distant from known point source inputs. These samples were then split, and used for side-by-side comparison of acute (lethal) and chronic (growth) toxicity tests. Survivorship exceeded 90% in all tests, including those sediments collected nearest the wastewater outfalls. Growth rates were contrasted among the various treatments to examine the utility of this end point in discriminating the outfall sites. Data on the spatial distribution, abundance, and size-frequency distribution of native populations was examined within the context of using growth rate as an indicator of toxic effects in natural populations as well.« less

PREDICTING CHRONIC LETHALITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA: THEORY OF ACCELERATED LIFE TESTING

EPA Science Inventory

A method for modeling aquatic toxicity date based on the theory of accelerated life testing and a procedure for maximum likelihood fitting the proposed model is presented. he procedure is computerized as software, which can predict chronic lethality of chemicals using data from a...

The Acute Risks of Exercise in Apparently Healthy Adults and Relevance for Prevention of Cardiovascular Events.

PubMed

Goodman, Jack M; Burr, Jamie F; Banks, Laura; Thomas, Scott G

2016-04-01

Increased physical activity (PA) is associated with improved quality of life and reductions in cardiovascular (CV) morbidity and all-cause mortality in the general population in a dose-response manner. However, PA acutely increases the risk of adverse CV event or sudden cardiac death (SCD) above levels expected at rest. We review the likelihood of adverse CV events related to exercise in apparently healthy adults and strategies for prevention, and contextualize our understanding of the long-term risk reduction conferred from PA. A systematic review of the literature was performed using electronic databases; additional hand-picked relevant articles from reference lists and additional sources were included after the search. The incidence of adverse CV events in adults is extremely low during and immediately after PA of varying types and intensities and is significantly lower in those with long-standing PA experience. The risk of SCD and nonfatal events during and immediately after PA remains extremely low (well below 0.01 per 10,000 participant hours); increasing age and PA intensity are associated with greater risk. In most cases of exercise-related SCD, occult CV disease is present and SCD is typically the first clinical event. Exercise acutely increases the risk of adverse CV events, with greater risk associated with vigorous intensity. The risks of an adverse CV event during and immediately after exercise are outweighed by the health benefits of vigorous exercise performed regularly. A key challenge remains the identification of occult structural heart disease and inheritable conditions that increase the chances of lethal arrhythmias during exercise. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any association? A literature review

PubMed Central

Oliveira, Natalia Mejias; Ferreira, Felipe Augusto Yamauti; Yonamine, Raquel Yumi; Chehter, Ethel Zimberg

2014-01-01

ABSTRACT In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug-induced pancreatitis should always be considered in the diagnosis of patients with abdominal pain and elevated pancreatic enzymes. PMID:24728257

An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia

PubMed Central

Periasamy, Sivakumar; Avram, Dorina; McCabe, Amanda; MacNamara, Katherine C.; Sellati, Timothy J.; Harton, Jonathan A.

2016-01-01

Inhalation of Francisella tularensis (Ft) causes acute and fatal pneumonia. The lung cytokine milieu favors exponential Ft replication, but the mechanisms underlying acute pathogenesis and death remain unknown. Evaluation of the sequential and systemic host immune response in pulmonary tularemia reveals that in contrast to overwhelming bacterial burden or cytokine production, an overt innate cellular response to Ft drives tissue pathology and host mortality. Lethal infection with Ft elicits medullary and extra-medullary myelopoiesis supporting recruitment of large numbers of immature myeloid cells and MDSC to the lungs. These cells fail to mature and die, leading to subsequent necrotic lung damage, loss of pulmonary function, and host death that is partially dependent upon immature Ly6G+ cells. Acceleration of this process may account for the rapid lethality seen with Ft SchuS4. In contrast, during sub-lethal infection with Ft LVS the pulmonary cellular response is characterized by a predominance of mature neutrophils and monocytes required for protection, suggesting a required threshold for lethal bacterial infection. Further, eliciting a mature phagocyte response provides transient, but dramatic, innate protection against Ft SchuS4. This study reveals that the nature of the myeloid cell response may be the primary determinant of host mortality versus survival following Francisella infection. PMID:27015566

Toxicity of hexahydro-1,3,5-trinitro-1,3,5-triazine to larval zebrafish (Danio rerio)

USGS Publications Warehouse

Mukhi, S.; Pan, X.; Cobb, G.P.; Patino, R.

2005-01-01

Hexahydro-1,3,5-trinitro-1,3,5-triazine, a cyclonitramine commonly known as RDX, is used in the production of military munitions. Contamination of soil, sediment, and ground and surface waters with RDX has been reported in different places around the world. Acute and subacute toxicities of RDX have been relatively well documented in terrestrial vertebrates, but among aquatic vertebrates the information available is limited. The objective of this study was to characterize the acute toxicity of RDX to larval zebrafish. Mortality (LC50) and incidence of vertebral column deformities (EC50) were two of the end points measured in this study. The 96-h LC50 was estimated at 22.98 and 25.64 mg l-1 in two different tests. The estimated no-observed-effective- concentration (NOEC) values of RDX on lethality were 13.27 ?? 0.05 and 15.32 ?? 0.30 mg l-1; and the lowest-observed-effective- concentration (LOEC) values were 16.52 ?? 0.05 and 19.09 ?? 0.23 mg l-1 in these two tests, respectively. The 96-h EC50 for vertebral deformities on survivors from one of the acute lethality tests was estimated at 20.84 mg l-1, with NOEC and LOEC of 9.75 ?? 0.34 and 12.84 ?? 0.34 mg l-1, respectively. Behavioral aberrations were also noted in this acute toxicity study, including the occurrence of whirling movement and lethargic behavior. The acute effects of RDX on survival, incidence of deformities, and behavior of larval zebrafish occurred at the high end of the most frequently reported concentrations of RDX in aquatic environments. The chronic effects of RDX in aquatic vertebrates need to be determined for an adequate assessment of the ecological risk of environmental RDX. ?? 2005 Elsevier Ltd. All rights reserved.

Phytochemistry, Brine shrimp lethality and mice acute oral toxicity studies on seed extracts of Vernonia anthelmintica.

PubMed

Jamil, Subia; Khan, Rafeeq Alam; Afroz, Syeda; Ahmed, Shadab

2016-11-01

Despite the widespread use of Vernonia anthelmintica seeds in traditional medicine, the need to establish the safety of the Vernonia anthelmintica is required to ascertain the safe use of this herbal medicine. The aim of the present study is to establish the acute toxicity profile of different extracts of Vernonia anthelmintica. Hexane and ethanol extract of Vernonia Anthelmintica has been studied for its brine shrimp lethality potential. Water decoction (WDVA), Hexane (HEVA) and Ethanol (EEVA) extracts of Vernonia anthelmintica has also been evaluated for their in-vivo acute oral toxicity in mice by Lorke's method. Phytochemistry of all three extracts was also evaluated for the presence of their secondary metabolites. All three extracts showed the presence of flavonoids and terpenoids, while alkaloids, tannins and fixed oils were present in HEVA and EEVA. Furthermore EEVA also showed presence of carbohydrates and HEVA also showed the presence of cardiac glycosides. Ethanol and hexane extracts of Vernonia anthelmintica showed a positive cytotoxicity in brine shrimp lethality test at 24 hours with LC50 104.16 (224.0-48.05)μg/ml and 216.11μg/ml (378.2-128.7) respectively as compared to standard drug etoposide LC50 7.46μg/ml. The oral LD50 for EEVA, HEVA and WDVA in mice by Lorke's method was greater than 5000mg/kg. The result of brine shrimp lethality test clearly exhibited the presence of bioactive compounds with cytotoxic potential; however seems to be safe for oral use since LD50 was higher than 5000mg/kg and thus safety of acute dosing in vivo practices is justified.

Exposure-dependent variation in cryolite induced lethality in the non-target insect, Drosophila melanogaster

PubMed Central

Podder, Sayanti

2014-01-01

The starting point of toxicity testing of any chemical in an organism is the determination of its Lethal Concentration 50 (LC50). In the present study, LC50 of a fluorinated insecticide cryolite is determined in a non-target insect model, Drosophila melanogaster. Interestingly, the result shows that acute LC50 of cryolite was much greater in comparison to the chronic one in case of Drosophila larvae. Larvae which were exposed to 65,000 to 70,000 µg/ml cryolite through food showed 50% mortality after 18 hours of acute exposure, whereas only 150 to 160 µg/ml cryolite was sufficient to cause 50% mortality in case of chronic exposure. Thus cryolite in a small amount when applied once cannot produce noticeable changes in Drosophila, whereas the same amount when used continuously can be fatal. The non-feeding pupal stage was also seen to be affected by chemical treatment. This suggests that the test chemical affects the developmental fate and results in failure of adult emergence. Absence of chemical-induced mortality in adults assumes that the toxicity of cryolite might be restricted to the preimaginal stages of the organism. Reduction in body size of larvae after ingestion of cryolite (with food) in acute treatment schedule is another interesting finding of this study. Some individuals consuming cryolite containing food cannot survive whereas the few survivors manifest a significant growth retardation which might be due to a tendency of refusal in feeding. Hence the present findings provide a scope of assessment of risk of other similar non-target groups. PMID:26038671

Epinephrine: The Drug of Choice for Anaphylaxis--A Statement of the World Allergy Organization

PubMed Central

2008-01-01

Anaphylaxis is an acute and potentially lethal multisystem allergic reaction. Most consensus guidelines for the past 30 years have held that epinephrine is the drug of choice and the first drug that should be administered in acute anaphylaxis. Some state that properly administered epinephrine has no absolute contraindication in this clinical setting. A committee of anaphylaxis experts assembled by the World Allergy Organization has examined the evidence from the medical literature concerning the appropriate use of epinephrine for anaphylaxis. The committee strongly believes that epinephrine is currently underused and often dosed suboptimally to treat anaphylaxis, is underprescribed for potential future self-administration, that most of the reasons proposed to withhold its clinical use are flawed, and that the therapeutic benefits of epinephrine exceed the risk when given in appropriate intramuscular doses. PMID:23282530

Acute Toxicity of Ochratoxins A and B in Chicks 1

PubMed Central

Peckham, John C.; Doupnik, Ben; Jones, Oscar H.

1971-01-01

Ochratoxins A and B were given to 1-day-old Babcock B-300 cockerels to evaluate acute toxic effects. Two trials with ochratoxin A gave 7-day oral median lethal dose estimates of 116 μg (3.3 mg/kg) and 135 μg (3.9 mg/kg) per chick. Chicks given daily oral doses of 100 μg of ochratoxin A died on the second day. Single subcutaneous doses of 400 μg of ochratoxin A were also lethal. The 7-day oral median lethal dose of B was estimated at 1,890 μg (54 mg/kg) per chick. Chicks given oral doses of 100 μg of ochratoxin B daily for 10 days survived. Sublethal doses of both ochratoxins A and B resulted in growth suppression which was proportional to the amount of ochratoxin given. Visceral gout was the principal gross finding. Microscopic examinations revealed acute nephrosis, hepatic degeneration or focal necrosis, and enteritis. Suppression of hematopoiesis in the bone marrow and depletion of lymphoid elements from the spleen and bursa of Fabricius were frequently seen. Both ochratoxins appeared to have similar pathological effects. This is the first report on the toxicity of ochratoxin B. PMID:4928604

Acute and chronic bioassays with New Zealand freshwater copepods using pentachlorophenol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willis, K.J.

The suitability for laboratory culture and comparative sensitivity of three species of New Zealand freshwater copepod (Calamoecia lucasi Brady, Boeckella delicata Percival, and Mesocyclops cf. leuckarti Claus) to pentachlorophenol (PCP) was assessed. Acute bioassays used two life stages (nauplii and adults). Acute 48-h lethality tests were conducted at 22 C with laboratory-cultured animals of all species and at varying temperatures with seasonally collected C. lucasi adults. Mean 48-h median lethal concentration values for nauplii ranged from 52 to 227 {micro}g/L PCP for C. lucasi and B. delicata, respectively, and from 106 to 173 {micro}g/L for adult C. Lucasi and M.more » Leuckarti, respectively. The survival rate in controls was {ge}95% in acute tests, with the exception of C. lucasi nauplii, in which it was 60%. Mean 48-h median lethal concentration values for seasonally collected C. lucasi adults were significantly higher in summer than in all other seasons. Chronic sublethal tests starting with nauplii <24 h old measured time to metamorphosis. Pentachlorophenol delayed metamorphosis in all species. Chronic toxicity values were 14.61, and 104 {micro}g/L PCP for C. lucasi, B. delicata, and M. leuckarti, respectively. The mortality rate in controls was also high in C. lucasi sublethal tests (65%), and of the three species, they were the most difficult to culture.« less

Toxicological Evaluation of Essential Oil From the Leaves of Croton argyrophyllus (Euphorbiaceae) on Aedes aegypti (Diptera: Culicidae) and Mus musculus (Rodentia: Muridae).

PubMed

Cruz, R C D; Silva, S L C E; Souza, I A; Gualberto, S A; Carvalho, K S; Santos, F R; Carvalho, M G

2017-07-01

Plant-derived essential oils can be used as insecticides for vector control. However, to establish their safety, it is necessary to perform toxicological studies. Herein, we evaluated the chemical composition and insecticidal activity of the essential oil from the leaves of Croton argyrophyllus on the third- and fourth-instar larvae and adult Aedes aegypti (L., 1762). We also evaluated the acute toxicity of the essential oil in adult female Mus musculus. The lethal concentration 50 (LC50) and 90 (LC90) of C. argyrophyllus essential oil on larvae of Ae. aegypti were 0.31 and 0.70 mg ml-1, respectively, and 5.92 and 8.94 mg ml-1, respectively, on Ae. aegypti adults. The major components of the essential oil were spathulenol (22.80%), (E)-caryophyllene (15.41%), α-pinene (14.07%), and bicyclogermacrene (10.43%). It also displayed acute toxicity in adults of Mus musculus; the intraperitoneal and oral lethal dose 50 (LD50) were 2,000 mg kg-1 and 2,500 mg kg-1, respectively. The results showed that the essential oil from C. argyrophyllus leaves has insecticidal activity on Ae. aegypti larvae and adults at an average lethal concentration below the median lethal dose needed to cause acute toxicity in the common mouse. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Acute Toxicity and Ecological Risk Assessment of Benzophenone and N,N-Diethyl-3 Methylbenzamide in Personal Care Products.

PubMed

Sun, Hong-Qin; Du, Yang; Zhang, Zi-Yang; Jiang, Wen-Jing; Guo, Yan-Min; Lu, Xi-Wu; Zhang, Yi-Min; Sun, Li-Wei

2016-09-19

Benzophenone (BP) and N,N -diethyl-3-methylbenzamide (DEET) are two chemicals often used in personal care products (PCPs). There is a lack of systematic ecotoxicological evaluations about the two chemicals to aquatic organisms. In the present study, the acute toxic effects on Chlorella vulgaris , Daphnia Magana , and Brachydanio rerio were tested and the ecotoxicological risks were evaluated. For BP, the 96-h half-maximal effective concentration (EC 50 ) on C. vulgaris was 6.86 mg/L; the 24-h median lethal concentration (LC 50 ) on D. magana was 7.63 mg/L; the 96-h LC 50 on B. rerio was 14.73 mg/L. For DEET, those were 270.72 mg/L, 40.74 mg/L, and 109.67 mg/L, respectively. The mixture toxicity of BP and DEET, on C. vulgaris , D. magana , and B. rerio all showed an additive effect. The induced predicted no-effect concentrations (PNECs) for BP and DEET by assessment factor (AF) method are 0.003 mg/L and 0.407 mg/L, respectively. Both are lower than the concentrations detected from environment at present, verifying that BP and DEET are low-risk chemicals to the environment.

Acute Toxicity and Ecological Risk Assessment of Benzophenone and N,N-Diethyl-3 Methylbenzamide in Personal Care Products

PubMed Central

Sun, Hong-Qin; Du, Yang; Zhang, Zi-Yang; Jiang, Wen-Jing; Guo, Yan-Min; Lu, Xi-Wu; Zhang, Yi-Min; Sun, Li-Wei

2016-01-01

Benzophenone (BP) and N,N-diethyl-3-methylbenzamide (DEET) are two chemicals often used in personal care products (PCPs). There is a lack of systematic ecotoxicological evaluations about the two chemicals to aquatic organisms. In the present study, the acute toxic effects on Chlorella vulgaris, Daphnia Magana, and Brachydanio rerio were tested and the ecotoxicological risks were evaluated. For BP, the 96-h half-maximal effective concentration (EC50) on C. vulgaris was 6.86 mg/L; the 24-h median lethal concentration (LC50) on D. magana was 7.63 mg/L; the 96-h LC50 on B. rerio was 14.73 mg/L. For DEET, those were 270.72 mg/L, 40.74 mg/L, and 109.67 mg/L, respectively. The mixture toxicity of BP and DEET, on C. vulgaris, D. magana, and B. rerio all showed an additive effect. The induced predicted no-effect concentrations (PNECs) for BP and DEET by assessment factor (AF) method are 0.003 mg/L and 0.407 mg/L, respectively. Both are lower than the concentrations detected from environment at present, verifying that BP and DEET are low-risk chemicals to the environment. PMID:27657095

Central nervous system damage due to acute paraquat poisoning: an experimental study with rat model.

PubMed

Wu, Bailin; Song, Bo; Yang, Haiqing; Huang, Boyuan; Chi, Bo; Guo, Yansu; Liu, Huaijun

2013-03-01

Paraquat (PQ) is a common herbicide and PQ poisoning is a major medical problem in Asia. However, few studies have focused on the acute neurotoxic changes caused by PQ. Here we report the acute neurotoxicological findings of rats treated with lethal dose of PQ. In substantia nigra (SN) and striatum we found obvious microglia (labeled by Iba-1) activation within one week. In SN and hippocampus, we detected increased oxidative stress in the neurons based on NeuN/8-OHdG immunofluorescence double labeling and laser cofocal microscopy. Moreover, we provided ultrastructural evidences of astrocyte edema and neurons apoptosis in rat brain by electron microscopy. Further studies will be needed with non-lethal dose of PQ to confirm these results and demonstrate the direct CNS toxicity of PQ. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparative acute toxicity of gallium(III), antimony(III), indium(III), cadmium(II), and copper(II) on freshwater swamp shrimp (Macrobrachium nipponense).

PubMed

Yang, Jen-Lee

2014-04-01

Acute toxicity testing were carried out the freshwater swamp shrimp, Macrobrachium nipponense, as the model animal for the semiconductor applied metals (gallium, antimony, indium, cadmium, and copper) to evaluate if the species is an suitable experimental animal of pollution in aquatic ecosystem. The static renewal test method of acute lethal concentrations determination was used, and water temperature was maintained at 24.0 ± 0.5°C. Data of individual metal obtained from acute toxicity tests were determined using probit analysis method. The median lethal concentration (96-h LC50) of gallium, antimony, indium, cadmium, and copper for M. nipponense were estimated as 2.7742, 1.9626, 6.8938, 0.0539, and 0.0313 mg/L, respectively. Comparing the toxicity tolerance of M. nipponense with other species which exposed to these metals, it is obviously that the M. nipponense is more sensitive than that of various other aquatic animals.

Temperature-dependent acute toxicity of methomyl pesticide on larvae of 3 Asian amphibian species.

PubMed

Lau, Edward Tak Chuen; Karraker, Nancy Elizabeth; Leung, Kenneth Mei Yee

2015-10-01

Relative to other animal taxa, ecotoxicological studies on amphibians are scarce, even though amphibians are experiencing global declines and pollution has been identified as an important threat. Agricultural lands provide important habitats for many amphibians, but often these lands are contaminated with pesticides. The authors determined the acute toxicity, in terms of 96-h median lethal concentrations, of the carbamate pesticide methomyl on larvae of 3 Asian amphibian species, the Asian common toad (Duttaphrynus melanostictus), the brown tree frog (Polypedates megacephalus), and the marbled pygmy frog (Microhyla pulchra), at 5 different temperatures (15 °C, 20 °C, 25 °C, 30 °C, and 35 °C) to examine the relationships between temperature and toxicity. Significant interspecific variation in methomyl sensitivity and 2 distinct patterns of temperature-dependent toxicity were found. Because high proportions of malformation among the surviving tadpoles were observed, a further test was carried out on the tree frog to determine effect concentrations using malformation as the endpoint. Concentrations as low as 1.4% of the corresponding 96-h median lethal concentrations at 25 °C were sufficient to cause malformation in 50% of the test population. As the toxicity of pesticides may be significantly amplified at higher temperatures, temperature effects should not be overlooked in ecotoxicological studies and derivation of safety limits in environmental risk assessment and management. © 2015 SETAC.

Factors Associated with Increased Risk for Lethal Violence in Intimate Partner Relationships among Ethnically Diverse Black Women

PubMed Central

Sabri, Bushra; Stockman, Jamila K.; Campbell, Jacquelyn C.; O’Brien, Sharon; Campbell, Doris; Callwood, Gloria B.; Bertrand, Desiree; Sutton, Lorna W.; Hart-Hyndman, Greta

2014-01-01

The purpose of this study was to identify factors associated with increased risk for lethal violence among ethnically diverse Black women in Baltimore, Maryland (MD) and the US Virgin Islands (USVI). Women with abuse experiences (n=456) were recruited from primary care, prenatal or family planning clinics in Baltimore, MD and St. Thomas and St. Croix, USVI. Logistic regression was used to examine factors associated with the risk for lethal violence among abused women. Factors independently related to increased risk of lethal violence included fear of abusive partners, PTSD symptoms, and use of legal resources. These factors must be considered in assessing safety needs of Black women in abusive relationships. PMID:25429191

Risk factor profile for sudden cardiac death during mountain hiking.

PubMed

Burtscher, M; Pachinger, O; Schocke, M F H; Ulmer, H

2007-07-01

Mountain hiking is associated with a death rate of about 4 deaths per 100,000 hikers annually. About 50 % of all fatalities during mountain hiking are sudden cardiac deaths (SCDs). But there are only few data available regarding risk factors and triggers associated with SCD during mountain hiking. Thus, a case-control analysis between persons who died suddenly during mountain hiking and randomly selected controls was carried out. Risk factor profiles of 179 males over the age of 34 who suffered SCD during mountain hiking were compared to those of 537 matched controls. Hikers who died suddenly during mountain hiking were much more likely to have had a prior MI (17% vs. 0.9%; p < 0.001), known coronary artery disease (CAD) without prior MI (17 % vs. 4%; p < 0.001), diabetes (6% vs. 1 %; p < 0.001), hypercholesterolemia (54 % vs. 20%; p < 0.001), and were less engaged in regular mountain sports activities (31% vs. 58%; p < 0.001) compared to hikers from the control group. Based on the reported relationship between traditional risk factors and coronary plaque morphology, acute plaque rupture with thrombus formation and subsequent lethal arrhythmias may be assumed to be a dominant mechanism precipitating SCD during hiking. In contrast, in skiers especially non-occlusive plaques may precipitate ischemia leading to an imbalance between oxygen demand and supply and subsequent lethal arrhythmias. As preventive measures recommended to hikers at risk, adaptation to regular mountain sports activities by an adequate training program and pharmacological interventions, e.g. lipid lowering drugs, aspirin, and beta-blockers, should be considered.

Synergistic effect of piperonyl butoxide on acute toxicity of pyrethrins to Hyalella azteca.

PubMed

Giddings, Jeffrey; Gagne, James; Sharp, Janice

2016-08-01

A series of acute toxicity tests with the amphipod Hyalella azteca was performed to quantify the synergistic effect of piperonyl butoxide (PBO) on pyrethrin toxicity. Concentrations of PBO <4 µg/L caused no toxicity enhancement, whereas toxicity increased with PBO concentrations between 4 µg/L and 15 µg/L. Additive toxicity calculations showed that true synergism accounted for an increase in pyrethrin toxicity (decrease in median lethal concentration) of 1.4-fold to 1.6-fold and varied only slightly between 4 µg/L and 15 µg/L PBO, whereas direct toxicity of PBO accounted for an additional increase in mixture toxicity (up to 3.2-fold) that was proportional to PBO concentration. The results can be used to assess the risk of measured or predicted co-occurring concentrations of PBO and pyrethrins in surface waters. Environ Toxicol Chem 2016;35:2111-2116. © 2016 SETAC. © 2016 SETAC.

Toxicity study of Vernonia cinerea.

PubMed

Latha, L Yoga; Darah, I; Jain, K; Sasidharan, S

2010-01-01

The methanol extract of Vernonia cinerea Less (Asteraceae), which exhibited antimicrobial activity, was tested for toxicity. In an acute toxicity study using mice, the median lethal dose (LD(50)) of the extract was greater than 2000 mg/kg, and we found no pathological changes in macroscopic examination by necropsy of mice treated with extract. As well as the oral acute toxicity study, the brine shrimp lethality test was also done. Brine shrimp test LC(50) values were 3.87 mg/mL (6 h) and 2.72 mg/mL (24 h), exhibiting no significant toxicity result. In conclusion, the methanol extract of V. cinerea did not produce toxic effects in mice and brine shrimp.

Acute Lethality after Fast-Neutron and X-Irradiation of Tribolium confusum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glenn, Norman D.; Ducoff, Howard S.

1976-01-01

The acute lethal effects of fast neutrons and of X-rays on adults and larvae of T. confusum are compared. The time course of mortality of adults of the Oklahoma strain was the same after midlethal doses of neutrons and X-rays, although the neutrons were about twice as effective as X-rays in producing lethality, based on LD 50(35). The neutron RBE for adults of the Ebony mutant strain was also about 2, but that for Oklahoma larvae was about 3.85. Larvae surviving midlethal doses of neutrons showed a tendency toward wing abnormalities and delayed pupation. Dose-fractionation recovery with neutron doses inmore » the midlethal range was not detectable in the adults or in the larvae. A considerable sparing effect of dose fractionation was found in X-irradiated adults. Finally, also presented are techniques for using a beam port of a Triga research reactor for fast-neutron irradiation and a method of neutron and gamma dosimetry.« less

Evaluation of an acute oral gavage method for assessment of pesticide toxicity in terrestrial amphibians.

PubMed

Fort, Douglas J; Mathis, Michael B; Kee, Faith; Whatling, Paul; Clerkin, David; Staveley, Jane; Habig, Clifford

2018-02-01

Development of an acute oral toxicity test with a terrestrial-phase amphibian was considered necessary to remove the uncertainty within the field of agrochemical risk assessments. The bullfrog (Lithobates catesbeianus) was selected for use as it is a representative of the family Ranidae and historically this species has been used as an amphibian test model species. Prior to definitive study, oral gavage methods were developed with fenthion and tetraethyl pyrophosphate. Dimethoate and malathion were subsequently tested with both male and female juvenile bullfrogs in comprehensive acute oral median lethal dose (LD50) studies. Juvenile bullfrogs were administered a single dose of the test article via oral gavage of a single gelatin capsule of dimethoate technical (dimethoate) or neat liquid Fyfanon ® Technical (synonym malathion), returned to their respective aquaria, and monitored for survival for 14 d. The primary endpoint was mortality, whereas behavioral responses, food consumption, body weight, and snout-vent length (SVL) were used to evaluate indications of sublethal toxicity (secondary endpoints). Acute oral LD50 values (95% fiducial interval) for dimethoate were 1459 (1176-1810, males) and 1528 (1275-1831, females), and for malathion they were 1829 (1480-2259, males) and 1672 (1280-2183, females) mg active substance/kg body weight, respectively. Based on the results of these studies, the methodology for the acute oral gavage administration of test items to terrestrial-phase amphibians was demonstrated as being a practical method of providing data for risk assessments. Environ Toxicol Chem 2018;37:436-450. © 2017 SETAC. © 2017 SETAC.

Habitat availability is a more plausible explanation than insecticide acute toxicity for U.S. grassland bird species declines

USGS Publications Warehouse

Hill, Jason M.; Egan, J. Franklin; Stauffer, Glenn E.; Diefenbach, Duane R.

2014-01-01

Grassland bird species have experienced substantial declines in North America. These declines have been largely attributed to habitat loss and degradation, especially from agricultural practices and intensification (the habitat-availability hypothesis). A recent analysis of North American Breeding Bird Survey (BBS) “grassland breeding” bird trends reported the surprising conclusion that insecticide acute toxicity was a better correlate of grassland bird declines in North America from 1980–2003 (the insecticide-acute-toxicity hypothesis) than was habitat loss through agricultural intensification. In this paper we reached the opposite conclusion. We used an alternative statistical approach with additional habitat covariates to analyze the same grassland bird trends over the same time frame. Grassland bird trends were positively associated with increases in area of Conservation Reserve Program (CRP) lands and cropland used as pasture, whereas the effect of insecticide acute toxicity on bird trends was uncertain. Our models suggested that acute insecticide risk potentially has a detrimental effect on grassland bird trends, but models representing the habitat-availability hypothesis were 1.3–21.0 times better supported than models representing the insecticide-acute-toxicity hypothesis. Based on point estimates of effect sizes, CRP area and agricultural intensification had approximately 3.6 and 1.6 times more effect on grassland bird trends than lethal insecticide risk, respectively. Our findings suggest that preserving remaining grasslands is crucial to conserving grassland bird populations. The amount of grassland that has been lost in North America since 1980 is well documented, continuing, and staggering whereas insecticide use greatly declined prior to the 1990s. Grassland birds will likely benefit from the de-intensification of agricultural practices and the interspersion of pastures, Conservation Reserve Program lands, rangelands and other grassland habitats into existing agricultural landscapes.

Habitat availability is a more plausible explanation than insecticide acute toxicity for U.S. grassland bird species declines.

PubMed

Hill, Jason M; Egan, J Franklin; Stauffer, Glenn E; Diefenbach, Duane R

2014-01-01

Grassland bird species have experienced substantial declines in North America. These declines have been largely attributed to habitat loss and degradation, especially from agricultural practices and intensification (the habitat-availability hypothesis). A recent analysis of North American Breeding Bird Survey (BBS) "grassland breeding" bird trends reported the surprising conclusion that insecticide acute toxicity was a better correlate of grassland bird declines in North America from 1980-2003 (the insecticide-acute-toxicity hypothesis) than was habitat loss through agricultural intensification. In this paper we reached the opposite conclusion. We used an alternative statistical approach with additional habitat covariates to analyze the same grassland bird trends over the same time frame. Grassland bird trends were positively associated with increases in area of Conservation Reserve Program (CRP) lands and cropland used as pasture, whereas the effect of insecticide acute toxicity on bird trends was uncertain. Our models suggested that acute insecticide risk potentially has a detrimental effect on grassland bird trends, but models representing the habitat-availability hypothesis were 1.3-21.0 times better supported than models representing the insecticide-acute-toxicity hypothesis. Based on point estimates of effect sizes, CRP area and agricultural intensification had approximately 3.6 and 1.6 times more effect on grassland bird trends than lethal insecticide risk, respectively. Our findings suggest that preserving remaining grasslands is crucial to conserving grassland bird populations. The amount of grassland that has been lost in North America since 1980 is well documented, continuing, and staggering whereas insecticide use greatly declined prior to the 1990s. Grassland birds will likely benefit from the de-intensification of agricultural practices and the interspersion of pastures, Conservation Reserve Program lands, rangelands and other grassland habitats into existing agricultural landscapes.

Habitat Availability Is a More Plausible Explanation than Insecticide Acute Toxicity for U.S. Grassland Bird Species Declines

PubMed Central

Hill, Jason M.; Egan, J. Franklin; Stauffer, Glenn E.; Diefenbach, Duane R.

2014-01-01

Grassland bird species have experienced substantial declines in North America. These declines have been largely attributed to habitat loss and degradation, especially from agricultural practices and intensification (the habitat-availability hypothesis). A recent analysis of North American Breeding Bird Survey (BBS) “grassland breeding” bird trends reported the surprising conclusion that insecticide acute toxicity was a better correlate of grassland bird declines in North America from 1980–2003 (the insecticide-acute-toxicity hypothesis) than was habitat loss through agricultural intensification. In this paper we reached the opposite conclusion. We used an alternative statistical approach with additional habitat covariates to analyze the same grassland bird trends over the same time frame. Grassland bird trends were positively associated with increases in area of Conservation Reserve Program (CRP) lands and cropland used as pasture, whereas the effect of insecticide acute toxicity on bird trends was uncertain. Our models suggested that acute insecticide risk potentially has a detrimental effect on grassland bird trends, but models representing the habitat-availability hypothesis were 1.3–21.0 times better supported than models representing the insecticide-acute-toxicity hypothesis. Based on point estimates of effect sizes, CRP area and agricultural intensification had approximately 3.6 and 1.6 times more effect on grassland bird trends than lethal insecticide risk, respectively. Our findings suggest that preserving remaining grasslands is crucial to conserving grassland bird populations. The amount of grassland that has been lost in North America since 1980 is well documented, continuing, and staggering whereas insecticide use greatly declined prior to the 1990s. Grassland birds will likely benefit from the de-intensification of agricultural practices and the interspersion of pastures, Conservation Reserve Program lands, rangelands and other grassland habitats into existing agricultural landscapes. PMID:24846309

PREDICTING CHRONIC TOXICITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA: CONCEPT AND LINEAR REGRESSION

EPA Science Inventory

A comprehensive approach to predicting chronic toxicity from acute.toxicity data was developed in which simultaneous consideration is given to concentration, degree of response, and time course of effect. onsistent endpoint (lethality) and degree of response (O%) were used to com...

Development of Chronic and Acute Golden Syrian Hamster Infection Models with Leptospira borgpetersenii serovar Hardjo

USDA-ARS?s Scientific Manuscript database

The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several species of Leptospira. Onset of an acute, lethal infection following infection with several pathogenic Leptospira species has been widely adopted for vaccine testing. An important exceptio...

Sudden cardiac death: the pro-arrhythmic interaction of an acute loading with an underlying substrate.

PubMed

Sutherland, George R

2017-10-21

Sudden cardiac death (SCD) is a complex phenomenon, occurring either in apparently normal individuals or in those where there is a recognized underlying cardiac abnormality. In both groups, the lethal arrhythmia has frequently been related to the physiologic trigger of either exercise or stress. Prior research into SCD has focused mainly on a combination of identifying either vulnerable myocardial substrates; pharmacological approaches to altering electrical activation/repolarisation in substrates; or the suppression of induced lethal arrhythmias with implantable defibrillators. However, it has been suggested that in a significant number of cases, the interaction of a transient induced trigger with a pre-existing electrical or mechanical substrate is the basis for the induction of the sustained lethal arrhythmia. In this manuscript we will discuss the precise mechanisms whereby one of such potential physiologic trigger: an acute change in systolic blood pressure, can induce a sequence of alterations in global and local cardiac mechanics which in turn result in regional left ventricular post-systolic deformation which, mediated (through stretch-induced changes in local mechano-electrical coupling) provokes local electrical after-depolarisations which can spill over into complex runs of premature ventricular beats. These local acute pressure/stretch induced runs of ventricular ectopy originate in either basal or apical normal myocardium and, in combination with a co-existing distal pro-arrhymic substrate, can interact to induce a lethal arrhythmia. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Drug-eluting stents and acute myocardial infarction: A lethal combination or friends?

PubMed Central

Otsuki, Shuji; Sabaté, Manel

2014-01-01

Primary percutaneous coronary intervention is the preferred reperfusion strategy for patients presenting with ST-segment elevation myocardial infarction (STEMI). First generation drug-eluting stents (DES), (sirolimus drug-eluting stents and paclitaxel drug-eluting stents), reduce the risk of restenosis and target vessel revascularization compared to bare metal stents. However, stent thrombosis emerged as a major safety concern with first generation DES. In response to these safety issues, second generation DES were developed with different drugs, improved stent platforms and more biocompatible durable or bioabsorbable polymeric coating. This article presents an overview of safety and efficacy of the first and second generation DES in STEMI. PMID:25276295

Carbon monoxide and lethal arrhythmias. Research report, Jul 85-Jan 89

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farber, J.P.; Schwartz, P.J.; Vanoli, E.

1990-01-01

The effect of acute exposure to carbon monoxide on ventricular arrhythmias was studied in dogs with a healed anterior myocardial infarction. The combination of mild exercise and acute myocardial ischemia induces ventricular fibrillation in 60 percent of the animals. Dogs that develop ventricular fibrillation are considered at high risk for sudden death and are defined as susceptible; dogs that survive the test without fatal arrhythmia are considered at low risk and are defined as 'resistant.' The effects of carboxyhemoglobin levels ranging from 5 to 15 percent were tested in resistant and susceptible dogs. A trend toward higher heart rates wasmore » observed at rest and during exercise in both resistant and susceptible dogs at all levels of carboxyhemoglobin, although significant differences were observed only with 15 percent carboxyhemoglobin. In resistant animals, in which acute myocardial ischemia is typically associated with bradycardia even under the control condition, the reflex response occurred earlier and was augmented after exposure to carbon monoxide. In both resistant and susceptible dogs, carbon monoxide exposure induced a worsening of ventricular arrhythmias in a minority of cases. The worsening was not reproducible in subsequent trials. These data indicate that acute exposure to carbon monoxide is seldom arrhythmogenic in dogs that have survived myocardial infarction. Nevertheless, the observation that carbon monoxide exposure increases heart rate at rest and during moderate exercise may have clinical implications relevant to patients with coronary artery disease.« less

The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

PubMed

Krivokrysenko, Vadim I; Toshkov, Ilia A; Gleiberman, Anatoli S; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K; Narizhneva, Natalya V; Singh, Vijay K; Whitnall, Mark H; Purmal, Andrei A; Shakhov, Alexander N; Gudkov, Andrei V; Feinstein, Elena

2015-01-01

There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters.

[Biodistribution and Postmortem Redistribution of Emamectin Benzoate in Intoxicated Mice].

PubMed

Tang, Wei-wei; Lin, Yu-cai; Lu, Yan-xu

2016-02-01

To investigate the lethal blood level, the target organs and tissues, the toxicant storage depots and the postmortem redistribution in mice died of emamectin benzoate poisoning. The mice model of emamectin benzoate poisoning was established via intragastric injection. The main poisoning symptoms and the clinical death times of mice were observed and recorded dynamically in the acute poisoning group as well as the sub-acute poisoning death group. The pathological and histomorphological changes of organs and tissues were observed after poisoning death. The biodistribution and postmortem redistribution of emamectin benzoate in the organs and tissues of mice were assayed by the enzyme-linked immunosorbent assay (ELISA) at 0h, 24h, 48h and 72h after death. The lethal blood concentrations and the concentrations of emamectin benzoate were detected by high performance liquid chromatography (HPLC) at different time points after death. The symptoms of nervous and respiratory system were observed within 15-30 min after intragastric injection. The average time of death was (45.8 ± 7.9) min in the acute poisoning group and (8.0 ± 1.4) d in the sub-acute poisoning group, respectively. The range of acute lethal blood level was 447.164 0-524.463 5 mg/L. The pathological changes of the organs and tissues were observed via light microscope and immunofluorescence microscope. The changes of emamectin benzoate content in the blood, heart, liver, spleen, lung, kidney and brain of poisoning mice showed regularity within 72 h after death (P < 0.05). The target organs of emamectin benzoate poisoning include heart, liver, kidney, lung, brain and contact position (stomach). The toxicant storage depots are kidney and liver. There is emamectin benzoate postmortem redistribution in mice.

[Management and new current French recommendations for tetanus care].

PubMed

Nicolai, Dominique; Farcet, Anaïs; Molines, Catherine; Delalande, Géraldine; Retornaz, Frédérique

2015-06-01

Tetanus is an acute severe disease induced by an exotoxin, often lethal. All cases occur in untreated or inadequately vaccinated patients and mainly in elderly patients who accumulate many risk factors. The current management of wounds faced difficulties in the assessment of immunization status and wound risks status. Indeed, all injuries can potentially lead to tetanus. Minor risks and chronic wounds are mainly found as tetanus cause. Vaccination remains the key element in reducing the morbidity and mortality associated with tetanus. It is estimated that the vaccine's coverage is fairly good, but decreases with age. To improve tetanus prevention, new vaccine recommendations have been established which recommend vaccine's injections at fixed age, but their impact seems to be limited especially in the elderly. The immunochromatographic tests have demonstrated cost-effectiveness in the Emergency department settings. They are currently not available outside hospital while general practionners also face a significant risk. Effectiveness of these tests should be studied in outpatients population including cost-effectiveness.

Large Dataset of Acute Oral Toxicity Data Created for Testing in Silico Models (ASCCT meeting)

EPA Science Inventory

Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are ...

Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

PubMed

Rispin, Amy; Farrar, David; Margosches, Elizabeth; Gupta, Kailash; Stitzel, Katherine; Carr, Gregory; Greene, Michael; Meyer, William; McCall, Deborah

2002-01-01

The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

Comparative risk assessment of the first-generation anticoagulant rodenticide diphacinone to raptors

USGS Publications Warehouse

Rattner, Barnett A.; Lazarus, Rebecca S.; Eisenreich, Karen M.; Horak, Katherine E.; Volker, Steven F.; Campton, Christopher M.; Eisemann, John D.; Meteyer, Carol U.; Johnson, John J.

2012-01-01

New regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides in the United States, and in some situations this action may be offset by expanded use of first-generation compounds. We have recently conducted several studies with captive adult American kestrels and eastern screech-owls examining the toxicity of diphacinone (DPN) using both acute oral and short-term dietary exposure regimens. Diphacinone evoked overt signs of intoxication and lethality in these raptors at exposure doses that were 20 to 30 times lower than reported for traditionally used wildlife test species (mallard and northern bobwhite). Sublethal exposure of kestrels and owls resulted in prolonged clotting time, reduced hematocrit, and/or gross and histological evidence of hemorrhage at daily doses as low as 0.16 mg DPN/kg body weight. Findings also demonstrated that DPN was far more potent in short-term 7-day dietary studies than in single-day acute oral exposure studies. Incorporating these kestrel and owl data into deterministic and probabilistic risk assessments indicated that the risks associated with DPN exposure for raptors are far greater than predicted in analyses using data from mallards and bobwhite. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Mortality prediction in patients with acute kidney injury requiring renal replacement therapy after cardiac surgery.

PubMed

Skarupskienė, Inga; Adukauskienė, Dalia; Kuzminskienė, Jurgita; Rimkutė, Laima; Balčiuvienė, Vilma; Žiginskienė, Edita; Kuzminskis, Vytautas; Adukauskaitė, Agnė; Pentiokinienė, Daiva; Bumblytė, Inga Arūnė

2017-01-01

Acute kidney injury (AKI) is a common and potentially serious postoperative complication after cardiac surgery, and it remains a cause of major morbidity and mortality. The aim of our study was to assess the prognostic illness severity score and to estimate the significant risk factors for poor outcome of patients with AKI requiring renal replacement therapy (RRT) after cardiac surgery. We retrospectively analyzed data of adult (>18 years) patients (n=111) who underwent open heart surgery and had developed AKI with need for RRT. Prognostic illness severity scores were calculated and perioperative risk factors of lethal outcome were assessed at the RRT initiation time. We defined three illness severity scores: Acute Physiology and Chronic Health Evaluation (APACHE II) as a general score, Sequential Organ Failure Assessment (SOFA) as an organ failure score, and Liano score as a kidney-specific disease severity score. Logistic regression was also used for the multivariate analysis of mortality risk factors. Hospital mortality was 76.5%. More than 7% of patients remained dialysis-dependent after their discharge from the hospital. The prognostic abilities of the scores were assessed for their discriminatory power. The area under the receiver-operating characteristic (ROC) curve of SOFA score was 0.719 (95% CI, 0.598-0.841), of Liano was 0.661 (95% CI, 0.535-0.787) and 0.668 (95% CI, 0.550-0.785) of APACHE II scores. From 16 variables analyzed for model selection, we reached a final logistic regression model, which demonstrated four variables significantly associated with patients' mortality. Glasgow coma score<14 points (OR=3.304; 95% CI, 1.130-9.662; P=0.003), mean arterial blood pressure (MAP)<63.5mmHg (OR=3.872; 95% CI, 1.011-13.616; P=0.035), serum creatinine>108.5μmol/L (OR=0.347; 95% CI, 0.123-0.998; P=0.046) and platelet count<115×10 9 /L (OR=3.731; 95% CI, 1.259-11.054; P=0.018) were independent risk factors for poor patient outcome. Our study demonstrated that SOFA score estimation is the most accurate to predict the fatal outcome in patients with AKI requiring RRT after cardiac surgery. Lethal patient outcome is related to Glasgow coma score, mean arterial blood pressure, preoperative serum creatinine and postoperative platelet count. Copyright © 2017 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Sp. z o.o. All rights reserved.

Lethal and sublethal effects of cypermethrin to Hypsiboas pulchellus tadpoles.

PubMed

Agostini, M Gabriela; Natale, Guillermo S; Ronco, Alicia E

2010-11-01

The study of the effects of the insecticide cypermethrin (CY) technical grade and its Sherpa® commercial formulation on Hypsiboas pulchellus tadpoles assessing lethality, behavior, growth, and abnormalities under standardized laboratory conditions is reported. Observed behaviors were identified and categorized by means of a ranking system according to the loss of mobility. Results of acute lethal effects indicate higher potency for Sherpa® at this level of assessment. All effects on behavior showed an increasing degree of injury as insecticide concentration increased. Organisms exposed to technical grade CY showed lower body length with respect to controls from 3.44 µg CY/L to higher concentrations, whereas those exposed to Sherpa® exhibited lower growth from 0.83 µg CY/L. Both forms of the tested insecticide caused abnormalities between 0.34 and 4.18 µg CY/L, but 100% of malformed individuals was detected from 34.4 µg CY/L for those exposed to the technical grade CY, and from 8.36 µg CY/L for those exposed to Sherpa®. This study proposes the use of easily identifiable and distinguishable sublethal end-points. The high input loads of CY in natural environments, the detected concentrations in the field, in addition to the low levels of this insecticide required to induce sublethal effects (which could eventually lead to death), allow for the conclusion that the insecticide is a risk factor for amphibians inhabiting agroecosystems.

Stromal derived factor 1α: A chemokine that delivers a two-pronged defence of the myocardium☆

PubMed Central

Bromage, Daniel I.; Davidson, Sean M.; Yellon, Derek M.

2014-01-01

Alleviating myocardial injury associated with ST elevation myocardial infarction is central to improving the global burden of coronary heart disease. The chemokine stromal cell-derived factor 1α (SDF-1α) has dual potential benefit in this regard. Firstly, SDF-1α is up-regulated in experimental and clinical studies of acute myocardial infarction (AMI) and regulates stem cell migration to sites of injury. SDF-1α delivery to the myocardium after AMI is associated with improved stem cell homing, angiogenesis, and left ventricular function in animal models, and improvements in heart failure and quality of life in humans. Secondly, SDF-1α may have a role in remote ischaemic conditioning (RIC), the phenomenon whereby non-lethal ischaemia–reperfusion applied to an organ or tissue remote from the heart protects the myocardium from lethal ischaemia–reperfusion injury (IRI). SDF-1α is increased in the serum of rats subjected to RIC and protects against myocardial IRI in ex vivo studies. Despite these potential pleiotropic effects, a limitation of SDF-1α is its short plasma half-life due to cleavage by dipeptidyl peptidase-4 (DPP-4). However, DPP-4 inhibitors increase the half-life of SDF-1α by preventing its degradation and are also protective against lethal IRI. In summary, SDF-1 potentially delivers a ‘two-pronged’ defence of the myocardium: acutely protecting it from IRI while simultaneously stimulating repair by recruiting stem cells to the site of injury. In this article we examine the evidence for acute and chronic cardioprotective roles of SDF-1α and discuss potential therapeutic manipulations of this mechanism with DPP-4 inhibitors to protect against lethal tissue injury in the clinical setting. PMID:24704323

Microalbuminuria and early renal response to lethal dose Shiga toxin type 2 in rats.

PubMed

Ochoa, Federico; Oltra, Gisela; Gerhardt, Elizabeth; Hermes, Ricardo; Cohen, Lilian; Damiano, Alicia E; Ibarra, Cristina; Lago, Nestor R; Zotta, Elsa

2012-01-01

In Argentina, hemolytic uremic syndrome (HUS) constitutes the most frequent cause of acute renal failure in children. Approximately 2%-4% of patients die during the acute phase, and one-third of the 96% who survive are at risk of chronic renal sequelae. Little information is available about the direct effect of Shiga toxin type 2 (Stx2) on the onset of proteinuria and the evolution of toxin-mediated glomerular or tubular injury. In this work, rats were injected intraperitoneally with recombinant Escherichia coli culture supernatant containing Stx2 (sStx2; 20 μg/kg body weight) to induce HUS. Functional, immunoblotting, and immunohistochemistry studies were carried out to determine alterations in slit diaphragm proteins and the proximal tubule endocytic system at 48 hours post-inoculation. We detected a significant increase in microalbuminuria, without changes in the proteinuria values compared to the control rats. In immunoperoxidase studies, the renal tubules and glomerular mesangium showed an increased expression of transforming growth factor β(1)(TGF-β(1)). The expression of megalin was decreased by immunoperoxidase and the cytoplasm showed a granular pattern of megalin expression by immunofluorescence techniques. Western blot analysis performed in the renal cortex from sStx2-treated and control rats using anti-nephrin and anti-podocalyxin antibodies showed a decreased expression of these proteins. We suggest that the alterations in slit diaphragm proteins and megalin expression could be related to the development of microalbuminuria in response to lethal doses of Stx2.

Studies on the lymphoid system of mice with lethal acute toxoplasmosis.

PubMed

Szeri, I; Csóka, R

1976-01-01

Acute toxoplasmosis was induced in CFLP mice by infecting them intraperitoneally with the 25 x 10(3) multiplicity of the virulent RH strain of Toxoplasma gondii. The lymphoid system of mice succumbing to acute toxoplasmosis showed characteristic changes. Significant spleen hypertrophy (spleen index: 1.76), severe thymus atrophy (thymus index: 0.27) and a striking decrease of the lymphocyte count in blood (86%) was found as compared with the uninfected controls.

Development of a Chronic Toxicity Testing Method for Daphnia pulex

DTIC Science & Technology

2015-08-01

survivorship) and sublethal endpoints (e.g., growth, reproduction) and are in concept more sensitive than acute lethality tests. • Control– negative ...organism is unable to swim /move after gentle agitation with a transfer pipette but is still alive • LC50-Lethal concentration at which a median effect on...from Zumwalt et al. (1994) The original apparatus uses water splitting channels to perform water changes on 8 beakers at once; the modified apparatus

Identification of novel uncertainty factors and thresholds of toxicological concern for health hazard and risk assessment: Application to cleaning product ingredients.

PubMed

Wang, Zhen; Scott, W Casan; Williams, E Spencer; Ciarlo, Michael; DeLeo, Paul C; Brooks, Bryan W

2018-04-01

Uncertainty factors (UFs) are commonly used during hazard and risk assessments to address uncertainties, including extrapolations among mammals and experimental durations. In risk assessment, default values are routinely used for interspecies extrapolation and interindividual variability. Whether default UFs are sufficient for various chemical uses or specific chemical classes remains understudied, particularly for ingredients in cleaning products. Therefore, we examined publicly available acute median lethal dose (LD50), and reproductive and developmental no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) values for the rat model (oral). We employed probabilistic chemical toxicity distributions to identify likelihoods of encountering acute, subacute, subchronic and chronic toxicity thresholds for specific chemical categories and ingredients in cleaning products. We subsequently identified thresholds of toxicological concern (TTC) and then various UFs for: 1) acute (LD50s)-to-chronic (reproductive/developmental NOAELs) ratios (ACRs), 2) exposure duration extrapolations (e.g., subchronic-to-chronic; reproductive/developmental), and 3) LOAEL-to-NOAEL ratios considering subacute/acute developmental responses. These ratios (95% CIs) were calculated from pairwise threshold levels using Monte Carlo simulations to identify UFs for all ingredients in cleaning products. Based on data availability, chemical category-specific UFs were also identified for aliphatic acids and salts, aliphatic alcohols, inorganic acids and salts, and alkyl sulfates. In a number of cases, derived UFs were smaller than default values (e.g., 10) employed by regulatory agencies; however, larger UFs were occasionally identified. Such UFs could be used by assessors instead of relying on default values. These approaches for identifying mammalian TTCs and diverse UFs represent robust alternatives to application of default values for ingredients in cleaning products and other chemical classes. Findings can also support chemical substitutions during alternatives assessment, and data dossier development (e.g., read across), identification of TTCs, and screening-level hazard and risk assessment when toxicity data is unavailable for specific chemicals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Carbon monoxide and lethal arrhythmias

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farber, J.P.; Schwartz, P.J.; Vanoli, E.

1990-12-01

The effect of acute exposure to carbon monoxide on ventricular arrhythmias was studied in a previously described chronically maintained animal model of sudden cardiac death. In 60 percent of dogs with a healed anterior myocardial infarction, the combination of mild exercise and acute myocardial ischemia induces ventricular fibrillation. The events in this model are highly reproducible, thus allowing study by internal control analysis. Dogs that develop ventricular fibrillation during the test of exercise and acute myocardial ischemia are considered at high risk for sudden death and are defined as 'susceptible'; dogs that survive the test without a fatal arrhythmia aremore » considered at low risk for sudden death and are defined as 'resistant.' In the current study, the effects of carboxyhemoglobin levels ranging from 5 to 15 percent were tested in resistant and susceptible dogs. A trend toward higher heart rates was observed at all levels of carboxyhemoglobin, although significant differences were observed only with 15 percent carboxyhemoglobin. This trend was observed at rest and during exercise in both resistant and susceptible dogs. In resistant animals, in which acute myocardial ischemia is typically associated with bradycardia even under the control condition, this reflex response occurred earlier and was augmented after exposure to carbon monoxide. This effect may depend on the increased hypoxic challenge caused by carbon monoxide, and thus on an augmentation of the neural reflex activation or a sensitization of the sinus node to acetylcholine induced by hypoxia. In both resistant and susceptible dogs, carbon monoxide exposure induced a worsening of ventricular arrhythmias in a minority of cases. This worsening was not reproducible in subsequent trials. These data indicate that acute exposure to carbon monoxide is seldom arrhythmogenic in dogs that have survived myocardial infarction. (Abstract Truncated)« less

Acute oral toxicity and brine shrimp lethality of Elaeis guineensis Jacq., (oil palm leaf) methanol extract.

PubMed

Syahmi, Abdul Rani Muhamad; Vijayarathna, Soundararajan; Sasidharan, Sreenivasan; Latha, Lachimanan Yoga; Kwan, Yuet Ping; Lau, Yee Ling; Shin, Lai Ngit; Chen, Yeng

2010-11-10

Elaeis guineensis (Arecaceae) is widely used in West African traditional medicine for treating various ailments. An evaluation on the toxicity of extracts of this plant is crucial to support the therapeutic claims. The acute oral toxicity and brine shrimp lethality of a methanolic extract of this plant was tested. Oral administration of crude extract at the highest dose of 5,000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that E. guineensis is nontoxic. Normal behavioral pattern, clinical signs and histology of vital organs confirm this evidence. The E. guineensis extracts screened for toxicity against brine shrimp had 50% lethal concentration (LC₅₀) values of more than 1.0 mg/mL (9.00 and 3.87 mg/mL, at 6 and 24 h, respectively), confirming that the extract was not toxic. Maximum mortalities occurred at 100 mg/mL concentration while the least mortalities happened to be at 0.195 mg/mL concentration. The results of both tests confirm that E. guineensis is nontoxic and hence safe for commercial utilization.

Asthma and risk of lethal prostate cancer in the Health Professionals Follow-Up Study.

PubMed

Platz, Elizabeth A; Drake, Charles G; Wilson, Kathryn M; Sutcliffe, Siobhan; Kenfield, Stacey A; Mucci, Lorelei A; Stampfer, Meir J; Willett, Walter C; Camargo, Carlos A; Giovannucci, Edward

2015-08-15

Inflammation, and more generally, the immune response are thought to influence the development of prostate cancer. To determine the components of the immune response that are potentially contributory, we prospectively evaluated the association of immune-mediated conditions, asthma and hayfever, with lethal prostate cancer risk in the Health Professionals Follow-up Study. We included 47,880 men aged 40-75 years with no prior cancer diagnosis. On the baseline questionnaire in 1986, the men reported diagnoses of asthma and hayfever and year of onset. On the follow-up questionnaires, they reported new asthma and prostate cancer diagnoses. We used Cox proportional hazards regression to estimate relative risks (RRs). In total, 9.2% reported ever having been diagnosed with asthma. In all, 25.3% reported a hayfever diagnosis at baseline. During 995,176 person-years of follow-up by 2012, we confirmed 798 lethal prostate cancer cases (diagnosed with distant metastases, progressed to distant metastasis or died of prostate cancer [N = 625]). Ever having a diagnosis of asthma was inversely associated with risk of lethal (RR = 0.71, 95% confidence interval [CI] = 0.51-1.00) and fatal (RR = 0.64, 95% CI = 0.42-0.96) disease. Hayfever with onset in the distant past was possibly weakly positively associated with risk of lethal (RR = 1.10, 95% CI = 0.92-1.33) and fatal (RR = 1.12, 95% CI = 0.91-1.37) disease. Men who were ever diagnosed with asthma were less likely to develop lethal and fatal prostate cancer. Our findings may lead to testable hypotheses about specific immune profiles in the etiology of lethal prostate cancer. © 2015 UICC.

Acute toxicity of 6 neonicotinoid insecticides to freshwater invertebrates.

PubMed

Raby, Melanie; Nowierski, Monica; Perlov, Dmitri; Zhao, Xiaoming; Hao, Chunyan; Poirier, David G; Sibley, Paul K

2018-05-01

Neonicotinoids are a group of insecticides commonly used in agriculture. Due to their high water solubility, neonicotinoids can be transported to surface waters and have the potential to be toxic to aquatic life. The present study assessed and compared the acute (48- or 96-h) toxicity of 6 neonicotinoids (acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, and thiamethoxam) to 21 laboratory-cultured and field-collected aquatic invertebrates spanning 10 aquatic arthropod orders. Test conditions mimicked species' habitat, with lentic taxa exposed under static conditions, and lotic taxa exposed under recirculating systems. Median lethal concentrations (LC50s) and median effect concentrations (EC50s; immobility) were calculated and used to construct separate lethal- and immobilization-derived species sensitivity distributions for each neonicotinoid, from which 5th percentile hazard concentrations (HC5s) were calculated. The results showed that the most sensitive invertebrates were insects from the orders Ephemeroptera (Neocloeon triangulifer) and Diptera (Chironomus dilutus), whereas cladocerans (Daphnia magna, Ceriodaphnia dubia) were the least sensitive. The HC5s were compared with neonicotinoid environmental concentrations from Ontario (Canada) monitoring studies. For all neonicotinoids except imidacloprid, the resulting hazard quotients indicated little to no hazard in terms of acute toxicity to aquatic communities in Ontario freshwater streams. For the neonicotinoid imidacloprid, a moderate hazard was found when only invertebrate immobilization, and not lethality, data were considered. Environ Toxicol Chem 2018;37:1430-1445. © 2018 SETAC. © 2018 SETAC.

Lethal effects of selected novel pesticides on immature stages of Trichogramma pretiosum (Hymenoptera: Trichogrammatidae).

PubMed

Khan, Muhammad Ashraf; Ruberson, John R

2017-12-01

Trichogramma pretiosum Riley is an important egg parasitoid and biological control agent of caterpillar pests. We studied the acute toxicity of 20 pesticides (14 insecticides/miticides, three fungicides and three herbicides) exposed to recommended field rates. Egg, larval, and pupal stages of the parasitoid in their hosts were dipped in formulated solutions of the pesticides and evaluated 10 days later for percentage of host eggs with holes, number of parasitoids emerged per egg with holes, and stage-specific mortality of immature as well as adult wasps within the host eggs. Seven insecticides (buprofezin, chlorantraniliprole, spirotetramat, flonicamid, flubendiamide) and miticides (spiromesifen, cyflumetofen), one herbicide (nicosulfuron), and three fungicides (myclobutanil, pyraclostrobin, trifloxystrobin + tebuconazole) caused no significant mortality to immature stages or pre-emergent adult parasitoids relative to controls. By contrast, seven insecticides/miticides (abamectin, acetamiprid, dinotefuran, fipronil, novaluron, spinetoram, tolfenpyrad) adversely affected immature and pre-emergent adult T. pretiosum, with tolfenpyrad being particularly lethal. Two herbicides had moderate (glufosinate ammonium) to severe (s-metolachlor) acute lethal effects on the immature parasitoids. This study corroborates earlier findings with adult T. pretiosum. Over half of the pesticides - and all the fungicides - tested in the current study would appear to be compatible with the use of T. pretiosum in integrated pest management programs, with respect to acute parasitoid mortality. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

[Spray for self-defense against subjects with aggressive behavior: review of the scientific literature on the use of oleoresin capsicum].

PubMed

Clerici, Carlo Alfredo; Pelettii, Gianfranco; Veneroni, Laura; de Micheli, Angelo

2012-01-01

ABSTRACT. In several countries oleoresin capsicum (OC) spray is being used as non lethal weapon in recent years. In 2009 in Italy a Security Act has established that self-defence spray devices can lawfully be purchased and possessed by citizens; at the same time corps of local police started to adopt these devices for self defence and aid in arresting aggressive individuals. This article analizes the multidisciplinar literature about the efficacy and possible acute and long-term health risks of pepper spray for exposed individuals and police or civilians users. The paper also reports updated considerations about correct use of this devices.

Protectiveness of species sensitivity distribution hazard concentrations for acute toxicity used in endangered species risk assessment.

PubMed

Raimondo, Sandy; Vivian, Deborah N; Delos, Charles; Barron, Mace G

2008-12-01

A primary objective of threatened and endangered species conservation is to ensure that chemical contaminants and other stressors do not adversely affect listed species. Assessments of the ecological risks of chemical exposures to listed species often rely on the use of surrogate species, safety factors, and species sensitivity distributions (SSDs) of chemical toxicity; however, the protectiveness of these approaches can be uncertain. We comprehensively evaluated the protectiveness of SSD first and fifth percentile hazard concentrations (HC1, HC5) relative to the application of safety factors using 68 SSDs generated from 1,482 acute (lethal concentration of 50%, or LC50) toxicity records for 291 species, including 24 endangered species (20 fish, four mussels). The SSD HC5s and HCls were lower than 97 and 99.5% of all endangered species mean acute LC50s, respectively. The HC5s were significantly less than the concentrations derived from applying safety factors of 5 and 10 to rainbow trout (Oncorhynchus mykiss) toxicity data, and the HCls were generally lower than the concentrations derived from a safety factor of 100 applied to rainbow trout toxicity values. Comparison of relative sensitivity (SSD percentiles) of broad taxonomic groups showed that crustaceans were generally the most sensitive taxa and taxa sensitivity was related to chemical mechanism of action. Comparison of relative sensitivity of narrow fish taxonomic groups showed that standard test fish species were generally less sensitive than salmonids and listed fish. We recommend the use of SSDs as a distribution-based risk assessment approach that is generally protective of listed species.

Assessment of predation risk through conspecific alarm odors by spiny lobsters

PubMed Central

2009-01-01

Strong “alarm odors” emanating from lethally injured conspecifics may indicate an imminent risk of predation to spiny lobsters. In laboratory trials,1 strong conspecific alarm odors elicited avoidance in Panulirus argus, a highly gregarious species that displays collective defense behavior, but not in Panulirus guttatus, a species that tends to aggregate when reproductive activity is high (spring) but not when it is low (late summer) and does not display collective defensive behavior. To reduce predation risk, however, lobsters may autotomize limbs, thus sustaining nonlethal injuries. I tested the response of these lobsters to scents emanating from intact, lethally-injured and non-lethally injured conspecifics. In P. argus, these scents elicited, respectively, attraction, avoidance and a random response, suggesting that, in P. argus, avoidance of conspecific alarm odors depends on their strength. In contrast, P. guttatus lobsters responded at random to scents of lethally injured conspecifics and showed a similar response to scents of intact and non-lethally injured conspecifics in the spring (attraction) and in the summer (random), reflecting the more cryptic defensive behavior of this species. Therefore, both species use conspecific alarm odors for risk-assessment, but each responds to these cues in the most effective way to reduce its risk of predation. PMID:19721871

Assessment of predation risk through conspecific alarm odors by spiny lobsters: How much is too much?

PubMed

Briones-Fourzán, Patricia

2009-07-01

Strong "alarm odors" emanating from lethally injured conspecifics may indicate an imminent risk of predation to spiny lobsters. In laboratory trials,1 strong conspecific alarm odors elicited avoidance in Panulirus argus, a highly gregarious species that displays collective defense behavior, but not in Panulirus guttatus, a species that tends to aggregate when reproductive activity is high (spring) but not when it is low (late summer) and does not display collective defensive behavior. To reduce predation risk, however, lobsters may autotomize limbs, thus sustaining nonlethal injuries. I tested the response of these lobsters to scents emanating from intact, lethally-injured and non-lethally injured conspecifics. In P. argus, these scents elicited, respectively, attraction, avoidance and a random response, suggesting that, in P. argus, avoidance of conspecific alarm odors depends on their strength. In contrast, P. guttatus lobsters responded at random to scents of lethally injured conspecifics and showed a similar response to scents of intact and non-lethally injured conspecifics in the spring (attraction) and in the summer (random), reflecting the more cryptic defensive behavior of this species. Therefore, both species use conspecific alarm odors for risk-assessment, but each responds to these cues in the most effective way to reduce its risk of predation.

Risk of Behaviors Associated with Lethal Violence and Functional Outcomes for Abused Women Who Do and Do Not Return to the Abuser Following a Community-Based Intervention

PubMed Central

Nava, Angeles; Gilroy, Heidi; Maddoux, John

2015-01-01

Abstract Background: To determine the differential risk of behaviors associated with lethal violence and functioning outcomes for abused women with children who received an intervention of shelter or justice services and return to the abuser were compared with women who did not return. Methods: The study was carried out using a matched-pair analysis of 152 women. Measures of risk of behaviors associated with lethal violence, type, and severity of abuse, and poor mental health symptoms were measured every 4 months for 24 months. Results: Irrespective of service used, women returning to the abuser reported significantly (p<0.001) more risk of behaviors associated with lethal violence compared to women who did not return. Additionally, severity of physical abuse was significantly higher (p<0.01) for women returning to the abuser who had been in a shelter but not for women who received a protection order. Similarly, levels of depression, posttraumatic stress disorder, and anxiety were significantly higher (p<0.01) for sheltered women who returned to the abuser but not for women using a protection order who returned. Conclusions: Risk of behaviors associated with lethal violence increases when abused women return to live with the abuser. Abused women should be informed of the heightened risk and greater probability for poor mental health. PMID:25714332

Risk of behaviors associated with lethal violence and functional outcomes for abused women who do and do not return to the abuser following a community-based intervention.

PubMed

McFarlane, Judith; Nava, Angeles; Gilroy, Heidi; Maddoux, John

2015-04-01

To determine the differential risk of behaviors associated with lethal violence and functioning outcomes for abused women with children who received an intervention of shelter or justice services and return to the abuser were compared with women who did not return. The study was carried out using a matched-pair analysis of 152 women. Measures of risk of behaviors associated with lethal violence, type, and severity of abuse, and poor mental health symptoms were measured every 4 months for 24 months. Irrespective of service used, women returning to the abuser reported significantly (p<0.001) more risk of behaviors associated with lethal violence compared to women who did not return. Additionally, severity of physical abuse was significantly higher (p<0.01) for women returning to the abuser who had been in a shelter but not for women who received a protection order. Similarly, levels of depression, posttraumatic stress disorder, and anxiety were significantly higher (p<0.01) for sheltered women who returned to the abuser but not for women using a protection order who returned. Risk of behaviors associated with lethal violence increases when abused women return to live with the abuser. Abused women should be informed of the heightened risk and greater probability for poor mental health.

Evaluation of Caenorhabditis elegans as an acute lethality and a neurotoxicity screening model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, P.L.

1988-01-01

This investigation evaluated C. elegans as a lethality and neurotoxicity screening model. The lethality experiments were performed in both agar and an aquatic medium. The salts of 8 metals (Hg, Be, Al, Cu, Zn, Pb, Cd, and Sr) were used in the agar studies and the salts of 14 metals (Ag, Hg, Cu, Be, Al, Pb, Cr, As, Tl, Zn, Cd, Ni, Sr, and Sb) were used in the aquatic tests. In each of these tests an LC50 value was determined. The data from the agar plates were compared to the published mammalian oral LD50 values for salts of themore » same metals. Within this set of chemicals C. elegans was found to be a predictor of mammalian acute lethality, generating LC50 values parallel to the rat and mouse LD50 values. The aquatic data were compared to data from EPA Ambient Water Quality Criteria documents. C. elegans was found to be less sensitive than Daphnia but generally more sensitive than the other invertebrate organisms that are presently used. The neurotoxicity testing also was performed in both agar and an aquatic media. The testing in agar was conducted with the salts of 4 metals (Cu, Be, Pb, and Hg) and 2 organophosphate pesticides (malathion and vapona). The studies in an aquatic medium tested the salts of 4 metals (Cu, Be, Pb, and Hg).« less

Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate specific antigen-era: incidence and survival

PubMed Central

Richman, Erin L.; Kenfield, Stacey A.; Stampfer, Meir J.; Giovannucci, Edward L.; Chan, June M.

2011-01-01

Red and processed meat may increase risk of advanced prostate cancer. Data on post-diagnostic diet and prostate cancer are sparse, but post-diagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g. men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27, 607 men followed from 1994–2008. We also performed a case-only survival analysis to examine post-diagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with non-metastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared to men who consumed less than 0.5 eggs per week (HR: 1.81; 95% confidence interval (CI): 1.13, 2.89; p-trend: 0.01). In the case-only survival analysis, we observed 123 events during 19,354 person-years. There were suggestive, but not statistically significant, positive associations between post-diagnostic poultry (HR ≥3.5 vs. <1.5 servings per week: 1.69; 95%CI: 0.96, 2.99; p-trend: 0.07) and post-diagnostic processed red meat (HR ≥3 vs. <0.5 servings per week: 1.45; 95%CI: 0.73, 2.87; p-trend: 0.08) and risk of progression of localized prostate cancer to lethal disease. In conclusion, consumption of eggs may increase risk of developing a lethal-form of prostate cancer among healthy men. PMID:21930800

An investigation of the interactive effects of the capability for suicide and acute agitation on suicidality in a military sample.

PubMed

Ribeiro, Jessica D; Bender, Theodore W; Buchman, Jennifer M; Nock, Matthew K; Rudd, M David; Bryan, Craig J; Lim, Ingrid C; Baker, Monty T; Knight, Chadwick; Gutierrez, Peter M; Joiner, Thomas E

2015-01-01

According to the interpersonal theory of suicide (1, 2), the difficulties inherently associated with death by suicide deter many individuals from engaging in suicidal behavior. Consistent with the notion that suicide is fearsome, acute states of heightened arousal are commonly observed in individuals immediately prior to lethal and near-lethal suicidal behavior. We suggest that among individuals who possess elevated levels of the capability for suicide, the heightened state of arousal experienced during periods of acute agitation may facilitate suicidal behavior in part because it would provide the necessary energy to approach a potentially lethal stimulus. Among individuals who are low on capability, the arousal experienced during agitation may result in further avoidance. In the present project we examine how acute agitation may interact with the capability for suicide to predict suicidality in a large military sample (n = 1,208) using hierarchical multiple regression. Results were in line with a priori hypotheses: among individuals high on capability, as agitation increases, suicidality increases whereas as agitation increases among individuals low on capability, suicidality decreases. Results held beyond the effects of thwarted belongingness, perceived burdensomeness, and suicidal cognitions. Beyond further substantiating the link between agitation and suicide, findings of the present study provide evidence for the construct validity of the acquired capability as well as offer initial evidence for moderating role of capability on the effect of agitation on suicide. Limitations of the current study highlight a need for future research that improves upon the techniques used in the present study. Implications for science and practice are discussed. © 2014 Wiley Periodicals, Inc.

IMMUNOMODULATION AND TREATMENT OF ACUTE DESTRUCTIVE PANCREATITIS IN A MULTIDISCIPLINARY SURGICAL HOSPITAL.

PubMed

Vinokurov, M M; Saveliev, V V; Gogolev, N M; Yalynskya, T V

2015-01-01

This work is based on the analysis of complex treatment of 497 patients with pancreatic necrosis treated at the surgical department of the Republican Hospital No2-Center for Emergency the Republic of Sakha (Yakutia) in the period from 2010 to 2015. The study was able to adapt and improve the two-tier immunocorretion in pancreatic necrosis in a multidisciplinary surgical hospital that along with the other constituents of intensive therapy has allowed a whole to reduce the amount of intra-abdominal and extraabdominal complications--sterile pancreatic necrosis phase--from 23.6% to 14.6 and 31 6% to 15.0% respectively, total lethality--from 17.6% to 7.2% lethality in patients with non-operated group--from 15.6% to 2.2% lethality in the group of patients operated--18.4% to 10.9%. In the phase of infectious complications of pancreatic necrosis lethality rate decreased from 45.8% to 37.7%.

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (Megascops asio).

PubMed

Rattner, Barnett A; Horak, Katherine E; Lazarus, Rebecca S; Eisenreich, Karen M; Meteyer, Carol U; Volker, Steven F; Campton, Christopher M; Eisemann, John D; Johnston, John J

2012-04-01

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 μg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian short-eared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (Megascops asio)

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Lazarus, Rebecca S.; Eisenreich, Karen M.; Meteyer, Carol U.; Volker, Steven F.; Campton, Christopher M.; Eisemann, John D.; Johnston, John J.

2012-01-01

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/ or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 μg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian shorteared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Sex-Specific Sub-Lethal Effects and Immune Response in Ceratitis capitata Wied. (Diptera: Tephritidae) Challenged with Spinosad.

PubMed

Mura, Maria Elena; Ruiu, Luca

2018-06-21

The main objective of this study was to investigate the effects of the insecticidal compound spinosad on the survival, reproduction, and immune functions of the Mediterranean fruit fly. The lethal and sub-lethal effects were determined on Ceratitis capitata Wied. (Diptera: Tephritidae) challenged with different concentrations of spinosad. A median lethal concentration of 0.28 ppm was observed on flies feeding for 5 days on a treated diet. A significant and concentration-dependent decrease in fecundity, egg hatch rate, and lifespan was also detected in treated compared with control flies. Gene expression analyses conducted on treated insects by RT-qPCR revealed an immunomodulatory action of sub-lethal concentrations of spinosad. Target transcripts included several genes involved in medfly immunity and male or female reproductive functions. While a significant upregulation was detected in treated males a short time after spinosad ingestion, most target genes were downregulated in treated females. Our study confirmed the high toxicity of spinosad to C. capitata , highlighting an indirect effect on insect lifespan and reproductive performance at sub-lethal doses. In addition to defining the acute and sub-lethal toxicity of spinosad against the fly, this study provides new insights on the interaction of this compound with insect physiology.

The Major Acute-Phase Protein, Serum Amyloid P Component, in Mice Is Not Involved in Endogenous Resistance against Tumor Necrosis Factor Alpha-Induced Lethal Hepatitis, Shock, and Skin Necrosis

PubMed Central

Van Molle, Wim; Hochepied, Tino; Brouckaert, Peter; Libert, Claude

2000-01-01

The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) induces lethal hepatitis when injected into d-(+)-galactosamine-sensitized mice on the one hand or systemic inflammatory response syndrome (SIRS) in normal mice on the other hand. We studied whether serum amyloid P component (SAP), the major acute-phase protein in mice, plays a protective role in both lethal models. For this purpose, we used SAP0/0 mice generated by gene targeting. We studied the lethal response of SAP0/0 or SAP+/+ mice to both lethal triggers but found no differences in the sensitivity of both types of mice. We also investigated whether SAP is involved in establishing two types of endogenous protection: one using a single injection of interleukin-1β (IL-1β) for desensitization and clearly involving a liver protein, the other by tolerizing mice for 5 days using small doses of human TNF-α. Although after IL-1β or after tolerization the SAP levels in the serum had risen fourfold in the control mice and not in the SAP0/0 mice, the same extents of desensitization and tolerization were achieved. Finally, we observed that the induction of hemorrhagic necrosis in the skin of mice by two consecutive local injections with TNF-α was not altered in SAP0/0 mice. We conclude that the presence or absence of SAP has no influence on the sensitivity of mice to TNF-α-induced hepatitis, SIRS, and hemorrhagic necrosis or on the endogenous protective mechanisms of desensitization or tolerization. PMID:10948120

Lethal exposure: An integrated approach to pathogen transmission via environmental reservoirs.

PubMed

Turner, Wendy C; Kausrud, Kyrre L; Beyer, Wolfgang; Easterday, W Ryan; Barandongo, Zoë R; Blaschke, Elisabeth; Cloete, Claudine C; Lazak, Judith; Van Ert, Matthew N; Ganz, Holly H; Turnbull, Peter C B; Stenseth, Nils Chr; Getz, Wayne M

2016-06-06

To mitigate the effects of zoonotic diseases on human and animal populations, it is critical to understand what factors alter transmission dynamics. Here we assess the risk of exposure to lethal concentrations of the anthrax bacterium, Bacillus anthracis, for grazing animals in a natural system over time through different transmission mechanisms. We follow pathogen concentrations at anthrax carcass sites and waterholes for five years and estimate infection risk as a function of grass, soil or water intake, age of carcass sites, and the exposure required for a lethal infection. Grazing, not drinking, seems the dominant transmission route, and transmission is more probable from grazing at carcass sites 1-2 years of age. Unlike most studies of virulent pathogens that are conducted under controlled conditions for extrapolation to real situations, we evaluate exposure risk under field conditions to estimate the probability of a lethal dose, showing that not all reservoirs with detectable pathogens are significant transmission pathways.

An analysis of lethal and sublethal interactions among type I and type II pyrethroid pesticide mixtures using standard Hyalella azteca water column toxicity tests.

PubMed

Hoffmann, Krista Callinan; Deanovic, Linda; Werner, Inge; Stillway, Marie; Fong, Stephanie; Teh, Swee

2016-10-01

A novel 2-tiered analytical approach was used to characterize and quantify interactions between type I and type II pyrethroids in Hyalella azteca using standardized water column toxicity tests. Bifenthrin, permethrin, cyfluthrin, and lambda-cyhalothrin were tested in all possible binary combinations across 6 experiments. All mixtures were analyzed for 4-d lethality, and 2 of the 6 mixtures (permethrin-bifenthrin and permethrin-cyfluthrin) were tested for subchronic 10-d lethality and sublethal effects on swimming motility and growth. Mixtures were initially analyzed for interactions using regression analyses, and subsequently compared with the additive models of concentration addition and independent action to further characterize mixture responses. Negative interactions (antagonistic) were significant in 2 of the 6 mixtures tested, including cyfluthrin-bifenthrin and cyfluthrin-permethrin, but only on the acute 4-d lethality endpoint. In both cases mixture responses fell between the additive models of concentration addition and independent action. All other mixtures were additive across 4-d lethality, and bifenthrin-permethrin and cyfluthrin-permethrin were also additive in terms of subchronic 10-d lethality and sublethal responses. Environ Toxicol Chem 2016;35:2542-2549. © 2016 SETAC. © 2016 SETAC.

Predictions of Leukemia Risks to Astronauts from Solar Particle Events

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; Atwell, W.; Kim, M. Y.; George, K. A.; Ponomarev, A.; Nikjoo, H.; Wilson, J. W.

2006-01-01

Leukemias consisting of acute and chronic myeloid leukemia and acute lymphatic lymphomas represent the earliest cancers that appear after radiation exposure, have a high lethality fraction, and make up a significant fraction of the overall fatal cancer risk from radiation for adults. Several considerations impact the recommendation of a preferred model for the estimation of leukemia risks from solar particle events (SPE's): The BEIR VII report recommends several changes to the method of calculation of leukemia risk compared to the methods recommended by the NCRP Report No. 132 including the preference of a mixture model with additive and multiplicative components in BEIR VII compared to the additive transfer model recommended by NCRP Report No. 132. Proton fluences and doses vary considerably across marrow regions because of the characteristic spectra of primary solar protons making the use of an average dose suspect. Previous estimates of bone marrow doses from SPE's have used an average body-shielding distribution for marrow based on the computerized anatomical man model (CAM). We have developed an 82-point body-shielding distribution that faithfully reproduces the mean and variance of SPE doses in the active marrow regions (head and neck, chest, abdomen, pelvis and thighs) allowing for more accurate estimation of linear- and quadratic-dose components of the marrow response. SPE's have differential dose-rates and a pseudo-quadratic dose response term is possible in the peak-flux period of an event. Also, the mechanistic basis for leukemia risk continues to improve allowing for improved strategies in choosing dose-rate modulation factors and radiation quality descriptors. We make comparisons of the various choices of the components in leukemia risk estimates in formulating our preferred model. A major finding is that leukemia could be the dominant risk to astronauts for a major solar particle event.

[Dermatomyositis associated with anti-MDA5 antibodies and pneumocystis pneumonia: Two lethal cases].

PubMed

Aymonier, M; Abed, S; Boyé, T; Barazzutti, H; Fournier, B; Morand, J-J

2017-04-01

Dermatomyositis associated with anti-MDA-5 autoantibodies is a recently-described clinical entity. Herein we report two lethal cases involving pneumocystis pneumonia. Case n o  1. A 56-year-old male patient developed cutaneous symptoms consistent with dermatomyositis without muscular involvement. Antinuclear antibodies were present and anti-MDA5 auto-antibodies were identified. The scan showed interstitial lung disease without infection. Significant improvement was obtained with corticosteroids. One month later, the patient presented acute respiratory illness (hypoxemia: PaO 2 60mmHg, exacerbation of lung disease evidenced by a scan, and diagnosis of pneumocystis pneumonia on bronchoalveolar lavage). He died despite appropriate antibiotic therapy and immunosuppressant therapy. Case n o  2. The second case concerned a 52-year-old Vietnamese man who developed more atypical cutaneous symptoms of dermatomyositis without muscular involvement. ANAb responses were positive (1/400) and MDA5 was present. The patient was treated with corticosteroids (40mg/d), hydroxychloroquine, and intravenous immunoglobulin. After significant improvement, the patient developed an acute respiratory illness due to superinfection with pneumocystis and he died despite specific treatment and cyclophosphamide bolus. In dermatomyositis, anti-MDA5 antibody screening is essential for the prognosis since the disease carries a risk of complication with severe lung disease. Bronchial fibroscopy with bronchoalveolar lavage should be considered at the time of diagnosis. Our two cases suggest the need for early screening for pneumocystis pneumonia in the event of respiratory distress and possibly for prophylactic treatment at the start of immunosuppressant therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

PubMed Central

Rodrigo, Ramón; Feliú, Felipe; Hasson, Daniel

2013-01-01

Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Major advances in the treatment of acute coronary syndromes and myocardial infarction, using cardiologic interventions, such as thrombolysis or percutaneous coronary angioplasty (PCA) have improved the clinical outcome of patients. Nevertheless, as a consequence of these procedures, the ischemic zone is reperfused, giving rise to a lethal reperfusion event accompanied by increased production of reactive oxygen species (oxidative stress). These reactive species attack biomolecules such as lipids, DNA, and proteins enhancing the previously established tissue damage, as well as triggering cell death pathways. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed at to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings have been disappointing. The use of antioxidant vitamins could be a suitable strategy with this purpose. In this review, we propose a systematic approach to the molecular basis of the cardioprotective effect of antioxidant vitamins in myocardial ischemia-reperfusion injury that could offer a novel therapeutic opportunity against this oxidative tissue damage. PMID:23936799

Risk-taking behaviors and subgrouping of suicide in Iran: A latent class analysis of national registries data.

PubMed

Hajebi, Ahmad; Abbasi-Ghahramanloo, Abbas; Hashemian, Seyed Sepehr; Khatibi, Seyed Reza; Ghasemzade, Masomeh; Khodadost, Mahmoud

2017-09-01

Suicide is one the most important public health problem which is rapidly growing concerns. The aim of this study was to subgroup suicide using LCA method. This cross-sectional study was conducted in Iran based on 66990 records registered in Ministry of Health in 2014. A case report questionnaire in the form of software was used for case registries. Latent class analysis was used to achieve the research objectives. Four latent classes were identified; (a) Non-lethal attempters without a history of psychiatric disorders, (b) Non-lethal attempters with a history of psychiatric disorders, (c) Lethal attempters without a history of psychiatric disorders, (d) Lethal attempters with a history of psychiatric disorders. The probability of completed/an achieved suicide is high in lethal attempter classes. Being male increases the risk of inclusion in lethal attempters' classes (OR = 4.93). Also, being single (OR = 1.16), having an age lower than 25 years (OR = 1.14) and being a rural citizen (OR = 2.36) associate with lethal attempters classes. The males tend to use more violent methods and have more completed suicide. Majority of the individuals are non-lethal attempters who need to be addressed by implementing preventive interventions and mental support provision. Copyright © 2017. Published by Elsevier B.V.

An assessment of two-step linear regression and a multifactor probit analysis as alternatives to acute to chronic ratios in the estimation of chronic response from acute toxicity data to derive water quality guidelines.

PubMed

Slaughter, Andrew R; Palmer, Carolyn G; Muller, Wilhelmine J

2007-04-01

In aquatic ecotoxicology, acute to chronic ratios (ACRs) are often used to predict chronic responses from available acute data to derive water quality guidelines, despite many problems associated with this method. This paper explores the comparative protectiveness and accuracy of predicted guideline values derived from the ACR, linear regression analysis (LRA), and multifactor probit analysis (MPA) extrapolation methods applied to acute toxicity data for aquatic macroinvertebrates. Although the authors of the LRA and MPA methods advocate the use of extrapolated lethal effects in the 0.01% to 10% lethal concentration (LC0.01-LC10) range to predict safe chronic exposure levels to toxicants, the use of an extrapolated LC50 value divided by a safety factor of 5 was in addition explored here because of higher statistical confidence surrounding the LC50 value. The LRA LC50/5 method was found to compare most favorably with available experimental chronic toxicity data and was therefore most likely to be sufficiently protective, although further validation with the use of additional species is needed. Values derived by the ACR method were the least protective. It is suggested that there is an argument for the replacement of ACRs in developing water quality guidelines by the LRA LC50/5 method.

Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos.

PubMed

Ganesan, Santhanamari; Anaimalai Thirumurthi, Naveenkumar; Raghunath, Azhwar; Vijayakumar, Savitha; Perumal, Ekambaram

2016-04-01

Nano-copper oxides are a versatile inorganic material. As a result of their versatility, the immense applications and usage end up in the environment causing a concern for the lifespan of various beings. The ambiguities surround globally on the toxic effects of copper oxide nanoparticles (CuO-NPs). Hence, the present study endeavored to study the sub-lethal acute exposure effects on the developing zebrafish embryos. The 48 hpf LC50 value was about 64 ppm. Therefore, we have chosen the sub-lethal dose of 40 and 60 ppm for the study. Accumulation of CuO-NPs was evidenced from the SEM-EDS and AAS analyzes. The alterations in the AChE and Na(+)/K(+)-ATPase activities disrupted the development process. An increment in the levels of oxidants with a concomitant decrease in the antioxidant enzymes confirmed the induction of oxidative stress. Oxidative stress triggered apoptosis in the exposed embryos. Developmental anomalies were observed with CuO-NPs exposure in addition to oxidative stress in the developing embryos. Decreased heart rate and hatching delay hindered the normal developmental processes. Our work has offered valuable data on the connection between oxidative stress and teratogenicity leading to lethality caused by CuO-NPs. A further molecular mechanism unraveling the uncharted connection between oxidative stress and teratogenicity will aid in the safe use of CuO-NPs. Copyright © 2015 John Wiley & Sons, Ltd.

A comparison of the efficacy of new asymmetric bispyridinium oximes (K027, K048) with currently available oximes against tabun by in vivo methods.

PubMed

Kassa, Jiri; Kuca, Kamil; Cabal, Jiri; Paar, Martin

2006-10-01

The potency of newly developed asymmetric bispyridinium oximes (K027, K048) in reactivating tabun-inhibited acetylcholinesterase (AChE) and in eliminating tabun-induced acute toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determined the percent of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats and showed that the reactivating efficacy of both newly developed oximes is comparable with obidoxime and trimedoxime, the most efficacious known reactivators of tabun-inhibited AChE. These were also found to be sufficiently efficacious in the elimination of acute lethal toxic effects in tabun-poisoned rats. The oxime HI-6, relatively efficacious against soman, did not seem to be an adequately effective oxime in reactivation of tabun-inhibited AChE and in counteracting acute lethal effects of tabun. In addition, our results confirm that the efficacy of oximes in reactivating tabun-inhibited AChE in blood, diaphragm, and brain correlates with the potency of oximes in protecting rats poisoned with supralethal doses of tabun.

An ecological risk assessment of the acute and chronic effects of the herbicide clopyralid to rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

Fairchild, J.F.; Allert, A.L.; Feltz, K.P.; Nelson, K.J.; Valle, J.A.

2009-01-01

Clopyralid (3,6-dichloro-2-pyridinecarboxylic acid) is a pyridine herbicide frequently used to control invasive, noxious weeds in the northwestern United States. Clopyralid exhibits low acute toxicity to fish, including the rainbow trout (Oncorhynchus mykiss) and the threatened bull trout (Salvelinus confluentus). However, there are no published chronic toxicity data for clopyralid and fish that can be used in ecological risk assessments. We conducted 30-day chronic toxicity studies with juvenile rainbow trout exposed to the acid form of clopyralid. The 30-day maximum acceptable toxicant concentration (MATC) for growth, calculated as the geometric mean of the no observable effect concentration (68 mg/L) and the lowest observable effect concentration (136 mg/L), was 96 mg/L. No mortality was measured at the highest chronic concentration tested (273 mg/L). The acute:chronic ratio, calculated by dividing the previously published 96-h acutely lethal concentration (96-h ALC50; 700 mg/L) by the MATC was 7.3. Toxicity values were compared to a four-tiered exposure assessment profile assuming an application rate of 1.12 kg/ha. The Tier 1 exposure estimation, based on direct overspray of a 2-m deep pond, was 0.055 mg/L. The Tier 2 maximum exposure estimate, based on the Generic Exposure Estimate Concentration model (GEENEC), was 0.057 mg/L. The Tier 3 maximum exposure estimate, based on previously published results of the Groundwater Loading Effects of Agricultural Management Systems model (GLEAMS), was 0.073 mg/L. The Tier 4 exposure estimate, based on published edge-of-field monitoring data, was estimated at 0.008 mg/L. Comparison of toxicity data to estimated environmental concentrations of clopyralid indicates that the safety factor for rainbow trout exposed to clopyralid at labeled use rates exceeds 1000. Therefore, the herbicide presents little to no risk to rainbow trout or other salmonids such as the threatened bull trout. ?? 2009 US Government.

Association between acute mountain sickness (AMS) and age: a meta-analysis.

PubMed

Wu, Yu; Zhang, Chi; Chen, Yu; Luo, Yong-Jun

2018-05-11

Acute mountain sickness (AMS) is a potentially lethal condition caused by acute hypoxia after ascending to altitudes higher than 2500 m in a short time. The main symptom of AMS is headache. Numerous risk factors of AMS have been examined, including gender, obesity, ascent rate, age and individual susceptibility. In previous studies, age was considered a predisposing factor for AMS. However, different opinions have been raised in recent years. To clarify the association between AMS and age, we conducted this meta-analysis. We obtained observational studies that explored risk factors for AMS by searching PubMed, Embase, China National Knowledge Internet (CNKI), the Wanfang database and CQVIP for articles published before March 2017. The studies included were required to provide the mean age and its standard deviation for subjects with and without AMS, the maximum altitude attained and the mode of ascent. The Lake Louse Score (LLS) or the Chinese AMS score (CAS) was used to judge the severity of AMS symptoms and incidence. Studies were pooled for the analysis by using a random effects model in RevMan 5.0. Meta-regression and subgroup analyses were conducted to identify sources of heterogeneity using Stata 14.2 and RevMan 5.0. In total, 17 studies were included, and the overall number of subjects with and without AMS was 1810 and 3014, respectively. The age ranged from 10 to 76 years. Analysis of the 17 included studies showed that age was not associated with AMS (mean difference (MD) = 0.10; 95% CI: -0.38-0.58; P = 0.69). This meta-analysis suggests that there is no association between age and the risk of AMS. Race, age, and ascent mode are common sources of heterogeneity, which may provide an analytical orientation for future heterogeneity analyses.

Does ethnicity matter in risk and protective factors for suicide attempts and suicide lethality?

PubMed Central

Choo, Carol C.; Harris, Keith M.; Chew, Peter K. H.; Ho, Roger C.

2017-01-01

This study explored ethnic differences in risk and protective factors for suicide attempts, for the major ethnic groups in Singapore, and ethnic differences in prediction of lethality. Three years of medical records related to suicide attempters (N = 666) who were admitted to the emergency department of a large teaching hospital in Singapore were subjected to analysis. Of the sample, 69.2% were female, 30.8% male; 63.8% Chinese, 15.8% Indian, and 15.0% Malay. Indians were over-represented in this sample, as compared with the ethnic distribution in the general population. Ages ranged from 10 to 85 years old (M = 29.7, SD = 16.1). Ethnic differences were found in risk and protective factors, and perceived lethality of suicide attempts. All available variables were subjected to regression analyses for Chinese, Indian and Malay attempters to arrive at parsimonious models for prediction of perceived lethality. The findings were discussed in regards to implications in assessment of suicide risk and primary prevention for the multiethnic society in Singapore. PMID:28426687

The acute toxicity of the metaldehyde on the climbing perch

NASA Astrophysics Data System (ADS)

Wahida Mohamad Ismail, Syamimi; Aini Dahalan, Farrah; Zakaria, Ammar; Mad Shakaff, Ali Yeon; Aqlima Ahmad, Siti; Shukor, Mohd Yunus Abd; Khalizan Sabullah, Mohd; Khalil, Khalilah Abdul; Jalil, Mohd Faizal Ab

2018-03-01

In Asia, Climbing perch (Anabas testudineus) is commonly found in paddy fields and irrigation systems. Due to its habitat, Climbing perch is exposed to toxic pesticides used in paddy fields such as metaldehyde which is one of the most widely used molluscicide. This study aims to determine the acute toxicity Lethal Concentration50 (LC50) of metaldehyde and its effect on the behaviour and physical changes of the Climbing perch. The fish mortality responses to six different metaldehyde concentrations ranging from 180 to 330 mg/L were investigated. The 96-h LC50 values were determined and analysed using three different analysis methods which is arithmetic, logarithmic and probit graphic. The LC50 values obtained in this study were 239, 234 and 232 mg/L, respectively. After 96-h of exposure to metaldehyde, the fish showed a series of abnormal behavioural response in all cases: imbalance position, and restlessness of movement. The LC50 values show that metaldehyde is moderately toxic to the Climbing perch indicating that metaldehyde is not destructive to Climbing perch. However, long term exposure of aquatic organisms to the metaldehyde means a continuous health risk for the fish population as they are more vulnerable and it is on high risk for human to consume this toxicated fishes.

Evaluation of the Flush/Fill and High-Pressure Air Purge Procedures for Converting Army Vehicles to Silicone Brake Fluid.

DTIC Science & Technology

1982-02-01

Inhlalation Ally lnon-lethal C’AR. NiLO FTA . TELR LDLo Acute or chronic All except inhalation Decath tDeathl LD50 Acute All except inhalation Not applic-ihle D...Improved Tow Vehicle US Army Europe & Seventh Army US Army Tank-Automotive Command ATTN: AEAGC- FMD ATTN: DRCPM-ITV-T APO NY 09403 Warren, Mi 48090

Acute renal failure and rhabdomyolysis in a patient with infectious mononucleosis: a case report.

PubMed

Aloizos, Stavros; Gourgiotis, Stavros; Oikonomou, Konstantinos; Stakia, Paraskevi

2008-10-07

We report a very rare case of acute renal failure and rhabdomyolysis in an Intensive Care treated 20-years-old male with upper airway obstruction due to Epstein-Barr infection.In our opinion this was a manifestation of the very rare and potentially lethal propofol infusion syndrome and not a direct complication of the underlying infection, although renal biopsy was not performed in our patient.

Mechanism of Action for Anti-Radiation Vaccine in Reducing the Biological Impact of High-Dose Irradiation

NASA Technical Reports Server (NTRS)

Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

2006-01-01

Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. We partially analyzed the biochemical characteristics of the SRDs. The SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

Mechanism of action for anti-radiation vaccine in reducing the biological impact of high-dose gamma irradiation

NASA Astrophysics Data System (ADS)

Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after high-dose gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naïve animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which they mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

Mechanism of Action for Anti-radiation Vaccine in Reducing the Biological Impact of High-dose Gamma Irradiation

NASA Technical Reports Server (NTRS)

Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

2007-01-01

Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract.

PubMed

Deshpande, Pallavi O; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2017-01-01

To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek ( Trigonella foenum-graecum L) seed extract in laboratory rats. The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively. The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture. IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity. Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during acute and subchronic oral toxicity studies in rats without mutagenicity or genotoxicity potetial. Abbreviations Used: 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control. 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control.

Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract

PubMed Central

Deshpande, Pallavi O.; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2017-01-01

Objective: To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek (Trigonella foenum-graecum L) seed extract in laboratory rats. Materials and Methods: The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively. Results: The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture. Conclusions: IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity. SUMMARY Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during acute and subchronic oral toxicity studies in rats without mutagenicity or genotoxicity potetial. Abbreviations Used: 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control. 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control PMID:28539737

Acute lethal toxicity of environmental pollutants to aquatic organisms.

PubMed

Yen, Jui-Hung; Lin, Kuo-Hsiung; Wang, Yei-Shung

2002-06-01

The acute lethal toxicity of environment pollutants including chlorophenol, haloalkane, quinone, and substituted nitrobenzene (i.e., nitrophenol, nitrobenzene, nitrotoluene, and aniline) compounds to aquatic organisms was determined. Determination of toxicity of chemicals was performed with chlorella, daphnia, carp, and tilapia. The toxicity of chlorophenols had no relation to the number of chlorine atoms on the benzene ring, but monochlorophenol had lower activity than more chlorine-substituted compounds. The tolerance levels of daphnia and carp to haloalkanes was found to be higher than that of chlorella; toxicity to chlorella was several hundred times higher than to daphnia. The toxicity of naphthoquinone compounds to chlorella and carp was higher than that of anthraquinone. A compound with a monochloride substitution on anthraquinone ring was less toxic to carp than those substituted with amine, hydroxyl, and dichlorine groups. Nitrobenzene compounds with an additional substitution group on the p position were extremely toxic to daphnia and carp. (c) 2002 Elsevier Science (USA).

Acute toxicity of fipronil to the stingless bee Scaptotrigona postica Latreille.

PubMed

Jacob, Cynthia Renata Oliveira; Soares, Hellen Maria; Carvalho, Stephan Malfitano; Nocelli, Roberta Cornélio Ferreira; Malaspina, Osmar

2013-01-01

Fipronil is an insecticide widely used to control a great number of pests, thus the aim of this study was to determine the lethal dose and lethal concentration (LD(50) and LC(50)) of this insecticide to the stingless bees Scaptotrigona postica Latreille, 1807. The LD(50) and LC(50) values obtained after 24 h of exposition were of 0.54 ng a.i./bee and 0.24 ng a.i./μL diet, respectively. These values were considered highly toxic to stingless bees.

Lethality of First Contact Dysentery Epidemics on Pacific Islands

PubMed Central

Shanks, G. Dennis

2016-01-01

Infectious diseases depopulated many isolated Pacific islands when they were first exposed to global pathogen circulation from the 18th century. Although the mortality was great, the lack of medical observers makes determination of what happened during these historical epidemics largely speculative. Bacillary dysentery caused by Shigella is the most likely infection causing some of the most lethal island epidemics. The fragmentary historical record is reviewed to gain insight into the possible causes of the extreme lethality that was observed during first-contact epidemics in the Pacific. Immune aspects of the early dysentery epidemics and postmeasles infection resulting in subacute inflammatory enteric disease suggest that epidemiologic isolation was the major lethality risk factor on Pacific islands in the 19th century. Other possible risk factors include human leukocyte antigen homogeneity from a founder effect and pathogen-induced derangement of immune tolerance to gut flora. If this analysis is correct, then Pacific islands are currently at no greater risk of emerging disease epidemics than other developing countries despite their dark history. PMID:27185765

Lethal exposure: An integrated approach to pathogen transmission via environmental reservoirs

PubMed Central

Turner, Wendy C.; Kausrud, Kyrre L.; Beyer, Wolfgang; Easterday, W. Ryan; Barandongo, Zoë R.; Blaschke, Elisabeth; Cloete, Claudine C.; Lazak, Judith; Van Ert, Matthew N.; Ganz, Holly H.; Turnbull, Peter C. B.; Stenseth, Nils Chr.; Getz, Wayne M.

2016-01-01

To mitigate the effects of zoonotic diseases on human and animal populations, it is critical to understand what factors alter transmission dynamics. Here we assess the risk of exposure to lethal concentrations of the anthrax bacterium, Bacillus anthracis, for grazing animals in a natural system over time through different transmission mechanisms. We follow pathogen concentrations at anthrax carcass sites and waterholes for five years and estimate infection risk as a function of grass, soil or water intake, age of carcass sites, and the exposure required for a lethal infection. Grazing, not drinking, seems the dominant transmission route, and transmission is more probable from grazing at carcass sites 1–2 years of age. Unlike most studies of virulent pathogens that are conducted under controlled conditions for extrapolation to real situations, we evaluate exposure risk under field conditions to estimate the probability of a lethal dose, showing that not all reservoirs with detectable pathogens are significant transmission pathways. PMID:27265371

Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats.

PubMed

Páleníček, Tomáš; Lhotková, Eva; Žídková, Monika; Balíková, Marie; Kuchař, Martin; Himl, Michal; Mikšátková, Petra; Čegan, Martin; Valeš, Karel; Tylš, Filip; Horsley, Rachel R

2016-08-01

MDAI (5,6-Methylenedioxy-2-aminoindane) has a reputation as a non-neurotoxic ecstasy replacement amongst recreational users, however the drug has been implicated in some severe and lethal intoxications. Due to this, and the fact that the drug is almost unexplored scientifically we investigated a broad range of effects of acute MDAI administration: pharmacokinetics (in sera, brain, liver and lung); behaviour (open field; prepulse inhibition, PPI); acute effects on thermoregulation (in group-/individually-housed rats); and systemic toxicity (median lethal dose, LD50) in Wistar rats. Pharmacokinetics of MDAI was rapid, maximum median concentration in serum and brain was attained 30min and almost returned to zero 6h after subcutaneous (sc.) administration of 10mg/kg MDAI; brain/serum ratio was ~4. MDAI particularly accumulated in lung tissue. In the open field, MDAI (5, 10, 20 and 40mg/kg sc.) increased exploratory activity, induced signs of behavioural serotonin syndrome and reduced locomotor habituation, although by 60min some effects had diminished. All doses of MDAI significantly disrupted PPI and the effect was present during the onset of its action as well as 60min after treatment. Unexpectedly, 40mg/kg MDAI killed 90% of animals in the first behavioural test, hence LD50 tests were conducted which yielded 28.33mg/kg sc. and 35mg/kg intravenous but was not established up to 40mg/kg after gastric administration. Disseminated intravascular coagulopathy (DIC) with brain oedema was concluded as a direct cause of death in sc. treated animals. Finally, MDAI (10, 20mg/kg sc.) caused hyperthermia and perspiration in group-housed rats. In conclusion, the drug had fast pharmacokinetics and accumulated in lipohilic tissues. Behavioural findings were consistent with mild, transient stimulation with anxiolysis and disruption of sensorimotor processing. Together with hyperthermia, the drug had a similar profile to related entactogens, especially 3,4-metyhlenedioxymethamphetamine (MDMA, ecstasy) and paramethoxymethamphetamine (PMMA). Surprisingly subcutaneous MDAI appears to be more lethal than previously thought and its serotonergic toxicity is likely exacerbated by group housing conditions. MDAI therefore poses greater risks to physical and mental health than recognised hitherto. Copyright © 2016 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidt, Tobias; Bertermann, Rüdiger; Rusch, George M.

2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a novel refrigerant intended for use in mobile air conditioning. It showed a low potential for toxicity in rodents studies with most NOAELs well above 10,000 ppm in guideline compliant toxicity studies. However, a developmental toxicity study in rabbits showed mortality at exposure levels of 5,500 ppm and above. No lethality was observed at exposure levels of 2,500 and 4,000 ppm. Nevertheless, increased subacute inflammatory heart lesions were observed in rabbits at all exposure levels. Since the lethality in pregnant animals may be due to altered biotransformation of HFO-1234yf and to evaluate the potential risk to pregnantmore » women facing a car crash, this study compared the acute toxicity and biotransformation of HFO-1234yf in male, female and pregnant female rabbits. Animals were exposed to 50,000 ppm and 100,000 ppm for 1 h. For metabolite identification by {sup 19}F NMR and LC/MS-MS, urine was collected for 48 h after inhalation exposure. In all samples, the predominant metabolites were S-(3,3,3-trifluoro-2-hydroxypropanyl)-mercaptolactic acid and N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine. Since no major differences in urinary metabolite pattern were observed between the groups, only N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine excretion was quantified. No significant differences in recovery between non-pregnant (43.10 ± 22.35 μmol) and pregnant female (50.47 ± 19.72 μmol) rabbits were observed, male rabbits exposed to 100,000 ppm for one hour excreted 86.40 ± 38.87 μmol. Lethality and clinical signs of toxicity were not observed in any group. The results suggest that the lethality of HFO-1234yf in pregnant rabbits unlikely is due to changes in biotransformation patterns or capacity in pregnant rabbits. -- Highlights: ► No lethality and clinical signs were observed. ► No differences in metabolic pattern between pregnant and non-pregnant rabbits. ► Rapid and similar metabolite excretion in all groups. ► Very low amount of biotransformation in all groups (< 0.1%).« less

Acute oral toxicity test of chemical compounds in silkworms.

PubMed

Usui, Kimihito; Nishida, Satoshi; Sugita, Takuya; Ueki, Takuro; Matsumoto, Yasuhiko; Okumura, Hidenobu; Sekimizu, Kazuhisa

2016-02-01

This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals.

The genotoxic effects of the imidacloprid-based insecticide formulation Glacoxan Imida on Montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae).

PubMed

Pérez-Iglesias, J M; Ruiz de Arcaute, C; Nikoloff, N; Dury, L; Soloneski, S; Natale, G S; Larramendy, M L

2014-06-01

The neonicotinoid insecticide imidacloprid (IMI) affects the insect central nervous system and is successfully applied to control pests for a variety of agricultural crops. In the current study, acute toxicity and genotoxicity of the IMI-containing commercial formulation insecticide Glacoxan Imida (35 percent IMI) was evaluated on Hypsiboas pulchellus (Anura: Hylidae) tadpoles exposed under laboratory conditions. A lethal effect was evaluated as the end point for lethality, whereas micronucleus (MN) frequency and DNA single-strand breaks evaluated by the single cell gel electrophoresis (SCGE) assay were employed as end points for genotoxicity. Sublethal end points were assayed within the 12.5-37.5mg/L IMI concentration range. Experiments were performed on tadpoles at stage 36 (range, 35-37) according to the classification proposed by Gosner. Lethality studies revealed an LC50 96h value of 52.622mg/L IMI. Increased frequency of MNs was only observed when 25.0mg/L was assayed for 96h, whereas no other nuclear abnormalities were induced. Increase of the genetic damage index was observed at 48h of treatment within the 12.5-37.5mg/L concentration range, whereas an increased frequency of DNA damage was observed only in tadpoles treated with 37.5mg/L IMI for 96h. This study represents the first evidence of the acute lethal and genotoxic effects exerted by IMI on tadpoles of an amphibian species native to Argentina under laboratory conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Development of status epilepticus, sustained calcium elevations and neuronal injury in a rat survival model of lethal paraoxon intoxication

PubMed Central

Deshpande, Laxmikant S.; Carter, Dawn S.; Phillips, Kristin F.; Blair, Robert E.; DeLorenzo, Robert J.

2014-01-01

Paraoxon (POX) is an active metabolite of organophosphate (OP) pesticide parathion that has been weaponized and used against civilian populations. Exposure to POX produces high mortality. OP poisoning is often associated with chronic neurological disorders. In this study, we optimize a rat survival model of lethal POX exposures in order to mimic both acute and long-term effects of POX intoxication. Male Sprague-Dawley rats injected with POX (4 mg/kg, ice-cold PBS, s.c.) produced a rapid cholinergic crisis that evolved into status epilepticus (SE) and death within 6–8 min. The EEG profile for POX induced SE was characterized and showed clinical and electrographic seizures with 7–10 Hz spike activity. Treatment of 100% lethal POX intoxication with an optimized three drug regimen (atropine, 2 mg/kg, i.p., 2-PAM, 25 mg/kg, i.m. and diazepam, 5 mg/kg, i.p.) promptly stopped SE and reduced acute mortality to 12% and chronic mortality to 18%. This model is ideally suited to test effective countermeasures against lethal POX exposure. Animals that survived the POX SE manifested prolonged elevations in hippocampal [Ca2+]i (Ca2+ plateau) and significant multifocal neuronal injury. POX SE induced Ca2+ plateau had its origin in Ca2+ release from intracellular Ca2+ stores since inhibition of ryanodine/ IP3 receptor lowered elevated Ca2+ levels post SE. POX SE induced neuronal injury and alterations in Ca2+ dynamics may underlie some of the long term morbidity associated with OP toxicity. PMID:24785379

The pathogenesis of bornaviral diseases in mammals.

PubMed

Tizard, Ian; Ball, Judith; Stoica, George; Payne, Susan

2016-12-01

Natural bornavirus infections and their resulting diseases are largely restricted to horses and sheep in Central Europe. The disease also occurs naturally in cats, and can be induced experimentally in laboratory rodents and numerous other mammals. Borna disease virus-1 (BoDV-1), the cause of most cases of mammalian Borna disease, is a negative-stranded RNA virus that replicates within the nucleus of target cells. It causes severe, often lethal, encephalitis in susceptible species. Recent events, especially the discovery of numerous new species of bornaviruses in birds and a report of an acute, lethal bornaviral encephalitis in humans, apparently acquired from squirrels, have revived interest in this remarkable family of viruses. The clinical manifestations of the bornaviral diseases are highly variable. Thus, in addition to acute lethal encephalitis, they can cause persistent neurologic disease associated with diverse behavioral changes. They also cause a severe retinitis resulting in blindness. In this review, we discuss both the pathological lesions observed in mammalian bornaviral disease and the complex pathogenesis of the neurologic disease. Thus infected neurons may be destroyed by T-cell-mediated cytotoxicity. They may die as a result of excessive inflammatory cytokine release from microglia. They may also die as a result of a 'glutaminergic storm' due to a failure of infected astrocytes to regulate brain glutamate levels.

Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury.

PubMed

Shigematsu, Misako; Koga, Tomoaki; Ishimori, Ayako; Saeki, Kazuko; Ishii, Yumiko; Taketomi, Yoshitaka; Ohba, Mai; Jo-Watanabe, Airi; Okuno, Toshiaki; Harada, Norihiro; Harayama, Takeshi; Shindou, Hideo; Li, Jian-Dong; Murakami, Makoto; Hoka, Sumio; Yokomizo, Takehiko

2016-10-05

Although pneumococcal infection is a serious problem worldwide and has a high mortality rate, the molecular mechanisms underlying the lethality caused by pneumococcus remain elusive. Here, we show that BLT2, a G protein-coupled receptor for leukotriene B 4 and 12(S)-hydroxyheptadecatrienoic acid (12-HHT), protects mice from lung injury caused by a pneumococcal toxin, pneumolysin (PLY). Intratracheal injection of PLY caused lethal acute lung injury (ALI) in BLT2-deficient mice, with evident vascular leakage and bronchoconstriction. Large amounts of cysteinyl leukotrienes (cysLTs), classically known as a slow reactive substance of anaphylaxis, were detected in PLY-treated lungs. PLY-dependent vascular leakage, bronchoconstriction, and death were markedly ameliorated by treatment with a CysLT1 receptor antagonist. Upon stimulation by PLY, mast cells produced cysLTs that activated CysLT1 expressed in vascular endothelial cells and bronchial smooth muscle cells, leading to lethal vascular leakage and bronchoconstriction. Treatment of mice with aspirin or loxoprofen inhibited the production of 12-HHT and increased the sensitivity toward PLY, which was also ameliorated by the CysLT1 antagonist. Thus, the present study identifies the molecular mechanism underlying PLY-dependent ALI and suggests the possible use of CysLT1 antagonists as a therapeutic tool to protect against ALI caused by pneumococcal infection.

Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury

PubMed Central

Shigematsu, Misako; Koga, Tomoaki; Ishimori, Ayako; Saeki, Kazuko; Ishii, Yumiko; Taketomi, Yoshitaka; Ohba, Mai; Jo-Watanabe, Airi; Okuno, Toshiaki; Harada, Norihiro; Harayama, Takeshi; Shindou, Hideo; Li, Jian-Dong; Murakami, Makoto; Hoka, Sumio; Yokomizo, Takehiko

2016-01-01

Although pneumococcal infection is a serious problem worldwide and has a high mortality rate, the molecular mechanisms underlying the lethality caused by pneumococcus remain elusive. Here, we show that BLT2, a G protein-coupled receptor for leukotriene B4 and 12(S)-hydroxyheptadecatrienoic acid (12-HHT), protects mice from lung injury caused by a pneumococcal toxin, pneumolysin (PLY). Intratracheal injection of PLY caused lethal acute lung injury (ALI) in BLT2-deficient mice, with evident vascular leakage and bronchoconstriction. Large amounts of cysteinyl leukotrienes (cysLTs), classically known as a slow reactive substance of anaphylaxis, were detected in PLY-treated lungs. PLY-dependent vascular leakage, bronchoconstriction, and death were markedly ameliorated by treatment with a CysLT1 receptor antagonist. Upon stimulation by PLY, mast cells produced cysLTs that activated CysLT1 expressed in vascular endothelial cells and bronchial smooth muscle cells, leading to lethal vascular leakage and bronchoconstriction. Treatment of mice with aspirin or loxoprofen inhibited the production of 12-HHT and increased the sensitivity toward PLY, which was also ameliorated by the CysLT1 antagonist. Thus, the present study identifies the molecular mechanism underlying PLY-dependent ALI and suggests the possible use of CysLT1 antagonists as a therapeutic tool to protect against ALI caused by pneumococcal infection. PMID:27703200

Personal history of non-melanoma skin cancer diagnosis and death from melanoma in women.

PubMed

Chen, Steven T; Li, Xin; Han, Jiali

2018-04-15

Melanoma incidence is increasing. We evaluated risk of melanoma death after diagnosis of non-melanoma skin cancer (NMSC). We followed 77,288 female American nurses from the Nurses' Health Study from 1986 to 2012. We used Cox proportional hazards models to determine the hazard ratio (HR) of lethal and non-lethal melanoma diagnosis and melanoma death, according to personal NMSC history. Among melanoma cases, we examined the HR of melanoma death and the odds ratio (OR) of melanoma with a Breslow thickness ≥0.8 mm or Clark's levels of IV and V according to history of NMSC. We documented 930 melanoma cases without NMSC history and 615 melanoma cases with NMSC history over 1.8 million person-years. The multivariate-adjusted HR (95% confidence interval) of melanoma death associated with personal history of NMSC was 2.89 (1.85-4.50). Women with history of NMSC were more likely to develop non-lethal melanoma than lethal melanoma (HR (95% CI): 2.31 (2.05-2.60) vs. 1.74 (1.05-2.87)). Among melanoma cases, women with history of NMSC had a non-significant decreased risk of melanoma deaths (0.87 (0.55-1.37)), Breslow thickness ≥0.8 mm (0.85 (0.59-1.21)) and Clark's levels IV and V (0.81(0.52-1.24)). Women with NMSC history were less likely to be diagnosed with a lethal melanoma than a non-lethal melanoma, but overall rate of melanoma diagnosis was increased in both subtypes, leading to the increased risk of melanoma death. Our findings suggest the continued need for dermatologic screening for patients after NMSC diagnosis, given increased melanoma risk. Early detection among NMSC patients may decrease deaths from melanoma. © 2017 UICC.

Ecologically-based clean-up criteria for nitroaromatic explosives using toxicity test results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duh, D.; Roberts, B.; Buzgo, S.

1995-12-31

A former trinitrotoluene (TNT) production and storage facility was the focus of a Remedial Investigation (RI). Contaminants identified during the RI included 2,4-dinitrotoluene (DNT), 2,6-DNT, and 2,4,6-TNT, PCBs, arsenic, lead and chromium. The Conceptual Site Model determined there to be several complete exposure pathways. One of these identified a route by which soil invertebrate communities could be affected through dermal contact and ingestion of soil contaminants. Maintenance of the soil invertebrate community was chosen as the assessment endpoints for this pathway in the Ecological Risk Assessment. The corresponding measurement endpoint was survival of earthworms in 14-day toxicity tests in whichmore » they were exposed to site soils. Seven surficial soil samples were collected from Areas of Concern. Each sample was evaluated for acute toxicity to earthworms using standard USEPA protocols. Chemical concentrations were also measured. An artificial soil was used as the control and diluent to establish the Lethal Concentration (LC{sub 50}) of the test soils to earthworms. From the toxicity test results and the corresponding chemical analysis, a matrix of toxicity and contaminant levels was developed. This table was used to determine a concentration of each contaminant at which no acute lethality would be expected. Lower bounds to the chemical specific LC{sub 50} values were determined and, based on sample-specific toxicity units, appropriate LC{sub 50} values were derived (333 mg/kg 2,4-DNT, 182 mg/kg 2,6-DNT, and 1960 mg/kg 2,4,6TNT). Extrapolation of this level to a chronic No Observable Adverse Effect Level (NOAEL) provided a means of proposing site-specific ecologically based clean-up criteria for the constituents of concern which would be protective of the chosen assessment endpoint.« less

[Acute lethal effect of the commercial formulation of the insecticides Imidacloprid, Spinosad y Thiocyclam hidrogenoxalate in Bombus atratus (Hymenoptera: Apidae) workers].

PubMed

Riaño Jiménez, Diego; Cure, José Ricardo

2016-12-01

The effect of insecticides on bees has gained great attention, however, there are few studies that explore this issue on Neotropical bees. Bombus atratus is a neotropical species broadly distributed in Colombia and is considered an important pollinator of both Andean ecosystems and agroecosystems. However, as for many wild bees species, the effect of insecticides on B. atratus is unknow. In this study we determined the acute median lethal dose (LD50) of commercial formulations of insecticides Imidacloprid, Spinosad and Thiocyclam hydrogen oxalate, widely used in Colombia to control several pests of important crops. The LD50 was carried out by oral and contact routes, following and modifying the EPPO and OECD guidelines to perform LD50 on A. mellifera. We evaluated five doses for each route and insecticide, in a total of 25 medium-size workers for each dose by duplicate. Mortality was registered at 24, 48 and 72 hours after the experiment; and data were analyzed with the Probit regression model. For Imidacloprid, contacts and oral LD50 were 0.048 µg/bee and 0.010 µg/bee, respectively. For Thiocyclam hydrogen oxalate, topical and oral LD50 were 0.244 µg/bee and 0.056 µg/bee, respectively. For Spinosad, the oral LD50 corresponded to 0.28 µg/bee; it was not possible to establish the LD50 for the contact route. The Hazard Quotient (HQ) and Index of Relative Toxicity indicated that all three active ingredients are highly toxic. We discussed the risk of the insecticides use on B. atratus, considering their chemical nature.

A Quantitative Structure Activity Relationship for acute oral toxicity of pesticides on rats: Validation, domain of application and prediction.

PubMed

Hamadache, Mabrouk; Benkortbi, Othmane; Hanini, Salah; Amrane, Abdeltif; Khaouane, Latifa; Si Moussa, Cherif

2016-02-13

Quantitative Structure Activity Relationship (QSAR) models are expected to play an important role in the risk assessment of chemicals on humans and the environment. In this study, we developed a validated QSAR model to predict acute oral toxicity of 329 pesticides to rats because a few QSAR models have been devoted to predict the Lethal Dose 50 (LD50) of pesticides on rats. This QSAR model is based on 17 molecular descriptors, and is robust, externally predictive and characterized by a good applicability domain. The best results were obtained with a 17/9/1 Artificial Neural Network model trained with the Quasi Newton back propagation (BFGS) algorithm. The prediction accuracy for the external validation set was estimated by the Q(2)ext and the root mean square error (RMS) which are equal to 0.948 and 0.201, respectively. 98.6% of external validation set is correctly predicted and the present model proved to be superior to models previously published. Accordingly, the model developed in this study provides excellent predictions and can be used to predict the acute oral toxicity of pesticides, particularly for those that have not been tested as well as new pesticides. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute toxicity and histopathological effects of naproxen in zebrafish (Danio rerio) early life stages.

PubMed

Li, Qian; Wang, Peipei; Chen, Ling; Gao, Hongwen; Wu, Lingling

2016-09-01

Zebrafish (Danio rerio) embryos and larvae were selected to investigate the potential risk and aquatic toxicity of a widely used pharmaceutical, naproxen. The acute toxicity of naproxen to embryos and larvae was measured, respectively. The histopathology was investigated in the liver of zebrafish larvae after 8-day embryo-larvae exposure to naproxen. The values of 96-h LC50 were 115.2 mg/L for embryos and 147.6 mg/L for larvae, indicating that zebrafish embryos were more sensitive than larvae to naproxen exposure. Large suites of symptoms were induced in zebrafish (D. rerio) early life stages by different dosages of naproxen, including hatching inhibition, lower heart rate, and morphological abnormalities. The most sensitive sub-lethal effect caused by naproxen was pericardial edema, the 72-h EC50 values of which for embryos and larvae were 98.3 and 149.0 mg/L, respectively. In addition, naproxen-treated zebrafish larvae exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. The results indicated that naproxen is a potential threat to aquatic organisms.

Evaluation of a novel risk assessment method for self-harm associated with Borderline Personality Disorder.

PubMed

Rao, Sathya; Broadbear, Jillian H; Thompson, Katherine; Correia, Anna; Preston, Martin; Katz, Paul; Trett, Robert

2017-10-01

Borderline personality disorder (BPD) is associated with frequent self-harm and suicidal behaviours. This study compared physician-assessed self-harm risk and intervention choice according to a (i) standard risk assessment and (ii) BPD-specific risk assessment methods. Forty-five junior and senior mental health physicians were assigned to standard or BPD-specific risk training groups. The assessment utilized a BPD case vignette containing four scenarios describing high/low lethality self-harm and chronic/new patterns of self-harm behaviour. Participants chose from among four interventions, each corresponding to a risk category. Standard and BPD-specific groups were alike in their assessment of self-harm risk. Divergence occurred on intervention choice for assessments of low lethality, chronic risk ( p<.01) and high lethality, chronic risk ( p<.005). Overall, psychiatrists were more likely than their junior colleagues to correctly assess risk and management options. Although standard and BPD-specific methods are well aligned for assessing self harm-associated risk, BPD-specific training raised awareness of BPD-appropriate interventions, particularly in the context of chronic patterns of self-harm behaviour. Wider dissemination of BPD-specific risk training may enhance the confidence of mental health clinicians in identifying the nature of self-harm risk as well as the most clinically appropriate interventions for clients with BPD.

Assessing the risk to green sturgeon from application of imidacloprid to control burrowing shrimp in Willapa Bay, Washington--Part II: controlled exposure studies.

PubMed

Frew, John A; Grue, Christian E

2015-11-01

The activities of 2 species of burrowing shrimp have a negative impact on the growth and survival of oysters reared on intertidal mudflats in Willapa Bay and Grays Harbor, Washington (USA). To maintain viable harvests, oyster growers proposed the application of the neonicotinoid insecticide imidacloprid onto harvested beds for the control of burrowing shrimp. In test applications, water column concentrations of imidacloprid were relatively low and dissipated rapidly. The foraging activities of the green sturgeon (listed in the US Endangered Species Act) could result in exposure to higher, more sustained imidacloprid concentrations within sediment porewater and from the consumption of contaminated shrimp. Controlled experiments were conducted using surrogate white sturgeon to determine acute and chronic effect concentrations, to examine overt effects at more environmentally realistic concentrations and durations of exposure, and to assess chemical depuration. The 96-h median lethal concentration was 124 mg L(-1) , and the predicted 35-d no-observed-adverse-effect concentration was 0.7 mg L(-1) . No overt effects were observed following environmentally relevant exposures. Imidacloprid half-life in plasma was greater than 32 h. Measured concentrations of imidacloprid in porewater were significantly lower than the derived acute and chronic effect concentrations for white sturgeon. Exposure risk quotients were calculated using the effect concentrations and estimated environmental exposure. The resulting values were considerably below the level of concern for direct effects from either acute or chronic exposure to an endangered species. © 2015 SETAC.

Determinants of the lethality of climate-related disasters in the Caribbean Community (CARICOM): a cross-country analysis

PubMed Central

Andrewin, Aisha N.; Rodriguez-Llanes, Jose M.; Guha-Sapir, Debarati

2015-01-01

Floods and storms are climate-related hazards posing high mortality risk to Caribbean Community (CARICOM) nations. However risk factors for their lethality remain untested. We conducted an ecological study investigating risk factors for flood and storm lethality in CARICOM nations for the period 1980–2012. Lethality - deaths versus no deaths per disaster event- was the outcome. We examined biophysical and social vulnerability proxies and a decadal effect as predictors. We developed our regression model via multivariate analysis using a generalized logistic regression model with quasi-binomial distribution; removal of multi-collinear variables and backward elimination. Robustness was checked through subset analysis. We found significant positive associations between lethality, percentage of total land dedicated to agriculture (odds ratio [OR] 1.032; 95% CI: 1.013–1.053) and percentage urban population (OR 1.029, 95% CI 1.003–1.057). Deaths were more likely in the 2000–2012 period versus 1980–1989 (OR 3.708, 95% CI 1.615–8.737). Robustness checks revealed similar coefficients and directions of association. Population health in CARICOM nations is being increasingly impacted by climate-related disasters connected to increasing urbanization and land use patterns. Our findings support the evidence base for setting sustainable development goals (SDG). PMID:26153115

A Market-Basket Approach to Predict the Acute Aquatic Toxicity of Munitions and Energetic Materials.

PubMed

Burgoon, Lyle D

2016-06-01

An ongoing challenge in chemical production, including the production of insensitive munitions and energetics, is the ability to make predictions about potential environmental hazards early in the process. To address this challenge, a quantitative structure activity relationship model was developed to predict acute fathead minnow toxicity of insensitive munitions and energetic materials. Computational predictive toxicology models like this one may be used to identify and prioritize environmentally safer materials early in their development. The developed model is based on the Apriori market-basket/frequent itemset mining approach to identify probabilistic prediction rules using chemical atom-pairs and the lethality data for 57 compounds from a fathead minnow acute toxicity assay. Lethality data were discretized into four categories based on the Globally Harmonized System of Classification and Labelling of Chemicals. Apriori identified toxicophores for categories two and three. The model classified 32 of the 57 compounds correctly, with a fivefold cross-validation classification rate of 74 %. A structure-based surrogate approach classified the remaining 25 chemicals correctly at 48 %. This result is unsurprising as these 25 chemicals were fairly unique within the larger set.

Lethal and sub-lethal effects of elevated CO2 concentrations on marine benthic invertebrates and fish.

PubMed

Lee, Changkeun; Hong, Seongjin; Kwon, Bong-Oh; Lee, Jung-Ho; Ryu, Jongseong; Park, Young-Gyu; Kang, Seong-Gil; Khim, Jong Seong

2016-08-01

Concern about leakage of carbon dioxide (CO2) from deep-sea storage in geological reservoirs is increasing because of its possible adverse effects on marine organisms locally or at nearby coastal areas both in sediment and water column. In the present study, we examined how elevated CO2 affects various intertidal epibenthic (benthic copepod), intertidal endobenthic (Manila clam and Venus clam), sub-tidal benthic (brittle starfish), and free-living (marine medaka) organisms in areas expected to be impacted by leakage. Acute lethal and sub-lethal effects were detected in the adult stage of all test organisms exposed to varying concentrations of CO2, due to the associated decline in pH (8.3 to 5.2) during 96-h exposure. However, intertidal organisms (such as benthic copepods and clams) showed remarkable resistance to elevated CO2, with the Venus clam being the most tolerant (LpH50 = 5.45). Sub-tidal species (such as brittle starfish [LpH50 = 6.16] and marine medaka [LpH50 = 5.91]) were more sensitive to elevated CO2 compared to intertidal species, possibly because they have fewer defensive capabilities. Of note, the exposure duration might regulate the degree of acute sub-lethal effects, as evidenced by the Venus clam, which showed a time-dependent effect to elevated CO2. Finally, copper was chosen as a model toxic element to find out the synergistic or antagonistic effects between ocean acidification and metal pollution. Combination of CO2 and Cu exposure enhances the adverse effects to organisms, generally supporting a synergistic effect scenario. Overall, the significant variation in the degree to which CO2 adversely affected organisms (viz., working range and strength) was clearly observed, supporting the general concept of species-dependent effects of elevated CO2.

Comparative toxicology for risk assessment of marine fishes and crustaceans. [Cyprinodon variegatus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suter, G.W. II; Rosen, A.E.

1988-05-01

The goal of this study was to collect data on the effects of chemicals on marine fishes and crustaceans and to evaluate the predictive power of the data for assessing risks to marine resources. The data sets consisted of acute median lethal concentrations (LC{sub 50s}) and chronic maximum acceptable toxicant concentrations (MATCs). They were analyzed with regression models and simple comparisons. The conclusions include the following: (1) the variability found in the marine data was comparable to that found in freshwater data; (2) the standard marine test fish Cyprinodon variegatus appears to be representative of marine fishes; (3) the responsesmore » of marine crustaceans are so highly diverse that the concept of a representative crustacean is questionable; (4) mysid and penaeid shrimp appear to be particularly sensitive to toxic chemicals. These conclusions are subject to the constraints of the existing limited data base and should be confirmed by a systematic study of the relative sensitivity of marine organisms to chemicals with diverse modes of action.« less

Comparison of Extracellular Striatal Acetylcholine and Brain Seizure Activity Following Acute Exposure to the Nerve Agents Cyclosarin and Tabun in Freely Moving Guinea Pigs

DTIC Science & Technology

2010-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Comparison of extracellular striatal acetylcholine and brain seizure activity following...lethality; nerve agents; organophosphorus compounds; seizure activity ; tabun 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER...acetylcholine and brain seizure activity following acute exposure to the nerve agents cyclosarin and tabun in freely moving guinea pigs John C

[A case of favourable outcome of the treatment of extremely severe acute poisoning with methanol].

PubMed

Batotsyrenov, B V; Livanov, G A; Vasil'ev, S A; Fedorov, A V; Antrianov, A Iu

2013-01-01

A case of favourable outcome of the treatment of extremely severe acute poisoning after prolonged exposure to lethal doses of methanol is reported. The complex treatment included urgent and effective elimination of the poison (multiple gastric lavage, hemodialysis), antidote therapy (administration of ethanol), correction of decompensated metabolic acidosis (alkali therapy and infusion therapy with reamberin). These measures had beneficial effect on the clinical course of poisoning and ensured its favourable outcome.

[A case of favourable outcome of severe acute intoxication with an animal poison after a bite by the monocled cobra].

PubMed

Livanov, G A; Batotsyrenkov, B V; Lodiagin, A N; Andrianov, A Iu; Kuznetsov, O A; Loladze, A T; Baranov, D V

2014-01-01

This paper reports a case of severe acute intoxication with an animal poison after a bite by the monocled cobra. Combined treatment including artificial lung ventilation, infusion-detoxication and desensitizing (hormonal) therapy, hemosorption, correction of metabolic disorders with cytoflavin, antibacterial therapy had positive effect on the patient's condition and ensured the favourable outcome ofpotentially lethal poisoning without the use ofa specific anti-snake venom serum.

Past, Present and Emerging Toxicity Issues for Jet Fuel

DTIC Science & Technology

2011-01-01

Statistically significant dominant lethal effects were not observed for either mice or rats (Air Force, 1978). However, because of the small sample...Adams, M.M., 2004. Immunological and hematological effects observed in B6C3F1 mice exposed to JP-8 jet fuel for 14 days. J. Toxicol. Environ. Health A...acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with

Sunburn prevalence among adults--United States, 1999, 2003, and 2004.

PubMed

2007-06-01

Episodic acute overexposure to ultraviolet (UV) radiation (i.e., sunburn) is an important risk factor for two types of skin cancer: basal cell carcinoma and melanoma. Melanoma is the most lethal type of skin cancer. In 2003, a total of 45,625 new cases of melanoma were diagnosed in the United States, and 7,818 persons died from the disease. A meta-analysis of 57 studies indicated that the relative risk for melanoma among persons with sunburn history compared with those without sunburn history was 2.03 (95% confidence interval [CI] = 1.73-2.37). Monitoring sunburn prevalence with population-based surveys allows an estimate of compliance with sun-protection behaviors, assessments of risk for developing skin cancer, and measurement of the success of prevention programs. To evaluate trends in sunburn prevalence among U.S. adults, CDC analyzed cross-sectional data from the 1999, 2003, and 2004 Behavioral Risk Factor Surveillance System (BRFSS) surveys. This report describes the results of that analysis, which indicated that sunburn prevalence among all adults increased from 31.8% in 1999 to 33.7% in 2004. Further research is needed to determine which interventions will best improve sun-protection behaviors among the public.

Outer Membrane Vesicle Vaccines from Biosafe Surrogates Prevent Acute Lethal Glanders in Mice

PubMed Central

Khan, Mohammad S. R.; Chirakul, Sunisa; Schweizer, Herbert P.; Tuanyok, Apichai

2018-01-01

Burkholderia mallei is a host-adapted Gram-negative mammalian pathogen that causes the severe disease glanders. Glanders can manifest as a rapid acute progression or a chronic debilitating syndrome primarily affecting solipeds and humans in close association with infected animals. In USA, B. mallei is classified as one of the most important bacterial biothreat agents. Presently, there is no licensed glanders vaccine available for humans or animals. In this work, outer membrane vesicles (OMVs) were isolated from three attenuated biosafe bacterial strains, Burkholderia pseudomallei Bp82, B. thailandensis E555, and B. thailandensis TxDOH and used to vaccinate mice. B. thailandensis OMVs induced significantly higher antibody responses that were investigated. B. mallei specific serum antibody responses were of higher magnitude in mice vaccinated with B. thailandensis OMVs compared to levels in mice vaccinated with B. pseudomallei OMVs. OMVs derived from biosafe strains protected mice from acute lethal glanders with vesicles from the two B. thailandensis strains affording significant protection (>90%) up to 35 days post-infection with some up to 60 days. Organ loads from 35-day survivors indicated bacteria colonization of the lungs, liver, and spleen while those from 60 days had high CFUs in the spleens. The highest antibody producing vaccine (B. thailandensis E555 OMVs) also protected C57BL/6 mice from acute inhalational glanders with evidence of full protection. PMID:29320408

Introduction of moribund category to OECD fish acute test and its effect on suffering and LC50 values.

PubMed

Rufli, Hans

2012-05-01

It has become common practice in many laboratories in Europe to introduce the criterion "moribund" to reduce the suffering in fish acute lethality tests. Fish with severe sublethal symptoms might be declared moribund and are removed from the test as soon as this occurs (premature discontinuation of experiment). Moribund fish affect main study outcomes as the median lethal concentration (LC50) derived on fish declared as moribund may be lower than the conventional LC50. This was evaluated by a retrospective analysis of 328 fish acute toxicity tests of an industry laboratory based on five different definitions of moribund, and of 111 tests from 10 other laboratories from Europe and the United States. Using the criterion of moribund 10 to 23% of the fish were being declared as moribund in 49 to 79% of the studies. In 36 to 52% of the studies, the LC50(moribund) was lower than the conventional LC50 depending on the definitions of moribund. An inclusion of the moribund criterion in an updated Organisation for Economic Cooperation and Development guideline for the acute fish toxicity test would reduce the period of suffering by up to 92 h, lowering the value of the main toxicity endpoint by a factor of approximately 2, and maximal by a factor of approximately 16. Copyright © 2012 SETAC.

Assessment of acute toxicity tests and rhizotron experiments to characterize lethal and sublethal control of soil-based pests.

PubMed

Agatz, Annika; Schumann, Mario M; French, Bryan W; Brown, Colin D; Vidal, Stefan

2018-03-24

Characterizing lethal and sublethal control of soil-based pests with plant protection products is particularly challenging due to the complex and dynamic interplay of the system components. Here, we present two types of studies: acute toxcity experiments (homogenous exposure of individuals in soil) and rhizotron experiments (heterogeneous exposure of individuals in soil) to investigate their ability to strengthen our understanding of mechanisms driving the effectivness of the plant protection product. Experiments were conducted using larvae of the western corn rootworm Diabrotica virgifera LeConte and three pesticide active ingredients: clothianidin (neonicotinoid), chlorpyrifos (organophosphate) and tefluthrin (pyrethroid). The order of compound concentrations needed to invoke a specific effect intensity (EC 50 values) within the acute toxicity tests was chlorpyrifos > tefluthrin > clothianidin. This order changed for the rhizotron experiments because application type, fate and transport of the compounds in the soil profile, and sublethal effects on larvae also influence their effectiveness in controlling larval feeding on corn roots. Beyond the pure measurement of efficacy through observing relative changes in plant injury to control plants, the tests generate mechanistic understanding for drivers of efficacy apart from acute toxicity. The experiments have the potential to enhance efficacy testing and product development, and might be useful tools for assessing resistance development in the future. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Lethality of First Contact Dysentery Epidemics on Pacific Islands.

PubMed

Shanks, G Dennis

2016-08-03

Infectious diseases depopulated many isolated Pacific islands when they were first exposed to global pathogen circulation from the 18th century. Although the mortality was great, the lack of medical observers makes determination of what happened during these historical epidemics largely speculative. Bacillary dysentery caused by Shigella is the most likely infection causing some of the most lethal island epidemics. The fragmentary historical record is reviewed to gain insight into the possible causes of the extreme lethality that was observed during first-contact epidemics in the Pacific. Immune aspects of the early dysentery epidemics and postmeasles infection resulting in subacute inflammatory enteric disease suggest that epidemiologic isolation was the major lethality risk factor on Pacific islands in the 19th century. Other possible risk factors include human leukocyte antigen homogeneity from a founder effect and pathogen-induced derangement of immune tolerance to gut flora. If this analysis is correct, then Pacific islands are currently at no greater risk of emerging disease epidemics than other developing countries despite their dark history. © The American Society of Tropical Medicine and Hygiene.

The role of monamine oxidase inhibition in the acute toxicity of chlordimeform.

DOT National Transportation Integrated Search

1977-08-01

This paper presents data from experiments on male rats performed to determine whether drugs which interfere with central amine mechanisms would decrease the lethality of the acaricide chlordimeform (and thus be of potential value as antidotes for acc...

Yersinia pestis YopE contains a dominant CD8 T cell epitope that confers protection in a mouse model of pneumonic plague.

PubMed

Lin, Jr-Shiuan; Szaba, Frank M; Kummer, Lawrence W; Chromy, Brett A; Smiley, Stephen T

2011-07-15

Septic bacterial pneumonias are a major cause of death worldwide. Several of the highest priority bioterror concerns, including anthrax, tularemia, and plague, are caused by bacteria that acutely infect the lung. Bacterial resistance to multiple antibiotics is increasingly common. Although vaccines may be our best defense against antibiotic-resistant bacteria, there has been little progress in the development of safe and effective vaccines for pulmonary bacterial pathogens. The Gram-negative bacterium Yersinia pestis causes pneumonic plague, an acutely lethal septic pneumonia. Historic pandemics of plague caused millions of deaths, and the plague bacilli's potential for weaponization sustains an ongoing quest for effective countermeasures. Subunit vaccines have failed, to date, to fully protect nonhuman primates. In mice, they induce the production of Abs that act in concert with type 1 cytokines to deliver high-level protection; however, the Y. pestis Ags recognized by cytokine-producing T cells have yet to be defined. In this study, we report that Y. pestis YopE is a dominant Ag recognized by CD8 T cells in C57BL/6 mice. After vaccinating with live attenuated Y. pestis and challenging intranasally with virulent plague, nearly 20% of pulmonary CD8 T cells recognize this single, highly conserved Ag. Moreover, immunizing mice with a single peptide, YopE(69-77), suffices to confer significant protection from lethal pulmonary challenge. These findings suggest YopE could be a valuable addition to subunit plague vaccines and provide a new animal model in which sensitive, pathogen-specific assays can be used to study CD8 T cell-mediated defense against acutely lethal bacterial infections of the lung.

Genotoxic effect of a binary mixture of dicamba- and glyphosate-based commercial herbicide formulations on Rhinella arenarum (Hensel, 1867) (Anura, Bufonidae) late-stage larvae.

PubMed

Soloneski, Sonia; Ruiz de Arcaute, Celeste; Larramendy, Marcelo L

2016-09-01

The acute toxicity of two herbicide formulations, namely, the 57.71 % dicamba (DIC)-based Banvel(®) and the 48 % glyphosate (GLY)-based Credit(®), alone as well as the binary mixture of these herbicides was evaluated on late-stage Rhinella arenarum larvae (stage 36) exposed under laboratory conditions. Mortality was used as an endpoint for determining acute lethal effects, whereas the single-cell gel electrophoresis (SCGE) assay was employed as genotoxic endpoint to study sublethal effects. Lethality studies revealed LC5096 h values of 358.44 and 78.18 mg L(-1) DIC and GLY for Banvel(®) and Credit(®), respectively. SCGE assay revealed, after exposure for 96 h to either 5 and 10 % of the Banvel(®) LC5096 h concentration or 5 and 10 % of the Credit(®) LC5096 h concentration, an equal significant increase of the genetic damage index (GDI) regardless of the concentration of the herbicide assayed. The binary mixtures of 5 % Banvel(®) plus 5 % Credit(®) LC5096 h concentrations and 10 % Banvel(®) plus 10 % Credit(®) LC5096 h concentrations induced equivalent significant increases in the GDI in regard to GDI values from late-stage larvae exposed only to Banvel(®) or Credit(®). This study represents the first experimental evidence of acute lethal and sublethal effects exerted by DIC on the species, as well as the induction of primary DNA breaks by this herbicide in amphibians. Finally, a synergistic effect of the mixture of GLY and DIC on the induction of primary DNA breaks on circulating blood cells of R. arenarum late-stage larvae could be demonstrated.

Intestinal Helminths Regulate Lethal Acute Graft Versus Host Disease and Preserve Graft Versus Tumor Effect in Mice

PubMed Central

Li, Yue; Chen, Hung-lin; Bannick, Nadine; Henry, Michael; Holm, Adrian N.; Metwali, Ahmed; Urban, Joseph F.; Rothman, Paul B.; Weiner, George J.; Blazar, Bruce R.; Elliott, David E.; Ince, M. Nedim

2014-01-01

Donor T lymphocyte transfer with hematopoietic stem cells suppresses residual tumor growth (graft-versus-tumor; GVT) in cancer patients undergoing bone marrow transplantation (BMT). However, donor T cell reactivity to host organs causes severe and potentially lethal inflammation, called graft-versus-host disease (GVHD). High dose steroids or other immune suppressives are used to treat GVHD that have limited ability to control the inflammation while incurring long-term toxicity. Novel strategies are needed to modulate GVHD, preserve GVT and improve the outcome of BMT. Regulatory T cells (Tregs) control alloantigen-sensitized inflammation of GVHD, sustain GVT and prevent mortality in bone marrow transplantation. Helminths colonizing the alimentary tract dramatically increase the Treg activity, thereby modulating intestinal or systemic inflammatory responses. These observations led us to hypothesize that helminths can regulate GVHD and maintain GVT in mice. Acute GVHD was induced in helminth (Heligmosomoides polygyrus)-infected or uninfected Balb/C recipients of C57BL/6 donor grafts. Helminth infection suppressed donor T cell inflammatory cytokine generation along with reduction in GVHD lethality and maintenance of GVT. H. polygyrus colonization promoted the survival of TGFβ generating recipient Tregs after a conditioning regimen with total body irradiation and led to a TGFβ-dependent in vivo expansion/maturation of donor Tregs after BMT. Helminths did not control GVHD, when T cells unresponsive to TGFβ-mediated immune regulation were used as donor T lymphocytes. These results suggest that helminths suppress acute GVHD, employing regulatory T cells and TGFβ-dependent pathways in mice. Helminthic regulation of GVHD and GVT through intestinal immune conditioning may improve the outcome of BMT. PMID:25527786

Killing wolves to prevent predation on livestock may protect one farm but harm neighbors.

PubMed

Santiago-Avila, Francisco J; Cornman, Ari M; Treves, Adrian

2018-01-01

Large carnivores, such as gray wolves, Canis lupus, are difficult to protect in mixed-use landscapes because some people perceive them as dangerous and because they sometimes threaten human property and safety. Governments may respond by killing carnivores in an effort to prevent repeated conflicts or threats, although the functional effectiveness of lethal methods has long been questioned. We evaluated two methods of government intervention following independent events of verified wolf predation on domestic animals (depredation) in the Upper Peninsula of Michigan, USA between 1998-2014, at three spatial scales. We evaluated two intervention methods using log-rank tests and conditional Cox recurrent event, gap time models based on retrospective analyses of the following quasi-experimental treatments: (1) selective killing of wolves by trapping near sites of verified depredation, and (2) advice to owners and haphazard use of non-lethal methods without wolf-killing. The government did not randomly assign treatments and used a pseudo-control (no removal of wolves was not a true control), but the federal permission to intervene lethally was granted and rescinded independent of events on the ground. Hazard ratios suggest lethal intervention was associated with an insignificant 27% lower risk of recurrence of events at trapping sites, but offset by an insignificant 22% increase in risk of recurrence at sites up to 5.42 km distant in the same year, compared to the non-lethal treatment. Our results do not support the hypothesis that Michigan's use of lethal intervention after wolf depredations was effective for reducing the future risk of recurrence in the vicinities of trapping sites. Examining only the sites of intervention is incomplete because neighbors near trapping sites may suffer the recurrence of depredations. We propose two new hypotheses for perceived effectiveness of lethal methods: (a) killing predators may be perceived as effective because of the benefits to a small minority of farmers, and (b) if neighbors experience side-effects of lethal intervention such as displaced depredations, they may perceive the problem growing and then demand more lethal intervention rather than detecting problems spreading from the first trapping site. Ethical wildlife management guided by the "best scientific and commercial data available" would suggest suspending the standard method of trapping wolves in favor of non-lethal methods (livestock guarding dogs or fladry) that have been proven effective in preventing livestock losses in Michigan and elsewhere.

Acute photo-induced toxicity and toxicokinetics of single compounds and mixtures of polycyclic aromatic hydrocarbons in zebrafish.

PubMed

Willis, Alison M; Oris, James T

2014-09-01

The present study examined photo-induced toxicity and toxicokinetics for acute exposure to selected polycyclic aromatic hydrocarbons (PAHs) in zebrafish. Photo-enhanced toxicity from co-exposure to ultraviolet (UV) radiation and PAHs enhanced the toxicity and exhibited toxic effects at PAH concentrations orders of magnitude below effects observed in the absence of UV. Because environmental exposure to PAHs is usually in the form of complex mixtures, the present study examined the photo-induced toxicity of both single compounds and mixtures of PAHs. In a sensitive larval life stage of zebrafish, acute photo-induced median lethal concentrations (LC50s) were derived for 4 PAHs (anthracene, pyrene, carbazole, and phenanthrene) to examine the hypothesis that phototoxic (anthracene and pyrene) and nonphototoxic (carbazole and phenanthrene) pathways of mixtures could be predicted from single exposures. Anthracene and pyrene were phototoxic as predicted; however, carbazole exhibited moderate photo-induced toxicity and phenanthrene exhibited weak photo-induced toxicity. The toxicity of each chemical alone was used to compare the toxicity of mixtures in binary, tertiary, and quaternary combinations of these PAHs, and a predictive model for environmental mixtures was generated. The results indicated that the acute toxicity of PAH mixtures was additive in phototoxic scenarios, regardless of the magnitude of photo-enhancement. Based on PAH concentrations found in water and circumstances of high UV dose to aquatic systems, there exists potential risk of photo-induced toxicity to aquatic organisms. © 2014 SETAC.

Impaired cardiac ischemic tolerance in spontaneously hypertensive rats is attenuated by adaptation to chronic and acute stress.

PubMed

Ravingerová, T; Bernátová, I; Matejíková, J; Ledvényiová, V; Nemčeková, M; Pecháňová, O; Tribulová, N; Slezák, J

2011-01-01

Chronic hypertension may have a negative impact on the myocardial response to ischemia. On the other hand, intrinsic ischemic tolerance may persist even in the pathologically altered hearts of hypertensive animals, and may be modified by short- or long-term adaptation to different stressful conditions. The effects of long-term limitation of living space (ie, crowding stress [CS]) and brief ischemia-induced stress on cardiac response to ischemia/reperfusion (I/R) injury are not yet fully characterized in hypertensive subjects. The present study was designed to test the influence of chronic and acute stress on the myocardial response to I/R in spontaneously hypertensive rats (SHR) compared with their effects in normotensive counterparts. In both groups, chronic, eight-week CS was induced by caging five rats per cage in cages designed for two rats (200 cm(2)/rat), while controls (C) were housed four to a cage in cages designed for six animals (480 cm(2)/rat). Acute stress was evoked by one cycle of I/R (5 min each, ischemic preconditioning) before sustained I/R in isolated Langendorff-perfused hearts of normotensive and SHR rats. At baseline conditions, the effects of CS were manifested only as a further increase in blood pressure in SHR, and by marked limitation of coronary perfusion in normotensive animals, while no changes in heart mechanical function were observed in any of the groups. Postischemic recovery of contractile function, severity of ventricular arrhythmias and lethal injury (infarction size) were worsened in the hypertrophied hearts of C-SHR compared with normotensive C. However, myo-cardial stunning and reperfusion-induced ventricular arrhythmias were attenuated by CS in SHR, which was different from deterioration of I/R injury in the hearts of normotensive animals. In contrast, ischemic preconditioning conferred an effective protection against I/R in both groups, although the extent of anti-infarct and anti-arrhythmic effects was lower in SHR. Both forms of stress may improve the altered response to ischemia in hypertensive subjects. In contrast to short-term preconditioning stress, chronic psychosocial stress was associated with a higher risk of lethal arrhythmias and contractile failure in normotensive animals exposed to an acute ischemic challenge.

High risk of streptococcal septicemia after high dose cytosine arabinoside treatment for acute myelogenous leukemia.

PubMed

Kern, W; Kurrle, E; Vanek, E

1987-08-17

Twenty-nine adult patients with acute myelogenous leukemia AML who received 40 treatment courses with high dose cytosine arabinoside (HD-A), alone or combined with other cytotoxic drugs, for remission induction (RI) or postremission intensive consolidation (IC) were retrospectively analysed for types and severity of infectious complications. In this paper, we report the unusually high rate of streptococcal septicemia in our patients. Of 13 bacteremic infections in a total of 45 infectious episodes, 10 were caused by streptococci (9 viridans streptococci, 1 group B hemolytic streptococcus). Three of them were lethal. After reviewing all documented cases of streptococcal septicemia in the same study period, four additional cases among adult patients with AML were identified. Three of them have had antileukemic chemotherapy without HD-A, while one have had HD-A as a conditioning regimen for bone marrow transplantation. Only three cases were documented to occur in adult patients with AML. Patients treated with HD-A for RI or IC had a significantly lower risk of streptococcal septicemia during previous chemotherapy-associated febrile neutropenic episodes (1/55 vs 10/45; P = 0.01). Neither prophylactic regimens including trimethoprim-sulfamethoxazole nor those without it were effective in preventing streptococcal septicemia. Further studies are needed to confirm these data before the value of additional or alternative prophylactic antibiotics is proven necessary.

AQUATIC TOXICITY MODE OF ACTION STUDIES APPLIED TO QSAR DEVELOPMENT

EPA Science Inventory

A series of QSAR models for predicting fish acute lethality were developed using systematically collected data on more than 600 chemicals. These models were developed based on the assumption that chemicals producing toxicity through a common mechanism will have commonality in the...

Prevention of Suicidal Behavior in Prisons

PubMed Central

2016-01-01

Abstract. Background: Worldwide, prisoners are at high risk of suicide. Research on near-lethal suicide attempts can provide important insights into risk and protective factors, and inform suicide prevention initiatives in prison. Aims: To synthesize findings of research on near-lethal attempts in prisons, and consider their implications for suicide prevention policies and practice, in the context of other research in custody and other settings. Method: We searched two bibliographic indexes for studies in any language on near-lethal and severe self-harm in prisoners, supplemented by targeted searches over the period 2000–2014. We extracted information on risk factors descriptively. Data were not meta-analyzed owing to heterogeneity of samples and methods. Results: We identified eight studies reporting associations between prisoner near-lethal attempts and specific factors. The latter included historical, prison-related, and clinical factors, including psychiatric morbidity and comorbidity, trauma, social isolation, and bullying. These factors were also identified as important in prisoners' own accounts of what may have contributed to their attempts (presented in four studies). Conclusion: Factors associated with prisoners' severe suicide attempts include a range of potentially modifiable clinical, psychosocial, and environmental factors. We make recommendations to address these factors in order to improve detection, management, and prevention of suicide risk in prisoners. PMID:27278569

Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders

PubMed Central

Hatcher, Christopher L.; Mott, Tiffany M.; Muruato, Laura A.; Sbrana, Elena

2016-01-01

Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain. PMID:27271739

Studies on fate and toxicity of nanoalumina in male albino rats: Lethality, bioaccumulation and genotoxicity.

PubMed

Morsy, Gamal M; El-Ala, Kawther S Abou; Ali, Atef A

2016-02-01

The purpose of this study is to follow-up the distribution, lethality percentile doses (LDs) and bioaccumulation of aluminium oxide nanoparticles (Al2O3-NPs, average diameter 9.83 ± 1.61 nm) in some tissues of male albino rats, and to evaluate its genotoxicity to the brain tissues, during acute and sublethal experiments. The LDs of Al2O3-NPs, including median lethal dose (LD50), were estimated after intraperitoneal injection. The computed LD50 at 24 and 48 h were 15.10 and 12.88 g/kg body weight (b.w.), respectively. For acute experiments, the bioaccumulation of aluminium (Al) in the brain, liver, kidneys, intestine and spleen was estimated after 48 h of injection with a single acute dose (3.9, 6.4 and 8.5 g/kg b.w.), while for sublethal experiments it was after 1, 3, 7, 14 and 28 days of injection with 1.3 g/kg b.w. once in 2 days. Multi-way analysis of variance affirmed that Al uptake, in acute experiments, was significantly affected by the injected doses, organs (brain, liver, kidneys, intestine and spleen) and their interactions, while for sublethal experiments an altogether effect based on time (1, 3, 7, 14, 28 days), doses (0 and 1.3 g), organs and their interactions was reported. In addition, Al accumulated in the brain, liver, kidney, intestine and spleen of rats administered with Al2O3-NPs were significantly higher than the corresponding controls, during acute and sublethal experiments. The uptake of Al by the spleen of rats injected with acute doses was greater than that accumulated by kidney>brain>intestine>liver, whereas the brain of rats injected with sublethal dose accumulated lesser amount of Al followed by the kidney

Determination of glycyrrhetic acid after consumption of liquorice and application to a fatality.

PubMed

Albermann, M E; Musshoff, F; Hagemeier, L; Madea, B

2010-04-15

Besides alcohol and drugs of abuse, several popular foods contain potentially toxic substances and cases of intoxication after consumption of these foods attract notice of forensic toxicology. This is also true for the case of a 34-year-old woman who was suspected to have suffered lethal acute intoxication from eating nothing but liquorice over a period of several months. The liquorice ingredient glycyrrhizin and its metabolite glycyrrhetic acid, which elicits a mineralocorticoid effect, were determined in the sort of liquorice the woman had consumed by using LC-MS/MS. In addition, a fast and sensitive procedure for the quantification of glycyrrhetic acid including a simple sample preparation was developed. The method was proven to be accurate and precise. In a liquorice ingestion experiment, 200 g of liquorice had to be eaten. Afterwards, concentrations of glycyrrhetic acid in the blood of up to 434 ng/ml were measured. Since only traces of glycyrrhetic acid had been found in the blood and stomach content of the deceased woman, the possibility of acute lethal glycyrrhetic acid intoxication could be eliminated. Excluding other causes of death, the woman is believed to have died from a lethal hyperglycemic coma. Nonetheless, the influence of harmful and toxic substances in food should be taken into consideration in special cases. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Lethal mechanisms in gastric volvulus.

PubMed

Omond, Kimberley J; Byard, Roger W

2017-01-01

A 55-year-old wheelchair-bound woman with severe cerebral palsy was found at autopsy to have marked distention of the stomach due to a volvulus. The stomach was viable, and filled with air and fluid and had pushed the left dome of the diaphragm upwards causing marked compression of the left lung with a mediastinal shift to the right (including the heart). There was no evidence of gastric perforation, ischaemic necrosis or peritonitis. Removal of the organ block revealed marked kyphoscoliosis. Histology confirmed the viability of the stomach and biochemistry showed no dehydration. Death in cases of acute gastric volvulus usually occurs because of compromise of the gastric blood supply resulting in ischaemic necrosis with distention from swallowed air and fluid resulting in perforation with lethal peritonitis. Hypovolaemic shock may also occur. However, the current case demonstrates an alternative lethal mechanism, that of respiratory compromise due to marked thoracic organ compression.

[Characteristics of antiischemic and nootropic properties of ademol in a rat model of acute brain ischemia].

PubMed

Khodakivs'kyĭ, O A

2013-01-01

In experiments with the rat model of acute disorder of encephalic circulation (bilateral carotid occlusion) it was found that introduction of derivate of adamantan 1-adamantiloxy-3-morfolino-2 propanol (under conventional name ademol) in the dose 2 mg/kg intraabdominal in treatment regimen (in an hour after reconstruction of insult and further 1 time every 24 hours during 21 days) was accompanied by a recovery of mnemotropic properties and is more effective than cytikolin, resulting in a decreased lethality and neurological deficiency in acute and recovery periods of insults. The data received proved the usefulness of development of ademol based cerebroprotective remedy.

Examining the impact of psychiatric diagnosis and comorbidity on the medical lethality of adolescent suicide attempts.

PubMed

McManama O'Brien, Kimberly H; Berzin, Stephanie C

2012-08-01

Specific psychiatric diagnoses and comorbidity patterns were examined to determine if they were related to the medical lethality of suicide attempts among adolescents presenting to an urban general hospital (N=375). Bivariate analysis showed that attempters with substance abuse disorders had higher levels of lethality than attempters without substance abuse. Regression results indicated having depression comorbid with any other diagnosis was not associated with medical lethality. However, having a substance abuse disorder was associated with higher suicide attempt lethality, highlighting the importance of substance abuse as a risk factor for lethal suicide attempts in adolescents. This finding stimulates critical thinking around the understanding of suicidal behavior in youth and the development and implementation of treatment strategies for suicidal adolescents with substance abuse disorders. © 2012 The American Association of Suicidology.

Establishing RIPDLIPI Lethality Tables for the General Population

DTIC Science & Technology

2018-02-01

Bibliography Anno, G. et al. (2003). “Dose response relationships for acute ionizing-radiation lethality”. In: Health Physics 84.5, pp. 565–575...The new LUTs were created using a plugin to HENRE ( Health Effects from Nuclear and Radiological Environments; (Oldson et al., 2017). HENRE includes

Novel symptomatology and changing epidemiology of domoic acid toxicosis in California sea lions (Zalophus californianus): an increasing risk to marine mammal health

PubMed Central

Goldstein, T; Mazet, J.A.K; Zabka, T.S; Langlois, G; Colegrove, K.M; Silver, M; Bargu, S; Van Dolah, F; Leighfield, T; Conrad, P.A; Barakos, J; Williams, D.C; Dennison, S; Haulena, M; Gulland, F.M.D

2007-01-01

Harmful algal blooms are increasing worldwide, including those of Pseudo-nitzschia spp. producing domoic acid off the California coast. This neurotoxin was first shown to cause mortality of marine mammals in 1998. A decade of monitoring California sea lion (Zalophus californianus) health since then has indicated that changes in the symptomatology and epidemiology of domoic acid toxicosis in this species are associated with the increase in toxigenic blooms. Two separate clinical syndromes now exist: acute domoic acid toxicosis as has been previously documented, and a second novel neurological syndrome characterized by epilepsy described here associated with chronic consequences of previous sub-lethal exposure to the toxin. This study indicates that domoic acid causes chronic damage to California sea lions and that these health effects are increasing. PMID:18006409

Elemental selenium at nano size possesses lower toxicity without compromising the fundamental effect on selenoenzymes: comparison with selenomethionine in mice.

PubMed

Wang, Huali; Zhang, Jinsong; Yu, Hanqing

2007-05-15

Glutathione peroxidase and thioredoxin reductase are major selenoenzymes through which selenium exerts powerful antioxidant effects. Selenium also elicits pro-oxidant effects at toxic levels. The antioxidant and pro-oxidant effects, or bioavailability and toxicity, of selenium depend on its chemical form. Selenomethionine is considered to be the most appropriate supplemental form due to its excellent bioavailability and lower toxicity compared to various selenium compounds. The present studies reveal that, compared with selenomethionine, elemental selenium at nano size (Nano-Se) possesses equal efficacy in increasing the activities of glutathione peroxidase and thioredoxin reductase but has much lower toxicity as indicated by median lethal dose, acute liver injury, and short-term toxicity. Our results suggest that Nano-Se can serve as an antioxidant with reduced risk of selenium toxicity.

Environmental risks and challenges associated with neonicotinoid insecticides

USGS Publications Warehouse

Hladik, Michelle L.; Main, Anson; Goulson, Dave

2018-01-01

Neonicotinoid use has increased rapidly in recent years, with a global shift towards insecticide applications as seed coatings rather than aerial spraying. While the use of seed coatings can lessen the amount of overspray and drift, the near universal and prophylactic use of neonicotinoid seed coatings on major agricultural crops has led to widespread detections in the environment (pollen, soil, water, honey). Pollinators and aquatic insects appear to be especially susceptible to the effects of neonicotinoids with current research suggesting that chronic sub-lethal effects are more prevalent than acute toxicity. Meanwhile, evidence of clear and consistent yield benefits from the use of neonicotinoids remains elusive for most crops. Future decisions on neonicotinoid use will benefit from weighing crop yield benefits versus environmental impacts to non-target organisms and considering whether there are more environmentally benign alternatives.

Risks of non-lethal weapon use: case studies of three French victims of stinger grenades.

PubMed

Scolan, V; Herry, C; Carreta, M; Stahl, C; Barret, L; Romanet, J P; Paysant, F

2012-11-30

The development of non-lethal weapons started in the 1960s. In France, they have been used by the police for about 10 years. We relate the cases of three French women, victims of stinger grenades, non-lethal weapons recently adopted by the French law enforcement to distract and disperse crowds. The three victims presented serious injuries requiring emergency surgical care. One lost her eye. Based on these cases, we discuss the lethal character of these weapons and propose measures to be taken to prevent their dramatic consequences. Although the danger is obviously less than for firearms, stinger grenades are nonetheless potentially lethal and cause serious physical injuries. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Justified Concern or Exaggerated Fear: The Risk of Anaphylaxis in Percutaneous Treatment of Cystic Echinococcosis—A Systematic Literature Review

PubMed Central

Neumayr, Andreas; Troia, Giuliana; de Bernardis, Chiara; Tamarozzi, Francesca; Goblirsch, Sam; Piccoli, Luca; Hatz, Christoph; Filice, Carlo; Brunetti, Enrico

2011-01-01

Percutaneous treatment (PT) emerged in the mid-1980s as an alternative to surgery for selected cases of abdominal cystic echinococcosis (CE). Despite its efficacy and widespread use, the puncture of echinococcal cysts is still far from being universally accepted. One of the main reasons for this reluctance is the perceived risk of anaphylaxis linked to PTs. To quantify the risk of anaphylactic reactions and lethal anaphylaxis with PT, we systematically searched MEDLINE for publications on PT of CE and reviewed the PT-related complications. After including 124 publications published between 1980 and 2010, we collected a total number of 5943 PT procedures on 5517 hepatic and non-hepatic echinococcal cysts. Overall, two cases of lethal anaphylaxis and 99 reversible anaphylactic reactions were reported. Lethal anaphylaxis occurred in 0.03% of PT procedures, corresponding to 0.04% of treated cysts, while reversible allergic reactions complicated 1.7% of PTs, corresponding to 1.8% of treated echinococcal cysts. Analysis of the literature shows that lethal anaphylaxis related to percutaneous treatment of CE is an extremely rare event and is observed no more frequently than drug-related anaphylactic side effects. PMID:21695106

Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: The GRAALL experience.

PubMed

Couturier, Marie-Anne; Huguet, Françoise; Chevallier, Patrice; Suarez, Felipe; Thomas, Xavier; Escoffre-Barbe, Martine; Cacheux, Victoria; Pignon, Jean-Michel; Bonmati, Caroline; Sanhes, Laurence; Bories, Pierre; Daguindau, Etienne; Dorvaux, Véronique; Reman, Oumedaly; Frayfer, Jamile; Orvain, Corentin; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé; Hunault-Berger, Mathilde; Tanguy-Schmidt, Aline

2015-11-01

Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4). © 2015 Wiley Periodicals, Inc.

Allopurinol Reduces the Lethality Associated with Acute Renal Failure Induced by Crotalus durissus terrificus Snake Venom: Comparison with Probenecid

PubMed Central

Frezzatti, Rodrigo; Silveira, Paulo Flavio

2011-01-01

Background Acute renal failure is one of the most serious complications of envenoming resulting from Crotalus durissus terrificus bites. This study evaluated the relevance of hyperuricemia and oxidative stress and the effects of allopurinol and probenecid in renal dysfunction caused by direct nephrotoxicity of C. d. terrificus venom. Methodology/Principal Findings Hematocrit, protein, renal function and redox status were assessed in mice. High ratio of oxidized/reduced glutathione and hyperuricemia induced by C. d. terrificus venom were ameliorated by both, allopurinol or probenecid, but only allopurinol significantly reduced the lethality caused by C. d. terrificus venom. The effectiveness of probenecid is compromised probably because it promoted hypercreatinemia and hypocreatinuria and worsed the urinary hypo-osmolality in envenomed mice. In turn, the highest effectiveness of allopurinol might be due to its ability to diminish the intracellular formation of uric acid. Conclusions/Significance Data provide consistent evidences linking uric acid with the acute renal failure induced by C. d. terrificus venom, as well as that this envenoming in mice constitutes an attractive animal model suitable for studying the hyperuricemia and that the allopurinol deserves to be clinically evaluated as an approach complementary to anti-snake venom serotherapy. PMID:21909449

Do Biopesticides Affect the Demographic Traits of a Parasitoid Wasp and Its Biocontrol Services through Sublethal Effects?

PubMed Central

Biondi, Antonio; Zappalà, Lucia; Stark, John D.; Desneux, Nicolas

2013-01-01

Pesticide risk assessments are usually based on short-term acute toxicity tests, while longer-term population dynamic related traits, critical to the success of biological control and Integrated Pest Management (IPM) programs, are often overlooked. This is increasingly important with respect to new biopesticides that frequently cause no short-term acute effects, but that can induce multiple physiological and behavioral sublethal effects, leading to a decrease in population growth and ecosystem services. In this study we assessed the lethal and sublethal effects of six biopesticides [abamectin, azadirachtin, Bacillus thuringiensis, borax plus citrus oil (Prev-Am®), emamectin benzoate, and spinosad], used in tomato crops to control the invasive pest Tuta absoluta (Lepidoptera: Gelechiidae), on adults and pupae of the parasitoid Bracon nigricans (Hymenoptera: Braconidae). Data on female survival and production of female offspring were used to calculate population growth indexes as a measure of population recovery after pesticide exposure. Spinosad caused 100% and 80% mortality in exposed adults (even 10 d after the treatment) and pupae, respectively. Although most of the biopesticides had low levels of acute toxicity, multiple sublethal effects were observed. The biocontrol activity of both females that survived 1-h and 10-d old residues, and females that emerged from topically treated pupae was significantly affected by the application of the neurotoxic insecticides emamectin benzoate and abamectin. Furthermore, very low B. nigricans demographic growth indices were estimated for these two insecticides, indicating potential local extinction of the wasp populations. Among the tested products, Bt proved to be the safest for B. nigricans adults and pupae. Our findings emphasize that acute toxicity assessment alone cannot fully predict the actual impact of pesticides on non-target parasitoids. Thus, sublethal effects related to the species specific life-history variables must be carefully considered in order to assess pesticide risks and to incorporate new pesticides, including biopesticides, into IPM programmes. PMID:24098793

Predation risk affects growth and reproduction of an invasive snail and its lethal effect depends on prey size

PubMed Central

Guo, Jing; Martín, Pablo R.; Zhang, Chunxia

2017-01-01

The behavior of invasive species under predation risk has been studied extensively, but their growth and reproductive responses have rarely been investigated. We conducted experiments with juveniles and adults of the invasive freshwater snail Pomacea canaliculata, and we observed changes in growth and reproduction in response to predation risk from a caged predator (Trachemys scripta elegans). P. canaliculata produced eggs earlier in the presence of predators and injured conspecifics compared with the control group (no risk), although the total number of egg masses laid by per female was exceeded by that of the controls after 15 days. Egg hatching success noticeably decreased under predation risk, and the incubation period was significantly prolonged; however, the oviposition height of the snails was not affected. A lethal effect of predation risk was detected in juvenile snails but not in adults. The growth of juvenile P. canaliculata was inhibited under predation risk, probably due to a reduction in food intake. Adult females exhibited a greater reduction in growth under predation risk than males, which likely resulted in part from the high reproductive investment of females in egg laying. These results indicate that P. canaliculata snails under predation risk face a trade-off between predator avoidance and growth and reproduction, where the lethal effect of predation risk is linked to the size of the prey. PMID:29136660

[Prognostic value of the lethal triad among patients with multiple trauma].

PubMed

González Balverde, María; Ramírez Lizardo, Ernesto J; Cardona Muñoz, Ernesto G; Totsuka Sutto, Sylvia E; García Benavides, Leonel

2013-11-01

Patients who have suffered multiple traumatic injuries, have a serious risk for death. Hypothermia, acidosis and coagulopathy are three complications in these patients, whose presence is known as lethal triad and indicates bad prognosis. To determine if the lethal triad in multiple trauma patients is associated with higher mortality and Injury Score Severity (ISS). One hundred multiple trauma patients aged 26 to 56 years (90 males), admitted to an emergency room, were studied. Body temperature, prothrombin time, partial thromboplastin time, platelet count and blood gases were determined on admission. Twenty six patients had the lethal triad and 15% died in the emergency room within the first 6 hours. No death was recorded among the 74 patients without the lethal triad. The mean ISS among patients with and without the lethal triad was 31.7 and 25.6, respectively (p < 0.05). The presence of the lethal triad among patients with multiple trauma is associated with a higher mortality and ISS.

STATISTICAL APPROACH TO PREDICTING CHRONIC TOXICITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA

EPA Science Inventory

A comprehensive approach to predicting chronic toxicity from cute toxicity data was developed in which simultaneous onsideration is given to concentration, degree of response, and ime course of effect. onsistent endpoint (lethality) and degree of response (0 percent) were used to...

Protection against Acute Lethal Viral Infections with the Native Steroid Dehydroepiandrosterone (DHEA)

DTIC Science & Technology

1988-01-01

of gout , hyperlipemia, and in post-coronary patients Protection Against Viral Inftiom With DHEA 311 [Regelson, 19881. In animal models [Yen, 19771 and...3333. Johnson DA, Schultz LD, Bedigian HG (1982): Immunodeficiency and reticulum cell sarcoma in mice segregating for HRS/J and SJL/J genes . Leukemia

Prediction of pesticide acute toxicity using two-dimensional chemical descriptors and target species classification

EPA Science Inventory

Previous modelling of the median lethal dose (oral rat LD50) has indicated that local class-based models yield better correlations than global models. We evaluated the hypothesis that dividing the dataset by pesticidal mechanisms would improve prediction accuracy. A linear discri...

Acute Effects of an Alternative Electronic-Control-Device Waveform in Swine

DTIC Science & Technology

2009-03-01

sequences in a normal individual. Bozeman [32] suggested that lethality due to ECD impact could be due to hyperkalemia related to muscle contraction...and our previous investigations [1, 2], there may be a wide margin of safety, relative to hyperkalemia , for most ECD applications. The increase in

78 FR 36671 - Acetamiprid; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

... one of the following methods: Federal eRulemaking Portal: http://www.regulations.gov . Follow the... validity, completeness, and reliability as well as the relationship of the results of the studies to human... toxic in acute lethality studies via the oral route of exposure and is minimally toxic via the dermal...

Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus).

PubMed

Laura, Bongiovanni; Nicola, Di Girolamo; Alessandro, Montani; Leonardo, Della Salda; Paolo, Selleri

2014-05-01

Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors.

Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus)

PubMed Central

Laura, Bongiovanni; Nicola, Di Girolamo; Alessandro, Montani; Leonardo, Della Salda; Paolo, Selleri

2014-01-01

Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors. PMID:25183148

Lethal and nonlethal violence against an intimate female partner: comparing male murderers to nonlethal abusers.

PubMed

Dobash, R Emerson; Dobash, Russell P; Cavanagh, Kate; Medina-Ariza, Juanjo

2007-04-01

Men's lethal and nonlethal violence against an intimate female partner are compared. Various risk factors are examined to compare men's lethal and nonlethal violence against an intimate woman partner. Relative to abusers, men who kill are generally more conventional with respect to childhood backgrounds, education, employment, and criminal careers, are more likely to be possessive and jealous, and are more likely to be separated from their partner at the time of the event. Men who kill are more likely to have used violence against a previous partner, to have sexually assaulted and strangled the victim, and to have used a weapon or instrument. However, they were less likely to have been drunk at the time of the event and/or to have previously used violence against the woman they killed. Overall, the findings do not support the notion of a simple progression from nonlethal to lethal violence and raise some dilemmas for the growing area of risk assessment.

Lifestyle and dietary factors in the prevention of lethal prostate cancer

PubMed Central

Wilson, Kathryn M; Giovannucci, Edward L; Mucci, Lorelei A

2012-01-01

The prevention of lethal prostate cancer is a critical public health challenge that would improve health and reduce suffering from this disease. In this review, we discuss the evidence surrounding specific lifestyle and dietary factors in the prevention of lethal prostate cancer. We present a summary of evidence for the following selected behavioral risk factors: obesity and weight change, physical activity, smoking, antioxidant intake, vitamin D and calcium, and coffee intake. PMID:22504869

Killing wolves to prevent predation on livestock may protect one farm but harm neighbors

PubMed Central

Cornman, Ari M.; Treves, Adrian

2018-01-01

Large carnivores, such as gray wolves, Canis lupus, are difficult to protect in mixed-use landscapes because some people perceive them as dangerous and because they sometimes threaten human property and safety. Governments may respond by killing carnivores in an effort to prevent repeated conflicts or threats, although the functional effectiveness of lethal methods has long been questioned. We evaluated two methods of government intervention following independent events of verified wolf predation on domestic animals (depredation) in the Upper Peninsula of Michigan, USA between 1998–2014, at three spatial scales. We evaluated two intervention methods using log-rank tests and conditional Cox recurrent event, gap time models based on retrospective analyses of the following quasi-experimental treatments: (1) selective killing of wolves by trapping near sites of verified depredation, and (2) advice to owners and haphazard use of non-lethal methods without wolf-killing. The government did not randomly assign treatments and used a pseudo-control (no removal of wolves was not a true control), but the federal permission to intervene lethally was granted and rescinded independent of events on the ground. Hazard ratios suggest lethal intervention was associated with an insignificant 27% lower risk of recurrence of events at trapping sites, but offset by an insignificant 22% increase in risk of recurrence at sites up to 5.42 km distant in the same year, compared to the non-lethal treatment. Our results do not support the hypothesis that Michigan’s use of lethal intervention after wolf depredations was effective for reducing the future risk of recurrence in the vicinities of trapping sites. Examining only the sites of intervention is incomplete because neighbors near trapping sites may suffer the recurrence of depredations. We propose two new hypotheses for perceived effectiveness of lethal methods: (a) killing predators may be perceived as effective because of the benefits to a small minority of farmers, and (b) if neighbors experience side-effects of lethal intervention such as displaced depredations, they may perceive the problem growing and then demand more lethal intervention rather than detecting problems spreading from the first trapping site. Ethical wildlife management guided by the “best scientific and commercial data available” would suggest suspending the standard method of trapping wolves in favor of non-lethal methods (livestock guarding dogs or fladry) that have been proven effective in preventing livestock losses in Michigan and elsewhere. PMID:29320512

Acute contact toxicity test of insecticides (Cipermetrina 25, Lorsban 48E, Thionex 35) on honeybees in the southwestern zone of Uruguay.

PubMed

Carrasco-Letelier, Leonidas; Mendoza-Spina, Yamandú; Branchiccela, María Belén

2012-07-01

Glyphosate-resistant soybean cultivation is expanding rapidly in Uruguay, with its land area having increased by 95 times during the past 10 years. Because of the region's Neotropical conditions, insecticide use is required to ensure adequate soybean productivity. However, in areas shared by soybean crops and beekeepers - such as the southwestern zone of Uruguay (SWZU) - the use of insecticides can increase the risks of honeybee death and honey contamination. Uruguayan commercial and legal guidelines set out practices and field doses designed to prevent acute intoxication with insecticides. However, honeybees in the SWZU are predominantly a polyhybrid subspecies different from that used to set international reference values, and hence they may have a different acute toxicity response, thus rendering such precautions ineffective. The aim of this work was to assess the acute toxicity response of polyhybrid honeybees in the SWZU to cypermethrin (commercial formulation: Cipermetrina 25 Agrin®), chlorpyrifos (commercial formulation: Lorsban 48E®), and endosulfan (commercial formulation: Thionex 35®). Acute toxicity bioassays were conducted to determine the median lethal dose (LD(50)) of each insecticide for the honeybees. The results indicate that, compared with EU reference values, SWZU honeybees have a higher toxicological sensitivity to chlorpyrifos and endosulfan, and a lower toxicological sensitivity to cypermethrin, based on the commercial formulations tested. However, when these results were adjusted according to their field dose equivalents, only chlorpyrifos emerged as a potential problem for beekeeping, as the maximum recommended field dose of Lorsban 48E® for soybean crops in Uruguay is 23 times the corresponding LD(50) for honeybees in the SWZU. Copyright © 2012 Elsevier Ltd. All rights reserved.

Role of acute ethanol exposure and TLR4 in early events of sepsis in a mouse model

PubMed Central

Bhatty, Minny; Jan, Basit L; Tan, Wei; Pruett, Stephen B; Nanduri, Bindu

2011-01-01

Sepsis is a major cause of death worldwide. The associated risks and mortality are known to significantly increase on exposure to alcohol (chronic or acute). The underlying mechanisms of the association of acute ethanol ingestion and poor prognosis of sepsis are largely unknown. The study described here was designed to determine in detail the role of ethanol and TLR4 in the pathogenesis of the sepsis syndrome. The effects of acute ethanol exposure and TLR4 on bacterial clearance, spleen cell numbers, peritoneal macrophage numbers, and cytokine production were evaluated using wild type and TLR4 hypo-responsive mice treated with ethanol and then challenged with a non pathogenic strain of Escherichia. coli (E. coli). Ethanol treated mice exhibited a decreased clearance of bacteria and produced lesser amounts of most pro-inflammatory cytokines in both strains of mice at two hours after challenge. Neither ethanol treatment nor a hypo-responsive TLR4 had significant effects on the cell numbers in the peritoneal cavity and spleen 2 hours post infection. The suppressive effect of acute ethanol exposure on cytokine and chemokine production was more pronounced in the wild type mice, but the untreated hyporesponsive mice produced less of most cytokines than untreated wild type mice. The major conclusion of this study is that acute ethanol exposure suppresses pro-inflammatory cytokine production and that a hypo-responsive TLR4 (in C3H/HeJ mice) decreases pro-inflammatory cytokine levels but the cytokines and other mediators induced through other receptors are sufficient to ultimately clear the infection but not enough to induce lethal septic shock. In addition, results reported here demonstrate previously unknown effects of acute ethanol exposure on LIF (leukemia inhibitory factor) and eotaxin and provide the first evidence that IL-9 is induced through TLR4 in vivo. PMID:21872420

Using accelerated life testing procedures to compare the relative sensitivity of rainbow trout and the federally listed threatened bull trout to three commonly used rangeland herbicides (picloram, 2,4-D, and clopyralid).

PubMed

Fairchild, James F; Allert, Ann; Sappington, Linda S; Nelson, Karen J; Valle, Janet

2008-03-01

We conducted 96-h static acute toxicity studies to evaluate the relative sensitivity of juveniles of the threatened bull trout (Salvelinus confluentus) and the standard cold-water surrogate rainbow trout (Onchorhyncus mykiss) to three rangeland herbicides commonly used for controlling invasive weeds in the northwestern United States. Relative species sensitivity was compared using three procedures: standard acute toxicity testing, fractional estimates of lethal concentrations, and accelerated life testing chronic estimation procedures. The acutely lethal concentrations (ALC) resulting in 50% mortality at 96 h (96-h ALC50s) were determined using linear regression and indicated that the three herbicides were toxic in the order of picloram acid > 2,4-D acid > clopyralid acid. The 96-h ALC50 values for rainbow trout were as follows: picloram, 41 mg/L; 2.4-D, 707 mg/L; and clopyralid, 700 mg/L. The 96-h ALC50 values for bull trout were as follows: picloram, 24 mg/L; 2.4-D, 398 mg/L; and clopyralid, 802 mg/L. Fractional estimates of safe concentrations, based on 5% of the 96-h ALC50, were conservative (overestimated toxicity) of regression-derived 96-h ALC5 values by an order of magnitude. Accelerated life testing procedures were used to estimate chronic lethal concentrations (CLC) resulting in 1% mortality at 30 d (30-d CLC1) for the three herbicides: picloram (1 mg/L rainbow trout, 5 mg/L bull trout), 2,4-D (56 mg/L rainbow trout, 84 mg/L bull trout), and clopyralid (477 mg/L rainbow trout; 552 mg/L bull trout). Collectively, the results indicated that the standard surrogate rainbow trout is similar in sensitivity to bull trout. Accelerated life testing procedures provided cost-effective, statistically defensible methods for estimating safe chronic concentrations (30-d CLC1s) of herbicides from acute toxicity data because they use statistical models based on the entire mortality:concentration:time data matrix.

Using accelerated life testing procedures to compare the relative sensitivity of rainbow trout and the federally listed threatened bull trout to three commonly used rangeland herbicides (picloram, 2,4-D, and clopyralid)

USGS Publications Warehouse

Fairchild, J.F.; Allert, A.; Sappington, L.S.; Nelson, K.J.; Valle, J.

2008-01-01

We conducted 96-h static acute toxicity studies to evaluate the relative sensitivity of juveniles of the threatened bull trout (Salvelinus confluentus) and the standard cold-water surrogate rainbow trout (Onchorhyncus mykiss) to three rangeland herbicides commonly used for controlling invasive weeds in the northwestern United States. Relative species sensitivity was compared using three procedures: standard acute toxicity testing, fractional estimates of lethal concentrations, and accelerated life testing chronic estimation procedures. The acutely lethal concentrations (ALC) resulting in 50% mortality at 96 h (96-h ALC50s) were determined using linear regression and indicated that the three herbicides were toxic in the order of picloram acid > 2,4-D acid > clopyralid acid. The 96-h ALC50 values for rainbow trout were as follows: picloram, 41 mg/L; 2.4-D, 707 mg/L; and clopyralid, 700 mg/L. The 96-h ALC50 values for bull trout were as follows: picloram, 24 mg/L; 2.4-D, 398 mg/L; and clopyralid, 802 mg/L. Fractional estimates of safe concentrations, based on 5% of the 96-h ALC50, were conservative (overestimated toxicity) of regression-derived 96-h ALC5 values by an order of magnitude. Accelerated life testing procedures were used to estimate chronic lethal concentrations (CLC) resulting in 1% mortality at 30 d (30-d CLC1) for the three herbicides: picloram (1 mg/L rainbow trout, 5 mg/L bull trout), 2,4-D (56 mg/L rainbow trout, 84 mg/L bull trout), and clopyralid (477 mg/L rainbow trout; 552 mg/L bull trout). Collectively, the results indicated that the standard surrogate rainbow trout is similar in sensitivity to bull trout. Accelerated life testing procedures provided cost-effective, statistically defensible methods for estimating safe chronic concentrations (30-d CLC1s) of herbicides from acute toxicity data because they use statistical models based on the entire mortality:concentration: time data matrix. ?? 2008 SETAC.

Microwave and Man—The Direct and Indirect Hazards, and the Precautions

PubMed Central

Merckel, Charles

1972-01-01

Microwave-radar is a form of electromagnetic energy with potential hazards to human health and safety. Its lethal and non-lethal harmful effects have been demonstrated in experimental animals. Lethal effects upon humans from exposure to microwave have not been proved. Alleged non-lethal effects have been limited primarily to cataractogenesis. Increasing use of microwave commercially in communications and domestically, as in micro-ovens, increases the hazard of exposure to microwave. Increasing use of devices which are at risk from microwave, such as implanted cardiac pacemakers and metal surgical appliances and electronic monitoring devices in operating rooms and clinics, present increasing environmental hazards. PMID:5039801

Mice Lacking RIP3 Kinase are not Protected from Acute Radiation Syndrome.

PubMed

Castle, Katherine D; Daniel, Andrea R; Moding, Everett J; Luo, Lixia; Lee, Chang-Lung; Kirsch, David G

2018-06-01

Exposure to high doses of ionizing radiation can cause lethal injury to normal tissue, thus inducing acute radiation syndrome. Acute radiation syndrome is caused by depletion of bone marrow cells (hematopoietic syndrome) and irreparable damage to the epithelial cells in the gastrointestinal tract (gastrointestinal syndrome). Although radiation initiates apoptosis in the hematopoietic and gastrointestinal compartments within the first few hours after exposure, alternative mechanisms of cell death may contribute to injury in these radiosensitive tissues. In this study, we utilized mice lacking a critical regulator of necroptosis, receptor interacting protein 3 (RIP3) kinase, to characterize the role of RIP3 in normal tissue toxicity after irradiation. Our results suggest that RIP3-mediated signaling is not a critical driver of acute radiation syndrome.

An acute toxicity study of Heliotropium scottae Rendle in mice.

PubMed

Wahome, W M; Muchiri, D J; Mugera, G M

1994-08-01

Twenty-four hour ip median lethal doses (LD50) of freeze-dried aqueous extracts of Heliotropium scottae Rendle leaves and stems in mice were determined and clinical signs noted. The LD50 of the leaf extract was 3.0 g/kg, while that of the stems was 3.5 g/kg. Clinical signs were excitement, prostration, rapid breathing, gasping for breath and death. The signs were the same for both the leaf and stem extracts. It was concluded that both the leaves and stems of H scottae have slight acute toxicity.

Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

PubMed Central

Carrion, Andres F.; Czul, Frank; Arosemena, Leopoldo R.; Selvaggi, Gennaro; Garcia, Monica T.; Tekin, Akin; Tzakis, Andreas G.; Martin, Paul; Ghanta, Ravi K.

2010-01-01

Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death. PMID:21234410

Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.

PubMed

Lindow, Janet C; Wunder, Elsio A; Popper, Stephen J; Min, Jin-Na; Mannam, Praveen; Srivastava, Anup; Yao, Yi; Hacker, Kathryn P; Raddassi, Khadir; Lee, Patty J; Montgomery, Ruth R; Shaw, Albert C; Hagan, Jose E; Araújo, Guilherme C; Nery, Nivison; Relman, David A; Kim, Charles C; Reis, Mitermayer G; Ko, Albert I

2016-11-01

Leptospirosis causes significant morbidity and mortality worldwide; however, the role of the host immune response in disease progression and high case fatality (>10-50%) is poorly understood. We conducted a multi-parameter investigation of patients with acute leptospirosis to identify mechanisms associated with case fatality. Whole blood transcriptional profiling of 16 hospitalized Brazilian patients with acute leptospirosis (13 survivors, 3 deceased) revealed fatal cases had lower expression of the antimicrobial peptide, cathelicidin, and chemokines, but more abundant pro-inflammatory cytokine receptors. In contrast, survivors generated strong adaptive immune signatures, including transcripts relevant to antigen presentation and immunoglobulin production. In an independent cohort (23 survivors, 22 deceased), fatal cases had higher bacterial loads (P = 0.0004) and lower anti-Leptospira antibody titers (P = 0.02) at the time of hospitalization, independent of the duration of illness. Low serum cathelicidin and RANTES levels during acute illness were independent risk factors for higher bacterial loads (P = 0.005) and death (P = 0.04), respectively. To investigate the mechanism of cathelicidin in patients surviving acute disease, we administered LL-37, the active peptide of cathelicidin, in a hamster model of lethal leptospirosis and found it significantly decreased bacterial loads and increased survival. Our findings indicate that the host immune response plays a central role in severe leptospirosis disease progression. While drawn from a limited study size, significant conclusions include that poor clinical outcomes are associated with high systemic bacterial loads, and a decreased antibody response. Furthermore, our data identified a key role for the antimicrobial peptide, cathelicidin, in mounting an effective bactericidal response against the pathogen, which represents a valuable new therapeutic approach for leptospirosis.

Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death

PubMed Central

Na, Rong; Zheng, S. Lilly; Han, Misop; Yu, Hongjie; Jiang, Deke; Shah, Sameep; Ewing, Charles M.; Zhang, Liti; Novakovic, Kristian; Petkewicz, Jacqueline; Gulukota, Kamalakar; Helseth, Donald L.; Quinn, Margo; Humphries, Elizabeth; Wiley, Kathleen E.; Isaacs, Sarah D.; Wu, Yishuo; Liu, Xu; Zhang, Ning; Wang, Chi-Hsiung; Khandekar, Janardan; Hulick, Peter J.; Shevrin, Daniel H.; Cooney, Kathleen A.; Shen, Zhoujun; Partin, Alan W.; Carter, H. Ballentine; Carducci, Michael A.; Eisenberger, Mario A.; Denmeade, Sam R.; McGuire, Michael; Walsh, Patrick C.; Helfand, Brian T.; Brendler, Charles B.; Ding, Qiang; Xu, Jianfeng; Isaacs, William B.

2017-01-01

Background Germline mutations in BRCA1/2 and ATM have been associated with prostate cancer (PCa) risk. Objective To directly assess whether germline mutations in these three genes distinguish lethal from indolent PCa and whether they confer any effect on age at death. Design, setting, and participants A retrospective case-case study of 313 patients who died of PCa and 486 patients with low-risk localized PCa of European, African, and Chinese descent. Germline DNA of each of the 799 patients was sequenced for these three genes. Outcome measurements and statistical analysis Mutation carrier rates and their effect on lethal PCa were analyzed using the Fisher’s exact test and Cox regression analysis, respectively. Results and limitations The combined BRCA1/2 and ATM mutation carrier rate was significantly higher in lethal PCa patients (6.07%) than localized PCa patients (1.44%), p = 0.0007. The rate also differed significantly among lethal PCa patients as a function of age at death (10.00%, 9.08%, 8.33%, 4.94%, and 2.97% in patients who died ≤60 yr, 61–65 yr, 66–70 yr, 71–75 yr, and over 75 yr, respectively, p = 0.046) and time to death after diagnosis (12.26%, 4.76%, and 0.98% in patients who died ≤5 yr, 6–10 yr, and > 10 yr after a PCa diagnosis, respectively, p = 0.0006). Survival analysis in the entire cohort revealed mutation carriers remained an independent predictor of lethal PCa after adjusting for race and age, prostate-specific antigen, and Gleason score at the time of diagnosis (hazard ratio = 2.13, 95% confidence interval: 1.24–3.66, p = 0.004). A limitation of this study is that other DNA repair genes were not analyzed. Conclusions Mutation status of BRCA1/2 and ATM distinguishes risk for lethal and indolent PCa and is associated with earlier age at death and shorter survival time. Patient summary Prostate cancer patients with inherited mutations in BRCA1/2 and ATM are more likely to die of prostate cancer and do so at an earlier age. PMID:27989354

Developing a Comprehensive Risk Assessment Framework for Geological Storage CO 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duncan, Ian

2014-08-31

The operational risks for CCS projects include: risks of capturing, compressing, transporting and injecting CO₂; risks of well blowouts; risk that CO 2 will leak into shallow aquifers and contaminate potable water; and risk that sequestered CO 2 will leak into the atmosphere. This report examines these risks by using information on the risks associated with analogue activities such as CO 2 based enhanced oil recovery (CO 2-EOR), natural gas storage and acid gas disposal. We have developed a new analysis of pipeline risk based on Bayesian statistical analysis. Bayesian theory probabilities may describe states of partial knowledge, even perhapsmore » those related to non-repeatable events. The Bayesian approach enables both utilizing existing data and at the same time having the capability to adsorb new information thus to lower uncertainty in our understanding of complex systems. Incident rates for both natural gas and CO 2 pipelines have been widely used in papers and reports on risk of CO 2 pipelines as proxies for the individual risk created by such pipelines. Published risk studies of CO 2 pipelines suggest that the individual risk associated with CO2 pipelines is between 10 -3 and 10 -4, which reflects risk levels approaching those of mountain climbing, which many would find unacceptably high. This report concludes, based on a careful analysis of natural gas pipeline failures, suggests that the individual risk of CO 2 pipelines is likely in the range of 10-6 to 10-7, a risk range considered in the acceptable to negligible range in most countries. If, as is commonly thought, pipelines represent the highest risk component of CCS outside of the capture plant, then this conclusion suggests that most (if not all) previous quantitative- risk assessments of components of CCS may be orders of magnitude to high. The potential lethality of unexpected CO 2 releases from pipelines or wells are arguably the highest risk aspects of CO 2 enhanced oil recovery (CO2-EOR), carbon capture, and storage (CCS). Assertions in the CCS literature, that CO 2 levels of 10% for ten minutes, or 20 to 30% for a few minutes are lethal to humans, are not supported by the available evidence. The results of published experiments with animals exposed to CO 2, from mice to monkeys, at both normal and depleted oxygen levels, suggest that lethal levels of CO 2 toxicity are in the range 50 to 60%. These experiments demonstrate that CO 2 does not kill by asphyxia, but rather is toxic at high concentrations. It is concluded that quantitative risk assessments of CCS have overestimated the risk of fatalities by using values of lethality a factor two to six lower than the values estimated in this paper. In many dispersion models of CO 2 releases from pipelines, no fatalities would be predicted if appropriate levels of lethality for CO 2 had been used in the analysis.« less

Correlation between In Vitro Cytotoxicity and In Vivo Lethal Activity in Mice of Epsilon Toxin Mutants from Clostridium perfringens

PubMed Central

Dorca-Arévalo, Jonatan; Pauillac, Serge; Díaz-Hidalgo, Laura; Martín-Satué, Mireia; Popoff, Michel R.; Blasi, Juan

2014-01-01

Epsilon toxin (Etx) from Clostridium perfringens is a pore-forming protein with a lethal effect on livestock, producing severe enterotoxemia characterized by general edema and neurological alterations. Site-specific mutations of the toxin are valuable tools to study the cellular and molecular mechanism of the toxin activity. In particular, mutants with paired cysteine substitutions that affect the membrane insertion domain behaved as dominant-negative inhibitors of toxin activity in MDCK cells. We produced similar mutants, together with a well-known non-toxic mutant (Etx-H106P), as green fluorescent protein (GFP) fusion proteins to perform in vivo studies in an acutely intoxicated mouse model. The mutant (GFP-Etx-I51C/A114C) had a lethal effect with generalized edema, and accumulated in the brain parenchyma due to its ability to cross the blood-brain barrier (BBB). In the renal system, this mutant had a cytotoxic effect on distal tubule epithelial cells. The other mutants studied (GFP-Etx-V56C/F118C and GFP-Etx-H106P) did not have a lethal effect or cross the BBB, and failed to induce a cytotoxic effect on renal epithelial cells. These data suggest a direct correlation between the lethal effect of the toxin, with its cytotoxic effect on the kidney distal tubule cells, and the ability to cross the BBB. PMID:25013927

Correlation between in vitro cytotoxicity and in vivo lethal activity in mice of epsilon toxin mutants from Clostridium perfringens.

PubMed

Dorca-Arévalo, Jonatan; Pauillac, Serge; Díaz-Hidalgo, Laura; Martín-Satué, Mireia; Popoff, Michel R; Blasi, Juan

2014-01-01

Epsilon toxin (Etx) from Clostridium perfringens is a pore-forming protein with a lethal effect on livestock, producing severe enterotoxemia characterized by general edema and neurological alterations. Site-specific mutations of the toxin are valuable tools to study the cellular and molecular mechanism of the toxin activity. In particular, mutants with paired cysteine substitutions that affect the membrane insertion domain behaved as dominant-negative inhibitors of toxin activity in MDCK cells. We produced similar mutants, together with a well-known non-toxic mutant (Etx-H106P), as green fluorescent protein (GFP) fusion proteins to perform in vivo studies in an acutely intoxicated mouse model. The mutant (GFP-Etx-I51C/A114C) had a lethal effect with generalized edema, and accumulated in the brain parenchyma due to its ability to cross the blood-brain barrier (BBB). In the renal system, this mutant had a cytotoxic effect on distal tubule epithelial cells. The other mutants studied (GFP-Etx-V56C/F118C and GFP-Etx-H106P) did not have a lethal effect or cross the BBB, and failed to induce a cytotoxic effect on renal epithelial cells. These data suggest a direct correlation between the lethal effect of the toxin, with its cytotoxic effect on the kidney distal tubule cells, and the ability to cross the BBB.

Oleoresin Capsicum toxicology evaluation and hazard review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Archuleta, M.M.

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

Microvesicles Derived from Mesenchymal Stem Cells Enhance Survival in a Lethal Model of Acute Kidney Injury

PubMed Central

Bruno, Stefania; Grange, Cristina; Collino, Federica; Deregibus, Maria Chiara; Cantaluppi, Vincenzo; Biancone, Luigi; Tetta, Ciro; Camussi, Giovanni

2012-01-01

Several studies demonstrated that treatment with mesenchymal stem cells (MSCs) reduces cisplatin mortality in mice. Microvesicles (MVs) released from MSCs were previously shown to favor renal repair in non lethal toxic and ischemic acute renal injury (AKI). In the present study we investigated the effects of MSC-derived MVs in SCID mice survival in lethal cisplatin-induced AKI. Moreover, we evaluated in vitro the effect of MVs on cisplatin-induced apoptosis of human renal tubular epithelial cells and the molecular mechanisms involved. Two different regimens of MV injection were used. The single administration of MVs ameliorated renal function and morphology, and improved survival but did not prevent chronic tubular injury and persistent increase in BUN and creatinine. Multiple injections of MVs further decreased mortality and at day 21 surviving mice showed normal histology and renal function. The mechanism of protection was mainly ascribed to an anti-apoptotic effect of MVs. In vitro studies demonstrated that MVs up-regulated in cisplatin-treated human tubular epithelial cells anti-apoptotic genes, such as Bcl-xL, Bcl2 and BIRC8 and down-regulated genes that have a central role in the execution-phase of cell apoptosis such as Casp1, Casp8 and LTA. In conclusion, MVs released from MSCs were found to exert a pro-survival effect on renal cells in vitro and in vivo, suggesting that MVs may contribute to renal protection conferred by MSCs. PMID:22431999

The ability of filgrastim to mitigate mortality following LD50/60 total-body irradiation is administration time-dependent.

PubMed

Farese, Ann M; Brown, Cassandra R; Smith, Cassandra P; Gibbs, Allison M; Katz, Barry P; Johnson, Cynthia S; Prado, Karl L; MacVittie, Thomas J

2014-01-01

The identification of the optimal administration schedule for an effective medical countermeasure is critical for the effective treatment of individuals exposed to potentially lethal doses of radiation. The efficacy of filgrastim (Neupogen®), a potential medical countermeasure, to improve survival when initiated at 48 h following total body irradiation in a non-human primate model of the hematopoietic syndrome of the acute radiation syndrome was investigated. Animals were exposed to total body irradiation, antero-posterior exposure, total midline tissue dose of 7.5 Gy, (target lethal dose 50/60) delivered at 0.80 Gy min, using linear accelerator-derived 6 MV photons. All animals were administered medical management. Following irradiation on day 0, filgrastim (10 μg kg d) or the control (5% dextrose in water) was administered subcutaneously daily through effect (absolute neutrophil count ≥ 1,000 cells μL for three consecutive days). The study (n = 80) was powered to demonstrate a 25% improvement in survival following the administration of filgrastim or control beginning at 48 ± 4 h post-irradiation. Survival analysis was conducted on the intention-to-treat population using a two-tailed null hypothesis at a 5% significance level. Filgrastim, initiated 48 h after irradiation, did not improve survival (2.5% increase, p = 0.8230). These data demonstrate that efficacy of a countermeasure to mitigate lethality in the hematopoietic syndrome of the acute radiation syndrome can be dependent on the interval between irradiation and administration of the medical countermeasure.

Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice.

PubMed

Martinez, Elisa C; Garg, Ravendra; Shrivastava, Pratima; Gomis, Susantha; van Drunen Littel-van den Hurk, Sylvia

2016-11-01

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in infants and young children. There are no licensed RSV vaccines available, and the few treatment options for high-risk individuals are either extremely costly or cause severe side effects and toxicity. Immunomodulation mediated by a novel formulation consisting of the toll-like receptor 3 agonist poly(I:C), an innate defense regulator peptide and a polyphosphazene (P-I-P) was evaluated in the context of lethal infection with pneumonia virus of mice (PVM). Intranasal delivery of a single dose of P-I-P protected adult mice against PVM when given 24 h prior to challenge. These animals experienced minimal weight loss, no clinical disease, 100% survival, and reduced lung pathology. Similar clinical outcomes were observed in mice treated up to 3 days prior to infection. P-I-P pre-treatment induced early mRNA and protein expression of key chemokine and cytokine genes, reduced the recruitment of neutrophils and eosinophils, decreased virus titers in the lungs, and modulated the delayed exacerbated nature of PVM disease without any short-term side effects. On day 14 post-infection, P-I-P-treated mice were confirmed to be PVM-free. These results demonstrate the capacity of this formulation to prevent PVM and possibly other viral respiratory infections. Copyright © 2016 Elsevier B.V. All rights reserved.

Pathways to Suicide in Australian Farmers: A Life Chart Analysis.

PubMed

Kunde, Lisa; Kõlves, Kairi; Kelly, Brian; Reddy, Prasuna; De Leo, Diego

2017-03-28

Farmers have been found to be at increased risk of suicide in Australia. The Interpersonal-Psychological Theory of Suicidal Behaviour suggests that the proximal factors leading to the suicidal desire or ideation include an individual's experiences of both perceived burdensomeness and thwarted belongingness. Suicidal desire with acquired capability to engage in lethal self-injury is predictive of suicidal behaviour. This study investigates the pathways to suicide of 18 Australian male farmers in order to understand the suicidal process and antecedents to suicide in Australian male farmers. The psychological autopsy (PA) method was used to generate life charts. Two pathways with distinct suicidal processes were identified: acute situational (romantic relationship problems and financial concerns/pending retirement) and protracted (long-term psychiatric disorder). Long working hours, interpersonal conflicts, physical illnesses and pain, alcohol abuse, access to firearms, and exposure to drought were additional common factors identified. An understanding of the interrelatedness of diverse distal and proximal risk factors on suicidal pathways in the wider environmental context for male farmers is required when developing and implementing rural suicide prevention activities.

Pathways to Suicide in Australian Farmers: A Life Chart Analysis

PubMed Central

Kunde, Lisa; Kõlves, Kairi; Kelly, Brian; Reddy, Prasuna; De Leo, Diego

2017-01-01

Farmers have been found to be at increased risk of suicide in Australia. The Interpersonal-Psychological Theory of Suicidal Behaviour suggests that the proximal factors leading to the suicidal desire or ideation include an individual’s experiences of both perceived burdensomeness and thwarted belongingness. Suicidal desire with acquired capability to engage in lethal self-injury is predictive of suicidal behaviour. This study investigates the pathways to suicide of 18 Australian male farmers in order to understand the suicidal process and antecedents to suicide in Australian male farmers. The psychological autopsy (PA) method was used to generate life charts. Two pathways with distinct suicidal processes were identified: acute situational (romantic relationship problems and financial concerns/pending retirement) and protracted (long-term psychiatric disorder). Long working hours, interpersonal conflicts, physical illnesses and pain, alcohol abuse, access to firearms, and exposure to drought were additional common factors identified. An understanding of the interrelatedness of diverse distal and proximal risk factors on suicidal pathways in the wider environmental context for male farmers is required when developing and implementing rural suicide prevention activities. PMID:28350368

A COMPARISON OF THE LETHAL AND SUBLETHAL TOXICITY OF ORGANIC CHEMICAL MIXTURES TO THE FATHEAD MINNOW (PIMEPHALES PROMELAS)

EPA Science Inventory

This study was designed to define the degree of concentration addition found for mixtures of certain xenobiotics that are thought to act through a similar or different mode of toxic action for the acute mortality and sublethal growth toxicity endpoints, and for a freshwater fish ...

40 CFR Appendix A to Part 300 - The Hazard Ranking System

Code of Federal Regulations, 2011 CFR

2011-07-01

... control groups. For HRS purposes, the response considered is cancer. [milligrams toxicant per kilogram...-2Containment factor values for surface water migration pathway. 4-3Drainage area values. 4-4Soil group... a group of exposed organisms. The LC50 is used in the HRS in assessing acute toxicity. LD 50 (lethal...

40 CFR Appendix A to Part 300 - The Hazard Ranking System

Code of Federal Regulations, 2012 CFR

2012-07-01

... control groups. For HRS purposes, the response considered is cancer. [milligrams toxicant per kilogram...-2Containment factor values for surface water migration pathway. 4-3Drainage area values. 4-4Soil group... a group of exposed organisms. The LC50 is used in the HRS in assessing acute toxicity. LD 50 (lethal...

Effects of acute low temperature events on development of Erysiphe necator and susceptibility of Vitis vinifera

USDA-ARS?s Scientific Manuscript database

Growth and development of Erysiphe necator (syn. Uncinula necator) has been extensively studied under controlled conditions, primarily with a focus on development within the optimal temperature range and the lethal effects of high temperatures. Little is known of the effect of cold temperatures on ...

Central nervous system radiation syndrome in mice from preferential 10B(n, alpha)7Li irradiation of brain vasculature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slatkin, D.N.; Stoner, R.D.; Rosander, K.M.

1988-06-01

Ionizing radiations were directed at the heads of anesthetized mice in doses that evoked the acute central nervous system (CNS) radiation syndrome. Irradiations were done using either a predominantly thermal neutron field at a nuclear reactor after intraperitoneal injection of 10B-enriched boric acid or 250-kilovolt-peak x-rays with and without previous intraperitoneal injection of equivalent unenriched boric acid. Since 10B concentrations were approximately equal to 3-fold higher in blood than in cerebral parenchyma during the reactor irradiations, more radiation from alpha and 7Li particles was absorbed by brain endothelial cells than by brain parenchymal cells. Comparison of the LD50 dose formore » CNS radiation lethality from the reactor experiments with the LD50 dose from the x-ray experiments gives results compatible with morphologic evidence that endothelial cell damage is a major determinant of acute lethality from the CNS radiation syndrome. It was also observed that boric acid is a low linear energy transfer radiation-enhancement agent in vivo.« less

Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gombar, V.K.; Enslein, K.; Hart, J.B.

1991-09-01

A quantitative structure-activity relationship (QSAR) model has been developed to estimate maximum tolerated doses (MTD) from structural features of chemicals and the corresponding oral acute lethal doses (LD50) as determined in male rats. The model is based on a set of 269 diverse chemicals which have been tested under the National Cancer Institute/National Toxicology Program (NCI/NTP) protocols. The rat oral LD50 value was the strongest predictor. Additionally, 22 structural descriptors comprising nine substructural MOLSTAC(c) keys, three molecular connectivity indices, and sigma charges on 10 molecular fragments were identified as endpoint predictors. The model explains 76% of the variance and ismore » significant (F = 35.7) at p less than 0.0001 with a standard error of the estimate of 0.40 in the log (1/mol) units used in Hansch-type equations. Cross-validation showed that the difference between the average deleted residual square (0.179) and the model residual square (0.160) was not significant (t = 0.98).« less

Moringa oleifera extract (Lam) attenuates Aluminium phosphide-induced acute cardiac toxicity in rats.

PubMed

Gouda, Ahmed S; El-Nabarawy, Nagla A; Ibrahim, Samah F

2018-01-01

Moringa oleifera extract (Lam) has many antioxidant and protective properties. Objective: to investigate the antioxidant activities of Lam in counteracting the high oxidative stress caused by acute sub-lethal aluminium phosphide (AlP) intoxication in rat heart. These activities will be detected by histopathological examination and some oxidative stress biomarkers. a single sub-lethal dose of Alp (2 mg/kg body weight) was administered orally, and Lam was given orally at a dose (100 mg/kg body weight) one hour after receiving AlP to rats. aluminium phosphide caused significant cardiac histopathological changes with a significant increase in malondialdehyde (MDA); lipid peroxidation marker; and a significant depletion of antioxidant enzymes (catalase and glutathione reductase). However, treatment with Lam protected efficiently the cardiac tissue of intoxicated rats by increasing antioxidants levels with slight decreasing in MDA production compared to untreated group. This study suggested that Moringa oleifera extract could possibly restore the altered cardiac histopathology and some antioxidant power in AlP intoxicated rats, and it could even be used as adjuvant therapy against AlP-induced cardiotoxicity.

Comparative evaluation of effects of ozonated and chlorinated thermal discharges on estuarine and fresh water organisms. First quarterly progress report, April 1979

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guerra, C.R.; DelMonaco, J.L.; Singletary, J.H.

1979-01-01

The biological evaluation program incorporates three types of experimental tests: acute (96 hour) toxicity studies; behavioral (avoidance) response studies; and physiological (cough) response studies. In addition, specimens used in testing are examined for physical damage resulting from exposure to chlorine or ozoen. The objective of the acute (96 hour) toxicity study is to determine the respective lethal levels (LC/sub 50/) of chlorinated and ozonated waters. The objective of the behavioral (avoidance) response study is to determine what (if any) concentrations of ozone and of chlorine will be avoided. The objective of physiological (cough) response study is to determine what concentrationsmore » of ozone and of chlorine are physiologically detected. Ozonated and chlorinated waters were evaluated in all studies for both the addition of increased temperature and without it. Results indicate that ozone is less toxic than chlorine under the test conditions used. The lethal levels vary according to species of water quality measurements at Bergen Generating Station, New York are tabulated. (JBG)« less

Can Winter-Active Bumblebees Survive the Cold? Assessing the Cold Tolerance of Bombus terrestris audax and the Effects of Pollen Feeding

PubMed Central

Owen, Emily L.; Bale, Jeffrey S.; Hayward, Scott A. L.

2013-01-01

There is now considerable evidence that climate change is disrupting the phenology of key pollinator species. The recently reported UK winter activity of the bumblebee Bombus terrestris brings a novel set of thermal challenges to bumblebee workers that would typically only be exposed to summer conditions. Here we assess the ability of workers to survive acute and chronic cold stress (via lower lethal temperatures and lower lethal times at 0°C), the capacity for rapid cold hardening (RCH) and the influence of diet (pollen versus nectar consumption) on supercooling points (SCP). Comparisons are made with chronic cold stress indices and SCPs in queen bumblebees. Results showed worker bees were able to survive acute temperatures likely to be experienced in a mild winter, with queens significantly more tolerant to chronic cold temperature stress. The first evidence of RCH in any Hymenoptera is shown. In addition, dietary manipulation indicated the consumption of pollen significantly increased SCP temperature. These results are discussed in the light of winter active bumblebees and climate change. PMID:24224036

Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders.

PubMed

Hatcher, Christopher L; Mott, Tiffany M; Muruato, Laura A; Sbrana, Elena; Torres, Alfredo G

2016-08-01

Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Overcoming myelosuppression due to synthetic lethal toxicity for FLT3-targeted acute myeloid leukemia therapy

PubMed Central

Warkentin, Alexander A; Lopez, Michael S; Lasater, Elisabeth A; Lin, Kimberly; He, Bai-Liang; Leung, Anskar YH; Smith, Catherine C; Shah, Neil P; Shokat, Kevan M

2014-01-01

Activating mutations in FLT3 confer poor prognosis for individuals with acute myeloid leukemia (AML). Clinically active investigational FLT3 inhibitors can achieve complete remissions but their utility has been hampered by acquired resistance and myelosuppression attributed to a ‘synthetic lethal toxicity’ arising from simultaneous inhibition of FLT3 and KIT. We report a novel chemical strategy for selective FLT3 inhibition while avoiding KIT inhibition with the staurosporine analog, Star 27. Star 27 maintains potency against FLT3 in proliferation assays of FLT3-transformed cells compared with KIT-transformed cells, shows no toxicity towards normal human hematopoiesis at concentrations that inhibit primary FLT3-mutant AML blast growth, and is active against mutations that confer resistance to clinical inhibitors. As a more complete understanding of kinase networks emerges, it may be possible to define anti-targets such as KIT in the case of AML to allow improved kinase inhibitor design of clinical agents with enhanced efficacy and reduced toxicity. DOI: http://dx.doi.org/10.7554/eLife.03445.001 PMID:25531068

Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: Engineering a recombination-resistant genome

NASA Astrophysics Data System (ADS)

Yount, Boyd; Roberts, Rhonda S.; Lindesmith, Lisa; Baric, Ralph S.

2006-08-01

Live virus vaccines provide significant protection against many detrimental human and animal diseases, but reversion to virulence by mutation and recombination has reduced appeal. Using severe acute respiratory syndrome coronavirus as a model, we engineered a different transcription regulatory circuit and isolated recombinant viruses. The transcription network allowed for efficient expression of the viral transcripts and proteins, and the recombinant viruses replicated to WT levels. Recombinant genomes were then constructed that contained mixtures of the WT and mutant regulatory circuits, reflecting recombinant viruses that might occur in nature. Although viable viruses could readily be isolated from WT and recombinant genomes containing homogeneous transcription circuits, chimeras that contained mixed regulatory networks were invariantly lethal, because viable chimeric viruses were not isolated. Mechanistically, mixed regulatory circuits promoted inefficient subgenomic transcription from inappropriate start sites, resulting in truncated ORFs and effectively minimize viral structural protein expression. Engineering regulatory transcription circuits of intercommunicating alleles successfully introduces genetic traps into a viral genome that are lethal in RNA recombinant progeny viruses. regulation | systems biology | vaccine design

Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer: Report From the 2015 Coffey-Holden Prostate Cancer Academy Meeting

PubMed Central

Miyahira, Andrea K.; Lang, Joshua M.; Den, Robert B.; Garraway, Isla P.; Lotan, Tamara L.; Ross, Ashley E.; Stoyanova, Tanya; Cho, Steve Y.; Simons, Jonathan W.; Pienta, Kenneth J.; Soule, Howard R.

2018-01-01

BACKGROUND The 2015 Coffey-Holden Prostate Cancer Academy Meeting, themed: “Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer,” was held in La Jolla, California from June 25 to 28, 2015. METHODS The Prostate Cancer Foundation (PCF) sponsors an annual, invitation-only, action-tank-structured meeting on a critical topic concerning lethal prostate cancer. The 2015 meeting was attended by 71 basic, translational, and clinical investigators who discussed the current state of the field, major unmet needs, and ideas for addressing earlier diagnosis and treatment of men with lethal prostate cancer for the purpose of extending lives and making progress toward a cure. RESULTS The questions addressed at the meeting included: cellular and molecular mechanisms of tumorigenesis, evaluating, and targeting the microenvironment in the primary tumor, advancing biomarkers for clinical integration, new molecular imaging technologies, clinical trials, and clinical trial design in localized high-risk and oligometastatic settings, targeting the primary tumor in advanced disease, and instituting multi-modal care of high risk and oligometastatic patients. DISCUSSION This article highlights the current status, greatest unmet needs, and anticipated field changes that were discussed at the meeting toward the goal of optimizing earlier interventions to potentiate cures in high-risk and oligometastatic prostate cancer patients. PMID:26477609

Multidisciplinary intervention of early, lethal metastatic prostate cancer: Report from the 2015 Coffey-Holden Prostate Cancer Academy Meeting.

PubMed

Miyahira, Andrea K; Lang, Joshua M; Den, Robert B; Garraway, Isla P; Lotan, Tamara L; Ross, Ashley E; Stoyanova, Tanya; Cho, Steve Y; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2016-02-01

The 2015 Coffey-Holden Prostate Cancer Academy Meeting, themed: "Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer," was held in La Jolla, California from June 25 to 28, 2015. The Prostate Cancer Foundation (PCF) sponsors an annual, invitation-only, action-tank-structured meeting on a critical topic concerning lethal prostate cancer. The 2015 meeting was attended by 71 basic, translational, and clinical investigators who discussed the current state of the field, major unmet needs, and ideas for addressing earlier diagnosis and treatment of men with lethal prostate cancer for the purpose of extending lives and making progress toward a cure. The questions addressed at the meeting included: cellular and molecular mechanisms of tumorigenesis, evaluating, and targeting the microenvironment in the primary tumor, advancing biomarkers for clinical integration, new molecular imaging technologies, clinical trials, and clinical trial design in localized high-risk and oligometastatic settings, targeting the primary tumor in advanced disease, and instituting multi-modal care of high risk and oligometastatic patients. This article highlights the current status, greatest unmet needs, and anticipated field changes that were discussed at the meeting toward the goal of optimizing earlier interventions to potentiate cures in high-risk and oligometastatic prostate cancer patients. © 2015 Wiley Periodicals, Inc.

Blue light treatment of Pseudomonas aeruginosa: Strong bactericidal activity, synergism with antibiotics and inactivation of virulence factors.

PubMed

Fila, Grzegorz; Kawiak, Anna; Grinholc, Mariusz Stanislaw

2017-08-18

Pseudomonas aeruginosa is among the most common pathogens responsible for both acute and chronic infections of high incidence and severity. Additionally, P. aeruginosa resistance to conventional antimicrobials has increased rapidly over the past decade. Therefore, it is crucial to explore new therapeutic options, particularly options that specifically target the pathogenic mechanisms of this microbe. The ability of a pathogenic bacterium to cause disease is dependent upon the production of agents termed 'virulence factors', and approaches to mitigate these agents have gained increasing attention as new antibacterial strategies. Although blue light irradiation is a promising alternative approach, only limited and preliminary studies have described its effect on virulence factors. The current study aimed to investigate the effects of lethal and sub-lethal doses of blue light treatment (BLT) on P. aeruginosa virulence factors. We analyzed the inhibitory effects of blue light irradiation on the production/activity of several virulence factors. Lethal BLT inhibited the activity of pyocyanin, staphylolysin, pseudolysin and other proteases, but sub-lethal BLT did not affect the production/expression of proteases, phospholipases, and flagella- or type IV pili-associated motility. Moreover, a eukaryotic cytotoxicity test confirmed the decreased toxicity of blue light-treated extracellular P. aeruginosa fractions. Finally, the increased antimicrobial susceptibility of P. aeruginosa treated with sequential doses of sub-lethal BLT was demonstrated with a checkerboard test. Thus, this work provides evidence-based proof of the susceptibility of drug-resistant P. aeruginosa to BLT-mediated killing, accompanied by virulence factor reduction, and describes the synergy between antibiotics and sub-lethal BLT.

The role of oxidative stress in organophosphate and nerve agent toxicity

PubMed Central

Pearson, Jennifer N.; Patel, Manisha

2016-01-01

Organophosphate nerve agents exert their toxicity through inhibition of acetylcholinesterase. The excessive stimulation of cholinergic receptors rapidly causes neuronal damage, seizures, death, and long-term neurological impairment in those that survive. Owing to the lethality of organophosphorus agents and the growing risk they pose, medical interventions that prevent organophosphate toxicity and the delayed injury response are much needed. Studies have shown that oxidative stress occurs in models of subacute, acute, and chronic exposure to organophosphate agents. Key findings of these studies include alterations in mitochondrial function and increased free radical–mediated injury, such as lipid peroxidation. This review focuses on the role of reactive oxygen species in organophosphate neurotoxicity and its dependence on seizure activity. Understanding the sources, mechanisms, and pathological consequences of organophosphate-induced oxidative stress can lead to the development of rational therapies for treating toxic exposures. PMID:27371936

The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

PubMed

MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

2012-10-01

The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for efficacy and interaction during the concomitant evolution of acute and delayed key organ-specific subsyndromes.

THE CANNABINOID RECEPTOR ANTAGONIST AM251 INCREASES PARAOXON AND CHLORPYRIFOS OXON TOXICITY IN RATS

PubMed Central

Liu, Jing; Pope, Carey

2014-01-01

Organophosphorus anticholinesterases (OPs) elicit acute toxicity by inhibiting acetylcholinesterase (AChE), leading to acetylcholine accumulation and overstimulation of cholinergic receptors. Endocannabinoids (eCBs, e.g., arachidonoyl ethanolamide [AEA] and 2-arachidonoyl glycerol [2-AG]) are neuromodulators that regulate neurotransmission by reducing neurotransmitter release. The eCBs are degraded by the enzymes fatty acid amide hydrolase (FAAH, primarily involved in hydrolysis of AEA) and monoacylglycerol lipase (MAGL, primarily responsible for metabolism of 2-AG). We previously reported that the cannabinoid receptor agonist WIN 55,212-2 reduced cholinergic toxicity after paraoxon exposure. This study compared the effects of the cannabinoid receptor antagonist AM251 on acute toxicity following either paraoxon (PO) or chlorpyrifos oxon (CPO). CPO was more potent in vitro than PO at inhibiting AChE (≈ 2 fold), FAAH (≈ 8 fold), and MAGL (≈ 19 fold). Rats were treated with vehicle, PO (0.3 and 0.6 mg/kg, sc.) or CPO (6 and 12 mg/kg, sc.) and subsets treated with AM251 (3 mg/kg, ip; 30 min after OP). Signs of toxicity were recorded for four hours and rats were then sacrificed. OP-treated rats showed dose-related involuntary movements, with AM251 increasing signs of toxicity with the lower dosages. PO and CPO elicited excessive secretions, but AM251 had no apparent effect with either OP. Lethality was increased by AM251 with the higher dosage of PO, but no lethality was noted with either dosage of CPO, with or without AM251. Both OPs caused extensive inhibition of hippocampal AChE and FAAH (>80–90%), but only CPO inhibited MAGL (37–50%). These results provide further evidence that eCB signaling can influence acute OP toxicity. The selective in vivo inhibition of MAGL by CPO may be important in the differential lethality noted between PO and CPO with AM251 co-administration. PMID:25447325

Lethal and sublethal effects of chlorine, phenol, and chlorine-phenol mixtures on the mud crab, Panopeus herbstii.

PubMed

Key, P B; Scott, G I

1986-11-01

The mud crab, Panopeus herbstii, was acutely exposed (96-hr) to chlorine-produced oxidants (CPO), phenol, and a CPO-phenolic mixture (1:1) to determine lethal and sublethal effects. The 96-hr (LC50) values were determined for each individual compound and mixture. Additionally, whole-animal respiration rates were measured following acute exposure to sublethal concentrations of each compound or mixture. Phenol uptake/depuration rates were measured in the phenol and CPO-phenol mixture concentrations. Results indicated 96-hr LC50 values of 1.06 mg/L for CPO (fiducial limits (FL) = 0.53-2.01 mg/L), 52.8 mg/L for phenol (FL = 45.6-64.5 mg/L), and 184.7 mg/L total toxicant units (TTU) for the CPO-phenol mixture (FL = 143.7-250.2 mg/L TTU). Statistical analysis indicated that the acute toxicity of the CPO-phenol mixture was less than additive. Sublethal studies indicated that only acute exposure to sublethal concentrations of CPO caused altered respiration rates. After 96-hr depuration, metabolic rates in all CPO-exposure crabs generally returned to control rates. Uptake/depuration rate studies indicated significantly lower phenol uptake rates in crabs exposed to the CPO-phenol mixture. These findings suggest that the less-than-additive toxicity of the CPO-phenol mixture may result from lowered uptake/depuration rate kinetics and indicate that the discharge of chlorinated-phenolic waste may not result in additive and/or synergistic interactions, but rather in less-than-additive effects on decapod aquatic species.

Responses of bay anchovy (Anchoa mitchilli) larvae under lethal and sublethal scenarios of crude oil exposure.

PubMed

Duffy, Tara A; Childress, William; Portier, Ralph; Chesney, Edward J

2016-12-01

Bay anchovy (Anchoa mitchilli) is an ecologically important zooplanktivorous fish inhabiting estuaries of the Gulf of Mexico and eastern North America from Maine to Florida. Because they have a protracted spawning season (spring through fall) and are abundant at all life stages in coastal estuaries, their eggs and larvae likely encountered oil that reached the coast during the Deepwater Horizon oil spill. We compared responses to oil exposure at different life stages and at lethal and sublethal conditions using acute, 24h exposures. In a series of experiments, bay anchovy larvae were exposed to high energy water accommodated fractions (HEWAF) and chemically-enhanced WAF (CEWAF) at two stages of larval development (5 and 21 days post hatch, dph). HEWAF oil exposures induced significantly greater life stage dependent sensitivity at 5 dph than at 21 dph but chemically dispersed (CEWAF) exposure mortality was more variable and LC 50s were not significantly different between 5 and 21dph larvae. Acute exposure to two low-level concentrations of CEWAF did not result in significant mortality over 24h, but resulted in a 25-77% reduction in larval survival and a 12-34% reduction in weight specific growth after six days of post-exposure growth following the initial 24h exposure. These results show that younger (5 dph) bay anchovy larvae are more vulnerable to acute oil exposure than older (21 dph) larvae, and that acute responses do not accurately reflect potential population level mortality and impacts to growth and development. Copyright © 2016 Elsevier Inc. All rights reserved.

The acute toxicity of chemically and physically dispersed crude oil to key arctic species under arctic conditions during the open water season

PubMed Central

Gardiner, William W; Word, Jack Q; Word, Jack D; Perkins, Robert A; McFarlin, Kelly M; Hester, Brian W; Word, Lucinda S; Ray, Collin M

2013-01-01

The acute toxicity of physically and chemically dispersed crude oil and the dispersant Corexit 9500 were evaluated for key Arctic species. The copepod Calanus glacialis, juvenile Arctic cod (Boreogadus saida), and larval sculpin (Myoxocephalus sp.) were tested under conditions representative of the Beaufort and Chukchi Seas during the ice-free season. The toxicity of 3 water-accommodated fractions (WAF) of Alaska North Slope crude oil was examined with spiked, declining exposures. A dispersant-only test was conducted with the copepod C. glacialis. Each preparation with oil (WAF, breaking wave WAF [BWWAF], and chemically enhanced WAF [CEWAF]) produced distinct suites of hydrocarbon constituents; the total concentrations of oil were lowest in WAF and highest in CEWAF preparations. The relative sensitivity for the different species and age classes was similar within each WAF type. Median lethal concentration values based on total petroleum hydrocarbons ranged from 1.6 mg/L to 4.0 mg/L for WAF and BWWAF treatments and from 22 mg/L to 62 mg/L for CEWAF. For Corexit 9500 exposures, median lethal concentration values ranged from 17 mg/L to 50 mg/L. The differences in the relative toxicity among the accommodated fractions indicated that the majority of petroleum hydrocarbons in the CEWAF are in less acutely toxic forms than the components that dominate the WAF or BWWAF. Further evaluation showed that the parent polycyclic aromatic hydrocarbon compounds, specifically naphthalene, were highly correlated to acute toxicity. Environ Toxicol Chem 2013;32:2284–2300. PMID:23765555

Psychosocial influences on prisoner suicide: a case-control study of near-lethal self-harm in women prisoners.

PubMed

Marzano, Lisa; Hawton, Keith; Rivlin, Adrienne; Fazel, Seena

2011-03-01

We examined the psychosocial influences on female prisoner suicide by carrying out a study of near-lethal self-harm. We interviewed 60 women prisoners who had recently engaged in near-lethal self-harm (cases) and 60 others who had never carried out near-lethal acts in prison (controls) from all closed female prison establishments in England and Wales, using mixed quantitative and qualitative methods. We gathered information on socio-demographic and criminological variables, life events and childhood trauma, exposure to suicidal behaviour, contributory and precipitating factors for near-lethal self-harm, social support and psychological characteristics. While socio-demographic factors were only modestly associated with near-lethal self-harm, being on remand, in single cell accommodation, and reporting negative experiences of imprisonment were strong correlates. Recent life events and past trauma, including different forms of childhood abuse, were also significantly associated with near-lethal self-harm, as were a family history of suicide and high scores on measures of depression, aggression, impulsivity and hostility, and low levels of self-esteem and social support. Our findings underline the importance of both individual and prison-related factors for suicide in custody, and hence the need for a comprehensive approach to suicide prevention in women's prisons. Given the multiple needs of female prisoners at-risk of self-harm and suicide, complex psychosocial interventions are likely to be required, including interventions for abused and bereaved women, and initiatives to improve staff-prisoner relationships and reduce bullying. The findings of this research may provide insights into factors leading to suicidal behaviour in other forensic and institutional settings, such as detention centres and psychiatric hospitals, and may assist in developing suicide prevention policies for prisoners and other at-risk populations. Copyright © 2011 Elsevier Ltd. All rights reserved.

Toxicity of trace element and salinity mixtures to striped bass (Morone saxatilis) and Daphnia magna

USGS Publications Warehouse

Dwyer, F.J.; Burch, S.A.; Ingersoll, C.G.; Hunn, J.B.

1992-01-01

Acute toxicity tests with reconstituted water were conducted to investigate the relationship between water hardness, salinity, and a mixture of trace elements found in irrigation drain waters entering Stillwater Wildlife Management Area (SWMA), near Fallon, Nevada. The SWMA has been the site of many fish kills in recent years, and previous toxicity studies indicated that one drain water, Pintail Bay, was acutely toxic to organisms acclimated or cultured in fresh water or salt water. This toxicity could reflect both the ionic composition of this saline water and the presence of trace elements. The lowest water salinity tested with Daphnia magna was near the upper salinity tolerance of these organisms; therefore, we were unable to differentiate between the toxic effects of ion composition and those of trace elements. In toxicity tests conducted with striped bass (Morone saxatilis), we found that the extent to which salinity was lethal to striped bass depended on the ion composition of that salinity. Survival of striped bass increased as hardness increased. In addition, a trace element mixture was toxic to striped bass, even though the concentrations of individual elements were below expected acutely lethal concentrations. Although salinity is an important water quality characteristic, the ionic composition of the water must be considered when one assesses the hazard of irrigation drain waters to aquatic organisms.

Successful bailout stenting strategy against lethal coronary dissection involving left main bifurcation.

PubMed

Kubota, Hiroshi; Nomura, Tetsuya; Hori, Yusuke; Yoshioka, Kenichi; Miyawaki, Daisuke; Urata, Ryota; Sugimoto, Takeshi; Kikai, Masakazu; Keira, Natsuya; Tatsumi, Tetsuya

2017-06-01

Catheter-induced coronary dissection involving left main bifurcation is a rare complication during cardiac catheterization but can become lethal unless it is treated appropriately. Interventional cardiologists always have to pay attention to the risk of complications related to cardiac catheterization and prepare for determining the best bailout strategy for the situation.

[The experience of organization of medical care of patients with acute coronary syndrome in multi-type hospital].

PubMed

Zagidullin, B I; Khairullin, I I; Stanichenko, N S; Zagidullin, I M; Zagidullin, N Sh

2016-01-01

In Naberezhnye Chelny, a number of structural and technological reformations of service of emergency medical care was implemented in 2009-2012. The reformation manifested in organization of unified emergency center of medical care of patients with acute coronary syndrome; joining up of cardiological departments of two hospitals; organization of X-ray surgical department; enhancement of logistics of admission department and interaction with emergency medical care; optimization of mode of medical care rendering at pre-hospital and hospital stages. The implemented reforms permitted increasing accessibility and timeliness of reperfusion therapy under acute coronary syndrome; to implement transcutaneous coronary interventions into practice and increase their number annually; to decrease “door-balloon” index up to 30-40%. As a result, lethality of acute myocardium infarction decreased from 12 to 3 to 5.8% in 2010-2014.

Factors modifying the response of large animals to low-intensity radiation exposure

NASA Technical Reports Server (NTRS)

Page, N. P.; Still, E. T.

1972-01-01

In assessing the biological response to space radiation, two of the most important modifying factors are dose protraction and dose distribution to the body. Studies are reported in which sheep and swine were used to compare the hematology and lethality response resulting from radiation exposure encountered in a variety of forms, including acute (high dose-rate), chronic (low dose-rate), combinations of acute and chronic, and whether received as a continuous or as fractionated exposure. While sheep and swine are basically similar in response to acute radiation, their sensitivity to chronic irradiation is markedly different. Sheep remain relatively sensitive as the radiation exposure is protracted while swine are more resistant and capable of surviving extremely large doses of chronic irradiation. This response to chronic irradiation correlated well with changes in radiosensitivity and recovery following an acute, sublethal exposure.

Toluene inducing acute respiratory failure in a spray paint sniffer.

PubMed

Peralta, Diego P; Chang, Aymara Y

2012-01-01

Toluene, formerly known as toluol, is an aromatic hydrocarbon that is widely used as an industrial feedstock and as a solvent. Like other solvents, toluene is sometimes also used as an inhalant drug for its intoxicating properties. It has potential to cause multiple effects in the body including death. I report a case of a 27-year-old male, chronic spray paint sniffer, who presented with severe generalized muscle weakness and developed acute respiratory failure requiring ventilatory support. Toluene toxicity was confirmed with measurement of hippuric acid of 8.0 g/L (normal <5.0 g/L). Acute respiratory failure is a rare complication of chronic toluene exposure that may be lethal if it is not recognized immediately. To our knowledge, this is the second case of acute respiratory failure due to toluene exposure.

Toluene inducing acute respiratory failure in a spray paint sniffer

PubMed Central

Peralta, Diego P.; Chang, Aymara Y.

2012-01-01

Summary Background: Toluene, formerly known as toluol, is an aromatic hydrocarbon that is widely used as an industrial feedstock and as a solvent. Like other solvents, toluene is sometimes also used as an inhalant drug for its intoxicating properties. It has potential to cause multiple effects in the body including death. Case Report: I report a case of a 27-year-old male, chronic spray paint sniffer, who presented with severe generalized muscle weakness and developed acute respiratory failure requiring ventilatory support. Toluene toxicity was confirmed with measurement of hippuric acid of 8.0 g/L (normal <5.0 g/L). Conclusions: Acute respiratory failure is a rare complication of chronic toluene exposure that may be lethal if it is not recognized immediately. To our knowledge, this is the second case of acute respiratory failure due to toluene exposure. PMID:23569498

Low forced vital capacity predicts cytotoxic chemotherapy-associated acute exacerbation of interstitial lung disease in patients with lung cancer.

PubMed

Enomoto, Yasunori; Inui, Naoki; Kato, Terufumi; Baba, Tomohisa; Karayama, Masato; Nakamura, Yutaro; Ogura, Takashi; Suda, Takafumi

2016-06-01

Although acute exacerbation of pre-existing interstitial lung disease (AE-ILD) associated with cytotoxic chemotherapy has been recognized as a severe complication in lung cancer treatment, its risk factors have not been fully studied. Among lung cancer patients receiving cytotoxic chemotherapy, patients with pre-existing ILD were identified based on the pretreatment high-resolution computed tomography (HRCT) findings. Chemotherapy-associated AE-ILD was defined as deterioration or development of dyspnea and HRCT findings of new bilateral ground-glass attenuations with/without non-segmental consolidation superimposed on pre-existing interstitial shadows, without evidence of pulmonary infection, congestion, or pulmonary embolism, within four weeks after the last administration of chemotherapy. Baseline characteristics were reviewed and the risk factors for chemotherapy-associated AE-ILD were evaluated by logistic regression analyses. Among 85 patients identified as having pre-existing ILD, chemotherapy-associated AE-ILD occurred in 26 patients (30.6%); 8 patients died and 11 patients had a severely deteriorated general condition despite intensive treatment. Compared with those without AE-ILD, patients with AE-ILD had significantly lower forced vital capacity (FVC) (median: 91.1% versus 76.6%, P=0.01). Univariate and multivariate logistic regression analyses identified baseline lower FVC and non-small cell lung cancer (NSCLC) as the risk factors for this severe event (odds ratio of FVC: 0.97, 95% confidence interval: 0.94-0.99; odds ratio of NSCLC: 4.65, 95% confidence interval: 1.10-19.76). Chemotherapy-associated AE-ILD was a frequent and lethal complication in lung cancer treatment for patients with pre-existing ILD. Spirometric assessment of pulmonary function may be useful to predict the event. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mortality differences between men and women following first myocardial infarction. RESCATE Investigators. Recursos Empleados en el Síndrome Coronario Agudo y Tiempo de Espera.

PubMed

Marrugat, J; Sala, J; Masiá, R; Pavesi, M; Sanz, G; Valle, V; Molina, L; Serés, L; Elosua, R

1998-10-28

Mortality after acute myocardial infarction is worse in women than in men, even after adjustment for comorbidity and age dissimilarities between sexes. To assess the influence of sex on survival after acute myocardial infarction. Inception cohort obtained in a prospective registry of patients with acute myocardial infarction from 1992 through 1994. Four teaching hospitals in northeastern Spain. All consecutive patients aged 80 years or younger with first acute myocardial infarction. A total of 331 women and 1129 men were included. Survival at 28 days and mortality or readmission at 6 months. Women were older (mean, 68.6 vs 60.1 years), presented more often with diabetes (52.9% vs 23.3%), hypertension (63.9% vs 42.3%), or previous angina (44.6% vs 37.4%), and developed more severe myocardial infarctions than men (acute pulmonary edema or cardiogenic shock occurred in 24.8% of women and 10.5% of men) (all P<.02). Men were more likely than women to receive thrombolytic therapy (41.3% vs 23.9%; P<.001), but rates of percutaneous transluminal angioplasty and coronary artery bypass graft surgery at 28 days were similar among men and women. The 28-day mortality rate was significantly higher among women (18.5% for women, 8.3% for men; P<.001). Revascularization procedures at 6 months were performed in a similar proportion of women and men. However, women had higher 6-month mortality rates (25.8% in women, 10.8% in men; P<.001) and readmission rates (23.3% for women, 12.2% for men; P<.001). After adjustment, women had greater risk of death than men at 28 days (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.12-2.65) and at 6 months (OR, 1.73; 95% CI, 1.18-2.52). In this study population, women experienced more lethal and severe first acute myocardial infarction than men, regardless of comorbidity, age, or previous angina.

Integrating metabolic performance, thermal tolerance, and plasticity enables for more accurate predictions on species vulnerability to acute and chronic effects of global warming.

PubMed

Magozzi, Sarah; Calosi, Piero

2015-01-01

Predicting species vulnerability to global warming requires a comprehensive, mechanistic understanding of sublethal and lethal thermal tolerances. To date, however, most studies investigating species physiological responses to increasing temperature have focused on the underlying physiological traits of either acute or chronic tolerance in isolation. Here we propose an integrative, synthetic approach including the investigation of multiple physiological traits (metabolic performance and thermal tolerance), and their plasticity, to provide more accurate and balanced predictions on species and assemblage vulnerability to both acute and chronic effects of global warming. We applied this approach to more accurately elucidate relative species vulnerability to warming within an assemblage of six caridean prawns occurring in the same geographic, hence macroclimatic, region, but living in different thermal habitats. Prawns were exposed to four incubation temperatures (10, 15, 20 and 25 °C) for 7 days, their metabolic rates and upper thermal limits were measured, and plasticity was calculated according to the concept of Reaction Norms, as well as Q10 for metabolism. Compared to species occupying narrower/more stable thermal niches, species inhabiting broader/more variable thermal environments (including the invasive Palaemon macrodactylus) are likely to be less vulnerable to extreme acute thermal events as a result of their higher upper thermal limits. Nevertheless, they may be at greater risk from chronic exposure to warming due to the greater metabolic costs they incur. Indeed, a trade-off between acute and chronic tolerance was apparent in the assemblage investigated. However, the invasive species P. macrodactylus represents an exception to this pattern, showing elevated thermal limits and plasticity of these limits, as well as a high metabolic control. In general, integrating multiple proxies for species physiological acute and chronic responses to increasing temperature helps providing more accurate predictions on species vulnerability to warming. © 2014 John Wiley & Sons Ltd.

A lethal murine infection model for dengue virus 3 in AG129 mice deficient in type I and II interferon receptors leads to systemic disease.

PubMed

Sarathy, Vanessa V; White, Mellodee; Li, Li; Gorder, Summer R; Pyles, Richard B; Campbell, Gerald A; Milligan, Gregg N; Bourne, Nigel; Barrett, Alan D T

2015-01-15

The mosquito-borne disease dengue (DEN) is caused by four serologically and genetically related viruses, termed DENV-1 to DENV-4. Infection with one DENV usually leads to acute illness and results in lifelong homotypic immunity, but individuals remain susceptible to infection by the other three DENVs. The lack of a small-animal model that mimics systemic DEN disease without neurovirulence has been an obstacle, but DENV-2 models that resemble human disease have been recently developed in AG129 mice (deficient in interferon alpha/beta and interferon gamma receptor signaling). However, comparable DENV-1, -3, and -4 models have not been developed. We utilized a non-mouse-adapted DENV-3 Thai human isolate to develop a lethal infection model in AG129 mice. Intraperitoneal inoculation of six to eight-week-old animals with strain C0360/94 led to rapid, fatal disease. Lethal C0360/94 infection resulted in physical signs of illness, high viral loads in the spleen, liver, and large intestine, histological changes in the liver and spleen tissues, and increased serum cytokine levels. Importantly, the animals developed vascular leakage, thrombocytopenia, and leukopenia. Overall, we have developed a lethal DENV-3 murine infection model, with no evidence of neurotropic disease based on a non-mouse-adapted human isolate, which can be used to investigate DEN pathogenesis and to evaluate candidate vaccines and antivirals. This suggests that murine models utilizing non-mouse-adapted isolates can be obtained for all four DENVs. Dengue (DEN) is a mosquito-borne disease caused by four DENV serotypes (DENV-1, -2, -3, and -4) that have no treatments or vaccines. Primary infection with one DENV usually leads to acute illness followed by lifelong homotypic immunity, but susceptibility to infection by the other three DENVs remains. Therefore, a vaccine needs to protect from all four DENVs simultaneously. To date a suitable animal model to mimic systemic human illness exists only for DENV-2 in immunocompromised mice using passaged viruses; however, models are still needed for the remaining serotypes. This study describes establishment of a lethal systemic DENV-3 infection model with a human isolate in immunocompromised mice and is the first report of lethal infection by a nonadapted clinical DENV isolate without evidence of neurological disease. Our DENV-3 model provides a relevant platform to test DEN vaccines and antivirals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Lethal pneumatosis coli in a 12-month-old child caused by acute intestinal gas gangrene after prolonged artificial nutrition: a case report

PubMed Central

Kircher, Stefan; Wössner, Rupert; Müller-Hermelink, Hans-Konrad; Völker, Hans-Ullrich

2008-01-01

Introduction Pneumatosis coli is a rare disease with heterogeneous symptoms which can be detected in the course of various acute and chronic intestinal diseases in children, such as necrotizing enterocolitis, intestinal obstruction and intestinal bacteriological infections. Case presentation We report the case of a 12-month-old boy who died of pneumatosis coli caused by an acute intestinal gas gangrene after prolonged artificial alimentation. Conclusion While intestinal gas gangrene is a highly uncommon cause of pneumatosis coli, it is important to consider it as a differential diagnosis, especially in patients receiving a prolonged artificial food supply. These patients may develop intestinal gas gangrene due to a dysfunctional intestinal barrier. PMID:18652650

A case of massive rhabdomyolysis following molindone administration.

PubMed

Johnson, S B; Alvarez, W A; Freinhar, J P

1986-12-01

Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction.

Sickle cell hepatopathy.

PubMed

Bandyopadhyay, Ranjana; Bandyopadhyay, Sanjay K; Dutta, Anita

2008-01-01

Sickle cell hepatopathy is a well-documented entity that ranges from the self-limiting hepatic right upper quadrant syndrome to the potentially lethal intrahepatic cholestasis and acute hepatic sequestration syndromes. We describe a 26-year-male with homozygous sickle cell disease who had this unique hepatic presentation and was documented to have characteristic findings of cholestasis, portal inflammation and sinusoidal dilatation on histopathology.

ANALYSIS OF THE MOTOR NEUROTOXICITY INDUCED BY ACUTE ORAL EXPOSURE TO MULTIPLE PYRETHROID COMPOUNDS IN THE RAT USING AN ADDITIVITY MODEL.

EPA Science Inventory

Use of pyrethroids has increased in the last decade, and co-exposure to multiple pyrethroids has been reported in humans. Pyrethroids produce neurotoxicity in mammals at dosages far below those producing lethality. The Food Quality Protection Act requires the EPA to consider cumu...

Suicide Lethality: A Concept Analysis.

PubMed

DeBastiani, Summer; De Santis, Joseph P

2018-02-01

Suicide is a significant health problem internationally. Those who complete suicide may have different behaviors and risk factors than those who attempt a non-fatal suicide. The purpose of this article is to analyze the concept of suicide lethality and propose a clear definition of the concept through the identification of antecedents, attributes, and consequences. A literature search for articles published in the English language between 1970 and 2016 was conducted using MEDLINE, the Cochrane Library, Pubmed, Psychlit, Ovid, PsycINFO, and Proquest. The bibliographies of all included studies were also reviewed to identify additional relevant citations. A concept analysis was conducted on the literature findings using six stages of Walker and Avant's method. The concept analysis differentiated between suicide, lethality, suicidal behavior, and suicide lethality. Presence of a suicide plan or a written suicide note was not found to be associated with the majority of completed suicides included in the definition of suicide lethality. There are a few scales that measure the lethality of a suicide attempt, but none that attempt to measure the concept of suicide lethality as described in this analysis. Clarifying the concept of suicide lethality encourages awareness of the possibility of different suicidal behaviors associated with different suicide outcomes and will inform the development of future nursing interventions. A clearer definition of the concept of suicide lethality will guide clinical practice, research, and policy development aimed at suicide prevention.

Ecotoxicological effect of ketamine: Evidence of acute, chronic and photolysis toxicity to Daphnia magna.

PubMed

Li, Shih-Wei; Wang, Yu-Hsiang; Lin, Angela Yu-Chen

2017-09-01

Ketamine has been increasingly used in medicine and has the potential for abuse or illicit use around the world. Ketamine cannot be removed by conventional wastewater treatment plants. Although ketamine and its metabolite norketamine have been detected to a significant degree in effluents and aquatic environments, their ecotoxicity effects in aquatic organisms remain undefined. In this study, we investigated the acute toxicity of ketamine and its metabolite, along with the chronic reproductive toxicity of ketamine (5-100μg/L) to Daphnia magna. Multiple environmental scenarios were also evaluated, including drug mixtures and sunlight irradiation toxicity. Ketamine and norketamine caused acute toxicity to D. magna, with half lethal concentration (LC 50 ) values of 30.93 and 25.35mg/L, respectively, after 48h of exposure. Irradiated solutions of ketamine (20mg/L) significantly increased the mortality of D. magna; pre-irradiation durations up to 2h rapidly increased the death rate to 100%. A new photolysis byproduct (M.W. 241) of norketamine that accumulates during irradiation was identified for the first time. The relevant environmental concentration of ketamine produced significant reproductive toxicity effects in D. magna, as revealed by the reduction of the number of total live offspring by 33.6-49.8% (p < 0.05). The toxicity results indicate that the environmental hazardous risks of the relevant ketamine concentration cannot be ignored and warrant further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

Electrocardiologic and related methods of non-invasive detection and risk stratification in myocardial ischemia: state of the art and perspectives

PubMed Central

Huebner, Thomas; Goernig, Matthias; Schuepbach, Michael; Sanz, Ernst; Pilgram, Roland; Seeck, Andrea; Voss, Andreas

2010-01-01

Background: Electrocardiographic methods still provide the bulk of cardiovascular diagnostics. Cardiac ischemia is associated with typical alterations in cardiac biosignals that have to be measured, analyzed by mathematical algorithms and allegorized for further clinical diagnostics. The fast growing fields of biomedical engineering and applied sciences are intensely focused on generating new approaches to cardiac biosignal analysis for diagnosis and risk stratification in myocardial ischemia. Objectives: To present and review the state of the art in and new approaches to electrocardiologic methods for non-invasive detection and risk stratification in coronary artery disease (CAD) and myocardial ischemia; secondarily, to explore the future perspectives of these methods. Methods: In follow-up to the Expert Discussion at the 2008 Workshop on "Biosignal Analysis" of the German Society of Biomedical Engineering in Potsdam, Germany, we comprehensively searched the pertinent literature and databases and compiled the results into this review. Then, we categorized the state-of-the-art methods and selected new approaches based on their applications in detection and risk stratification of myocardial ischemia. Finally, we compared the pros and cons of the methods and explored their future potentials for cardiology. Results: Resting ECG, particularly suited for detecting ST-elevation myocardial infarctions, and exercise ECG, for the diagnosis of stable CAD, are state-of-the-art methods. New exercise-free methods for detecting stable CAD include cardiogoniometry (CGM); methods for detecting acute coronary syndrome without ST elevation are Body Surface Potential Mapping, functional imaging and CGM. Heart rate variability and blood pressure variability analyses, microvolt T-wave alternans and signal-averaged ECG mainly serve in detecting and stratifying the risk for lethal arrythmias in patients with myocardial ischemia or previous myocardial infarctions. Telemedicine and ambient-assisted living support the electrocardiological monitoring of at-risk patients. Conclusions: There are many promising methods for the exercise-free, non-invasive detection of CAD and myocardial ischemia in the stable and acute phases. In the coming years, these new methods will help enhance state-of-the-art procedures in routine diagnostics. The future can expect that equally novel methods for risk stratification and telemedicine will transition into clinical routine. PMID:21063467

NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dekundy, Andrzej; Kaminski, Rafal M.; Zielinska, Elzbieta

2007-03-15

Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.8 mg/kg), on convulsant and lethal properties of an OP pesticide dichlorvos or a carbamate drug physostigmine, were studied in mice. Both dichlorvos and physostigmine induced dose-dependent seizure activity and lethality. Atropine did not prevent the occurrence of convulsions but decreased the lethal effects ofmore » both dichlorvos and physostigmine. MK-801 or CPP blocked or attenuated, respectively, dichlorvos-induced convulsions. Contrariwise, NMDA antagonists had no effect in physostigmine-induced seizures or lethality produced by dichlorvos or physostigmine. Concurrent pretreatment with atropine and either MK-801 or CPP blocked or alleviated seizures produced by dichlorvos, but not by physostigmine. Both MK-801 and CPP co-administered with atropine enhanced its antilethal effects in both dichlorvos and physostigmine poisoning. In both saline- and AChE inhibitor-treated mice, no interaction of the investigated antidotes with brain cholinesterase was found. The data indicate that both muscarinic ACh and NMDA receptor-mediated mechanisms contribute to the acute toxicity of AChE inhibitors, and NMDA receptors seem critical to OP-induced seizures.« less

Cancer risk coefficient for patient undergoing kyphoplasty surgery using Monte Carlo method

NASA Astrophysics Data System (ADS)

Santos, Felipe A.; Santos, William S.; Galeano, Diego C.; Cavalcante, Fernanda R.; Silva, Ademir X.; Souza, Susana O.; Júnior, Albérico B. Carvalho

2017-11-01

Kyphoplasty surgery is widely used for pain relief in patients with vertebral compression fracture (VCF). For this surgery, an X-ray emitter that provides real-time imaging is employed to guide the medical instruments and the surgical cement used to fill and strengthen the vertebra. Equivalent and effective doses related to high temporal resolution equipment has been studied to assess the damage and more recently cancer risk. For this study, a virtual scenario was prepared using MCNPX code and a pair of UF family simulators. Two projections with seven tube voltages for each one were simulated. The organ in the abdominal region were those who had higher cancer risk because they receive the primary beam. The risk of lethal cancer is on average 20% higher in AP projection than in LL projection. This study aims at estimating the risk of cancer in organs and the risk of lethal cancer for patient submitted to kyphoplasty surgery.

Relative toxicity testing of spacecraft materials. 2: Aircraft materials

NASA Technical Reports Server (NTRS)

Lawrence, W. H.

1980-01-01

The relative toxicity of thermodegradation (pyrolysis/combustion) products of aircraft materials was studied. Two approaches were taken to assess the biological activity of the pyrolysis/combustion products of these materials: (1) determine the acute lethality to rats from inhalation of these pyrolysates and (2) examine the tendency for sublethal exposure to the pyrolysates to disrupt behavioral (shock avoidance) performance of exposed rats. The ralative importance of lethality vs. behavioral effects in selection of a material may be dictated by whether or not individuals potentially exposed to such products, would have an opportunity to escape if they were behaviorally capable of doing so. If so, the second parameter would assume greater importance, but if not the first parameter may be of much greater importance in selecting materials.

[The impact of non-thrombolytic management of acute ischemic stroke in older individuals: the experience of the Federal District, Brazil].

PubMed

Moura, Mirian; Casulari, Luiz Augusto

2015-07-01

To analyze the impact of a non-specific, decentralized treatment protocol for ischemic stroke in older individuals on the quality of the care provided in the public health care system (SUS, Sistema Único de Saúde) in the Federal District. This retrospective historical control study employed data from the SUS Hospital Information System (SIH/SUS). Two time periods were compared: before and after the adoption of a protocol based on non-specific measures (medical therapy without alteplase) and decentralized care. A set of 2 369 admissions of patients older than 60 years with ischemic stroke was analyzed for the period of 2006/2007, and 5 207 admissions for 2010/2011. The variables were frequency, length of stay, mortality, lethality of ischemic stroke, intensive care unit (ICU) admission, and hospital reimbursement for ischemic stroke admissions. Effectiveness was evaluated based on mortality and lethality rates and efficiency was evaluated based on length of stay, use of ICU, and reimbursed amounts. In the second time period, there was an increase of 119.8% in the number of ischemic stroke admissions (P = 0.0001), increase of 27.3% in absolute mortality, decrease of 5.0% in lethality rate (P = 0.02), and increase of 130.6% in ICU utilization rate (P = 0.0001). There was no difference between the periods regarding mean number of inpatient days and reimbursed amounts. The indicators used in the present study showed improved effectiveness of acute ischemic stroke treatment with the use of a non-specific, decentralized protocol. However, no impact was observed on efficiency.

The ability of filgrastim to mitigate mortality following LD50/60 total-body irradiation is administration time-dependent

PubMed Central

Farese, AM; Brown, CR; Smith, CP; Gibbs, AM; Katz, B P; Johnson, CS; Prado, K; MacVittie, TJ

2013-01-01

The identification of the optimal administration schedule for an effective medical countermeasure is critical for the effective treatment of individuals exposed to potentially lethal doses of radiation. The efficacy of filgrastim (Neupogen®), a potential medical countermeasure, to improve survival when initiated at 48 hours following total body irradiation in a nonhuman primate model of the hematopoietic syndrome of the acute radiation syndrome was investigated. Animals were exposed to total body irradiation, antero-posterior exposure, total midline tissue dose of 7.5 Gray, (target lethal dose 50/60) delivered at 0.80 Gray minute-1, using linear accelerator-derived 6 Megavolt photons. All animals were administered medical management. Following irradiation on day 0, filgrastim (10 μg kg day-1) or the control (5% dextrose in water) was administered subcutaneously, daily through effect (absolute neutrophil count ≥ 1,000 cells μL-1 for 3 consecutive days). The study (n = 80) was powered to demonstrate a 25% improvement in survival following the administration of filgrastim or control beginning at 48 ± 4 hours post-irradiation. Survival analysis was conducted on the intention-to-treat population using a two-tailed null hypothesis at a 5% significance level. Filgrastim, initiated 48 hours after irradiation, did not improve survival (2.5% increase, P = 0.8230). These data demonstrate that efficacy of a countermeasure to mitigate lethality in the hematopoietic syndrome of the acute radiation syndrome can be dependent on the interval between irradiation and administration of the medical countermeasure. PMID:24276548

Ebola GP-specific monoclonal antibodies protect mice and guinea pigs from lethal Ebola virus infection.

PubMed

Qiu, Xiangguo; Fernando, Lisa; Melito, P Leno; Audet, Jonathan; Feldmann, Heinz; Kobinger, Gary; Alimonti, Judie B; Jones, Steven M

2012-01-01

Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3-4 MAbs to test their protection against a lethal challenge with mouse- or guinea pig-adapted EBOV. Each of the 8 MAbs (100 µg) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3-4 MAbs completely protected the majority of animals, while administration at 2-3 dpi achieved 50-100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection.

A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters.

PubMed

Vergote, Valentijn; Laenen, Lies; Vanmechelen, Bert; Van Ranst, Marc; Verbeken, Erik; Hooper, Jay W; Maes, Piet

2017-10-01

Hantavirus, the hemorrhagic causative agent of two clinical diseases, is found worldwide with variation in severity, incidence and mortality. The most lethal hantaviruses are found on the American continent where the most prevalent viruses like Andes virus and Sin Nombre virus are known to cause hantavirus pulmonary syndrome. New World hantavirus infection of immunocompetent hamsters results in an asymptomatic infection except for Andes virus and Maporal virus; the only hantaviruses causing a lethal disease in immunocompetent Syrian hamsters mimicking hantavirus pulmonary syndrome in humans. Hamsters, immunosuppressed with dexamethasone and cyclophosphamide, were infected intramuscularly with different New World hantavirus strains (Bayou virus, Black Creek Canal virus, Caño Delgadito virus, Choclo virus, Laguna Negra virus, and Maporal virus). In the present study, we show that immunosuppression of hamsters followed by infection with a New World hantavirus results in an acute disease that precisely mimics both hantavirus disease in humans and Andes virus infection of hamsters. Infected hamsters showed specific clinical signs of disease and moreover, histological analysis of lung tissue showed signs of pulmonary edema and inflammation within alveolar septa. In this study, we were able to infect immunosuppressed hamsters with different New World hantaviruses reaching a lethal outcome with signs of disease mimicking human disease.

Impact of non-constant concentration exposure on lethality of inhaled hydrogen cyanide.

PubMed

Sweeney, Lisa M; Sommerville, Douglas R; Channel, Stephen R

2014-03-01

The ten Berge model, also known as the toxic load model, is an empirical approach in hazard assessment modeling for estimating the relationship between the inhalation toxicity of a chemical and the exposure duration. The toxic load (TL) is normally expressed as a function of vapor concentration (C) and duration (t), with TL equaling C(n) × t being a typical form. Hypothetically, any combination of concentration and time that yields the same "toxic load" will give a constant biological response. These formulas have been developed and tested using controlled, constant concentration animal studies, but the validity of applying these assumptions to time-varying concentration profiles has not been tested. Experiments were designed to test the validity of the model under conditions of non-constant acute exposure. Male Sprague-Dawley rats inhaled constant or pulsed concentrations of hydrogen cyanide (HCN) generated in a nose-only exposure system for 5, 15, or 30 min. The observed lethality of HCN for the 11 different C versus t profiles was used to evaluate the ability of the model to adequately describe the lethality of HCN under the conditions of non-constant inhalation exposure. The model was found to be applicable under the tested conditions, with the exception of the median lethality of very brief, high concentration, discontinuous exposures.

Weapon Involvement in the Victimization of Children.

PubMed

Mitchell, Kimberly J; Hamby, Sherry L; Turner, Heather A; Shattuck, Anne; Jones, Lisa M

2015-07-01

To report the prevalence of weapons involved in the victimization of youth with particular emphasis on weapons with a "high lethality risk" and how such exposure fits into the broader victimization and life experiences of children and adolescents. Data were collected as part of the Second National Survey of Children's Exposure to Violence, a nationally representative telephone survey of youth ages 2 to 17 years and caregivers (N = 4114) conducted in 2011. Estimates from the Second National Survey of Children's Exposure to Violence indicate that almost 14 million youth, ages 2–17, in the United States have been exposed to violence involving a weapon in their lifetimes as witnesses or victims,or .1 in 5 children in this age group [corrected]. More than 2 million youth in the United States (1 in 33) have been directly assaulted in incidents where the high lethality risk weapons of guns and knives were used. Differences were noted between victimizations involving higher and lower lethality risk weapons as well as between any weapon involvement versus none. Poly-victims, youth with 7 or more victimization types, were particularly likely to experience victimization with any weapon, as well as victimization with a highly lethal weapon compared with nonpoly-victims. Findings add to the field's broadening conceptualization of youth victimization highlighting the potentially highly consequential risk factor of weapon exposure as a component of victimization experiences on the mental health of youth. Further work on improving gun safety practices and taking steps to reduce children's exposure to weapon-involved violence is warranted to reduce this problem. Copyright © 2015 by the American Academy of Pediatrics.

Short self-reported sleep duration and suicidal behavior: a cross-sectional study.

PubMed

Blasco-Fontecilla, Hilario; Alegria, Analucia A; Lopez-Castroman, Jorge; Legido-Gil, Teresa; Saiz-Ruiz, Jeronimo; de Leon, Jose; Baca-Garcia, Enrique

2011-09-01

Prior studies on the association between sleep disturbances and suicidal behavior did not explore whether or not short sleep is a marker of suicide intent, lethality or risk. Cross-sectional. Suicide attempters (SAs) (n=434). Controls included 83 psychiatric inpatients who have never been SAs, and 509 healthy controls. Short sleep was defined by self-assessment as ≤ 5 h per day. The MINI and the DSM-IV version of the International Personality Disorder Examination Screening Questionnaire were used to diagnose Axis I and Axis II diagnoses, respectively. Suicide intent and lethality were evaluated through the Beck's Suicidal Intent Scale (SIS) and the Risk-Rescue Rating Scale (RRRS), respectively. Beck's Medical Lethality Scale (BMLS) was administered to assess the degree of medical injury, and the SAD PERSONS mnemonic scale was used to evaluate suicide risk. Chi-square tests and logistic regression analyses explored frequencies of short sleep in 3 samples. Chi-square tests explored whether or not suicide intent, lethality and risk were greater in SAs with short-sleep versus those without short-sleep. Short sleep was more prevalent in SAs than in psychiatric controls only in males. In female SAs, short sleep was significantly associated with several SIS items and high scores in the SAD PERSONS. Sleep duration was assessed only by self-report. The association between short sleep and suicidal behavior may be partly explained by confounders. Short sleep may be a marker of severity of suicidal behavior among female SAs. Copyright © 2011 Elsevier B.V. All rights reserved.

Graft-vs-leukemia activity and graft-vs-host disease induced by allogeneic Th1- and Th2-type CD4+ T cells in mice.

PubMed

Zeis, M; Uharek, L; Hartung, G; Glass, B; Steinmann, J; Schmitz, N

2001-01-01

The transfer of allogeneic lymphocytes contained in a hematopoietic stem cell graft confers an immune-mediated antileukemic effect, termed the graft-vs-leukemia (GVL) effect. Graft-vs-host disease (GVHD), the most detrimental complication of allogeneic BMT, largely resides within the same lymphocyte population. Therefore, separation of GVL- and GVH-reactions is a long-standing goal of experimental studies dealing with allogeneic transplantation of hematopoietic stem cells. The objective of the current study was to assess the potential of Th1- and Th2-type CD4+ T cells in mediating GVHD and GVL effects in a fully allogeneic murine transplant model. BALB/c (H-2d) mice were given a dose of A20 (H-2d, B-cell leukemia) cells two days prior to lethal total body irradiation (TBI) and transplantation of fully mismatched (C57BL/6, H-2b) T-cell depleted (anti-Thy1.2, CD90) bone marrow (TCD-BM) cells. Graded numbers of either unmanipulated, Th1- or Th2-polarized highly enriched CD4+ donor type T cells (10(6) or 10(7)) were administered 2 h posttransplant. Infusion of 10(6) of unmanipulated, Th1-, or Th2-primed CD4+ T cells resulted in moderate GVHD-related mortality (40%, 50%, 10%) and significantly improved long-term survival (50%, 45%, 46% surviving the observation period of 120 days) as compared to animals receiving TCD-BM alone (18%). The administration of 10(7) unmanipulated or Th1-type CD4+ T cells given shortly after transplantation led to death of all mice within 50 days due to fatal acute GVHD. In contrast, the adoptive transfer of 10(7) Th2-primed CD4+ T cells resulted in significant improvement of long-term survival (80%) compared to the TCD-BM group. This powerful GVL effect was associated with a substantially lower incidence of lethal acute GVHD (10%) if compared to the results of transplantation of Th1-type CD4+ T cells. These results demonstrate that allogeneic Th2-type CD4+ T cells given post BMT can induce GVL effects in a cell-dose-dependent manner without increasing the risk of severe acute GVHD.

Prevention of suicidal behavior

PubMed Central

Hegerl, Ulrich

2016-01-01

More than 800 000 people die every year from suicide, and about 20 times more attempt suicide. In most countries, suicide risk is highest in older males, and risk of attempted suicide is highest in younger females. The higher lethal level of suicidal acts in males is explained by the preference for more lethal methods, as well as other factors. In the vast majority of cases, suicidal behavior occurs in the context of psychiatric disorders, depression being the most important one. Improving the treatment of depression, restricting access to lethal means, and avoiding the Werther effect (imitation suicide) are central aspects of suicide prevention programs. In several European regions, the four-level intervention concept of the European Alliance Against Depression (www.EAAD.net), simultaneously targeting depression and suicidal behavior, has been found to have preventive effects on suicidal behavior. It has already been implemented in more than 100 regions in Europe. PMID:27489458

Pheochromocytoma presenting as an acute coronary syndrome complicated by acute heart failure: The challenge of a great mimic.

PubMed

Sanna, Giuseppe Damiano; Talanas, Giuseppe; Fiore, Giuseppina; Canu, Antonella; Terrosu, Pierfranco

2016-10-01

Pheochromocytoma is a rare neuroendocrine tumor with a highly variable clinical presentation. The serious and potentially lethal cardiovascular complications of these tumors are related to the effects of secreted catecholamines. We describe a case of a 50-year-old woman urgently admitted to our hospital because of symptoms and clinical and instrumental findings consistent with an acute coronary syndrome complicated by acute heart failure. Urgent coronary angiography showed normal coronary arteries. During her hospital stay, the recurrence of episodes characterized by a sudden increase in blood pressure, cold sweating, and nausea allowed us to hypothesize a pheochromocytoma. The diagnosis was confirmed by elevated levels of urinary catecholamines and by the finding of a left adrenal mass on magnetic resonance imaging. The patient underwent left adrenalectomy. Therefore, the initial diagnosis was critically reappraised and reviewed as a cardiac manifestation of a pheochromocytoma during catecholaminergic crisis.

Effect of reduced risk pesticides for use in greenhouse vegetable production on Bombus impatiens (Hymenoptera: Apidae).

PubMed

Gradish, Angela E; Scott-Dupree, Cynthia D; Shipp, Les; Harris, C Ron; Ferguson, Gillian

2010-02-01

Bumble bees [Bombus impatiens (Cresson)] are widely used for supplemental pollination of greenhouse vegetables and are at risk of pesticide exposure while foraging. The objective of this study was to determine the lethal and sub-lethal effects of four insecticides (imidacloprid, abamectin, metaflumizone and chlorantraniliprole) and three fungicides (myclobutanil, potassium bicarbonate and cyprodinil + fludioxonil) used or with potential for use in Ontario greenhouse vegetable production to B. impatiens. Imidacloprid, abamectin, and metaflumizone were harmful to worker bees following direct contact, while chlorantraniliprole and all fungicides tested were harmless. Worker bees fed imidacloprid-contaminated pollen had shortened life spans and were unable to produce brood. Worker bees consumed less pollen contaminated with abamectin. Metaflumizone, chlorantraniliprole and all fungicides tested caused no sub-lethal effects in bumble bee micro-colonies. We conclude that the new reduced risk insecticides metaflumizone and chlorantraniliprole and the fungicides myclobutanil, potassium bicarbonate and cyprodinil + fludioxonil are safe for greenhouse use in the presence of bumble bees. This information can be used preserve greenhouse pollination programs while maintaining acceptable pest management.

Preventing lethal violence in schools: the case for entry-based weapons screening.

PubMed

Mawson, Anthony R; Lapsley, Peter M; Hoffman, Allan M; Guignard, John C

2002-04-01

Violence-related behavior in schools has declined in recent years, but the perception of risk remains high. Disturbingly high percentages of students and teachers report staying home out of fear, and many students bring weapons to school for protection. Current proposals for preventing school violence include punishing the violence-prone, expulsion for weapon carriers, and creating a culture of nonviolence through various behavioral methods like conflict resolution. None of these proposals address the issue of lethal violence and hence personal safety. The risk of lethal violence in schools (related mainly to firearms) could be substantially reduced by creating an effective barrier between firearms and people. This could be achieved by using entry-based weapons detection systems similar to those now used in airports and courts. Decreasing the risk and fear of violence by converting schools into weapons-free zones would also be expected to increase attendance and improve scholastic performance. Randomized, controlled studies should be undertaken to evaluate the efficacy and cost-effectiveness of entry-based weapons detection systems for achieving these outcomes.

Acute toxicity of ibogaine and noribogaine.

PubMed

Kubiliene, Asta; Marksiene, Rūta; Kazlauskas, Saulius; Sadauskiene, Ilona; Razukas, Almantas; Ivanov, Leonid

2008-01-01

To evaluate acute toxic effect of ibogaine and noribogaine on the survival of mice and determine median lethal doses of the substances mentioned. White laboratory mice were used for the experiments. Ibogaine and noribogaine were administered intragastrically to mice via a stomach tube. Control animals received the same volume of saline. The median lethal dose was calculated with the help of a standard formula. To determine the median lethal dose of ibogaine, the doses of 100, 300, 400, and 500 mg/kg were administered intragastrically to mice. The survival time of mice after the drug administration was recorded, as well as the number of survived mice in each group. Upon administration of ibogaine at a dose of 500 mg/kg, all mice in this dose group died. Three out of four mice died in the group, which received 300 mg/kg of ibogaine. No mouse deaths were observed in the group, which received 100 mg/kg of ibogaine. The determined LD(50) value of ibogaine equals to 263 mg/kg of body mass. In order to determine the median lethal dose of noribogaine, the doses of 300, 500, 700, and 900 mg/kg were administered to mice intragastrically. Noribogaine given at a dose of 500 mg/kg had no impact on the mouse survival. The increase of noribogaine dose to 700 mg/kg of mouse body mass led to the death of three out of four mice in the group. Upon administration of noribogaine at a dose of 900 mg/kg, all mice in this group died. The LD(50) value of noribogaine in mice determined on the basis of the number of dead mice and the size of the doses used equals to 630 mg/kg of mouse body mass. The behavior of mice was observed upon administration of ibogaine or noribogaine. Low doses of ibogaine and noribogaine had no impact on the mouse behavior. External effects (convulsions, nervous behaviour, limb paralysis) were observed only when substances were administrated at higher doses. It has been determined that the median lethal dose of ibogaine and noribogaine equals to 263 mg and 630 mg/kg of mouse body mass, respectively. The toxicity of ibogaine is 2.4 times higher than that of noribogaine.

Sublethal and Reproductive Effects of Acute and Chronic Exposure to Flowback and Produced Water from Hydraulic Fracturing on the Water Flea Daphnia magna.

PubMed

Blewett, Tamzin A; Delompré, Perrine L M; He, Yuhe; Folkerts, Erik J; Flynn, Shannon L; Alessi, Daniel S; Goss, Greg G

2017-03-07

Hydraulic fracturing is an industrial process allowing for the extraction of gas or oil. To fracture the rocks, a proprietary mix of chemicals is injected under high pressure, which later returns to the surface as flowback and produced water (FPW). FPW is a complex chemical mixture consisting of trace metals, organic compounds, and often, high levels of salts. FPW toxicity to the model freshwater crustacean Daphnia magna was characterized utilizing acute (48 h median lethal concentrations; LC 50 ) and chronic (21 day) exposures. A decrease in reproduction was observed, with a mean value of 18.5 neonates produced per replicate over a 21 day chronic exposure to 0.04% FPW, which was a significant decrease from the average of 64 neonates produced in the controls. The time to first brood was delayed in the highest FPW (0.04%) treatment. Neonates exhibited an LC 50 of 0.19% of full-strength FPW, making them more sensitive than adults, which displayed an LC 50 value of 0.75%. Quantitative PCR highlighted significant changes in expression of genes encoding xenobiotic metabolism (cyp4) and moulting (cut). This study is the first to characterize chronic FPW toxicity and will help with the development of environmental monitoring and risk assessment of FPW spills.

Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model

PubMed Central

Kuai, Qiyuan; Wang, Chunyan; Wang, Yanbing; Li, Weijing; Zhang, Gongqing; Qiao, Zhixin; He, Min; Wang, Xuanlin; Wang, Yu; Jiang, Xingwei; Su, Lihua; He, Yuezhong; Ren, Suping; Yu, Qun

2016-01-01

A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction. Valproic acid (VPA) regulated the energy metabolism of hemorrhagic heart by reducing lactate synthesis and protecting the mitochondrial ultrastructure and respiration, which were attributable to the inhibition of lactate dehydrogenase A activity and the increased myeloid cell leukemia-1 (mcl-1) gene expression, ultimately facilitating ATP production and consumption. MCL-1, the key target of VPA, mediated this cardioprotective effect under acute severe hemorrhage conditions. Our results suggest that HDACIs promote cardioprotection by improving energy metabolism during hemorrhagic injury and could therefore be an effective strategy to counteract this process in the clinical setting. PMID:27910887

Lethal and sub-lethal responses of native freshwater mussels exposed to granular Bayluscide®, a sea lamprey larvicide

USGS Publications Warehouse

Newton, Teresa; Boogaard, Michael A.; Gray, Brian R.; Hubert, Terrance D.; Schloesser, Nicholas

2017-01-01

The invasive sea lamprey (Petromyzon marinus) poses a substantial threat to fish communities in the Great Lakes. Efforts to control sea lamprey populations typically involve treating tributary streams with lampricides on a recurring cycle. The presence of a substantial population of larval sea lampreys in the aquatic corridor between Lakes Huron and Erie prompted managers to propose a treatment using the granular formulation of Bayluscide® that targets larval sea lampreys that reside in sediments. However, these treatments could cause adverse effects on native freshwater mussels—imperiled animals that also reside in sediments. We estimated the risk of mortality and sub-lethal effects among eight species of adult and sub-adult mussels exposed to Bayluscide® for durations up to 8 h to mimic field applications. Mortality was appreciable in some species, especially in sub-adults (range, 23–51%). The lethal and sub-lethal effects were positively associated with the duration of exposure in most species and life stage combinations. Estimates of the median time of exposure that resulted in lethal and sub-lethal effects suggest that sub-adults were often affected by Bayluscide® earlier than adults. Siphoning activity and burrowing position of mussels during exposure may have moderated the uptake of Bayluscide® and may have influenced lethal and sub-lethal responses. Given that the various species and life stages were differentially affected, it will be difficult to predict the effects of Bayluscide® treatments on mussels.

Optical tracking of embryonic vertebrates behavioural responses using automated time-resolved video-microscopy system

NASA Astrophysics Data System (ADS)

Walpitagama, Milanga; Kaslin, Jan; Nugegoda, Dayanthi; Wlodkowic, Donald

2016-12-01

The fish embryo toxicity (FET) biotest performed on embryos of zebrafish (Danio rerio) has gained significant popularity as a rapid and inexpensive alternative approach in chemical hazard and risk assessment. The FET was designed to evaluate acute toxicity on embryonic stages of fish exposed to the test chemical. The current standard, similar to most traditional methods for evaluating aquatic toxicity provides, however, little understanding of effects of environmentally relevant concentrations of chemical stressors. We postulate that significant environmental effects such as altered motor functions, physiological alterations reflected in heart rate, effects on development and reproduction can occur at sub-lethal concentrations well below than LC10. Behavioral studies can, therefore, provide a valuable integrative link between physiological and ecological effects. Despite the advantages of behavioral analysis development of behavioral toxicity, biotests is greatly hampered by the lack of dedicated laboratory automation, in particular, user-friendly and automated video microscopy systems. In this work we present a proof-of-concept development of an optical system capable of tracking embryonic vertebrates behavioral responses using automated and vastly miniaturized time-resolved video-microscopy. We have employed miniaturized CMOS cameras to perform high definition video recording and analysis of earliest vertebrate behavioral responses. The main objective was to develop a biocompatible embryo positioning structures that were suitable for high-throughput imaging as well as video capture and video analysis algorithms. This system should support the development of sub-lethal and behavioral markers for accelerated environmental monitoring.

Acute and chronic toxicity of nickel to rainbow trout (Oncorhynchus mykiss).

PubMed

Brix, Kevin V; Keithly, James; DeForest, David K; Laughlin, Jim

2004-09-01

Of the fish species tested in chronic Ni exposures, rainbow trout (Oncorhynchus mykiss) is the most sensitive. To develop additional Ni toxicity data and to investigate the toxic mode of action for Ni, we conducted acute (96-h) and chronic (85-d early life-stage) flow-through studies using rainbow trout. In addition to standard toxicological endpoints, we investigated the effects of Ni on ionoregulatory physiology (Na, Ca, and Mg). The acute median lethal concentration for Ni was 20.8 mg/L, and the 24-h gill median lethal accumulation was 666 nmol/g wet weight. No effects on plasma Ca, Mg, or Na were observed during acute exposure. In the chronic study, no significant effects on embryo survival, swim-up, hatching, or fingerling survival or growth were observed at dissolved Ni concentrations up to 466 microg/L, the highest concentration tested. This concentration is considerably higher than the only other reported chronic no-observed-effect concentration (<33 microg/L) for rainbow trout. Accumulation of Ni in trout eggs indicates the chorion is only a partial barrier with 36%, 63%, and 1% of total accumulated Ni associated with the chorion, yolk, and embryo, respectively. Whole-egg ion concentrations were reduced by Ni exposure. However, most of this reduction occurred in the chorion rather than in the embryos, and no effects on hatching success or larval survival were observed as a result. Plasma ion concentrations measured in swim-up fingerlings at the end of the chronic-exposure period were not significantly reduced by exposure to Ni. Nickel accumulated on the gill in an exponential manner but plateaued in trout plasma at waterborne Ni concentrations of 118 microg/L or greater. Consistent with previous studies, Ni did not appear to disrupt ionoregulation in acute exposures of rainbow trout. Our results also suggest that Ni is not an ionoregulatory toxicant in long-term exposures, but the lack of effects in the highest Ni treatment precludes a definitive conclusion.

In vitro sensitivity of granulo-monocytic progenitors as a new toxicological cell system and endpoint in the ACuteTox Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cerrato, Laura; Valeri, Antonio; Bueren, Juan A.

The ACuteTox Project (part of the EU 6th Framework Programme) was started up in January 2005. The aim of this project is to develop a simple and robust in vitro strategy for prediction of human acute systemic toxicity, which could replace animal tests used for regulatory purposes. Our group is responsible for the characterization of the effect of the reference chemicals on the hematopoietic tissue. CFU-GM assay based on the culture of human mononuclear cord blood cells has been used to characterize the effects of the selected compounds on the myeloid progenitors. Previous results have shown the relevance of themore » CFU-GM assay for the prediction of human acute neutropenia after treatment of antitumoral compounds, and this assay has been recently approved by the ECVAM's Scientific Advisory Committee. Among the compounds included in the study there were pharmaceuticals, environmental pollutants and industrial chemicals. Eleven out of 55 chemicals did not show any cytotoxic effect at the maximum concentration tested. The correlation coefficients of CFU-GM IC50, IC70 and IC90 values with human LC50 values (50% lethal concentration calculated from time-related sublethal and lethal human blood concentrations) were 0.4965, 0.5106 and 0.5142 respectively. Although this correlation is not improve respect to classical in vitro basal cytotoxicity tests such as 3T3 Neutral Red Uptake, chemicals which deviate substantially in the correlation with these assays (colchicine, digoxin, 5-Fluorouracil and thallium sulfate) fitted very well in the linear regression analysis of the CFU-GM progenitors. The results shown in the present study indicate that the sensitivity of CFU-GM progenitors correlates better than the sensitivity of HL-60 cells with human LC50 values and could help to refine the predictability for human acute systemic toxicity when a given chemical may affect to the hematopoietic myeloid system.« less

A rare case of thrombotic microangiopathy triggered by acute pancreatitis.

PubMed

Singh, Kevin; Nadeem, Ahmed Jamal; Doratotaj, Behzad

2017-05-15

Thrombotic microangiopathy (TMA) occurring after acute pancreatitis is rarely described. Without prompt intervention, TMA can be, and often is, lethal, so prompt recognition is important. Here, we present a case of a 61-year-old woman with a history of alcohol misuse who presented with epigastric pain, nausea and vomiting after binge drinking. Elevated serum lipase and imaging were suggestive of acute-on-chronic pancreatitis. Although the patient's symptoms of acute pancreatitis subsided, her anaemia, thrombocytopenia and acute kidney injury worsened. A peripheral blood smear revealed schistocytes, prompting suspicion for TMA. Therapeutic plasma exchange (TPE) was promptly initiated and she completed 10 TPE sessions that improved her anaemia and serum creatinine and resolved the thrombocytopenia. Since TPE was effective and the ADAMTS13 assay revealed 55% activity in the absence of anti-ADAMTS13 IgG prior to initiation of therapy, a confident diagnosis of TMA caused by acute pancreatitis was made. There was no evidence of relapse 2 years later. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Bioavailability, ecotoxicity, and geological characteristics of trace lead in sediments from two sites on Negro River, Uruguay, South America.

PubMed

Míguez, Diana M; Huertas, Raquel; Carrara, María V; Carnikián, Agustín; Bouvier, María E; Martínez, María J; Keel, Karen; Pioda, Carolina; Darré, Elena; Pérez, Ramiro; Viera, Santiago; Massa, Enrique

2012-04-01

Bioassays of two sites along the Rio Negro in Uruguay indicate ecotoxicity, which could be attributable to trace concentrations of lead in river sediments. Monthly samples at two sites at Baygorria and Bonete locations were analyzed for both particle size and lead. Lead was determined by atomic spectrometry in river water and sediment and particle size by sieving and sedimentation. Data showed that Baygorria's sediments have greater percentage of clay than Bonete's (20.4 and 5.8%, respectively). Lead was measurable in Baygorria's sediments, meanwhile in Bonete's, it was always below the detection limit. In water samples, lead was below detection limit at both sites. Bioassays using sub-lethal growth and survival test with Hyalella curvispina amphipod, screening with bioluminescent bacteria Photobacterium leiognathi, and acute toxicity bioassay with Pimephales promelas fish indicated toxicity at Baygorria, with much less effect at Bonete. Even though no lethal effects could be demonstrated, higher sub-lethal toxicity was found in samples from Baygorria site, showing a possible concentration of the contaminant in the clay fraction.

Study on the prevalence and neonatal lethality in patients with selected congenital anomalies as per the data of the National Registry of Congenital Anomalies of Argentina.

PubMed

Bidondo, María Paz; Groisman, Boris; Gili, Juan A; Liascovich, Rosa; Barbero, Pablo; Pingray, Verónica

2015-08-01

Congenital anomalies (CAs) account for 26% of infant mortality in Argentina. The lethality rate for CAs measures the risk of death among affected infants. To describe the prevalence at birth of a group of selected CAs, to estimate the neonatal lethality rate, and to examine its association with different variables. The study was conducted using data provided by the National Registry of Congenital Anomalies. Prevalences of encephalocele, spina bifida, gastroschisis, omphalocele, diaphragmatic hernia, esophageal atresia, intestinal atresia, or anorectal malformation were estimated (2009-2013 period). Lethality was assessed at 7 and 28 days of life in affected infants with an isolated anomaly (2013). Association with the following variables was analyzed: sex, gestational age, birth weight, antenatal ultrasound screening, percentage of unmet basic needs in the district where the mother lives, geographic region, and level of care at the hospital where the delivery took place. Gastroschisis was the most prevalent CA (8.53/10,000 births), while diaphragmatic hernia was the CA with the highest neonatal lethality rate (66.67%). Out of all selected CAs, there was a significant association between an higher gestational age and survival at 7 days -OR: 0.81 (0.70-0.95)- and survival at 28 days -OR: 0.79 (95% confidence interval |-CI-|: 0.68-0.91)-. A higher percentage of unmet basic needs was associated with a higher lethality for diaphragmatic hernia -OR: 1.59 (95% CI: 1.30-1.95)- and for intestinal atresia or anorectal malformation -OR: 16.00 (95% CI: 1.63-157.24)-. The high prevalence of gastroschisis is consistent with the increase observed globally. Prematurity and a high percentage of unmet basic needs increased the risk of death among affected infants.

Differential sensitivity of developmental stages of the South American toad to a fungicide based on fludioxonil and metalaxyl-M.

PubMed

Svartz, Gabriela; Acquaroni, Mercedes; Pérez Coll, Cristina

2018-06-07

Agricultural fungicide application in Argentina has increased twice since 2008, with Maxim® XL (2.5% fludioxonil +1% metalaxyl-M) as one of the most used fungicide formulation. The toxicity of this pesticide on Rhinella arenarum was assessed by means of continuous (from embryo and larval development) and 24-h pulse exposure standardized bioassays. Lethality was concentration- and exposure time-dependent. Maxim® XL caused a progressive lethal effect along the bioassays with higher toxicity on embryos than larvae, obtaining 50% lethal concentrations at 96, 336, and 504 h of 10.85, 2.89, and 1.71 mg/L for embryos, and 43.94, 11.79, and 5.76 mg/L for larvae respectively. Lethal 504-h no observed effect concentration values for embryos and larvae were 1 and 2.5 mg/L respectively. A stage-dependent toxicity of Maxim® XL was also demonstrated within the embryo development, with early stages more sensitive than the later ones, and blastula as the most sensitive developmental stage. The risk quotients obtained for chronic risk assessment determined a potential threat for the survival and continuity of R. arenarum populations under these conditions. The results indicate that the levels of the fungicide reaching amphibian habitats could be risky for the early development of this amphibian species. This study also emphasizes the necessity to evaluate the chronic effects of fungicides in pesticide risk assessment.

[IMPROVEMENT AND CHOICE OF COLOSTOMY METHOD IN THE TREATMENT OF PATIENTS, SUFFERING AN ACUTE OBTURATIVE IMPASSABILITY OF LARGE BOWEL].

PubMed

Kustryo, V I; Langazo, O V

2015-11-01

Colostomy was done in 49 patients, suffering an acute obturative impassability of large bowel (AOILB). In 28 patients (1st group) colostomy was conducted in accordance to standard method; in 21 (2nd group)--in accordance to the method, proposed by us. Application of the method proposed for surgical treatment of AOILB have guaranteed a reduction of postoperative paracolostomal complications rate in 6.8 times, of postoperative lethality--in 2.2 times, duration of the patient stationary treatment--in 1.4 times, the rate of dressings and the dressing material expanses--in 10 times.

Lethal acute demyelinization with encephalo-myelitis as a complication of cured Cushing's disease.

PubMed

Chevalier, N; Hieronimus, S; Vandenbos, F; Delmont, E; Cua, E; Cherick, F; Paquis, P; Michiels, J-F; Fenichel, P; Brucker-Davis, F

2010-12-01

Cushing's disease is usually associated with higher mortality rate, especially from cardiovascular causes. Development or exacerbation of autoimmune or inflammatory diseases is known to occur in patients with hypercortisolism after cure. We report for the first time a 34-year old woman with a psychiatric background, who developed four months after the surgical cure of Cushing's disease an acute disseminated encephalomyelitis (ADEM) presenting initially as a psychiatric illness. We hypothesize that the recent correction of hypercortisolism triggered ADEM and that the atypical presentation, responsible for diagnosis delay, led to the death of this patient. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Stevens-Johnson Syndrome associated with methotrexate treatment for acute lymphoblastic leukemia: a case report.

PubMed

Akıncı, Burcu; Siviş, Zuhal Ö; Şahin, Akkız; Karapınar, Deniz Y; Balkan, Can; Kavaklı, Kaan; Aydınok, Yeşim

2018-06-01

Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare mucocutaneous diseases which are associated with a prolonged course and potentially lethal outcome. They are mostly drug induced and mortality rates are very high. Although mostly skin is involved, multiple organ systems such as cardiovascular, pulmonary, gastrointestinal, and urinary systems may be affected. Here, we report a case of Stevens- Johnson Syndrome associated with methotrexate treatment who developed acute cardiac failure and gastrointestinal hemorrhage beside skin findings. He had been treated with intravenous immunglobulin and methylprednisolone succesfully and continued chemotherapy with methotrexate treatment again. Sociedad Argentina de Pediatría.

Severe acute radiation syndrome: treatment of a lethally 60Co-source irradiated accident victim in China with HLA-mismatched peripheral blood stem cell transplantation and mesenchymal stem cells.

PubMed

Guo, Mei; Dong, Zheng; Qiao, Jianhui; Yu, Changlin; Sun, Qiyun; Hu, Kaixun; Liu, Guangxian; Wei, Li; Yao, Bo; Man, Qiuhong; Sun, Xuedong; Liu, Zhiqing; Song, Zhiwu; Yu, Chengze; Chen, Ying; Luo, Qingliang; Liu, Sugang; Ai, Hui-Sheng

2014-03-01

This is a case report of a 32-year-old man exposed to a total body dose of 14.5 Gy γ-radiation in a lethal (60)Co-source irradiation accident in 2008 in China. Frequent nausea, vomiting and marked neutropenia and lymphopenia were observed from 30 min to 45 h after exposure. HLA-mismatched peripheral blood stem cell transplantation combined with infusion of mesenchymal stem cells was used at Day 7. Rapid hematopoietic recovery, stable donor engraftment and healing of radioactive skin ulceration were achieved during Days 18-36. The patient finally developed intestinal obstruction and died of multi-organ failure on Day 62, although intestinal obstruction was successfully released by emergency bowel resection.

Proposed Pathophysiologic Framework to Explain Some ...

EPA Pesticide Factsheets

The paper proposes a pathophysiologic framework to explain the well-established epidemiological association between exposure to ambient air particle pollution and premature cardiovascular mortality, and offers insights into public health solutions that extend beyond regularory environmental protections to actions that can be taken by individuals, public health officials, healthcare professionals, city and regional planners, local and state governmental officials and all those who possess the capacity to improve cardiovascular health within the popula­tion.The foundation of the framework rests on the contribution of traditional cardiovascular risk factors acting alone and in concert with long-term exposures to air pollutants to create a conditional susceptibility for clinical vascular events, such as myocardial ischemia and infarction; stroke and lethal ventricular arrhythmias. The conceprual framework focuses on the fact that short-term exposures to ambient air particulate matter (PM) are associated with vascular thrombosis (acute coronary syndrome. stroke, deep venous thrombosis. and pulmonary embolism ) and electrical dysfunction (ventricular arrhythmia); and that individuals having prevalent heart disease are at greatest risk. Moreover, exposure is concomitant with changes in autonomic nervous system balance, systemic in­flammation, and prothrombotic/anti-thrombotic and profibrinolytic-antifibrinolytic balance.Thus, a comprehensive solution to the problem o

Elemental selenium at nano size (Nano-Se) as a potential chemopreventive agent with reduced risk of selenium toxicity: comparison with se-methylselenocysteine in mice.

PubMed

Zhang, Jinsong; Wang, Xufang; Xu, Tongwen

2008-01-01

Selenium (Se) is an essential trace element with a narrow margin between beneficial and toxic effects. As a promising chemopreventive agent, its use requires consumption over the long term, so the toxicity of Se is always a crucial concern. Based on clinical findings and recent studies in selenoprotein gene-modified mice, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect of Se. Furthermore, upregulation of phase 2 enzymes by Se has been implicated as a possible chemopreventive mechanism at supranutritional dietary levels. Se-methylselenocysteine (SeMSC), a naturally occurring organic Se product, is considered as one of the most effective chemopreventive selenocompounds. The present study revealed that, as compared with SeMSC, elemental Se at nano size (Nano-Se) possessed equal efficacy in increasing the activities of glutathione peroxidase, thioredoxin reductase, and glutathione S-transferase, but had much lower toxicity as indicated by median lethal dose, acute liver injury, survival rate, and short-term toxicity. Our results suggest that Nano-Se can serve as a potential chemopreventive agent with reduced risk of Se toxicity.

Access to means of suicide, occupation and the risk of suicide: a national study over 12 years of coronial data.

PubMed

Milner, A; Witt, K; Maheen, H; LaMontagne, A D

2017-04-04

Availability of lethal means is a significant risk factor for suicide. This study investigated whether occupations with greater access to lethal means had higher suicide rates than those without access, and further, whether this relationship differed for females versus males. A retrospective mortality study was conducted across the Australian population over the period 2001 to 2012. Data from the Australian Bureau of Statistics, which collects Census information on occupation for the Australian population, and the National Coroners Information System, which records information on suicide deaths, were combined. Employed suicide records were coded by occupation and work-related access to lethal means. Descriptive analysis and negative binomial regression were used to assess the relationship between access to means and suicide. Persons in occupations with access to firearms, medicines or drugs, and carbon monoxide more frequently used these methods to end their lives than those without access to means. Females employed in occupations with access to means had suicide rates that were 3.02 times greater (95% CI 2.60 to 3.50, p < 0.001) than those employed in occupations without access. Males in occupations with access had suicide rates that were 1.24 times greater than those without access (95% CI 1.16 to 1.33, p < 0.001). Work-related access to means is a risk factor for suicide in the employed population, but is associated with a greater risk for females than males. The findings of this study suggest the importance of controlling access to lethal methods in occupations where these are readily available.

Chronic toxicity of copper to five benthic invertebrates in laboratory-formulated sediment: sensitivity comparison and preliminary risk assessment.

PubMed

Roman, Yblin E; De Schamphelaere, Karel A C; Nguyen, Lien T H; Janssen, Colin R

2007-11-15

Five benthic organisms commonly used for sediment toxicity testing were chronically (28 to 35 days) exposed to copper in standard laboratory-formulated sediment (following Organization for Economic Cooperation and Development guidelines) and lethal and sub-lethal toxicities were evaluated. Sub-lethal endpoints considered were reproduction and biomass production for Lumbriculus variegatus, growth and reproduction for Tubifex tubifex, growth and emergence for Chironomus riparius, and growth for Gammarus pulex and Hyalella azteca. Expressed on whole-sediment basis the observed lethal sensitivity ranking (from most to least sensitive) was: G. pulex>L. variegatus>H. azteca=C. riparius=T. tubifex, with median chronic lethal concentrations (LC50) between 151 and 327 mg/kg dry wt. The sub-lethal sensitivity ranking (from most to least sensitive, with the most sensitive endpoint between parentheses): C. riparius (emergence)>T. tubifex (reproduction)=L. variegatus (reproduction)>G. pulex (growth)>H. azteca (growth), with median effective concentrations (EC50) between 59.2 and 194 mg/kg dry wt. No observed effect concentrations (NOEC) or 10% effective concentrations (EC10) for the five benthic invertebrates were used to perform a preliminary risk assessment for copper in freshwater sediment by means of (a) the "assessment factor approach" or (b) the statistical extrapolation approach (species sensitivity distribution). Depending on the data (NOEC or EC10) and the methodology used, we calculated a Predicted No Effect Concentration (PNEC) for sediment between 3.3 and 47.1 mg Cu/dry wt. This range is similar to the range of natural (geochemical) background concentrations of copper in sediments in Europe, i.e. 90% of sediments have a concentration between 5 and 49 mg Cu/kg dry wt. A detailed analysis of the outcome of this preliminary exercise highlighted that multiple issues need to be explored for achieving a scientifically more sound risk assessment and for the development of robust sediment quality criteria for copper, including (i) the use of the assessment factor approach vs. the statistical extrapolation approach, (ii) the importance of bioavailability modifying factors (e.g., organic carbon, acid volatile sulfide), and (iii) the influence of prevailing geochemical (bioavailable) background concentrations on the copper sensitivity of local benthic biota.

A Physiologic-Based Approach to the Treatment of Acute Hyperkalemia

PubMed Central

Shingarev, Roman; Allon, Michael

2014-01-01

Hyperkalemia is a common and potentially lethal disorder. Given its variable presentation clinicians should have a high index of suspicion, especially in patients with chronic kidney disease. The present case highlights key physiological mechanisms in the development of hyperkalemia and provides an outline for emergent treatment. In this context, we discuss specific mechanisms of action of available treatments of hyperkalemia. PMID:20570423

Acute Oral Toxicity of DMSO (Dimethyl Sulfoxide) Process Stream Samples in Male and Female Mice.

DTIC Science & Technology

1983-12-01

4 Lethal Dose Calculations ......... o............. o................. 6 Clinical Observations .................... o...8217 . -, . ,. - - . . . - . .. .. . . . . . ., . , . .. .. . . . . . . . . 1% L - u0 2 C 3 q m r " ,- White--7 Clinical Observations On the day of dosing, the animals were...kg, 2.8 ml/kg). The predominant clinical signs were depression, inactivity, excitation, and aggression, with mild to moderate loss of equilibrium. The

Toxic and genotoxic effects of the imazethapyr-based herbicide formulation Pivot H® on montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae).

PubMed

Pérez-Iglesias, J M; Soloneski, S; Nikoloff, N; Natale, G S; Larramendy, M L

2015-09-01

Acute lethal and sublethal toxicity of the imidazolinone imazethapyr (IMZT)-based commercial formulation herbicide Pivot H® (10.59% IMZT) was evaluated on Hypsiboas pulchellus tadpoles. Whereas mortality was used as the end point for lethality, frequency of micronuclei (MNs) and other nuclear abnormalities as well as DNA single-strand breaks evaluated by the single cell gel electrophoresis assay were employed to test genotoxicity. Behavioral, growth, developmental, and morphological abnormalities were also employed as sublethal end points. Mortality studies revealed equivalent LC50 (96h) values of 1.49mg/L (confidence limit, 1.09-1.63) and 1.55mg/L (confidence limit, 1.51-1.60) IMZT for Gosner stage (GS) 25 and GS36, respectively. Behavioral changes, i.e., irregular swimming and immobility, as well as a decreased frequency of keratodonts were observed. The herbicide increased the frequency of MNs in circulating erythrocytes of tadpoles exposed for 48h to the highest concentration assayed (1.17mg/L). However, regardless of the concentration of the herbicide assayed, an enhanced frequency of MNs was observed in tadpoles exposed for 96h. The herbicide was able to induce other nuclear abnormalities, i.e., blebbed and notched nuclei, only when tadpoles were exposed for 96h. In addition, we observed that exposure to IMZT within the 0.39-1.17mg/L range increased the genetic damage index in treatments lasting for both 48 and 96h. This study represents the first evidence of acute lethal and sublethal effects exerted by IMZT on amphibians. Finally, our findings highlight the properties of this herbicide that jeopardize nontarget living species exposed to IMZT. Copyright © 2015 Elsevier Inc. All rights reserved.

Alterations to Juvenile Zebrafish (Danio rerio) Swim Performance after Acute Embryonic Exposure to Sub-lethal Exposures of Hydraulic Fracturing Flowback and Produced Water.

PubMed

Folkerts, Erik J; Blewett, Tamzin A; He, Yuhe; Goss, Greg G

2017-12-01

Hydraulic fracturing flowback and produced water (FPW) is a wastewater produced during fracturing activities in an operating well which is hyper saline and chemically heterogeneous in nature, containing both anthropogenic and petrogenic chemicals. Determination of FPW associated toxicity to embryonic fish is limited, while investigation into how embryonic exposures may affect later life stages is not yet studied. Zebrafish embryos (24hrs post fertilization) were acutely exposed to 2.5% and 5% FPW fractions for either 24 or 48hrs and returned to freshwater. After either 24 or 48h exposures, embryos were examined for expression of 3 hypoxia related genes. Erythropoietin (epoa) but not hypoxia inducible factor (hif1aa) nor hemoglobin -ß chain (hbbe1.1) was up-regulated after either 24 or 48h FPW exposure. Surviving embryos were placed in freshwater and grown to a juvenile stage (60days post fertilization). Previously exposed zebrafish were analyzed for both swim performance (U crit and U max ) and aerobic capacity. Fish exposed to both sediment containing (FPW-S) or sediment free (FPW-SF) FPW displayed significantly reduced aerobic scope and U crit /U max values compared to control conditions. Our results collectively suggest that organics present in our FPW sample may be responsible for sub-lethal fitness and metabolic responses. We provide evidence supporting the theory that the cardio-respiratory system is impacted by FPW exposure. This is the first known research associating embryonic FPW exposures to sub-lethal performance related responses in later life fish stages. Copyright © 2017 Elsevier B.V. All rights reserved.

Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vito, Stephen T., E-mail: stvito@ucdavis.edu; Austin, Adam T., E-mail: aaustin@ucdavis.edu; Banks, Christopher N., E-mail: Christopher.Banks@oehha.ca.gov

Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABA{sub A}R) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABA{sub A}R positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizuresmore » and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABA{sub A}R antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication. - Highlights: • Acute TETS intoxication causes delayed and persistent neuroinflammation. • Diazepam given post-TETS prevents lethal tonic seizures but not neuroinflammation. • A soluble epoxide hydrolase inhibitor alters TETS-induced neuroinflammation. • Acute TETS intoxication may be more effectively treated by a combinatorial therapy.« less

H2S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

PubMed Central

SONOBE, TAKASHI; HAOUZI, PHILIPPE

2015-01-01

Context Hydrogen sulfide (H2S) intoxication produces an acute depression in cardiac contractility-induced circulatory failure, which has been shown to be one of the major contributors to the lethality of H2S intoxication or to the neurological sequelae in surviving animals. Methylene blue (MB), a phenothiazinium dye, can antagonize the effects of the inhibition of mitochondrial electron transport chain, a major effect of H2S toxicity. Objectives We investigated whether MB could affect the immediate outcome of H2S-induced coma in unanesthetized animals. Second, we sought to characterize the acute cardiovascular effects of MB and two of its demethylated metabolites—azure B and thionine—in anesthetized rats during lethal infusion of H2S. Materials and methods First, MB (4 mg/kg, intravenous [IV]) was administered in non-sedated rats during the phase of agonal breathing, following NaHS (20 mg/kg, IP)-induced coma. Second, in 4 groups of urethane-anesthetized rats, NaHS was infused at a rate lethal within 10 min (0.8 mg/min, IV). Whenever cardiac output (CO) reached 40% of its baseline volume, MB, azure B, thionine, or saline were injected, while sulfide infusion was maintained until cardiac arrest occurred. Results Seventy-five percent of the comatose rats that received saline (n = 8) died within 7 min, while all the 7 rats that were given MB survived (p = 0.007). In the anesthetized rats, arterial, left ventricular pressures and CO decreased during NaHS infusion, leading to a pulseless electrical activity within 530 s. MB produced a significant increase in CO and dP/dtmax for about 2 min. A similar effect was produced when MB was also injected in the pre-mortem phase of sulfide exposure, significantly increasing survival time. Azure B produced an even larger increase in blood pressure than MB, while thionine had no effect. Conclusion MB can counteract NaHS-induced acute cardiogenic shock; this effect is also produced by azure B, but not by thionine, suggesting that the presence of methyl groups is a prerequisite for producing this protective effect. PMID:25965774

Coffee Consumption and Prostate Cancer Risk and Progression in the Health Professionals Follow-up Study

PubMed Central

Kasperzyk, Julie L.; Rider, Jennifer R.; Kenfield, Stacey; van Dam, Rob M.; Stampfer, Meir J.; Giovannucci, Edward; Mucci, Lorelei A.

2011-01-01

Background Coffee contains many biologically active compounds, including caffeine and phenolic acids, that have potent antioxidant activity and can affect glucose metabolism and sex hormone levels. Because of these biological activities, coffee may be associated with a reduced risk of prostate cancer. Methods We conducted a prospective analysis of 47 911 men in the Health Professionals Follow-up Study who reported intake of regular and decaffeinated coffee in 1986 and every 4 years thereafter. From 1986 to 2006, 5035 patients with prostate cancer were identified, including 642 patients with lethal prostate cancers, defined as fatal or metastatic. We used Cox proportional hazards models to assess the association between coffee and prostate cancer, adjusting for potential confounding by smoking, obesity, and other variables. All P values were from two-sided tests. Results The average intake of coffee in 1986 was 1.9 cups per day. Men who consumed six or more cups per day had a lower adjusted relative risk for overall prostate cancer compared with nondrinkers (RR = 0.82, 95% confidence interval [CI] = 0.68 to 0.98, Ptrend = .10). The association was stronger for lethal prostate cancer (consumers of more than six cups of coffee per day: RR = 0.40, 95% CI = 0.22 to 0.75, Ptrend = .03). Coffee consumption was not associated with the risk of nonadvanced or low-grade cancers and was only weakly inversely associated with high-grade cancer. The inverse association with lethal cancer was similar for regular and decaffeinated coffee (each one cup per day increment: RR = 0.94, 95% CI = 0.88 to 1.01, P = .08 for regular coffee and RR = 0.91, 95% CI = 0.83 to 1.00, P = .05 for decaffeinated coffee). The age-adjusted incidence rates for men who had the highest (≥6 cups per day) and lowest (no coffee) coffee consumption were 425 and 519 total prostate cancers, respectively, per 100 000 person-years and 34 and 79 lethal prostate cancers, respectively, per 100 000 person-years. Conclusions We observed a strong inverse association between coffee consumption and risk of lethal prostate cancer. The association appears to be related to non-caffeine components of coffee. PMID:21586702

Quiescent complement in nonhuman primates during E coli Shiga toxin-induced hemolytic uremic syndrome and thrombotic microangiopathy.

PubMed

Lee, Benjamin C; Mayer, Chad L; Leibowitz, Caitlin S; Stearns-Kurosawa, D J; Kurosawa, Shinichiro

2013-08-01

Enterohemorrhagic Escherichia coli (EHEC) produce ribosome-inactivating Shiga toxins (Stx1, Stx2) responsible for development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI). Some patients show complement activation during EHEC infection, raising the possibility of therapeutic targeting of complement for relief. Our juvenile nonhuman primate (Papio baboons) models of endotoxin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and AKI with glomerular thrombotic microangiopathy. There were no significant increases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) or Stx2 (n = 5) in plasma samples from T0 to euthanasia at 49.5 to 128 hours post-challenge. d-dimer and cell injury markers (HMGB1, histones) confirmed coagulopathy and cell injury. Thus, complement activation is not required for the development of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical models, and benefits or risks of complement inhibition should be studied further for this infection.

'Refeeding syndrome' in a Kuwaiti child: clinical diagnosis and management.

PubMed

Al Sharkawy, Ibrahim; Ramadan, Dina; El-Tantawy, Amira

2010-01-01

To report a case of refeeding syndrome in a Kuwaiti child, its clinical presentation and management. A 13-month-old Kuwaiti boy presented with acute severe malnutrition in the form of marasmic kwashiorkor. On admission, blood sugar and serum electrolytes were normal but on the 3rd day he developed typical biochemical features of refeeding syndrome in the form of hyperglycemia, severe hypophosphatemia, hypokalemia, hypocalcemia and hypomagnesemia. The child then received treatment appropriate for refeeding syndrome in the form of lower calorie intake with gradual increase, as well as supplementation of electrolytes, thiamine and vitamins and he eventually made a safe recovery. This case showed that during rehabilitation of a malnourished child, a severe potentially lethal electrolyte disturbance (refeeding syndrome) can occur. Careful monitoring of electrolytes before and during the refeeding phase was needed and helped to detect this syndrome early. We suggest that slow and gradual calorie increase in the 'at-risk' patient can help prevent its occurrence. Copyright (c) 2010 S. Karger AG, Basel.

[Treatment of acute and recurrent Clostridium difficile infections : What is new?

PubMed

von Braun, A; Lübbert, C

2018-05-01

The incidence of clostridium difficile infections (CDI) remains on a high level globally. In Germany, the number of severe or even lethal cases continues to increase. The main risk factor for the development of CDI is exposure to broad spectrum antibiotics, which disturb the physiological microbiome and therefore enable colonization with C. difficile. According to the updated US and European guidelines, orally administered vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin but has the advantage of a lower rate of recurrence. Furthermore, recent clinical studies were able to demonstrate that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. In recent years, several new antibiotics with narrow-spectrum acitivity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI; however, pivotal clinical trials have so far not been completed.

Suicide in China: unique demographic patterns and relationship to depressive disorder.

PubMed

Law, Samuel; Liu, Pozi

2008-02-01

Recent research on suicide in China reveals several unique findings: 1) female suicides outnumber male suicides by a 3:1 ratio; 2) rural suicides outnumber urban suicides by a 3:1 ratio; 3) a large upsurge of young adult and older adult suicides has occurred; 4) a comparatively high national suicide rate two to three times the global average is evident; and, most startlingly, 5) a low rate of psychiatric illness, particularly depression, exists in suicide victims. The strongest empirical data suggest that these trends result from a high number of rural, young females who experience acute interpersonal or financial crises and then impulsively attempt suicide using lethal pesticides or poisons. Other suicide risk factors in China are similar to those that are well known internationally. Interactive sociological, cultural, and economic hypotheses unique to China provide further insight. Among those, the cultural-socioeconomic disadvantages of the Chinese rural female and cultural attitudes toward suicide are particularly noteworthy.

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

PubMed

Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

2017-06-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

Subchronic chloroform priming protects mice from a subsequently administered lethal dose of chloroform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Philip, Binu K.; Anand, Sathanandam S.; Palkar, Prajakta S.

2006-10-01

Protection offered by pre-exposure priming with a small dose of a toxicant against the toxic and lethal effects of a subsequently administered high dose of the same toxicant is autoprotection. Although autoprotection has been extensively studied with diverse toxicants in acute exposure regimen, not much is known about autoprotection after priming with repeated exposure. The objective of this study was to investigate this concept following repeated exposure to a common water contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30 days, were challenged with a normally lethalmore » dose of chloroform (750 mg chloroform/kg po) 24 h after the last exposure. As expected, 90% of the unprimed mice died between 48 and 96 h after administration of the lethal dose in contrast to 100% survival of mice primed with chloroform. Time course studies indicated lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice. Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of {sup 14}C-chloroform-derived radiolabel did not differ between livers of unprimed and primed mice after lethal dose exposure, indicating that protection in liver is neither due to decreased bioactivation nor increased detoxification. Kidney GSH and glutathione reductase activity were upregulated, with a concomitant reduction in oxidized glutathione in the primed mice following lethal dose challenge, leading to decreased renal covalent binding of {sup 14}C-chloroform-derived radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine (BSO) intervention led to 70% mortality in primed mice challenged with lethal dose. These data suggest that higher detoxification may play a role in the lower initiation of kidney injury observed in primed mice. Exposure of primed mice to a lethal dose of chloroform led to 40% lower chloroform levels (AUC{sub 15-360min}) in the systemic circulation. Exhalation of {sup 14}C-chloroform was unchanged in primed as compared to unprimed mice (AUC{sub 1-6h}). Urinary excretion of {sup 14}C-chloroform was higher in primed mice after administration of the lethal dose. However, neither slightly higher urinary elimination nor unchanged expiration can account for the difference in systemic levels of chloroform. Liver and kidney regeneration was inhibited by the lethal dose in unprimed mice leading to progressive injury, organ failure, and 90% mortality. In contrast, sustained and highly stimulated compensatory hepato- and nephrogenic repair prevented the progression of injury resulting in 100% survival of primed mice challenged with the lethal dose. These findings affirm the critical role of tissue regeneration and favorable detoxification (only in kidney) of the lethal dose of chloroform in subchronic chloroform priming-induced autoprotection.« less

The rate of fatality and demographic characteristics associated with various suicide methods: a community-based study in Northern Taiwan.

PubMed

Lee, Chun-Yi; Wu, Ya-Wen; Chen, Chih-Ken; Wang, Liang-Jen

2014-01-01

Understanding lethality and risk factors of suicide methods is an initial step in suicide prevention. To investigate the fatality rate and demographic characteristics of various suicide methods. This study enrolled consecutive individuals with episodes of suicide attempts registered in a surveillance database in a city with a high rate of suicide mortality in Taiwan, from January 1, 2006, to December 31, 2010. In total, 3,089 suicide attempt events (including 2,583 nonfatal suicides and 506 completed suicides) occurred during the study period. Overall, the fatality rate of suicides was 16.4%. Charcoal burning accounted for the most suicide deaths (37.6%), with a fatality rate of 50.1%. Suicide by hanging carried the highest fatality rate (81.2%). Males tended to choose more lethal methods and had higher fatality rates compared with females. Elders and married persons were less likely to attempt suicide by charcoal burning. The case fatality ratio increased along with age among suicide attempts, but not in those using charcoal burning. The choice of suicide methods and lethality might be influenced by one's demographic characteristics. RESULTS from this study may provide clues for establishing suicide prevention strategies such as restricting access to common lethal suicide methods in the high-risk group.

Acute and sub-acute toxicological assessment of the aqueous seed extract of Persea americana mill (Lauraceae) in rats.

PubMed

Ozolua, Raymond I; Anaka, Ogochukwu N; Okpo, Stephen O; Idogun, Sylvester E

2009-07-03

The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD(50)) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD(50) could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.

Comprehensive characterization of the acute and chronic toxicity of the neonicotinoid insecticide thiamethoxam to a suite of aquatic primary producers, invertebrates, and fish.

PubMed

Finnegan, Meaghean C; Baxter, Leilan R; Maul, Jonathan D; Hanson, Mark L; Hoekstra, Paul F

2017-10-01

Thiamethoxam is a neonicotinoid insecticide used widely in agriculture to control a broad spectrum of chewing and sucking insect pests. Recent detection of thiamethoxam in surface waters has raised interest in characterizing the potential impacts of this insecticide to aquatic organisms. We report the results of toxicity testing (acute and chronic) conducted under good laboratory practices for more than 30 freshwater species (insects, molluscs, crustaceans, algae, macrophytes, and fish) and 4 marine species (an alga, a mollusc, a crustacean, and a fish). As would be anticipated for a neonicotinoid, aquatic primary producers and fish were the least sensitive organisms tested, with acute median lethal and effect concentrations (LC50/EC50) observed to be ≥80 mg/L in all cases, which far exceeds surface water exposure concentrations. Tested molluscs, worms, and rotifers were similarly insensitive (EC50 ≥ 100 mg/L), except for Lumbriculus sp., with an EC50 of 7.7 mg/L. In general, insects were the most sensitive group in the study, with most acute EC50 values < 1 mg/L. However, the crustaceans Asellus aquaticus and Ostracoda exhibited a sensitivity similar to that of insects (acute EC50 < 1 mg/L), and the midge larvae Chaoborus sp. were relatively insensitive compared with other insects (EC50 > 5.5 mg/L). The most sensitive chronic response was for Chironomus riparius, with a 30-d no-observed-effect concentration (NOEC; emergence) of 0.01 mg/L. Observed toxicity to the tested marine organisms was comparable to that of freshwater species. We used the reported data to construct species sensitivity distributions for thiamethoxam, to calculate 5% hazard concentrations (HC5s) for acute data (freshwater invertebrates), and compared these with measured concentrations from relevant North American surface waters. Overall, based on acute toxicity endpoints, the potential acute risk to freshwater organisms was found to be minimal (likelihood of exceeding HC5s < 1%). Environ Toxicol Chem 2017;36:2838-2848. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc.

Insufficient Sleep and Risk of Prostate Cancer in a Large Swedish Cohort.

PubMed

Markt, Sarah C; Grotta, Alessandra; Nyren, Olof; Adami, Hans-Olov; Mucci, Lorelei A; Valdimarsdottir, Unnur A; Stattin, Pär; Bellocco, Rino; Lagerros, Ylva Trolle

2015-09-01

There are some data to suggest that insufficient sleep, including short sleep duration and sleep disruption, may be associated with an increased risk of cancer. We investigated the association between sleep duration and sleep disruption and risk of prostate cancer. Prospective cohort study. Sweden. A total of 14,041 men in the Swedish National March Cohort. None. Habitual sleep duration and sleep disruption were self-reported in 1997. Prostate cancer diagnoses, including lethal (metastases at diagnosis or death from prostate cancer) and advanced (stage T4, N1, or M1 at diagnosis or death from prostate cancer), were determined from linkage to nationwide cancer registries through 2010. We conducted Cox proportional hazards regression adjusted for potential confounding variables. During 13 years of follow-up, we identified 785 cases of incident prostate cancer, including 118 lethal and 127 advanced cases. Four percent of men reported sleeping 5 h or less a night, and 2% reported sleeping 9 h or more per night. We found no association between sleep duration and risk of prostate cancer overall or for advanced/lethal disease. We also did not find an association between prostate cancer and sleep disruption, as defined by difficulty falling asleep, difficulty maintaining sleep, sleep quality, and restorative power of sleep. In this large prospective study from Sweden, we found no association between habitual sleep duration or sleep disruption and risk of prostate cancer. © 2015 Associated Professional Sleep Societies, LLC.

Latent Microsporidiosis Caused by Encephalitozoon cuniculi in Immunocompetent Hosts: A Murine Model Demonstrating the Ineffectiveness of the Immune System and Treatment with Albendazole

PubMed Central

Kotkova, Michaela; Sak, Bohumil; Kvetonova, Dana; Kvac, Martin

2013-01-01

Background Microsporidia are obligate intracellular parasites causing severe infections with lethal outcome in immunocompromised hosts. However, these pathogens are more frequently reported as latent infections in immunocompetent individuals and raises questions about the potential risk of reactivation following induced immunosuppression. Aims To evaluate the possibility latent microsporidiosis, efficacy or albendazole, and reactivation, the authors monitored the course of E. cuniculi infection in immunocompetent BALB/c mice and immunodeficient SCID mice using molecular methods. Methods Mice were per orally infected with 107 spores of E. cuniculi. Selected groups were treated with albendazole, re-infected or chemically immunosuppressed by dexamethasone. The presence of microsporidia in the host’s organs and feces were determined using PCR methods. Changes in numbers of lymphocytes in blood and in spleen after induction of immunosuppression were confirmed using flow cytometry analysis. Results Whereas E. cuniculi caused lethal microsporidiosis in SCID mice, the infection in BABL/c mice remained asymptomatic despite parasite dissemination into many organs during the acute infection phase. Albendazole treatment led to microsporidia elimination from organs in BALB/c mice. In SCID mice, however, only a temporary reduction in number of affected organs was observed and infection re-established post-treatment. Dexamethasone treatment resulted in a chronic microsporidia infection disseminating into most organs in BALB/c mice. Although the presence of E. cuniculi in organs of albendazole- treated mice was undetectable by PCR, it was striking that infection was reactivated by immunosuppression treatment. Conclusion Our results demonstrated that microsporidia can successfully survive in organs of immunocompetent hosts and are able to reactivate from undetectable levels and spread within these hosts after induction of immunosuppression. These findings stress the danger of latent microsporidiosis as a life-threatening risk factor especially for individuals undergoing chemotherapy and in transplant recipients of organs originating from infected donors. PMID:23593356

Phytochemical screening and toxicity studies on the methanol extract of the seeds of moringa oleifera.

PubMed

Ajibade, Temitayo Olabisi; Arowolo, Ruben; Olayemi, Funsho Olakitike

2013-05-07

The seeds of Moringa oleifera were collected, air-dried, pulverized, and subjected to cold extraction with methanol. The methanol extract was screened phytochemically for its chemical components and used for acute and sub-acute toxicity studies in rats. The phytochemical screening revealed the presence of saponins, tannins, terpenes, alkaloids, flavonoids, carbohydrates, and cardiac glycosides but the absence of anthraquinones. Although signs of acute toxicity were observed at a dose of 4,000 mg kg-1 in the acute toxicity test, and mortality was recorded at 5,000 mg kg-1, no adverse effect was observed at concentrations lower than 3,000 mg kg-1. The median lethal dose of the extract in rat was 3,873 mg kg-1. Sub-acute administration of the seed extract caused significant (p<0.05) increase in the levels of alanine and aspartate transferases (ALT and AST), and significant (p<0.05) decrease in weight of experimental rats, at 1,600 mg kg-1. The study concludes that the extract of seeds of M. oleifera is safe both for medicinal and nutritional uses.

Acute oral safety study of sodium caseinate glycosylated via maillard reaction with galactose in rats.

PubMed

Anadón, Arturo; Martínez, Maria A; Ares, Irma; Castellano, Victor; Martínez-Larrañaga, Maria R; Corzo-Martínez, Marta; Moreno, F Javier; Villamiel, Mar

2014-03-01

In order to potentially use sodium caseinate (SC) glycated with galactose (Gal) in the food industry as a new functional ingredient with proved technological and biological properties, an evaluation of oral acute toxicity has been carried out. An acute safety study with SC-Gal glycoconjugates in the Wistar rat with a single oral gavage dose of 2,000 mg/kg of body weight was conducted. The SC-Gal glycoconjugates were well tolerated; no adverse effects or mortality was observed during the 2-week observation period. No abnormal signs, behavioral changes, body weight changes, or alterations in food and water consumption occurred. After this period, no changes in hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology were detected. It was concluded that SC-Gal glycoconjugates obtained via the Maillard reaction were well tolerated in rats at an acute oral dose of 2,000 mg/kg of body weight. The SC-Gal glycoconjugates have a low order of acute toxicity, and the oral 50 % lethal dose for male and female rats is in excess of 2,000 mg/kg of body weight.

The acute lethal dose 50 (LD50) of caffeine in albino rats.

PubMed

Adamson, Richard H

2016-10-01

An acute LD50 is a statistically derived amount of a substance that can be expected to cause death in 50% of the animals when given by a specified route as a single dose and the animals observed for a specified time period. Although conducting routine acute toxicity testing in rodents has been criticized, it can serve useful functions and also have practical implications. Material safety data sheets (MSDS) will reflect the acute toxicity of a substance and may require workers to wear protective gear, if appropriate, based on the LD50. There is no information in the scientific published literature which calculates a mean LD50 and standard deviation for caffeine administered orally to rats, using studies performed under good laboratory practice (GLP) or equivalent. This report does that and should be useful to manufacturers, packagers, transporters and regulators of this material. Using data from studies that are reproducible and reliable, the most accurate estimate of the acute LD50 of caffeine administered orally in male albino rats is hereby reported to be 367/mg/kg. Copyright © 2016 Elsevier Inc. All rights reserved.

Dietary acrylamide and risk of prostate cancer.

PubMed

Wilson, Kathryn M; Giovannucci, Edward; Stampfer, Meir J; Mucci, Lorelei A

2012-07-15

Acrylamide has been designated by IARC as a "probable human carcinogen." High levels are formed during cooking of many commonly consumed foods including French fries, potato chips, breakfast cereal and coffee. Two prospective cohort studies and two case-control studies in Europe found no association between acrylamide intake and prostate cancer. We examined this association in a large prospective cohort of 47,896 US men in the Health Professionals' Follow-up Study, using updated dietary acrylamide intake from food frequency questionnaires in 1986, 1990, 1994, 1998 and 2002. From 1986 through 2006, we documented 5025 cases of prostate cancer, and 642 lethal cancers. We used Cox proportional hazards models to assess the association between acrylamide intake from diet and prostate cancer risk overall as well as risk of advanced or lethal cancer. Acrylamide intake ranged from a mean of 10.5 mcg/day in the lowest quintile to 40.1 mcg/day in the highest quintile; coffee and potato products were largest contributors to intake. The multivariate-adjusted relative risk of prostate cancer was 1.02 (95% confidence interval: 0.92-1.13) for the highest versus lowest quintile of acrylamide intake (p-value for trend = 0.90). Results were similar when restricted to never smokers and to men who had prostate-specific antigen (PSA) tests. There was no significant association for dietary acrylamide and risk of lethal, advanced or high-grade disease, or for different latency periods ranging from 0-4 years to 12-16 years. We found no evidence that acrylamide intake, within the range of US diets, is associated with increased risk of prostate cancer. Copyright © 2011 UICC.

Cardiac fibrillation risk of Taser weapons.

PubMed

Leitgeb, Norbert

2014-06-01

The debate on potential health hazards associated with delivering electric discharges to incapacitated subjects, in particular on whether electric discharge weapons are lethal, less lethal or non-lethal, is still controversial. The cardiac fibrillation risks of Taser weapons X26 and X3 have been investigated by measuring the delivered high-tension pulses in dependence on load impedance. Excitation thresholds and sinus-to-Taser conversion factors have been determined by numerical modeling of endocardial, myocardial, and epicardial cells. Detailed quantitative assessment of cardiac electric exposure has been performed by numerical simulation at the normal-weighted anatomical model NORMAN. The impact of anatomical variation has been quantified at an overweight model (Visible Man), both with a spatial resolution of 2 × 2 × 2 mm voxels. Spacing and location of dart electrodes were systematically varied and the worst-case position determined. Based on volume-weighted cardiac exposure assessment, the fibrillation probability of the worst-case hit was determined to 30% (Taser X26) and 9% (Taser X3). The overall risk assessment of Taser application accounting for realistic spatial hit distributions was derived from training sessions of police officers under realistic scenarios and by accounting for the influence of body (over-)weight as well as gender. The analysis of the results showed that the overall fibrillation risk of Taser use is not negligible. It is higher at Taser X26 than at Taser X3 and amounts to about 1% for Europeans with an about 20% higher risk for Asians. Results demonstrate that enhancement as well as further reduction of fibrillation risk depends on responsible use or abuse of Taser weapons.

Acute Poisoning in Children in Bahia, Brazil

PubMed Central

Rodrigues Mendonça, Dilton; Menezes, Marta Silva; Matos, Marcos Antônio Almeida; Rebouças, Daniel Santos; Filho, Jucelino Nery da Conceição; de Assis, Reginara Souza; Carneiro, Leila

2016-01-01

Acute poisoning is a frequent accident in childhood, particularly in children under 4 years of age. This was a descriptive study with data collected from standardized forms of the Poison Control Center and patient record charts. All the cases of acute poisoning in children aged 0 to 14 years during the period 2008 to 2012 were selected. The variables studied comprised characteristics of the events and toxic agents, clinical development, and outcome. A total of 657 cases of acute poisoning, with higher frequency in the age-group from 1 to 4 years (48.7%) and male sex (53.4%), were recorded. The occurrences were accidental in 92% of the cases, and 5.8% were due to suicide attempts. Among the toxic agents, medications (28.5%), venomous animals (19.3%), nonvenomous animals (10%), household cleaning products (9.0%), and raticide agents (8.7%) predominated. The majority of cases were characterized as light (73.5%) and around 18% required hospitalization, and there was low lethality (0.5%). PMID:27335994

Long-term evaluation of lethal and sublethal toxicity of industrial effluents using Daphnia magna and Moina macrocopa.

PubMed

Yi, Xianliang; Kang, Sung-Wook; Jung, Jinho

2010-06-15

Acute toxicity and feeding rate inhibition of effluent from a wastewater treatment plant and its adjacent stream water on Daphnia magna and Moina macrocopa were comparatively studied. The acute toxicity of the final effluent (FE) fluctuated greatly over the sampling period from January to August 2009. Toxicity identification results of the FE in July 2009 showed that Cu originating from the Fenton's reagent was likely a key toxicant. In addition, the feeding rate of both species was still inhibited by the FEs in which acute toxicity was not observed. These findings indicate that the feeding response would be a useful tool for monitoring sublethal effects of industrial effluents. For the acute toxicity test, M. macrocopa was more sensitive than D. magna, but the opposite result was true in the case of the feeding rate inhibition. These suggest that different species have different sensitivities to toxic chemicals and to the test methods. Copyright 2010 Elsevier B.V. All rights reserved.

Pembrolizumab-induced acute thrombosis: A case report.

PubMed

Kunimasa, Kei; Nishino, Kazumi; Kimura, Madoka; Inoue, Takako; Tamiya, Motohiro; Kumagai, Toru; Imamura, Fumio

2018-05-01

Acute thrombosis has not been reported in the literature so far in lung cancer patients as an immune-related adverse event (irAE) associated with PD-1 pathway inhibitors. Here, we for the first time present two NSCLC (non-small cell lung cancer) patients suffering from acute thrombosis as a pembrolizumab-induced irAE. Immediate treatment with continuous heparin infusion improved their symptoms and enabled them to continue pembrolizumab administration. Ethical approval was given by the ethics committee of Osaka International Cancer Institute and the informed consents were given by the patients. Serum D-dimer level testing, venous ultrasonography, enhanced computed tomography (CT). Continuous heparin infusion, direct oral anticoagulants (DOAC). Immediate continuous heparin infusion improved their symptoms and continuing pembrolizumab with direct oral anticoagulant successfully induced tumor shrinkage. Reinvigoration of exhausted T cells by pembrolizumab induced systemic inflammation possibly resulting in development of thrombosis. Although acute thrombosis is a rare irAE, it may lead to cessation of treatment and can be lethal.

[Using of reamberin for correction of free radicals disturbances in patients with acute severe methadone poisonings].

PubMed

Shilov, V V; Vasil'ev, S A; Batotsyrenov, B V; Loladze, A T; Kuznetsov, O A

2012-03-01

The article deals with the materials, which have been received in the process of the examination and treatment of 44 patients with acute severe methadone poisonings. It has been revealed, that gravity of these patient's condition depends on intensity of hypoxia due to breath deficiency because of the methadone. The development of hypoxia, in its turn, cause violations of antiradical protection system and intensification of processes of peroxide lipid oxidation. It has been registered that the including of reamberin into the complex program of the intensive therapy of acute severe methadone poisonings lead to a more rapid restoration of antiradical protection system and to a decrease of activity of processes of peroxide lipid oxidation. The correction of hypoxia and free-radical violations led to improvement of the acute poisonings clinic, what had been characterized by a decrease of coma-period duration, duration of treatment with artificial lung ventilation, a decrease of secondary lung complications and a decrease of lethality.

Upper temperature tolerance of loach minnow under acute, chronic, and fluctuating thermal regimes

USGS Publications Warehouse

Widmer, A.M.; Carveth, C.J.; Bonar, Scott A.; Simms, J.R.

2006-01-01

We used four methods to estimate the upper lethal temperature of loach minnow Rhinichthys cobitis: the lethal thermal method (LTM), chronic lethal method (CLM), acclimated chronic exposure (ACE) method with static temperatures, and ACE method with diel temperature fluctuations. The upper lethal temperature of this species ranged between 32??C and 38??C, depending on the method and exposure time; however, temperatures as low as 28??C resulted in slowed growth compared with the control groups. In LTM trials, we increased temperatures 0.3??C/min and death occurred at 36.8 ?? 0.2??C (mean ?? SE) for fish (37-19 mm total length) acclimated to 30??C and at 36.4 ?? 0.07??C for fish acclimated to 25??C. In CLM trials, temperatures were increased more slowly (1??C/d), allowing fish to acclimate. Mean temperature at death was 33.4 ?? 0.1??C for fish 25-35 mm and 32.9 ?? 0.4??C for fish 45-50 mm. In the ACE experiment with static temperatures, we exposed fish for 30 d to four constant temperatures. No fish (20-40 mm) survived beyond 30 d at 32??C and the 30-d temperature lethal to 50% of the test animals was 30.6??C. Growth at static 28??C and 30??C was slower than growth at 25??C, suggesting that fish were stressed at sublethal temperatures. In ACE trials with diel temperature fluctuations of 4,6, and 10??C and a 32??C peak temperature, over 80% of fish (20-40 mm) survived 30 d. Although brief exposures to 32??C were not lethal, the growth of fish in the three fluctuating-temperature treatments was significantly less than the growth at the ambient temperature (25-29??C). To minimize thermal stress and buffer against temperature spikes, we recommend that loach minnow habitat be managed to avoid water temperatures above 28??C. ?? Copyright by the American Fisheries Society 2006.

Orally administered live attenuated Salmonella Typhimurium protects mice against lethal infection with H1N1 influenza virus.

PubMed

Kamble, Nitin Machindra; Hajam, Irshad Ahmed; Lee, John Hwa

2017-03-01

Pre-stimulation of toll-like receptors (TLRs) by agonists has been shown to increase protection against influenza virus infection. In this study, we evaluated the protective response generated against influenza A/Puerto Rico/8/1934 (PR8; H1N1) virus by oral and nasal administration of live attenuated Salmonella enterica serovar Typhimurium, JOL911 strain, in mice. Oral and nasal inoculation of JOL911 significantly increased the mRNA copy number of TLR-2, TLR4 and TLR5, and downstream type I interferon (IFN) molecules, IFN-α and IFN-β, both in peripheral blood mononuclear cells (PBMCs) and in lung tissue. Similarly, the mRNA copy number of interferon-inducible genes (ISGs), Mx and ISG15, were significantly increased in both the orally and the nasally inoculated mice. Post PR8 virus lethal challenge, the nasal JOL911 and the PBS control group mice showed significant loss of body weight with 70% and 100% mortality, respectively, compared to only 30% mortality in the oral JOL911 group mice. Post sub-lethal challenge, the significant reduction in PR8 virus copy number in lung tissue was observed in oral [on day 4 and 6 post-challenge (dpc)] and nasal (on 4dpc) than the PBS control group mice. The lethal and sub-lethal challenge showed that the generated stimulated innate resistance (StIR) in JOL911 inoculated mice conferred resistance to acute and initial influenza infection but might not be sufficient to prevent the PR8 virus invasion and replication in the lung. Overall, the present study indicates that oral administration of attenuated S. Typhimurium can pre-stimulate multiple TLR pathways in mice to provide immediate early StIR against a lethal H1N1 virus challenge. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of field-realistic doses of glyphosate on honeybee appetitive behaviour.

PubMed

Herbert, Lucila T; Vázquez, Diego E; Arenas, Andrés; Farina, Walter M

2014-10-01

Glyphosate (GLY) is a broad-spectrum herbicide used for weed control. The sub-lethal impact of GLY on non-target organisms such as insect pollinators has not yet been evaluated. Apis mellifera is the main pollinator in agricultural environments and is a well-known model for behavioural research. Honeybees are also accurate biosensors of environmental pollutants and their appetitive behavioural response is a suitable tool with which to test sub-lethal effects of agrochemicals. We studied the effects of field-realistic doses of GLY on honeybees exposed chronically or acutely to the herbicide. We focused on sucrose sensitivity, elemental and non-elemental associative olfactory conditioning of the proboscis extension response (PER), and foraging-related behaviour. We found a reduced sensitivity to sucrose and learning performance for the groups chronically exposed to GLY concentrations within the range of recommended doses. When olfactory PER conditioning was performed with sucrose reward with the same GLY concentrations (acute exposure), elemental learning and short-term memory retention decreased significantly compared with controls. Non-elemental associative learning was also impaired by an acute exposure to GLY traces. Altogether, these results imply that GLY at concentrations found in agro-ecosystems as a result of standard spraying can reduce sensitivity to nectar reward and impair associative learning in honeybees. However, no effect on foraging-related behaviour was found. Therefore, we speculate that successful forager bees could become a source of constant inflow of nectar with GLY traces that could then be distributed among nestmates, stored in the hive and have long-term negative consequences on colony performance. © 2014. Published by The Company of Biologists Ltd.

Absolute probability estimates of lethal vessel strikes to North Atlantic right whales in Roseway Basin, Scotian Shelf.

PubMed

van der Hoop, Julie M; Vanderlaan, Angelia S M; Taggart, Christopher T

2012-10-01

Vessel strikes are the primary source of known mortality for the endangered North Atlantic right whale (Eubalaena glacialis). Multi-institutional efforts to reduce mortality associated with vessel strikes include vessel-routing amendments such as the International Maritime Organization voluntary "area to be avoided" (ATBA) in the Roseway Basin right whale feeding habitat on the southwestern Scotian Shelf. Though relative probabilities of lethal vessel strikes have been estimated and published, absolute probabilities remain unknown. We used a modeling approach to determine the regional effect of the ATBA, by estimating reductions in the expected number of lethal vessel strikes. This analysis differs from others in that it explicitly includes a spatiotemporal analysis of real-time transits of vessels through a population of simulated, swimming right whales. Combining automatic identification system (AIS) vessel navigation data and an observationally based whale movement model allowed us to determine the spatial and temporal intersection of vessels and whales, from which various probability estimates of lethal vessel strikes are derived. We estimate one lethal vessel strike every 0.775-2.07 years prior to ATBA implementation, consistent with and more constrained than previous estimates of every 2-16 years. Following implementation, a lethal vessel strike is expected every 41 years. When whale abundance is held constant across years, we estimate that voluntary vessel compliance with the ATBA results in an 82% reduction in the per capita rate of lethal strikes; very similar to a previously published estimate of 82% reduction in the relative risk of a lethal vessel strike. The models we developed can inform decision-making and policy design, based on their ability to provide absolute, population-corrected, time-varying estimates of lethal vessel strikes, and they are easily transported to other regions and situations.

First case of Pseudoclavibacter bifida bacteremia in an immunocompromised host with chronic obstructive pulmonary disease (COPD).

PubMed

Oyaert, Matthijs; De Baere, Thierry; Breyne, Joke; De Laere, Emmanuel; Mariën, Stan; Waets, Peter; Laffut, Wim

2013-06-01

Pseudoclavibacter spp. are Gram-positive, aerobic, catalase-positive, coryneform bacteria belonging to the family of Microbacteriaceae. Identification of these species with conventional biochemical assays is difficult. This case report of a Pseudoclavibacter bifida bacteremia occurring in an immunocompromised host diagnosed with an acute exacerbation of chronic obstructive pulmonary disease, with a lethal outcome, confirms that this organism may be a human pathogen.

Effect of acute pesticide exposure on bee spatial working memory using an analogue of the radial-arm maze

NASA Astrophysics Data System (ADS)

Samuelson, Elizabeth E. W.; Chen-Wishart, Zachary P.; Gill, Richard J.; Leadbeater, Ellouise

2016-12-01

Pesticides, including neonicotinoids, typically target pest insects by being neurotoxic. Inadvertent exposure to foraging insect pollinators is usually sub-lethal, but may affect cognition. One cognitive trait, spatial working memory, may be important in avoiding previously-visited flowers and other spatial tasks such as navigation. To test this, we investigated the effect of acute thiamethoxam exposure on spatial working memory in the bumblebee Bombus terrestris, using an adaptation of the radial-arm maze (RAM). We first demonstrated that bumblebees use spatial working memory to solve the RAM by showing that untreated bees performed significantly better than would be expected if choices were random or governed by stereotyped visitation rules. We then exposed bees to either a high sub-lethal positive control thiamethoxam dose (2.5 ng-1 bee), or one of two low doses (0.377 or 0.091 ng-1) based on estimated field-realistic exposure. The high dose caused bees to make more and earlier spatial memory errors and take longer to complete the task than unexposed bees. For the low doses, the negative effects were smaller but statistically significant, and dependent on bee size. The spatial working memory impairment shown here has the potential to harm bees exposed to thiamethoxam, through possible impacts on foraging efficiency or homing.

Comparison of extracellular striatal acetylcholine and brain seizure activity following acute exposure to the nerve agents cyclosarin and tabun in freely moving guinea pigs.

PubMed

O'Donnell, John C; Acon-Chen, Cindy; McDonough, John H; Shih, Tsung-Ming

2010-11-01

Organophosphorus nerve agents like cyclosarin and tabun are potent cholinesterase inhibitors. The inhibition of acetylcholinesterase, which is responsible for breaking down acetylcholine (ACh) at the synapse and neuromuscular junction, leads to a build-up of extracellular ACh and a series of toxic consequences including hypersecretion, tremor, convulsion/seizure, respiratory distress, coma, and death. This study employed simultaneous and continuous electroencephalographic recording and striatal microdialysis collection for quantification of ACh changes (via subsequent HPLC analysis) during acute exposure to a 1.0 × LD(50) subcutaneous dose of either cyclosarin or tabun to investigate differences in cholinergic and behavioral effects. Information about the unique mechanisms and consequences of different nerve agents is intended to aid in the development of broad-spectrum medical countermeasures for nerve agents. At the dose administered, non-seizure and sustained seizure responses were observed in both agent groups and in the tabun-exposed group some subjects experienced an unsustained seizure response. Significant extracellular ACh increases were only observed in seizure groups. Cyclosarin and tabun were found to exhibit some unique cholinergic and ictogenic characteristics. Lethality only occurred in subjects experiencing sustained seizure, and there was no difference in lethality between agent groups that progressed to sustained seizure.

Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians.

PubMed

Ghose, Sonia L; Donnelly, Maureen A; Kerby, Jacob; Whitfield, Steven M

2014-09-01

Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency's ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions. © 2014 SETAC.

Does acute lead (Pb) contamination influence membrane fatty acid composition and freeze tolerance in intertidal blue mussels in arctic Greenland?

PubMed

Thyrring, Jakob; Juhl, Bodil Klein; Holmstrup, Martin; Blicher, Martin E; Sejr, Mikael K

2015-11-01

In their natural habitats, organisms are exposed to multiple stressors. Heavy metal contamination stresses the cell membrane due to increased peroxidation of lipids. Likewise, sub-zero air temperatures potentially reduce membrane functionality in ectothermal animals. We tested if acute lead (Pb) exposure for 7 days would influence survival in intertidal blue mussels (Mytilus edulis) after exposure to realistic sub-zero air temperatures. A full factorial experiment with five tissue Pb concentrations between 0 and 3500 μg Pb/g and six sub-zero temperatures from 0 to -17 °C were used to test the hypothesis that sub-lethal effects of Pb may increase the lethality caused by freezing in blue mussels exposed to temperatures simulating Greenland winter conditions. We found a significant effect of temperature on mortality. However, the short-term exposure to Pb did not result in any effects of Pb, nor did we find interactions between Pb and temperature. We analysed the relative abundance of major phospholipid fatty acids (PLFAs) in the gill tissue, but we found no significant effect of Pb tissue concentration on PLFA composition. Results suggest that Pb accumulation has limited effects on freeze tolerance and does not induce membrane damage in terms of persistent lipid peroxidation.

Oxidative stress induces senescence in human mesenchymal stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brandl, Anita; Meyer, Matthias; Bechmann, Volker

Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated {beta}-galactosidase positivity. Prolongedmore » low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.« less

Effects of CFT Legumine (5% Rotenone) on tadpole survival and metamorphosis of Chiricahua leopard frogs Lithobates chiricahuensis, Northern leopard frogs L. pipiens, and American bullfrogs L. catesbeianus

USGS Publications Warehouse

Alvarez, Guillermo; Caldwell, Colleen A.; Kruse, Carter G.

2017-01-01

Amphibians may experience collateral effects if exposed to CFT Legumine (5% rotenone), a piscicide that is used to remove invasive fish. A series of 48-h static toxicity tests assessed the acute effects of CFT Legumine on multi-aged tadpoles of the federally listed Chiricahua leopard frog Lithobates chiricahuensis, the widespread northern leopard frog L. pipiens, and the increasingly invasive American bullfrog L. catesbeianus. At the earliest Gosner stages (GS 21–25), Chiricahua leopard frogs were more sensitive to CFT Legumine (median lethal concentration [LC50] = 0.41–0.58 mg/L) than American bullfrogs (LC50 = 0.63–0.69 mg/L) and northern leopard frogs (LC50 = 0.91 and 1.17 mg/L). As tadpoles developed (i.e., increase in GS), their sensitivity to rotenone decreased. In a separate series of 48-h static nonrenewal toxicity tests, tadpoles (GS 21–25 and GS 31–36) of all three species were exposed to piscicidal concentrations of CFT Legumine (0.5, 1.0, and 2.0 mg/L) to assess postexposure effects on metamorphosis. In survivors of all three species at both life stages, the time to tail resorption was nearly doubled in comparison with that of controls. For example, mid-age (GS 31–36) Chiricahua leopard frog tadpoles required 210.7 h to complete tail resorption, whereas controls required 108.5 h. However, because tail resorption is a relatively short period in metamorphosis, the total duration of development (days from posthatch to complete metamorphosis) and the final weight did not differ in either age-group surviving nominal concentrations of 0.5-, 1.0-, and 2.0-mg/L CFT Legumine relative to controls. This research demonstrates that the CFT Legumine concentrations commonly used in field applications to remove unwanted fish could result in considerable mortality of the earliest stages of Lithobates species. In addition to acute lethality, piscicide treatments may result in delayed tail resorption, which places the tadpoles at risk by increasing their vulnerability to predation and pathogens.

General Medical, Mental Health, and Demographic Risk Factors Associated With Suicide by Firearm Compared With Other Means.

PubMed

Boggs, Jennifer M; Beck, Arne; Hubley, Sam; Peterson, Edward L; Hu, Yong; Williams, L Keoki; Prabhakar, Deepak; Rossom, Rebecca C; Lynch, Frances L; Lu, Christine Y; Waitzfelder, Beth E; Owen-Smith, Ashli A; Simon, Gregory E; Ahmedani, Brian K

2018-06-01

Mitigation of suicide risk by reducing access to lethal means, such as firearms and potentially lethal medications, is a highly recommended practice. To better understand groups of patients at risk of suicide in medical settings, the authors compared demographic and clinical risk factors between patients who died by suicide by using firearms or other means with matched patients who did not die by suicide (control group). In a case-control study in 2016 from eight health care systems within the Mental Health Research Network, 2,674 suicide cases from 2010-2013 were matched to a control group (N=267,400). The association between suicide by firearm or other means and medical record information on demographic characteristics, general medical disorders, and mental disorders was assessed. The odds of having a mental disorder were higher among cases of suicide involving a method other than a firearm. Fourteen general medical disorders were associated with statistically significant (p<.001) greater odds of suicide by firearm, including traumatic brain injury (TBI) (odds ratio [OR]=23.53), epilepsy (OR=3.17), psychogenic pain (OR=2.82), migraine (OR=2.35), and stroke (OR=2.20). Fifteen general medical disorders were associated with statistically significant (p<.001) greater odds of suicide by other means, with particularly high odds for TBI (OR=7.74), epilepsy (OR=3.28), HIV/AIDS (OR=6.03), and migraine (OR=3.17). Medical providers should consider targeting suicide risk screening for patients with any mental disorder, TBI, epilepsy, HIV, psychogenic pain, stroke, and migraine. When suicide risk is detected, counseling on reducing access to lethal means should include both firearms and other means for at-risk groups.

Straightening Beta: Overdispersion of Lethal Chromosome Aberrations following Radiotherapeutic Doses Leads to Terminal Linearity in the Alpha–Beta Model

PubMed Central

Shuryak, Igor; Loucas, Bradford D.; Cornforth, Michael N.

2017-01-01

Recent technological advances allow precise radiation delivery to tumor targets. As opposed to more conventional radiotherapy—where multiple small fractions are given—in some cases, the preferred course of treatment may involve only a few (or even one) large dose(s) per fraction. Under these conditions, the choice of appropriate radiobiological model complicates the tasks of predicting radiotherapy outcomes and designing new treatment regimens. The most commonly used model for this purpose is the venerable linear-quadratic (LQ) formalism as it applies to cell survival. However, predictions based on the LQ model are frequently at odds with data following very high acute doses. In particular, although the LQ predicts a continuously bending dose–response relationship for the logarithm of cell survival, empirical evidence over the high-dose region suggests that the survival response is instead log-linear with dose. Here, we show that the distribution of lethal chromosomal lesions among individual human cells (lymphocytes and fibroblasts) exposed to gamma rays and X rays is somewhat overdispersed, compared with the Poisson distribution. Further, we show that such overdispersion affects the predicted dose response for cell survival (the fraction of cells with zero lethal lesions). This causes the dose response to approximate log-linear behavior at high doses, even when the mean number of lethal lesions per cell is well fitted by the continuously curving LQ model. Accounting for overdispersion of lethal lesions provides a novel, mechanistically based explanation for the observed shapes of cell survival dose responses that, in principle, may offer a tractable and clinically useful approach for modeling the effects of high doses per fraction. PMID:29312888

[High-dosage glucocorticoid therapy in acute heart infarct and in cardiogenic shock].

PubMed

Krosch, H; Schäbitz, J

1977-11-15

40 patients with cardiogenic shock in consequence of contractility insufficiency of the heart were treated with high doses of prednisolon for short time. In 10 cases a good result of the treatment was to be seen so that the lethality quota was smaller than that of a reference group of the same age. The pharmacodynamic effect is seen in an improvement of the micro-circulation by a peripheric vasodilatation. 10 patients with acute myocardial infarction got a therapy with glucocorticoid combined with a treatment with anti-coagulants during the first both weeks. In this connection modern experimental examinations of animals are discussed which showed that glucocorticoides improve the anoxy tolerance of the heart muscle cell.

An agent-based model of cattle grazing toxic Geyer's larkspur.

PubMed

Jablonski, Kevin E; Boone, Randall B; Meiman, Paul J

2018-01-01

By killing cattle and otherwise complicating management, the many species of larkspur (Delphinium spp.) present a serious, intractable, and complex challenge to livestock grazing management in the western United States. Among the many obstacles to improving our understanding of cattle-larkspur dynamics has been the difficulty of testing different grazing management strategies in the field, as the risk of dead animals is too great. Agent-based models (ABMs) provide an effective method of testing alternate management strategies without risk to livestock. ABMs are especially useful for modeling complex systems such as livestock grazing management, and allow for realistic bottom-up encoding of cattle behavior. Here, we introduce a spatially-explicit, behavior-based ABM of cattle grazing in a pasture with a dangerous amount of Geyer's larkspur (D. geyeri). This model tests the role of herd cohesion and stocking density in larkspur intake, finds that both are key drivers of larkspur-induced toxicosis, and indicates that alteration of these factors within realistic bounds can mitigate risk. Crucially, the model points to herd cohesion, which has received little attention in the discipline, as playing an important role in lethal acute toxicosis. As the first ABM to model grazing behavior at realistic scales, this study also demonstrates the tremendous potential of ABMs to illuminate grazing management dynamics, including fundamental aspects of livestock behavior amidst ecological heterogeneity.

The Future Combat System: Minimizing Risk While Maximizing Capability

DTIC Science & Technology

2000-05-01

ec /W hl Co nv /T ra ck Co nv /W hl El ec /T rac El ec /W hl Crew &Misc Power Mgt Propulsion Lethality Structure /Surviv Conv / ETC Lethality Missile...also examines the wheeled versus tracked debate. The paper concludes by recommending some of the technologies for further development under a parallel...versus tracked debate. The paper concludes by recommending some of the technologies for further development under a parallel acquisition strategy

Characterization of the dinophysistoxin-2 acute oral toxicity in mice to define the Toxicity Equivalency Factor.

PubMed

Abal, Paula; Louzao, M Carmen; Cifuentes, José Manuel; Vilariño, Natalia; Rodriguez, Ines; Alfonso, Amparo; Vieytes, Mercedes R; Botana, Luis M

2017-04-01

Ingestion of shellfish with dinophysistoxin-2 (DTX2) can lead to diarrheic shellfish poisoning (DSP). The official control method of DSP toxins in seafood is the liquid chromatography-mass spectrometry analysis (LC-MS). However in order to calculate the total toxicity of shellfish, the concentration of each compound must be multiplied by individual Toxicity Equivalency Factor (TEF). Considering that TEFs caused some controversy and the scarce information about DTX2 toxicity, the aim of this study was to characterize the oral toxicity of DTX2 in mice. A 4-Level Up and Down Procedure allowed the characterization of DTX2 effects and the estimation of DTX2 oral TEF based on determination of the lethal dose 50 (LD50). DTX2 passed the gastrointestinal barrier and was detected in urine and feces. Acute toxicity symptoms include diarrhea and motionless, however anatomopathology study and ultrastructural images restricted the toxin effects to the gastrointestinal tract. Nevertheless enterocytes microvilli and tight junctions were not altered, disconnecting DTX2 diarrheic effects from paracellular epithelial permeability. This is the first report of DTX2 oral LD 50 (2262 μg/kg BW) indicating that its TEF is about 0.4. This result suggests reevaluation of the present TEFs for the DSP toxins to better determine the actual risk to seafood consumers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advanced medical countermeasures for radiological accidents and nuclear disasters: prevention, prophylaxis, treatment and pre- and post-exposure management.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

Countermeasures against nuclear terrorism to prevent or limit the number of irradiated human population or radiation intoxications include early identification of the nuclear terrorism event and all persons which exposed by radiation, decontamination program and procedures, radiation control, and medical countermeasures which include medical diagnosis,differential diagnosis of Acute Radiation Syndromes by Immune Enzyme Assay , pre-exposure vaccination with Human Antiradiation Vaccine, post-exposure specific treatment - de-intoxication with Radiation Antidote IgG (blocking Antiradiation Antibodies). Our Advanced Medical Technology elaborated as a part of effective countermeasure include Plan of Action.Countermeasures against nuclear terrorism to prevent or limit the number of high level of lethality and severe forms of radiation illness or intoxications include A.early identification of the nuclear terrorism event and persons exposed,b. appropriate decontamination, c. radiation control, and d.medical countermeasures and medical management of ARS. Medical countermeasures, which include medical interventions such as active immuneprophylaxis with Human Antiradiation Vaccine , passive immune-prophylaxis with Antiradiation Antitoxins immune-globulins IgG , and chemoprophylaxis - post-exposure antioxidants prophylaxis and antibioticprophylaxis. Medical countermeasures with Antiradiation Vaccine should be initiated before an exposure (if individuals are identified as being at high risk for exposure)but after a confirmed exposure event Antiradiation Vaccine not effective and Antiradiation Antidot IgG must be applyed for treatment of Acute Radiation Syndromes.

Evaluating the Zebrafish Embryo Toxicity Test for Pesticide ...

EPA Pesticide Factsheets

Given the numerous chemicals used in society, it is critical to develop tools for accurate and efficient evaluation of potential risks to human and ecological receptors. Fish embryo acute toxicity tests are 1 tool that has been shown to be highly predictive of standard, more resource-intensive, juvenile fish acute toxicity tests. However, there is also evidence that fish embryos are less sensitive than juvenile fish for certain types of chemicals, including neurotoxicants. The utility of fish embryos for pesticide hazard assessment was investigated by comparing published zebrafish embryo toxicity data from pesticides with median lethal concentration 50% (LC50) data for juveniles of 3 commonly tested fish species: rainbow trout, bluegill sunfish, and sheepshead minnow. A poor, albeit significant, relationship (r2 = 0.28; p < 0.05) was found between zebrafish embryo and juvenile fish toxicity when pesticides were considered as a single group, but a much better relationship (r2 = 0.64; p < 0.05) when pesticide mode of action was factored into an analysis of covariance. This discrepancy is partly explained by the large number of neurotoxic pesticides in the dataset, supporting previous findings that commonly used fish embryo toxicity test endpoints are particularly insensitive to neurotoxicants. These results indicate that it is still premature to replace juvenile fish toxicity tests with embryo-based tests such as the Organisation for Economic Co-op

Arterial elastic fiber structure. Function and potential roles in acute aortic dissection.

PubMed

Pratt, B; Curci, J

2010-10-01

The lethality of acute aortic dissection is well recognized. Successful treatment and prevention of aortic dissection is going to be dependent upon an improved understanding of the molecular and physiologic events which predispose to dissection development and propagation. In this review, we will focus on the elastic fiber, one of the critical elements of the aortic wall matrix. Mechanical or functional failure of the elastin in the wall of the aorta likely predisposes to dissection as well as the post-dissection aortic degeneration with aneurysm formation. Insight into the role of the elastin and the elastic fiber in aortic dissection has recently been accelerated by research into the molecular mechanisms associated with hereditary propensity for aortic dissection, such as Marfan syndrome. These studies have implicated both structural and metabolic contributions of alterations in the scaffolding proteins in matrix elastic fibers. In particular, increased transforming growth factor-β (TGF-β) activity may play a prominent role in predisposing the aortic wall to dissection. The events which predispose to post-dissection aortic degeneration are somewhat less well defined. However, the loss of the structural integrity of the remaining elastic fibers leaves the wall weaker and prone to dilatation and rupture. It appears likely that the upregulation of several potent proteases, particularly those of the matrix metalloproteinase (MMP) family such as MMP-9, are participating in the subsequent matrix damage. Novel medical treatments based on this pathologic data have been proposed and in some cases have made it to clinical trials. The ongoing study evaluating whether therapeutic inhibition of TGF-β may be useful in reducing the risk of aortic dissection in patients at high risk represents one promising new strategy in the treatment of this deadly disease.

Effects of two polybrominated diphenyl ethers (BDE-47, BDE-209) on the swimming behavior, population growth and reproduction of the rotifer Brachionus plicatilis.

PubMed

Sha, Jingjing; Wang, You; Lv, Jianxia; Wang, Hong; Chen, Hongmei; Qi, Leilei; Tang, Xuexi

2015-02-01

Polybrominated diphenyl ethers (PBDEs) are new kinds of persistent organic pollutants (POPs) and their potential threats to the equilibrium and sustainability of marine ecosystems have raised worldwide concerns. Here, two kinds of PBDEs, tetra-BDE (BDE-47) and deca-BDE (BDE-209) were applied, and their toxic effects on the swimming behavior, population growth and reproduction of Brachionus plicatilis were investigated. The results showed that: (1) The actual concentrations of BDE-47 and -209 in the seawater phase measured by GC-MS (Gas Chromatography-Mass Spectrometer) were much lower than their nominal concentrations. (2) In accordance with the 24-hr acute tests, BDE-209 did not show any obvious swimming inhibition to rotifers, but a good correlation did exist between the swimming inhibition rate and BDE-47 concentration suggesting that BDE-47 is more toxic than BDE-209. (3) Both BDE-47 and -209 had a significant influence on the population growth and reproduction parameters of B. plicatilis including the population growth rate, the ratio of ovigerous females/non-ovigerous females (OF/NOF), the ratio of mictic females/amictic females (MF/AF), resting egg production and the mictic rate, which indicate that these parameters in B. plicatilis population were suitable for monitoring and assessing PBDEs. Our results suggest that BDE-47 and -209 are not acute lethal toxicants and may pose a low risk to marine rotifers at environmental concentrations for short-term exposure. They also accumulate differently into rotifers. Further research data are needed to understand the mechanisms responsible for the effects caused by PBDEs and to assess their risks accurately. Copyright © 2014. Published by Elsevier B.V.

The impact of temperature stress and pesticide exposure on mortality and disease susceptibility of endangered Pacific salmon.

PubMed

Dietrich, Joseph P; Van Gaest, Ahna L; Strickland, Stacy A; Arkoosh, Mary R

2014-08-01

Anthropogenic stressors, including chemical contamination and temperature stress, may contribute to increased disease susceptibility in aquatic animals. Specifically, the organophosphate pesticide malathion has been detected in surface waters inhabited by threatened and endangered salmon. In the presence of increasing water temperatures, malathion may increase susceptibility to disease and ultimately threaten salmon survival. This work examines the effect of acute and sublethal exposures to malathion on ocean-type subyearling Chinook salmon held under two temperature regimes. Chinook salmon were exposed to malathion at optimal (11 °C) or elevated (19 and 20 °C) temperatures. The influence of temperature on the acute toxicity of malathion was determined by generating 96-h lethal concentration (LC) curves. A disease challenge assay was also used to assess the effects of sublethal malathion exposure. The malathion concentration that resulted in 50% mortality (LC50; 274.1 μg L(-1)) of the Chinook salmon at 19 °C was significantly less than the LC50 at 11 °C (364.2 μg L(-1)). Mortality increased 11.2% in Chinook salmon exposed to malathion at the elevated temperature and challenged with Aeromonas salmonicida compared to fish held at the optimal temperature and exposed to malathion or the carrier control. No difference in disease challenge mortality was observed among malathion-exposed and unexposed fish at the optimal temperature. The interaction of co-occurring stressors may have a greater impact on salmon than if they occur in isolation. Ecological risk assessments considering the effects of an individual stressor on threatened and endangered salmon may underestimate risk when additional stressors are present in the environment. Published by Elsevier Ltd.

Lethal Forethought: Delayed Reward Discounting Differentiates High- and Low-Lethality Suicide Attempts in Old Age

PubMed Central

Dombrovski, Alexandre Y.; Szanto, Katalin; Siegle, Greg J.; Wallace, Meredith L.; Forman, Steven D.; Sahakian, Barbara; Reynolds, Charles F.; Clark, Luke

2011-01-01

Background The decision to commit suicide may be impulsive, but lethal suicidal acts often involve planning and forethought. People who attempt suicide make disadvantageous decisions in other contexts, but nothing is known about the way they decide about the future. Can the willingness to postpone future gratification differentiate between individuals prone to serious, premeditated and less serious, unplanned suicidal acts? Methods Four groups of depressed participants aged 60+ made choices between smaller immediate and larger delayed monetary rewards: 15 who made high-lethality suicide attempts, 14 who made low-lethality suicide attempts, 12 who seriously contemplated suicide, and 42 people with depression but no history of suicidal thoughts. The reference group was 31 psychiatrically healthy elders. Results Individuals who had made low-lethality attempts displayed an exaggerated preference for immediate rewards compared to non-suicidal depressed and healthy controls. Those who had carried out high-lethality suicide attempts were more willing to delay future rewards, compared to low-lethality attempters. Better planned suicide attempts were also associated with willingness to wait for larger rewards. These effects were unchanged after accounting for education, global cognitive function, substance use disorders, psychotropic medications, and possible brain injury from attempts. Discount rates were correlated with having debt but were not significantly associated with income, hopelessness, depressive severity, premorbid IQ, age at first attempt, or choice of violent means. Conclusions While clinicians often focus on impulsivity in patients at risk for suicide, these data suggest that identifying biological characteristics and treatments for non-impulsive suicidal older people may be even more important. PMID:21329911

Minimally invasive transcriptome profiling in salmon: detection of biological response in rainbow trout caudal fin following exposure to environmental chemical contaminants.

PubMed

Veldhoen, Nik; Stevenson, Mitchel R; Skirrow, Rachel C; Rieberger, Kevin J; van Aggelen, Graham; Meays, Cynthia L; Helbing, Caren C

2013-10-15

An increasing number of anthropogenic chemicals have demonstrated potential for disruption of biological processes critical to normal growth and development of wildlife species. Both anadromous and freshwater salmon species are at risk of exposure to environmental chemical contaminants that may affect migratory behavior, environmental fitness, and reproductive success. A sensitive metric in determination of the presence and impact of such environmental chemical contaminants is through detection of changes in the status of gene transcript levels using a targeted quantitative real-time polymerase chain reaction assay. Ideally, the wildlife assessment strategy would incorporate conservation-centered non-lethal practices. Herein, we describe the development of such an assay for rainbow trout, Oncorhynchus mykiss, following an acute 96 h exposure to increasing concentrations of either 17α-ethinyl estradiol or cadmium. The estrogenic screen included measurement of mRNA encoding estrogen receptor α and β isoforms, vitellogenin, vitelline envelope protein γ, cytochrome p450 family 19 subfamily A, aryl hydrocarbon receptor, and the stress indicator, catalase. The metal exposure screen included evaluation of the latter two mRNA transcripts along with those encoding the metallothionein A and B isoforms. Exposure-dependent transcript abundance profiles were detected in both liver and caudal fin supporting the use of the caudal fin as a non-lethally obtained tissue source. The potential for both transcriptome profiling and genotypic sex determination from fin biopsy was extended, in principle, to field-captured Chinook salmon (Oncorhynchus tshawytscha). Copyright © 2013 Elsevier B.V. All rights reserved.

hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

PubMed

Nogawa, Hisashi; Kawai, Tomoyuki

2014-10-15

Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

Three homicides with darts tainted with succinylcholine: autopsy and toxicology.

PubMed

Xing, Jingjun; Li, Wenhe; Tong, Fang; Liang, Yue; He, Guanglong; Zhou, Yiwu

2016-11-01

In emergency departments, intoxication with the muscle relaxant succinylcholine (SUX) often leads to a potentially lethal respiratory paralysis or other deleterious side effects. However, homicide cases with SUX poisoning are very rare because the toxic or lethal concentration ranges of SUX have not yet been determined. We described three uncommon homicide cases due to acute poisoning by darts contaminated with SUX. All the victims died quickly (less than 30 min) after being shot by an especially designed dart gun. Succinylmonocholine (SMC), a metabolite of SUX, was used as a marker to detect the latter. HPLC-MS/MS analysis demonstrated the presence of SUX in the droplet residues of the darts and SMC in the blood and urine in all cases. SMC concentrations of 0.45, 14.0, and 17.9 ng/ml were detected in the victims' blood and 259.0 ng/ml in the urine from the third case. The main pathological changes consisted of hemorrhage of the injured soft tissues, visceral congestion, severe pulmonary edema, and multifocal petechial hemorrhage of the heart and lungs. Taken together, the findings supported a diagnosis of fatal SUX poisoning. Futhermore, our study provided a reference for the lethal concentrations of SUX poisoning.

Post-exposure treatment of non-human primates lethally infected with Ebola virus with EBOTAb, a purified ovine IgG product.

PubMed

Dowall, Stuart D; Jacquot, Frédéric; Landon, John; Rayner, Emma; Hall, Graham; Carbonnelle, Caroline; Raoul, Hervé; Pannetier, Delphine; Cameron, Ian; Coxon, Ruth; Al Abdulla, Ibrahim; Hewson, Roger; Carroll, Miles W

2017-06-22

Despite sporadic outbreaks of Ebola virus (EBOV) over the last 4 decades and the recent public health emergency in West Africa, there are still no approved vaccines or therapeutics for the treatment of acute EBOV disease (EVD). In response to the 2014 outbreak, an ovine immunoglobulin therapy was developed, termed EBOTAb. After promising results in the guinea pig model of EBOV infection, EBOTAb was tested in the cynomolgus macaque non-human primate model of lethal EBOV infection. To ensure stringent therapeutic testing conditions to replicate likely clinical usage, EBOTAb was first delivered 1, 2 or 3 days post-challenge with a lethal dose of EBOV. Results showed a protective effect of EBOTAb given post-exposurally, with survival rates decreasing with increasing time after challenge. Viremia results demonstrated that EBOTAb resulted in a decreased circulation of EBOV in the bloodstream. Additionally, assay of liver enzymes and histology analysis of local tissues identified differences between EBOTAb-treated and untreated groups. The results presented demonstrate that EBOTAb conferred protection against EBOV when given post-exposure and should be explored and developed further as a potential intervention strategy for future outbreaks, which are likely to occur.

Adaptation of a Biomarker-Based Sepsis Mortality Risk Stratification Tool for Pediatric Acute Respiratory Distress Syndrome.

PubMed

Yehya, Nadir; Wong, Hector R

2018-01-01

The original Pediatric Sepsis Biomarker Risk Model and revised (Pediatric Sepsis Biomarker Risk Model-II) biomarker-based risk prediction models have demonstrated utility for estimating baseline 28-day mortality risk in pediatric sepsis. Given the paucity of prediction tools in pediatric acute respiratory distress syndrome, and given the overlapping pathophysiology between sepsis and acute respiratory distress syndrome, we tested the utility of Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II for mortality prediction in a cohort of pediatric acute respiratory distress syndrome, with an a priori plan to revise the model if these existing models performed poorly. Prospective observational cohort study. University affiliated PICU. Mechanically ventilated children with acute respiratory distress syndrome. Blood collection within 24 hours of acute respiratory distress syndrome onset and biomarker measurements. In 152 children with acute respiratory distress syndrome, Pediatric Sepsis Biomarker Risk Model performed poorly and Pediatric Sepsis Biomarker Risk Model-II performed modestly (areas under receiver operating characteristic curve of 0.61 and 0.76, respectively). Therefore, we randomly selected 80% of the cohort (n = 122) to rederive a risk prediction model for pediatric acute respiratory distress syndrome. We used classification and regression tree methodology, considering the Pediatric Sepsis Biomarker Risk Model biomarkers in addition to variables relevant to acute respiratory distress syndrome. The final model was comprised of three biomarkers and age, and more accurately estimated baseline mortality risk (area under receiver operating characteristic curve 0.85, p < 0.001 and p = 0.053 compared with Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II, respectively). The model was tested in the remaining 20% of subjects (n = 30) and demonstrated similar test characteristics. A validated, biomarker-based risk stratification tool designed for pediatric sepsis was adapted for use in pediatric acute respiratory distress syndrome. The newly derived Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model demonstrates good test characteristics internally and requires external validation in a larger cohort. Tools such as Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model have the potential to provide improved risk stratification and prognostic enrichment for future trials in pediatric acute respiratory distress syndrome.

An evaluation of the influence of substrate on the response of juvenile freshwater mussels (fatmucket, Lampsilis siliquoidea) in acute water exposures to ammonia

USGS Publications Warehouse

Miao, J.; Barnhart, M.C.; Brunson, E.L.; Hardesty, D.K.; Ingersoll, C.G.; Wang, N.

2010-01-01

Acute 96-h ammonia toxicity to three-month-old juvenile mussels (Lampsilis siliquoidea) was evaluated in four treatments (water-only, water-only with feeding, water and soil, and water and sand) using an exposure unit designed to maintain consistent pH and ammonia concentrations in overlying water and in pore water surrounding the substrates. Median effect concentrations (EC50s) for total ammonia nitrogen in the four treatments ranged from 5.6 to 7.7mg/L and median lethal concentrations (LC50s) ranged from 7.0 to 11mg/L at a mean pH of 8.4. Similar EC50s or LC50s with overlapping 95% confidence intervals among treatments indicated no influence of substrate on the response of mussels in acute exposures to ammonia. ?? 2010 SETAC.

Unconventional repertoire profile is imprinted during acute chikungunya infection for natural killer cells polarization toward cytotoxicity.

PubMed

Petitdemange, Caroline; Becquart, Pierre; Wauquier, Nadia; Béziat, Vivien; Debré, Patrice; Leroy, Eric M; Vieillard, Vincent

2011-09-01

Chikungunya virus (CHIKV) is a worldwide emerging pathogen. In humans it causes a syndrome characterized by high fever, polyarthritis, and in some cases lethal encephalitis. Growing evidence indicates that the innate immune response plays a role in controlling CHIKV infection. We show here that CHIKV induces major but transient modifications in NK-cell phenotype and function soon after the onset of acute infection. We report a transient clonal expansion of NK cells that coexpress CD94/NKG2C and inhibitory receptors for HLA-C1 alleles and are correlated with the viral load. Functional tests reveal cytolytic capacity driven by NK cells in the absence of exogenous signals and severely impaired IFN-γ production. Collectively these data provide insight into the role of this unique subset of NK cells in controlling CHIKV infection by subset-specific expansion in response to acute infection, followed by a contraction phase after viral clearance.

Pharmacogenetics in Acute Lymphoblastic Leukemia

PubMed Central

Cheok, Meyling H.; Pottier, Nicolas; Kager, Leo

2009-01-01

Progress in the treatment of acute leukemia in children has been remarkable, from a disease being lethal four decades ago to current cure rates exceeding 80%. This exemplary progress is largely due to the optimization of existing treatment modalities rather than the discovery of new antileukemic agents. However, despite these high cure rates, the annual number of children whose leukemia relapses after their initial therapy remains greater than that of new cases of most types of childhood cancers. The aim of pharmacogenetics is to develop strategies to personalize treatment and tailor therapy to individual patients, with the goal of optimizing efficacy and safety through better understanding of human genome variability and its influence on drug response. In this review, we summarize recent pharmacogenomic studies related to the treatment of pediatric acute lymphoblastic leukemia. These studies illustrate the promise of pharmacogenomics to further advance the treatment of human cancers, with childhood leukemia serving as a paradigm. PMID:19100367

Leukemia inhibitory factor protects against experimental lethal Escherichia coli septic shock in mice.

PubMed Central

Waring, P M; Waring, L J; Billington, T; Metcalf, D

1995-01-01

Leukemia inhibitory factor (LIF) has recently been associated with septic shock in humans. In this study we sought to determine, in mice, the role of LIF in septic shock. During sublethal endotoxemia, serum LIF levels, as determined by radio-receptor competition assay, peaked at 2 h and were low (3 ng/ml), whereas in lethal Escherichia coli septic shock serum LIF levels rose progressively (> 30 ng/ml) in the premorbid phase coincident with the development of tissue injury. Single i.v. injections of high doses (up to 50 micrograms per mouse) of recombinant murine LIF had no obvious acute detrimental effects, whereas continued i.p. administration (30 micrograms per mouse per day) for 3-4 days induced a fatal catabolic state without evidence of preceding hemodynamic collapse or shock. Simultaneous or subsequent administration of high doses of LIF had no effect on mortality from sublethal and lethal E. coli septic shock, whereas prior administration conferred significant protection against lethality (P << 0.001 by log-rank test), an effect that was dose and interval dependent. This protective effect resembled endotoxin tolerance and was characterized by suppression of E. coli-induced serum tumor necrosis factor concentration (P < 0.05), reduction in the number of viable bacteria (P < 0.05), and prevention of sepsis-induced tissue injury. These observations suggest that systemic LIF production is part of the host response to both endotoxin and sepsis-induced tissue injury. Images Fig. 2 Fig. 5 PMID:7877978

Filgrastim Improves Survival in Lethally Irradiated Nonhuman Primates

PubMed Central

Farese, Ann M.; Cohen, Melanie V.; Katz, Barry P.; Smith, Cassandra P.; Gibbs, Allison; Cohen, Daniel M.; MacVittie, Thomas J.

2015-01-01

Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n =22) or filgrastim-treated (n =24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality [20.8% (5/24)] compared to the controls [59.1% (13/22)]. Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome. PMID:23210705

The Effect of Oseltamivir on the Disease Progression of Lethal Influenza A Virus Infection: Plasma Cytokine and miRNA Responses in a Mouse Model

PubMed Central

Chockalingam, Ashok K.; Hamed, Salaheldin; Goodwin, David G.; Rosenzweig, Barry A.; Pang, Eric; Boyne II, Michael T.

2016-01-01

Lethal influenza A virus infection leads to acute lung injury and possibly lethal complications. There has been a continuous effort to identify the possible predictors of disease severity. Unlike earlier studies, where biomarkers were analyzed on certain time points or days after infection, in this study biomarkers were evaluated over the entire course of infection. Circulating proinflammatory cytokines and/or miRNAs that track with the onset and progression of lethal A/Puerto Rico/8/34 (PR8) influenza A virus infection and their response to oseltamivir treatment were investigated up to 10 days after infection. Changes in plasma cytokines (IL-1β, IL-10, IL-12p70, IL-6, KC, TNF-α, and IFN-γ) and several candidate miRNAs were profiled. Among the cytokines analyzed, IL-6 and KC/GRO cytokines appeared to correlate with peak viral titer. Over the selected 48 miRNAs profiled, certain miRNAs were up- or downregulated in a manner that was dependent on the oseltamivir treatment and disease severity. Our findings suggest that IL-6 and KC/GRO cytokines can be a potential disease severity biomarker and/or marker for the progression/remission of infection. Further studies to explore other cytokines, miRNAs, and lung injury proteins in serum with different subtypes of influenza A viruses with varying disease severity may provide new insight into other unique biomarkers. PMID:27110056

Human prevalence of the spotted fever group (SFG) rickettsiae in endemic zones of Northwestern Colombia.

PubMed

Londoño, Andrés F; Acevedo-Gutiérrez, Leidy Y; Marín, Diana; Contreras, Verónica; Díaz, Francisco J; Valbuena, Gustavo; Labruna, Marcelo B; Hidalgo, Marylin; Arboleda, Margarita; Mattar, Salim; Solari, Sergio; Rodas, Juan D

2017-06-01

In February 2006, an outbreak of human rickettsiosis occurred in the municipality of Necoclí Colombia, with 35% of lethality. This episode was, followed by two more, one in the municipality of Los Cordobas in 2007 with a 54% of lethality and the other one in the municipality of Turbo in 2008 with 27% of lethality. The aim of this study was to perform serological tests in healthy persons to determine the seroprevalence of antibodies against spotted fever group (SFG) rickettsiae and develop a survey to study some infection risk-related factors. A cross-sectional study was performed in 2011 and 2012. A blood sample and survey of associated factors was performed in healthy persons. A prevalence of 32%-41% was found in healthy people. From the multivariate analysis, we found that people living more than 16 years in these sites had a 79% higher risk of being seropositive and a 46% higher risk when they reported having birds in their houses if the variable of having a horse was included in the model. In conclusion, this study shows endemicity of at least one spotted fever group Rickettsia in the study zone. Copyright © 2017 Elsevier GmbH. All rights reserved.

Psychosocial Characteristics and Social Networks of Suicidal Prisoners: Towards a Model of Suicidal Behaviour in Detention

PubMed Central

Rivlin, Adrienne; Hawton, Keith; Marzano, Lisa; Fazel, Seena

2013-01-01

Prisoners are at increased risk of suicide. Investigation of both individual and environmental risk factors may assist in developing suicide prevention policies for prisoners and other high-risk populations. We conducted a matched case-control interview study with 60 male prisoners who had made near-lethal suicide attempts in prison (cases) and 60 male prisoners who had not (controls). We compared levels of depression, hopelessness, self-esteem, impulsivity, aggression, hostility, childhood abuse, life events (including events occurring in prison), social support, and social networks in univariate and multivariate models. A range of psychosocial factors was associated with near-lethal self-harm in prisoners. Compared with controls, cases reported higher levels of depression, hopelessness, impulsivity, and aggression, and lower levels of self-esteem and social support (all p values <0.001). Adverse life events and criminal history factors were also associated with near-lethal self-harm, especially having a prior prison spell and having been bullied in prison, both of which remained significant in multivariate analyses. The findings support a model of suicidal behaviour in prisoners that incorporates imported vulnerability factors, clinical factors, and prison experiences, and underscores their interaction. Strategies to reduce self-harm and suicide in prisoners should include attention to such factors. PMID:23922671

THERAPIST PERCEPTIONS OF INTIMATE PARTNER VIOLENCE: A REPLICATION OF HARWAY AND HANSEN2019;S STUDY AFTER MORE THAN A DECADE

PubMed Central

Dudley, Desreen Raphael; McCloskey, Kathy; Kustron, Debora A.

2014-01-01

More than a decade ago, Hansen, Harway, and Cervantes (1991) and Harway and Hansen (1993) conducted a research study examining mental health providers’ ability to accurately perceive violence within couples presenting for therapy and to intervene in a manner in which to reduce the risk of danger to couples. The results were alarming, with 40% of therapists sampled failing to perceive intimate partner violence (IPV) and virtually no therapists intervening to reduce the risk of lethality. Harway and colleagues questioned how well-trained and informed therapists were in assessing IPV. The present study replicates Harway and colleagues’ study with the expectation that, over a decade later, therapists are better prepared to accurately identify IPV issues and intervene effectively to reduce the risk of lethality. Reproducing the two main procedures used in the original study, 111 psychologists, clinical social workers, and marriage and family therapists were asked to respond to a survey. Results show that therapists have indeed improved their ability to identify IPV issues. Twenty percent of therapists predicted an increase in conflict, compared to 4% in the original sample. However, almost no therapists accurately predicted lethality in either study. Implications concerning IPV training for therapists are discussed. PMID:24729677

Postinoculation PMPA Treatment, but Not Preinoculation Immunomodulatory Therapy, Protects against Development of Acute Disease Induced by the Unique Simian Immunodeficiency Virus SIVsmmPBj

PubMed Central

Hodge, Shekema; de Rosayro, Juliette; Glenn, Amanda; Ojukwu, Ifeoma C.; Dewhurst, Stephen; McClure, Harold M.; Bischofberger, Norbert; Anderson, Daniel C.; Klumpp, Sherry A.; Novembre, Francis J.

1999-01-01

The fatal disease induced by SIVsmmPBj4 clinically resembles endotoxic shock, with the development of severe gastrointestinal disease. While the exact mechanism of disease induction has not been fully elucidated, aspects of virus biology suggest that immune activation contributes to pathogenesis. These biological characteristics include induction of peripheral blood mononuclear cell (PBMC) proliferation, upregulation of activation markers and Fas ligand expression, and increased levels of apoptosis. To investigate the role of immune activation and viral replication on disease induction, animals infected with SIVsmmPBj14 were treated with one of two drugs: FK-506, a potent immunosuppressive agent, or PMPA, a potent antiretroviral agent. While PBMC proliferation was blocked in vitro with FK-506, pig-tailed macaques treated preinoculation with FK-506 were not protected from acutely lethal disease. However, these animals did show some evidence of modulation of immune activation, including reduced levels of CD25 antigen and FasL expression, as well as lower tissue viral loads. In contrast, macaques treated postinoculation with PMPA were completely protected from the development of acutely lethal disease. Treatment with PMPA beginning as late as 5 days postinfection was able to prevent the PBj syndrome. Plasma and cellular viral loads in PMPA-treated animals were significantly lower than those in untreated controls. Although PMPA-treated animals showed acute lymphopenia due to SIVsmmPBj14 infection, cell subset levels subsequently recovered and returned to normal. Based upon subsequent CD4+ cell counts, the results suggest that very early treatment following retroviral infection can have a significant effect on modifying the subsequent course of disease. These results also suggest that viral replication is an important factor involved in PBJ-induced disease. These studies reinforce the idea that the SIVsmmPBj model system is useful for therapy and vaccine testing. PMID:10482616

An enriched stable-isotope approach to determine the gill-zinc binding properties of juvenile rainbow trout (Oncorhynchus mykiss) during acute zinc exposures in hard and soft waters

USGS Publications Warehouse

Todd, A.S.; Brinkman, S.; Wolf, R.E.; Lamothe, P.J.; Smith, K.S.; Ranville, J.F.

2009-01-01

The objective of the present study was to employ an enriched stable-isotope approach to characterize Zn uptake in the gills of rainbow trout (Oncorhynchus mykiss) during acute Zn exposures in hard water (???140 mg/L as CaCO 3) and soft water (???30 mg/L as CaCO3). Juvenile rainbow trout were acclimated to the test hardnesses and then exposed for up to 72 h in static exposures to a range of Zn concentrations in hard water (0-1,000 ??g/L) and soft water (0-250 ??g/L). To facilitate detection of new gill Zn from endogenous gill Zn, the exposure media was significantly enriched with 67Zn stable isotope (89.60% vs 4.1% natural abundance). Additionally, acute Zn toxicity thresholds (96-h median lethal concentration [LC50]) were determined experimentally through traditional, flow-through toxicity tests in hard water (580 ??g/L) and soft water (110 ??g/L). Following short-term (???3 h) exposures, significant differences in gill accumulation of Zn between hard and soft water treatments were observed at the three common concentrations (75, 150, and 250 ??g/L), with soft water gills accumulating more Zn than hard water gills. Short-term gill Zn accumulation at hard and soft water LC50s (45-min median lethal accumulation) was similar (0.27 and 0.20 ??g/g wet wt, respectively). Finally, comparison of experimental gill Zn accumulation, with accumulation predicted by the biotic ligand model, demonstrated that model output reflected short-term (<1 h) experimental gill Zn accumulation and predicted observed differences in accumulation between hard and soft water rainbow trout gills. Our results indicate that measurable differences exist in short-term gill Zn accumulation following acclimation and exposure in different water hardnesses and that short-term Zn accumulation appears to be predictive of Zn acute toxicity thresholds (96-h LC50s). ?? 2009 SETAC.

Fear and loathing in the benthos: Responses of aquatic insect larvae to the pesticide imidacloprid in the presence of chemical signals of predation risk.

PubMed

Pestana, João L T; Loureiro, Susana; Baird, Donald J; Soares, Amadeu M V M

2009-06-28

The influence of interactions between pesticide exposure and perceived predation risk on the lethal and sub-lethal responses of two aquatic insects was investigated using the pesticide imidacloprid, and a combination of predator-release kairomones from trout and alarm substances from conspecifics. Laboratory experiments examined feeding and respiration rates of the caddisfly Sericostoma vittatum as well as the growth, emergence and respiration rates of the midge Chironomus riparius, exposed to sub-lethal concentrations of imidacloprid. The effects of the two stressors on burrowing behaviour of both species were also assessed. The results show significant effects of environmentally relevant concentrations of imidacloprid on all endpoints studied. Perceived predation risk also elicited sub-lethal effects in C. riparius and S. vittatum, the latter species being less responsive to predation cues. The effects of simultaneous exposure to both types of stressors were assessed using two different approaches: analysis of variance and conceptual models [concentration addition (CA) and independent action (IA)] normally used for the evaluation of contaminant mixture exposure. Both statistical approaches showed no significant interactions on responses in simultaneous exposures in the majority of parameters assessed with only a signification deviation from the reference CA and IA models being found for C. riparius respiration data contrary to the ANOVA results. Exposure to imidacloprid also compromised antipredator behavioural responses of both insect species, with potential negative consequences in terms of mortality from predation in the field. The results obtained demonstrate that natural and anthropogenic stressors can be treated within the same framework providing compatible data for modelling. For an improved interpretation of ecological effects it will be important to expand the mechanistic study of effects of combined exposure to pesticides and perceived predation risk by measuring different endpoints over a wider range of pesticide concentrations.

Pathways to Late-Life Suicidal Behavior: Cluster Analysis and Predictive Validation of Suicidal Behavior in a Sample of Older Adults With Major Depression.

PubMed

Szanto, Katalin; Galfalvy, Hanga; Vanyukov, Polina M; Keilp, John G; Dombrovski, Alexandre Y

Clinical heterogeneity is a key challenge to understanding suicidal risk, as different pathways to suicidal behavior are likely to exist. We aimed to identify such pathways by uncovering latent classes of late-life depression cases and relating them to prior and future suicidal behavior. Data were collected from June 2010 to September 2015. In this longitudinal study we examined distinct associations of clinical and cognitive/decision-making factors with suicidal behavior in 194 older (50+ years) nondemented, depressed patients; 57 nonpsychiatric healthy controls provided benchmark data. The DSM-IV was used to establish diagnostic criteria. We identified multivariate patterns of risk factors, defining clusters based on personality traits, perceived social support, cognitive performance, and decision-making in an analysis blinded to participants' history of suicidal behavior. We validated these clusters using past and prospective suicidal ideation and behavior. Of 5 clusters identified, 3 were associated with high risk for suicidal behavior: (1) cognitive deficits, dysfunctional personality, low social support, high willingness to delay future rewards, and overrepresentation of high-lethality attempters; (2) high-personality pathology (ie, low self-esteem), minimal or no cognitive deficits, and overrepresentation of low-lethality attempters and ideators; (3) cognitive deficits, inability to delay future rewards, and similar distribution of high- and low-lethality attempters. There were significant between-cluster differences in number (P < .001) and lethality (P = .002) of past suicide attempts and in the likelihood of future suicide attempts (P = .010, 30 attempts by 22 patients, 2 fatal) and emergency psychiatric hospitalizations to prevent suicide (P = .005, 31 participants). Three pathways to suicidal behavior in older patients were found, marked by (1) very high levels of cognitive and dispositional risk factors suggesting a dementia prodrome, (2) dysfunctional personality traits, and (3) impulsive decision-making and cognitive deficits. © Copyright 2018 Physicians Postgraduate Press, Inc.

Injury Pattern and Mortality of Noncompressible Torso Hemorrhage in UK Combat Casualties

DTIC Science & Technology

2013-08-01

body disruption (5.1%), and multiple-organ failure (4.0%). On multivariate analysis, major arterial and pulmonary hilar injury are most lethal with odds...death. Major arterial and pulmonary hilar injuries are independent predictors of mortality. (J Trauma Acute Care Surg. 2013;75: S263YS268. Copyright...physiologic or procedural indices of shock.8 Anatomic refers to those injuries to a named torso vessel, pulmonary injury (massive hemothorax or hilar

Traumatic Pancreatitis: A Rare Complication of Cardiopulmonary Resuscitation.

PubMed

Aziz, Muhammad

2017-08-17

An elderly gentleman was successfully revived after undergoing cardiopulmonary resuscitation (CPR) for cardiac arrest. Post CPR, the patient developed acute pancreatitis which was likely complication of inappropriately delivered chest compressions which caused further complications and resulted in the death of the patient. This case underlines the importance of quality chest compressions that includes correct placement of hands by the operator giving chest compressions to avoid lethal injuries to the receiver.

Experimental Therapeutics Against the Toxic and Lethal Effects Resulting from Acute Exposure to Nerve Agents Without Carbamate Pretreatment in Guinea Pigs

DTIC Science & Technology

2010-09-01

or VX. Guinea pigs chronically instrumented for concurrent recordings of EEG, cardiorespiratory activities , diaphragm and skeletal muscle EMG were... activities , or any debilitating effects. The animals were asymptomatic within 30 min following therapy and survived the agent challenge 24 hr later. In...For a thorough efficacy evaluation, the animals were chronically instrumented to permit concurrent recordings of central nervous system activity

Medical Managment of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group

DTIC Science & Technology

2004-06-15

Women† Precautions G-CSF or filgrastim Subcutaneous administration of 5 g/kg of body weight per day, continued until ANC 1.0 109 cells/L...lymphohematopoietic elements. Several studies have indicated that administra- tion of antibiotics reduces mortality rates in irradiated dogs in the...hematopoiesis of normal dogs and on hematopoietic recovery after otherwise lethal total body irradiation. Blood. 1989;74:1308-13. [PMID: 2475186] 10

Biodefense-driven murine model of pneumonic melioidosis.

PubMed

Jeddeloh, J A; Fritz, D L; Waag, D M; Hartings, J M; Andrews, G P

2003-01-01

A whole-body mouse model of pneumonic melioidosis was established for future evaluation of biodefense vaccine candidates. The aerosol 50% lethal doses of Burkholderia pseudomallei strain 1026b for BALB/c and C57BL/6 mice and the times to death, dissemination in organs, and tissue loads after exposure of the mice to low- and high-dose aerosols are reported. In addition, rpsL mutant backgrounds were attenuated in this acute model of disease.

Hospital admissions for asthma and acute bronchitis in El Paso, Texas: do age, sex, and insurance status modify the effects of dust and low wind events?

PubMed

Grineski, Sara E; Staniswalis, Joan G; Bulathsinhala, Priyangi; Peng, Yanlei; Gill, Thomas E

2011-11-01

El Paso County (Texas) is prone to still air inversions and is one of the dust "hot spots" in North America. In this context, we examined the sub-lethal effects of airborne dust and low wind events on human respiratory health (i.e., asthma and acute bronchitis) between 2000 and 2003, when 110 dust and 157 low wind events occurred. Because environmental conditions may not affect everyone the same, we explored the effects of dust and low wind within three age groups (children, adults, and the elderly), testing for effect modifications by sex and insurance status, while controlling for weather and air pollutants. We used a case-crossover design using events matched with referent days on the same day-of-the-week, month, and year with conditional logistic regression to estimate the probability of hospital admission, while controlling for apparent temperature (lag 1), nitrogen dioxide, and particulate matter of 2.5μm or less. Children (aged 1-17) were 1.19 (95% confidence interval: 1.00-1.41) times more likely to be hospitalized for asthma three days after a low wind event, and 1.33 (95% CI: 1.01-1.75) times more likely to be hospitalized for acute bronchitis one day after a dust event than on a clear day. Girls were more sensitive to acute bronchitis hospitalizations after dust events (1.83, 95% CI: 1.09-3.08) than boys, but less sensitive than boys to acute bronchitis hospitalizations after low wind events (0.68, 95% CI: 0.46-1.00). We found general trends with regard to dust and low wind events being associated with increased odds of hospitalization for asthma and bronchitis amongst all ages and adults (aged 18-64). Adults covered by Medicaid and adults without health insurance had higher risks of hospitalization for asthma and acute bronchitis after both low wind and dust events. Results suggest that there were respiratory health effects associated with dust and low wind events in El Paso, with stronger impacts among children and poor adults. Girls and boys with acute bronchitis were differentially sensitive to dust and low wind events. Copyright © 2011 Elsevier Inc. All rights reserved.

Hospital admissions for asthma and acute bronchitis in El Paso, Texas: Do age, sex, and insurance status modify the effects of dust and low wind events?

PubMed Central

Staniswalis, Joan G.; Bulathsinhala, Priyangi; Peng, Yanlei; Gill, Thomas E.

2013-01-01

Background El Paso County (Texas) is prone to still air inversions and is one of the dust “hot spots” in North America. In this context, we examined the sub-lethal effects of airborne dust and low wind events on human respiratory health (i.e., asthma and acute bronchitis) between 2000 and 2003, when 110 dust and 157 low wind events occurred. Because environmental conditions may not affect everyone the same, we explored the effects of dust and low wind within three age groups (children, adults, and the elderly), testing for effect modifications by sex and insurance status, while controlling for weather and air pollutants. Methods We used a case-crossover design using events matched with referent days on the same day-of-the-week, month, and year with conditional logistic regression to estimate the probability of hospital admission, while controlling for apparent temperature (lag 1), nitrogen dioxide, and particulate matter of 2.5 micrometers or less. Results Children (aged 1–17) were 1.19 (95% confidence interval: 1.00–1.41) times more likely to be hospitalized for asthma three days after a low wind event, and 1.33 (95% CI: 1.01–1.75) times more likely to be hospitalized for acute bronchitis one day after a dust event than on a clear day. Girls were more sensitive to acute bronchitis hospitalizations after dust events (1.83, 95% CI: 1.09–3.08) than boys, but less sensitive than boys to acute bronchitis hospitalizations after low wind events (0.68, 95% CI: 0.46–1.00). We found general trends with regard to dust and low wind events being associated with increased odds of hospitalization for asthma and bronchitis amongst all ages and adults (aged 18–64). Adults covered by Medicaid and adults without health insurance had higher risks of hospitalization for asthma and acute bronchitis after both low wind and dust event Conclusions Results suggest that there were respiratory health effects associated with dust and low wind events in El Paso, with stronger impacts among children and poor adults. Girls and boys with acute bronchitis were differentially sensitive to dust and low wind events. PMID:21782162

Adverse pregnancy outcomes around incinerators and crematoriums in Cumbria, north west England, 1956–93

PubMed Central

Dummer, T; Dickinson, H; Parker, L

2003-01-01

Study objective: To investigate the risk of stillbirth, neonatal death, and lethal congenital anomaly among babies of mothers living close to incinerators and crematoriums in Cumbria, north west England, 1956–93. Design: Retrospective cohort study. Logistic regression was used to investigate the risk of each outcome in relation to proximity at birth to incinerators and crematoriums, adjusting for social class, year of birth, birth order, and multiple births. Continuous odds ratios for trend with proximity to sites were estimated. Setting: All 3234 stillbirths, 2663 neonatal deaths, and 1569 lethal congenital anomalies among the 244 758 births to mothers living in Cumbria, 1956–1993. Main results: After adjustment for social class, year of birth, birth order, and multiple births, there was an increased risk of lethal congenital anomaly, in particular spina bifida (odds ratio 1.17, 95% CI: 1.07 to 1.28) and heart defects (odds ratio 1.12, 95% CI: 1.03 to 1.22) around incinerators and an increased risk of stillbirth (odds ratio 1.04, 95% CI: 1.01 to 1.07) and anencephalus (odds ratio 1.05, 95% CI: 1.00 to 1.10) around crematoriums. Conclusions: The authors cannot infer a causal effect from the statistical associations reported in this study. However, as there are few published studies with which to compare our results, the risk of spina bifida, heart defects, stillbirth, and anencephalus in relation to proximity to incinerators and crematoriums should be investigated further, in particular because of the increased use of incineration as a method of waste disposal. PMID:12775795

Dietary acrylamide and risk of prostate cancer

PubMed Central

Wilson, Kathryn M.; Giovannucci, Edward; Stampfer, Meir J.; Mucci, Lorelei A.

2011-01-01

Acrylamide has been designated by IARC as a “probable human carcinogen.” High levels are formed during cooking of many commonly consumed foods including French fries, potato chips, breakfast cereal, and coffee. Two prospective cohort studies and two case-control studies in Europe found no association between acrylamide intake and prostate cancer. We examined this association in a large prospective cohort of 47,896 U.S. men in the Health Professionals’ Follow-up Study, using updated dietary acrylamide intake from food frequency questionnaires in 1986, 1990, 1994, 1998, and 2002. From 1986 through 2006, we documented 5025 cases of prostate cancer, and 642 lethal cancers. We used Cox proportional hazards models to assess the association between acrylamide intake from diet and prostate cancer risk overall as well as risk of advanced or lethal cancer. Acrylamide intake ranged from a mean of 10.5 mcg/day in the lowest quintile to 40.1 mcg/day in the highest quintile; coffee and potato products were largest contributors to intake. The multivariate-adjusted relative risk of prostate cancer was 1.02 (95% confidence interval: 0.92–1.13) for the highest versus lowest quintile of acrylamide intake (p-value for trend=0.90). Results were similar when restricted to never smokers and to men who had PSA tests. There was no significant association for dietary acrylamide and risk of lethal, advanced, or high-grade disease, or for different latency periods ranging from 0–4 years to 12–16 years. We found no evidence that acrylamide intake, within the range of U.S. diets, is associated with increased risk of prostate cancer. PMID:21866549

Inflammatory Cell Infiltrates in Acute and Chronic Thoracic Aortic Dissection.

PubMed

Wu, Darrell; Choi, Justin C; Sameri, Aryan; Minard, Charles G; Coselli, Joseph S; Shen, Ying H; LeMaire, Scott A

2013-12-01

Thoracic aortic dissection (TAD) is a highly lethal cardiovascular disease. Injury to the intima and media allows pulsatile blood to enter the media, leading to dissection formation. Inflammatory cells then infiltrate the site of aortic injury to clear dead cells and damaged tissue. This excessive inflammation may play a role in aneurysm formation after dissection. Using immunohistochemistry, we compared aortic tissues from patients with acute TAD (n = 11), patients with chronic TAD (n = 35), and donor controls (n = 20) for the presence of CD68+ macrophages, neutrophils, mast cells, and CD3+ T lymphocytes. Tissue samples from patients with acute or chronic TAD generally had significantly more inflammatory cells in both the medial and adventitial layers than did the control samples. In tissues from patients with acute TAD, the adventitia had more of the inflammatory cells studied than did the media. The pattern of increase in inflammatory cells was similar in chronic and acute TAD tissues, except for macrophages, which were seen more frequently in the adventitial layer of acute TAD tissue than in the adventitia of chronic TAD tissue. The inflammatory cell content of both acute and chronic TAD tissue was significantly different from that of control tissue. However, the inflammatory cell profile of aneurysmal chronic TAD was similar to that of acute TAD. This may reflect a sustained injury response that contributes to medial degeneration and aneurysm formation.

Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

PubMed

Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

2017-11-01

Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride

PubMed Central

Sauerheber, Richard

2013-01-01

The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings. PMID:23840230

Kratom: a dangerous player in the opioid crisis.

PubMed

Tayabali, Khadija; Bolzon, Colin; Foster, Paul; Patel, Janki; Kalim, Mohammad Omar

2018-01-01

Kratom use as a herbal supplement is on the rise in the United States, with reported medical outcomes and lethal effects suggesting a public health threat. Even though the Drug Enforcement Administration has included kratom on its drugs of concern list and the FDA has published a press release to identify it as an opioid with a potential for abuse, its therapeutic and side effects are still not well defined in the literature. Here, we present a case of a 32-year-old man with a history of kratom use who became acutely ill with a brief prodromal illness, followed by jaundice and elevated liver enzymes showing a cholestatic picture, and his successful treatment. In this case, we emphasize the need for awareness of kratom exposure as a key contributor in the expansion of the opioid crisis, with therapeutic benefits earned at the expense of potentially lethal side effects.

Physiologic conditions affect toxicity of ingested industrial fluoride.

PubMed

Sauerheber, Richard

2013-01-01

The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

Acute toxicity and biodegradation of endosulfan by the polychaeta Perinereis aibuhitensis in an indoor culture

NASA Astrophysics Data System (ADS)

Kang, Kyoung Ho; Zhang, Litao; Zhang, Zhifeng; Sui, Zhenghong; Hur, Junwook

2013-01-01

The polychaete Perinereis aibuhitensis, a key species in estuarine ecosystems, can improve the culture condition of sediment. Endosulfan is an organochlorine pesticide used globally to control insects and mites; however, it is a source of pollution in aquaculture as a result of runoff or accidental release. In this study, we evaluated the toxicity of endosulfan to polychaeta and its ability to improve polluted sediment. Specifically, the effects of a series of endosulfan concentrations (0, 1.25, 2.5, 5, 10, 15, and 20 mg/L) were investigated, and the results indicated that the 24-h median lethal concentration (24-h LC50) was 55.57 mg/L, while the 48-h median lethal concentration (48-h LC50) was 15.56 mg/L, and the safe concentration was about 1.556 mg/L. In a 30-d exposure experiment, the animal specimen could decompose endosulfan effectively while improving endosulfan-polluted aquatic sediment.

Lethal effect of dehydroleucodine (DhL) on amphibian Bufo arenarum embryos.

PubMed

Moreno, Liliana Elizabeth; Juárez, Américo Osvaldo; Pelzer, Lilian Eugenia

2012-03-01

The dehydroleucodine is a sesquiterpene lactone isolated from Artemisia douglasiana Besser which is used in popular medicine. Toxicity tests using embryos of amphibian have been widely used in order to predict toxic effects of different compounds. However, to our knowledge, there are not studies focussed on the toxic effects of dehydroleucodine on Bufo arenarum, which is an anuran widely distributed in South America. The effect of dehydroleucodine on the survival of embryos was evaluated in an acute test during the early life stage of B. arenarum embryos. Lethality and the degree of adverse effects were dehydroleucodine dose-dependent. Overall, amphibian early life stages appeared to be more susceptible to the embryotoxicity associated with exposure to dehydroleucodine, especially at concentration greater that 3mM. This increased susceptibility may result from the relatively high rate of cellular differentiation and morphogenesis that occurs at this early stage of development. Copyright © 2012 Elsevier Ltd. All rights reserved.

Acute toxic responses of the freshwater planarian, Dugesia dorotocephala, to methylmercury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Best, J.B.; Morita, M.; Ragin, J.

1981-07-01

Toxic responses of planaria to various aquatic habitat concentrations of methylmercury chloride (MMC) were investigated. One hundred percent lethality occurred within 5 h in 2 ppM MMC, 24 h in 1 ppM MMC, and 5 days in 0.5 ppM MMC. No deaths occurred in 0.2 ppM MMC over a 10 day period, however, non-lethal toxic responses were observed. Varying degrees of head resorption, progressing caudally from the snout were observed. With continuing exposure, partial head regeneration and recovery toward more normal appearance occurred by 10 days. Teratogenic effects were observed in surgical decapitation experiments. Head regeneration was retarded in 0.1more » and 0.2 ppM MMC. Malformations, visible lesions, or gross behavioral abnormalities were produced by 2 week exposure of planaria to concentrations of 20 ppB MMC or lower. (RJC)« less

Are insect repellents toxic to freshwater insects? A case study using caddisflies exposed to DEET.

PubMed

Campos, Diana; Gravato, Carlos; Quintaneiro, Carla; Koba, Olga; Randak, Tomas; Soares, Amadeu M V M; Pestana, João L T

2016-04-01

Stream ecosystems face ever-increasing pressures by the presence of emergent contaminants, such as, personal care products. N, N-diethyl-3-methylbenzamide (DEET) is a synthetic insect repellent that is being found in surface waters environments in concentrations up to 33.4 μg/L. Information concerning DEET's toxicity in the aquatic environment is still limited and focused only on its acute effects on model species. Our main objective was to assess the effects of DEET exposure to a caddisfly non-target species using sub-lethal endpoints. For that, we chose Sericostoma vittatum, an important shredder in Portuguese freshwaters that has been already used in different ecotoxicological assays. Besides acute tests, S. vittatum were exposed during 6 days to a gradient of DEET concentrations (8, 18 and 40.5 mg/L) to assess effects on feeding behaviour and biochemical responses, such as, lipid peroxidation levels (LPO), catalase and acetylcholinesterase (AChE) activities, and also assess effects on energy reserves and consumption. Acute tests revealed a 48 h-LC50 of 80.12 mg/L and DEET exposure caused feeding inhibition with a LOEC of 36.80 mg/L. Concerning the biochemical responses, DEET caused no effects in LPO nor on catalase activity. A non-significant decrease in AChE activity was observed. Regarding energetic reserves, exposure to DEET caused a significant reduction in S. vittatum carbohydrates levels. These results add important information for the risk assessment of insect repellents in the aquatic environment and suggest that reported environmental concentrations of DEET are not toxic to non-target freshwater insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Joint acute and endocrine disruptive toxicities of malathion, cypermethrin and prochloraz to embryo-larval zebrafish, Danio rerio.

PubMed

Guo, Dongmei; Wang, Yanhua; Qian, Yongzhong; Chen, Chen; Jiao, Bining; Cai, Leiming; Wang, Qiang

2017-01-01

It remains a daunting challenge to determine ecotoxicological risks of exposure to mixtures of endocrine disrupting chemicals (EDCs) in environmental toxicology. In the present study, we investigated acute and endocrine disruptive toxicities of cypermethrin (CPM), malathion (MAL), prochloraz (PRO) and their binary mixtures of MAL + CPM and MAL + PRO to the early life stages of zebrafish. In the acute lethal toxicity test, three pesticides exhibited different levels of toxicity to zebrafish larvae, and the order of toxicity was as follows: CPM > PRO > MAL. The binary mixture of MAL + CPM displayed a synergistic effect on zebrafish larvae after exposure for 24, 48, 72 and 96 h. However, binary mixture of MAL + PRO showed an antagonistic effect. To evaluate the estrogenic effect, the expression of genes in the hypothalamic-pituitary-gonadal axis was assessed after zebrafish embryos were exposed to CPM, MAL, PRO and their binary mixtures from blastula stage (1 h post-fertilization, 1 hpf) to 14 dpf (14 d post-fertilization). Our data indicated that the transcription patterns of many key genes (vtg1, vtg2, era, erβ1, erβ2, cyp19a1a and cyp19a1b) were affected in hatched zebrafish after exposure to CPM, MAL and PRO. Moreover, following exposure to binary mixtures of 1000 μg/L MAL +4 μg/L CPM and 1000 μg/L MAL +900 μg/L PRO, the gene expressions were significantly changed compared with the individual pesticides. Our data provided a better understanding of bidirectional interactions of toxic response induced by these pesticides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

PubMed Central

Armstrong, Paul C.; Kirkby, Nicholas S.; Zain, Zetty N.; Emerson, Michael; Mitchell, Jane A.; Warner, Timothy D.

2011-01-01

Background Clinical use of selective inhibitors of cyclooxygenase (COX)-2 appears associated with increased risk of thrombotic events. This is often hypothesised to reflect reduction in anti-thrombotic prostanoids, notably PGI2, formed by COX-2 present within endothelial cells. However, whether COX-2 is actually expressed to any significant extent within endothelial cells is controversial. Here we have tested the effects of acute inhibition of COX on platelet reactivity using a functional in vivo approach in mice. Methodology/Principal Findings A non-lethal model of platelet-driven thromboembolism in the mouse was used to assess the effects of aspirin (7 days orally as control) diclofenac (1 mg.kg−1, i.v.) and parecoxib (0.5 mg.kg−1, i.v.) on thrombus formation induced by collagen or the thromboxane (TX) A2-mimetic, U46619. The COX inhibitory profiles of the drugs were confirmed in mouse tissues ex vivo. Collagen and U46619 caused in vivo thrombus formation with the former, but not latter, sensitive to oral dosing with aspirin. Diclofenac inhibited COX-1 and COX-2 ex vivo and reduced thrombus formation in response to collagen, but not U46619. Parecoxib inhibited only COX-2 and had no effect upon thrombus formation caused by either agonist. Conclusions/Significance Inhibition of COX-1 by diclofenac or aspirin reduced thrombus formation induced by collagen, which is partly dependent upon platelet-derived TXA2, but not that induced by U46619, which is independent of platelet TXA2. These results are consistent with the model demonstrating the effects of COX-1 inhibition in platelets, but provide no support for the hypothesis that acute inhibition of COX-2 in the circulation increases thrombosis. PMID:21629780

Evaluating the zebrafish embryo toxicity test for pesticide hazard screening.

PubMed

Glaberman, Scott; Padilla, Stephanie; Barron, Mace G

2017-05-01

Given the numerous chemicals used in society, it is critical to develop tools for accurate and efficient evaluation of potential risks to human and ecological receptors. Fish embryo acute toxicity tests are 1 tool that has been shown to be highly predictive of standard, more resource-intensive, juvenile fish acute toxicity tests. However, there is also evidence that fish embryos are less sensitive than juvenile fish for certain types of chemicals, including neurotoxicants. The utility of fish embryos for pesticide hazard assessment was investigated by comparing published zebrafish embryo toxicity data from pesticides with median lethal concentration 50% (LC50) data for juveniles of 3 commonly tested fish species: rainbow trout, bluegill sunfish, and sheepshead minnow. A poor, albeit significant, relationship (r 2  = 0.28; p < 0.05) was found between zebrafish embryo and juvenile fish toxicity when pesticides were considered as a single group, but a much better relationship (r 2  = 0.64; p < 0.05) when pesticide mode of action was factored into an analysis of covariance. This discrepancy is partly explained by the large number of neurotoxic pesticides in the dataset, supporting previous findings that commonly used fish embryo toxicity test endpoints are particularly insensitive to neurotoxicants. These results indicate that it is still premature to replace juvenile fish toxicity tests with embryo-based tests such as the Organisation for Economic Co-operation and Development Fish Embryo Acute Toxicity Test for routine pesticide hazard assessment, although embryo testing could be used with other screening tools for testing prioritization. Environ Toxicol Chem 2017;36:1221-1226. © 2016 SETAC. © 2016 SETAC.

Decitabine, Filgrastim, Cladribine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

ClinicalTrials.gov

2018-04-16

Mixed Phenotype Acute Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent High Risk Myelodysplastic Syndrome; Refractory Acute Myeloid Leukemia; Refractory High Risk Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

Decision-making competence and attempted suicide

PubMed Central

Szanto, Katalin; Bruine de Bruin, Wändi; Parker, Andrew M; Hallquist, Michael N; Vanyukov, Polina M; Dombrovski, Alexandre Y

2015-01-01

Objective The propensity of people vulnerable to suicide to make poor life decisions is increasingly well documented. Do they display an extreme degree of decision biases? The present study used a behavioral decision approach to examine the susceptibility of low-lethality and high-lethality suicide attempters to common decision biases, which may ultimately obscure alternative solutions and deterrents to suicide in a crisis. Method We assessed older and middle-aged individuals who made high-lethality (medically serious; N=31) and low-lethality suicide attempts (N=29). Comparison groups included suicide ideators (N=30), non-suicidal depressed (N=53), and psychiatrically healthy participants (N=28). Attempters, ideators, and non-suicidal depressed participants had unipolar non-psychotic major depression. Decision biases included sunk cost (inability to abort an action for which costs are irrecoverable), framing (responding to superficial features of how a problem is presented), under/overconfidence (appropriateness of confidence in knowledge), and inconsistent risk perception. Data were collected between June of 2010 and February of 2014. Results Both high- and low-lethality attempters were more susceptible to framing effects, as compared to the other groups included in this study (p≤ 0.05, ηp2 =.06). In contrast, low-lethality attempters were more susceptible to sunk costs than both the comparison groups and high-lethality attempters (p≤ 0.01, ηp2 =.09). These group differences remained after accounting for age, global cognitive performance, and impulsive traits. Premorbid IQ partially explained group differences in framing effects. Conclusion Suicide attempters’ failure to resist framing may reflect their inability to consider a decision from an objective standpoint in a crisis. Low-lethality attempters’ failure to resist sunk-cost may reflect their tendency to confuse past and future costs of their behavior, lowering their threshold for acting on suicidal thoughts. PMID:26717535

Decision-making competence and attempted suicide.

PubMed

Szanto, Katalin; Bruine de Bruin, Wändi; Parker, Andrew M; Hallquist, Michael N; Vanyukov, Polina M; Dombrovski, Alexandre Y

2015-12-01

The propensity of people vulnerable to suicide to make poor life decisions is increasingly well documented. Do they display an extreme degree of decision biases? The present study used a behavioral-decision approach to examine the susceptibility of low-lethality and high-lethality suicide attempters to common decision biases that may ultimately obscure alternative solutions and deterrents to suicide in a crisis. We assessed older and middle-aged (42-97 years) individuals who made high-lethality (medically serious) (n = 31) and low-lethality suicide attempts (n = 29). Comparison groups included suicide ideators (n = 30), nonsuicidal depressed participants (n = 53), and psychiatrically healthy participants (n = 28). Attempters, ideators, and nonsuicidal depressed participants had nonpsychotic major depression (DSM-IV criteria). Decision biases included sunk cost (inability to abort an action for which costs are irrecoverable), framing (responding to superficial features of how a problem is presented), underconfidence/overconfidence (appropriateness of confidence in knowledge), and inconsistent risk perception. Data were collected between June 2010 and February 2014. Both high- and low-lethality attempters were more susceptible to framing effects as compared to the other groups included in this study (P ≤ .05, ηp2 = 0.06). In contrast, low-lethality attempters were more susceptible to sunk costs than both the comparison groups and high-lethality attempters (P ≤ .01, ηp2 = 0.09). These group differences remained after accounting for age, global cognitive performance, and impulsive traits. Premorbid IQ partially explained group differences in framing effects. Suicide attempters' failure to resist framing may reflect their inability to consider a decision from an objective standpoint in a crisis. Failure of low-lethality attempters to resist sunk cost may reflect their tendency to confuse past and future costs of their behavior, lowering their threshold for acting on suicidal thoughts. © Copyright 2015 Physicians Postgraduate Press, Inc.

Hope as a Predictor of Interpersonal Suicide Risk

ERIC Educational Resources Information Center

Davidson, Collin L.; Wingate, LaRicka R.; Rasmussen, Kathy A.; Slish, Meredith L.

2009-01-01

The current study hypothesized that (1) hope would negatively predict burdensomeness, thwarted belongingness, and acquired capability to enact lethal injury; (2) hope would negatively predict suicidal ideation; and (3) the interpersonal suicide risk factors would predict suicidal ideation. Results indicated that hope negatively predicted…

Reducing Human Radiation Risks on Deep Space Missions

DTIC Science & Technology

2017-09-01

Roadmap (2016). .........................................................108 Figure 53. Risk Assessment for Acute Radiation Syndrome Due to SPEs...Risk of Acute Radiation Syndromes Due to Solar Particle Events Figure 53 highlights the fact that acute radiation syndrome is a short-term risk...acceptable for long-term missions. Figure 53. Risk Assessment for Acute Radiation Syndrome Due to SPEs. Source: NASA Human Research Roadmap (2016

Pesticide risk assessment in free-ranging bees is weather and landscape dependent.

PubMed

Henry, Mickaël; Bertrand, Colette; Le Féon, Violette; Requier, Fabrice; Odoux, Jean-François; Aupinel, Pierrick; Bretagnolle, Vincent; Decourtye, Axel

2014-07-10

The risk assessment of plant protection products on pollinators is currently based on the evaluation of lethal doses through repeatable lethal toxicity laboratory trials. Recent advances in honeybee toxicology have, however, raised interest on assessing sublethal effects in free-ranging individuals. Here, we show that the sublethal effects of a neonicotinoid pesticide are modified in magnitude by environmental interactions specific to the landscape and time of exposure events. Field sublethal assessment is therefore context dependent and should be addressed in a temporally and spatially explicit way, especially regarding weather and landscape physiognomy. We further develop an analytical Effective Dose (ED) framework to help disentangle context-induced from treatment-induced effects and thus to alleviate uncertainty in field studies. Although the ED framework involves trials at concentrations above the expected field exposure levels, it allows to explicitly delineating the climatic and landscape contexts that should be targeted for in-depth higher tier risk assessment.

Skin penetration assessment of less lethal kinetic energy munitions.

PubMed

Bir, Cynthia A; Stewart, Shelby J; Wilhelm, Marianne

2005-11-01

The development of less-lethal technologies has provided law enforcement personnel with an alternative to lethal force. Although the less lethal projectile was produced to engender non-penetrating wounds, case studies show that there have been a number of reported penetrating injuries ranging from minor to significant in morbidity. The objective of this study was to determine the energy per unit area required to penetrate various regions of the body. Eight unembalmed postmortem human specimens were procured for this testing. Each specimen sustained a maximum of 25 impacts consisting of shots to the anterior and posterior thorax, abdomen, and legs. A 12-gauge, fin-stabilized, rubber rocket round was used as the impactor for all of the conducted tests. The energy density required for 50% risk of penetration varied from 23.99 J/cm2 for the location on the anterior rib (p = 0.000) to 52.74 J/cm2 for the location on the posterior rib (p = 0.001).

Non-cancer effects in acute radiation syndrome survivors in Ukraine.

PubMed

Belyi, David; Kovalenko, Aleksander; Bazyka, Dmitrij; Bebeshko, Vladimir

2010-06-01

The 1986 Chernobyl Nuclear Power Plant accident that occurred is known as the most severe nuclear disaster in the history of humankind. Acute radiation syndrome (ARS) was diagnosed in 237 persons but only 134 of those were confirmed, including 28 patients who died due to lethal total-body gamma-irradiation and severe skin injuries caused by beta/gamma-emitting radionuclides. A small group of ARS survivors offers an interesting observational insight pertinent to the on-going discussions about long-term non-cancer effects of ionizing radiation. This descriptive study summarizes more than 20 y of follow-up, makes attempts to offer a prognosis for the Chernobyl ARS survivors' health, and explores the link between the outcomes of interest and radiation exposure.

Effect of fibrin glue occlusion of the hepatobiliary tract on thioacetamide-induced liver failure.

PubMed

Schmandra, T C; Bauer, H; Petrowsky, H; Herrmann, G; Encke, A; Hanisch, E

2001-07-01

Expression and activation of hepatocyte growth factor (HGF) is stimulated by a complex system of interacting proteins, with thrombin playing an initial role in this process. The impact of temporary occlusion of the hepatobiliary tract with fibrin glue (major component thrombin) on the HGF system in acute and chronic liver damage in a rat model was investigated. Chronic liver damage was induced in 40 rats by daily intraperitoneal application of thioacetamide (100 mg/kg) for 14 days. After 7 days half of them received an injection of 0.2 mL fibrin glue into the hepatobiliary system. Daily intraperitoneal administration of thioacetamide continued for 7 consecutive days. The rats were then sacrificed for blood and tissue analysis. Acute liver failure was induced in 12 rats by intraperitoneal administration of a lethal dose of thioacetamide (500 mg/kg per day for 3 days) after an injection with 0.2 mL fibrin glue into their hepatobiliary tract. Survival rates and histological outcome were investigated and compared with control animals. Fibrin glue occluded rats showed significantly lower liver enzyme activities and serum levels of bilirubin, creatinine and urea nitrogen. Immunohistochemistry revealed a significant increase in c-met-, HGFalpha- and especially HGFbeta-positive cells. Rats subjected to a lethal dose of thioacetamide survived when fibrin glue was applied 24 hours prior to the toxic challenge. These animals showed normal liver structure and no clinical abnormalities. Fibrin glue occlusion of the hepatobiliary tract induces therapeutic and prophylactic effects on chronic and acute liver failure by stimulating the HGF system. Therefore, fibrin glue occlusion might be useful in treating toxic liver failure.

Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice

PubMed Central

Sennello, Joseph A.; Fayad, Raja; Pini, Maria; Gove, Melissa E.; Ponemone, Venkatesh; Cabay, Robert J.; Siegmund, Britta; Dinarello, Charles A.; Fantuzzi, Giamila

2008-01-01

Obesity is associated with increased severity of acute pancreatitis (AP). The cytokines IL-18 and IL-12 are elevated in patients with AP, and IL-18 levels are high in obesity. We aimed to develop a pathologically relevant model to study obesity-associated severe AP. Lean WT and obese leptin-deficient ob/ob mice received two injections of IL-12 plus IL-18. Survival, pancreatic inflammation, and biochemical markers of AP were measured. Dosing with IL-12 plus IL-18 induced 100% lethality in ob/ob mice; no lethality was observed in WT mice. Disruption of pancreatic exocrine tissue and acinar cell death as well as serum amylase and lipase levels were significantly higher in ob/ob than in WT mice. Edematous AP developed in WT mice, whereas obese ob/ob mice developed necrotizing AP. Adipose tissue necrosis and saponification were present in cytokine-injected ob/ob but not in WT mice. Severe hypocalcemia and elevated acute-phase response developed in ob/ob mice. The cytokine combination induced high levels of regenerating protein 1 and pancreatitis-associated protein expression in the pancreas of WT but not of ob/ob mice. To differentiate the contribution of obesity to that of leptin deficiency, mice received short- and long-term leptin replacement therapy. Short-term leptin reconstitution in the absence of major weight loss did not protect ob/ob mice, whereas leptin deficiency in the absence of obesity resulted in a significant reduction in the severity of the pancreatitis. In conclusion, we developed a pathologically relevant model of AP in which obesity per se is associated with increased severity. PMID:18515422

Influence of hyperforin on the morphology of internal organs and biochemical parameters, in experimental model in mice.

PubMed

Negreş, Simona; Scutari, Corina; Ionică, Floriana Elvira; Gonciar, Veaceslav; Velescu, Bruno Ştefan; Şeremet, Oana Cristina; Zanfirescu, Anca; Zbârcea, Cristina Elena; Ştefănescu, Emil; Ciobotaru, Emilia; ChiriŢă, Cornel

2016-01-01

Hyperforin (HY) is used to treat depression and skin irritation and has been shown a number of pharmacological activities. The literature does no cite data on changes that may occur in the body after HY intake (ethylene diammonium salt - EDS) in long-term administration. From this point of view, the present work is a key to determining the pharmacotoxicological profile of the HY-EDS, in long-term administration. In present research, the influence of toxic doses of HY-EDS was investigated on the biochemical serum parameters and the histopathological changes in internal organs on the experimental mice model. For acute toxicity determination, the HY-EDS was tested in doses of 2000-5000 mg÷kg, administered once per day orally. For subacute toxicity, the HY-EDS was tested in three groups of mice, in doses of 50, 75 and 100 mg÷kg÷day, administered once daily, for 28 consecutive days. As concern acute toxicity, a lethal effect has not occurred at any of the two tested doses and HY-EDS was classified as Class V toxic: median lethal dose (LD50) >5000 mg÷kg, p.o. After 14 days of follow-up in acute toxicity, the experimental results showed a statistically significant increase of aspartate transaminase (AST) and alanine transaminase (ALT), compared to the control group. There were no changes in creatinine and serum glucose compared to the control group. After the administration of repeated doses, it was observed an increase of serum transaminases and alkaline phosphatase. Histological examination revealed that the liver injuries were in an initial stage, making them reversible in case of HY-EDS treatment discontinuation. There was no evidence of kidney damage to any of the doses of HY-EDS.

Neglected tropical diseases in Brazilian children and adolescents: data analysis from 2009 to 2013.

PubMed

Brandão, Eduardo; Romero, Sebastián; da Silva, Maria Almerice Lopes; Santos, Fred Luciano Neves

2017-11-03

Neglected tropical diseases (NTDs) prevail in conditions of poverty and contribute to the maintenance of social inequality. Out of the NTDs prioritized by the Brazilian Ministry of Health, four parasitic infections require mandatory notification: acute Chagas disease, leishmaniasis, malaria, and schistosomiasis. Data on the behaviour of these NTDs in the young population are currently limited. This study seeks to analyse the epidemiological aspects of these parasitic infections in children and adolescents in Brazil. A retrospective exploratory ecological study was conducted. A spatial analysis of the cases reported between 2009 and 2013 in individuals aged between 0 and 19 years that were notified through the Health Notification Aggravation Information System (SINAN) was performed. In total, 64,567 cases of cutaneous and visceral leishmaniasis, malaria, schistosomiasis, and acute Chagas disease were recorded in the SINAN database, representing a rate of 20.15 cases per 100,000 inhabitants. The average age of the cases was 12.2 years and 62.32% were male. Four hundred and three deaths related to these obligatorily reported parasites were recorded, indicating a case fatality rate of 0.62%. Visceral leishmaniasis and acute Chagas disease had the highest rates of lethality. A heterogeneous spatial distribution of the studied parasites was observed. The number of cases and the lethality rate described in this study show that these diseases still represent a serious problem for public health in Brazil. This points to the need to encourage new research and the reformulation of social, economic, and public health policies aimed at ensuring better health and living conditions for all individuals, especially those among the populations considered vulnerable, as is the case of the young.

Intramitochondrial Zn2+ accumulation via the Ca2+ uniporter contributes to acute ischemic neurodegeneration

PubMed Central

Medvedeva, Yuliya V.; Weiss, John H.

2014-01-01

Ca2+ and Zn2+ have both been implicated in the induction of acute ischemic neurodegeneration. We recently examined changes in intracellular Zn2+ and Ca2+ in CA1 pyramidal neurons subjected to oxygen glucose deprivation (OGD), and found that Zn2+ rises precede and contribute to the onset of terminal Ca2+ rises (“Ca2+ deregulation”), which are causatively linked to a lethal loss of membrane integrity. The present study seeks to examine the specific role of intramitochondrial Zn2+ accumulation in ischemic injury, using blockers of the mitochondrial Ca2+ uniporter (MCU), through which both Zn2+ and Ca2+ appear able to enter the mitochondrial matrix. In physiological extracellular Ca2+, treatment with the MCU blocker, Ruthenium Red (RR), accelerated the Ca2+ deregulation, most likely by disrupting mitochondrial Ca2+ buffering and thus accelerating the lethal cytosolic Ca2+ overload. However, when intracellular Ca2+ overload was slowed, either by adding blockers of major Ca2+ entry channels or by lowering the concentration of Ca2+ in the extracellular buffer, Ca2+ deregulation was delayed, and under these conditions either Zn2+ chelation or MCU blockade resulted in similar further delays of the Ca2+ deregulation. In parallel studies using the reactive oxygen species (ROS) indicator, hydroethidine, lowering Ca2+ surprisingly accelerated OGD induced ROS generation, and in these low Ca2+ conditions, either Zn2+ chelation or MCU block slowed the ROS generation. These studies suggest that, during acute ischemia, Zn2+ entry into mitochondria via the MCU induces mitochondrial dysfunction (including ROS generation) that occurs upstream of, and contributes to the terminal Ca2+ deregulation. PMID:24787898

Acute toxicity of organophosphorus compounds in guinea pigs is sex- and age-dependent and cannot be solely accounted for by acetylcholinesterase inhibition.

PubMed

Fawcett, William P; Aracava, Yasco; Adler, Michael; Pereira, Edna F R; Albuquerque, Edson X

2009-02-01

This study was designed to test the hypothesis that the acute toxicity of the nerve agents S-[2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate (VX), O-pinacolyl methylphosphonofluoridate (soman), and O-isopropyl methylphosphonofluoridate (sarin) in guinea pigs is age- and sex-dependent and cannot be fully accounted for by the irreversible inhibition of acetylcholinesterase (AChE). The subcutaneous doses of nerve agents needed to decrease 24-h survival of guinea pigs by 50% (LD(50) values) were estimated by probit analysis. In all animal groups, the rank order of LD(50) values was sarin > soman > VX. The LD(50) value of soman was not influenced by sex or age of the animals. In contrast, the LD(50) values of VX and sarin were lower in adult male than in age-matched female or younger guinea pigs. A colorimetric assay was used to determine the concentrations of nerve agents that inhibit in vitro 50% of AChE activity (IC(50) values) in guinea pig brain extracts, plasma, red blood cells, and whole blood. A positive correlation between LD(50) values and IC(50) values for AChE inhibition would support the hypothesis that AChE inhibition is a major determinant of the acute toxicity of the nerve agents. However, such a positive correlation was found only between LD(50) values and IC(50) values for AChE inhibition in brain extracts from neonatal and prepubertal guinea pigs. These results demonstrate for the first time that the lethal potencies of some nerve agents in guinea pigs are age- and sex-dependent. They also support the contention that mechanisms other than AChE inhibition contribute to the lethality of nerve agents.

Intestinal helminths regulate lethal acute graft-versus-host disease and preserve the graft-versus-tumor effect in mice.

PubMed

Li, Yue; Chen, Hung-Lin; Bannick, Nadine; Henry, Michael; Holm, Adrian N; Metwali, Ahmed; Urban, Joseph F; Rothman, Paul B; Weiner, George J; Blazar, Bruce R; Elliott, David E; Ince, M Nedim

2015-02-01

Donor T lymphocyte transfer with hematopoietic stem cells suppresses residual tumor growth (graft-versus-tumor [GVT]) in cancer patients undergoing bone marrow transplantation (BMT). However, donor T cell reactivity to host organs causes severe and potentially lethal inflammation called graft-versus-host disease (GVHD). High-dose steroids or other immunosuppressive drugs are used to treat GVHD that have limited ability to control the inflammation while incurring long-term toxicity. Novel strategies are needed to modulate GVHD, preserve GVT, and improve the outcome of BMT. Regulatory T cells (Tregs) control alloantigen-sensitized inflammation of GVHD, sustain GVT, and prevent mortality in BMT. Helminths colonizing the alimentary tract dramatically increase the Treg activity, thereby modulating intestinal or systemic inflammatory responses. These observations led us to hypothesize that helminths can regulate GVHD and maintain GVT in mice. Acute GVHD was induced in helminth (Heligmosomoides polygyrus)-infected or uninfected BALB/c recipients of C57BL/6 donor grafts. Helminth infection suppressed donor T cell inflammatory cytokine generation and reduced GVHD-related mortality, but maintained GVT. H. polygyrus colonization promoted the survival of TGF-β-generating recipient Tregs after a conditioning regimen with total body irradiation and led to a TGF-β-dependent in vivo expansion/maturation of donor Tregs after BMT. Helminths did not control GVHD when T cells unresponsive to TGF-β-mediated immune regulation were used as donor T lymphocytes. These results suggest that helminths suppress acute GVHD using Tregs and TGF-β-dependent pathways in mice. Helminthic regulation of GVHD and GVT through intestinal immune conditioning may improve the outcome of BMT. Copyright © 2015 by The American Association of Immunologists, Inc.

[Interest of ambulatory simplified acute physiology score (ASAPS) applied to patients admitted in an intensive care unit of an infectious diseases unit in Dakar].

PubMed

Dia, N M; Diallo, I; Manga, N M; Diop, S A; Fortes-Deguenonvo, L; Lakhe, N A; Ka, D; Seydi, M; Diop, B M; Sow, P S

2015-08-01

The evaluation of patients by a scale of gravity allows a better categorization of patients admitted in intensive care unit (ICU). Our study had for objective to estimate interest of Ambulatory Simplified Acute Physiologic Score (ASAPS) applied to patients admitted in ICU of infectious diseases department of FANN hospital. It was about a descriptive and analytical retrospective study, made from the data found in patients' files admitted into the USI infectious diseases department of FANN hospital in Dakar, from January 1(st), 2009 till December 31st, 2009.The data of 354 patients' files were analyzed. The sex-ratio was 1.77 with an average age of 37.6 years ± 19.4 years old [5-94 years]. The majority of the patients were unemployed paid (39.6%). The most frequent failures were the following ones: neurological (80.5%), cardio-respiratory (16.7%). The average duration of stay was 6.2 days ± 8.2 days going of less than 24 hours to more than 10 weeks. The deaths arose much more at night (53.1%) than in the daytime (46.9%) and the strongest rate of death was recorded in January (61.5%), most low in October (26.7%). The global mortality was 48.3%. The rate of lethality according to the highest main diagnosis was allocated to the AIDS (80.5%). The average ambulatory simplified acute physiology score was 5.3 ± 3.6 with extremes of 0 and 18. The deaths in our series increased with this index (p = 0.000005). The female patients had a rate of lethality higher than that of the men people, 55.5% against 44.2% (p = 0.03). In spite of a predictive score of a high survival (ASAPS < 8), certain number of patients died (n = 105) that is 61.4% of the deaths. The metabolic disturbances, hyperleukocytosis or leukopenia when realised, the presence of a chronic disease, seemed also to influence this lethality. ASAPS only, although interesting, would not good estimate the gravity of patients, where from the necessity thus of a minimum biological balance sheet. It seems better adapted for patients with a high value (ASAPS≥8). This score when it is low, is not correlated, in our study, at a high survival rate as waited in this population.

Short-term exposure to low doses of rotenone induces developmental, biochemical, behavioral, and histological changes in fish.

PubMed

Melo, Karina Motta; Oliveira, Rhaul; Grisolia, Cesar Koppe; Domingues, Inês; Pieczarka, Julio Cesar; de Souza Filho, José; Nagamachi, Cleusa Yoshiko

2015-09-01

Rotenone, a natural compound derived from plants of the genera Derris and Lonchocarpus, is used worldwide as a pesticide and piscicide. This study aims to assess short-term toxicity of rotenone to early-life stages of the fish Danio rerio and Poecilia reticulata using a wide and integrative range of biomarkers (developmental, biochemical, behavioral, and histopathological). Moreover, the species sensitivity distribution (SSD) approach was used to compare rotenone acute toxicity to fish species. Toxicity tests were based on the OECD protocols, fish embryo toxicity test (for D. rerio embryos), and fish acute toxicity test (for P. reticulata juveniles). D. rerio embryos were used to estimate lethal concentrations and analyze embryonic and enzymatic alterations (activity of catalase, glutathione-S-transferase, and cholinesterase), while P. reticulata juveniles were used for the assessment of histological damage in the gills and liver. Rotenone induced significant mortality in zebrafish embryos with a 96-h lethal concentration 50% (LC50) = 12.2 μg/L. Rotenone was embryotoxic, affecting the development of D. rerio embryos, which showed cardiac edema; tail deformities; loss of equilibrium; and a general delay characterized by lack of tail detachment, delayed somite formation, yolk sac absorption, and lack of pigmentation. Biochemical biomarker inhibition was observed for concentrations ≥1 μg/L for CAT and glutathione-S-transferase (GST) and for cholinesterase (ChE) in concentration from 10 μg/L. Behavioral changes were observed for P. reticulata juveniles exposed to concentrations equal to or above 25 μg/L of rotenone; moreover, histological damage in the liver and gills of fish exposed to concentrations equal to or above 2.5 μg/L could be observed. A hazard concentration 5% (HC5) of 3.2 μg/L was estimated considering the acute toxicity data for different fish species (n = 49). Lethal and sublethal effects of rotenone raise a concern about its effects on nontarget fish species, especially because rotenone and its metabolite rotenolone are frequently reported in the microgram range in natural environments for several days after field applications. Rotenone should be used with caution. Given the high toxicity and wide range of sublethal effects here reported, further studies in a chronic exposure scenario are recommended.

[Analysis of epidemiological characteristics of acute pesticide poisoning during 2007-2013 in Jinan, China].

PubMed

Liu, Shouqin; Zhou, Lin; Yan, Ling; Zhang, Jun; Han, Jing

2014-06-01

To investigate the epidemiological characteristics of acute pesticide poisoning in Jinan, China and to provide effective proposals for the prevention and control of pesticide poisoning. Reported cases of acute pesticide poisoning from 2007 to 2013 in Jinan were collected and subjected to statistical analysis using SPSS 17. A total of 4852 cases of acute pesticide poisoning were reported from 2007 to 2013 in Jinan. The fatality rate was 14.10%. The incidence of non-occupational poisoning accounted for 94.23% (4 572/4 852). The incidence of occupational poisoning showed a decreasing trend from 2007 to 2013, with most cases poisoned by insecticides (236 cases, accounting for 82.86% of all cases of occupational poisoning). Among non-occupational poisoning cases, fatality rate was higher in cases aged 60 years or over than in those under 60 years; fatality rate was higher among male cases (16.11%) than among female cases (13.79%); herbicides had a significantly higher lethal rate (22.25%) than insecticides (14.02%) (P < 0.05). More attention should be paid to acute pesticide poisoning in Jinan, and effective management measures should be taken immediately.

Blood groups and acute aortic dissection type III.

PubMed

Fatic, Nikola; Nikolic, Aleksandar; Vukmirovic, Mihailo; Radojevic, Nemanja; Zornic, Nenad; Banzic, Igor; Ilic, Nikola; Kostic, Dusan; Pajovic, Bogdan

2017-04-01

Acute aortic type III dissection is one of the most catastrophic events, with in-hospital mortality ranging between 10% and 12%. The majority of patients are treated medically, but complicated dissections, which represent 15% to 20% of cases, require surgical or thoracic endovascular aortic repair (TEVAR). For the best outcomes adequate blood transfusion support is required. Interest in the relationship between blood type and vascular disease has been established. The aim of our study is to evaluate distribution of blood groups among patients with acute aortic type III dissection and to identify any kind of relationship between blood type and patient's survival. From January 2005 to December 2014, 115 patients with acute aortic type III dissection were enrolled at the Clinic of Vascular and Endovascular Surgery in Belgrade, Serbia and retrospectively analyzed. Patients were separated into two groups. The examination group consisted of patients with a lethal outcome, and the control group consisted of patients who survived. The analysis of the blood groups and RhD typing between groups did not reveal a statistically significant difference ( p = 0.220). Our results indicated no difference between different blood groups and RhD typing with respect to in-hospital mortality of patients with acute aortic dissection type III.

Chronic and Acute Relational Risk Factors for Dating Aggression in Adolescence and Young Adulthood

PubMed Central

Furman, Wyndol

2016-01-01

Dating aggression is a prevalent and costly public health concern. Using a relational risk framework, this study examined acute and chronic relational risk factors (negative interactions, jealousy, support, & relationship satisfaction) and their effects on physical and psychological dating aggression. The study also examined the interaction between chronic and acute risk, allowing us to assess how changes in acute risk have differing effects depending on whether the individual is typically at higher chronic risk. A sample of 200 youth (100 female) completed seven waves of data, which spanned nine years from middle adolescence to young adulthood (M age at Wave 1 = 15.83). Using hierarchical linear modeling, analyses revealed both acute (within-person) and chronic (between-person) levels in jealousy, negative interactions, and relationship satisfaction, were associated with physical and psychological dating aggression. Significant interactions between chronic and acute risk emerged in predicting physical aggression for negative interactions, jealousy, and relationship satisfaction such that those with higher levels of chronic risk are more vulnerable to increases in acute risk. These interactions between chronic and acute risk indicate that risk is not static, and dating aggression is particularly likely to occur at certain times for youth at high risk for dating aggression. Such periods of increased risk may provide opportunities for interventions to be particularly effective in preventing dating aggression or its consequences. Taken together, these findings provide support for the role of relational risk factors for dating aggression. They also underscore the importance of considering risk dynamically. PMID:26832727

Chronic and Acute Relational Risk Factors for Dating Aggression in Adolescence and Young Adulthood.

PubMed

Collibee, Charlene; Furman, Wyndol

2016-04-01

Dating aggression is a prevalent and costly public health concern. Using a relational risk framework, this study examined acute and chronic relational risk factors (negative interactions, jealousy, support, and relationship satisfaction) and their effects on physical and psychological dating aggression. The study also examined the interaction between chronic and acute risk, allowing us to assess how changes in acute risk have differing effects depending on whether the individual is typically at higher chronic risk. A sample of 200 youth (100 female) completed seven waves of data, which spanned 9 years from middle adolescence to young adulthood (M age at Wave 1 = 15.83). Using hierarchical linear modeling, analyses revealed both acute (within-person) and chronic (between-person) levels in jealousy, negative interactions, and relationship satisfaction, were associated with physical and psychological dating aggression. Significant interactions between chronic and acute risk emerged in predicting physical aggression for negative interactions, jealousy, and relationship satisfaction such that those with higher levels of chronic risk are more vulnerable to increases in acute risk. These interactions between chronic and acute risk indicate that risk is not static, and dating aggression is particularly likely to occur at certain times for youth at high risk for dating aggression. Such periods of increased risk may provide opportunities for interventions to be particularly effective in preventing dating aggression or its consequences. Taken together, these findings provide support for the role of relational risk factors for dating aggression. They also underscore the importance of considering risk dynamically.

Effects of water quality parameters on boron toxicity to Ceriodaphnia dubia.

PubMed

Dethloff, Gail M; Stubblefield, William A; Schlekat, Christian E

2009-07-01

The potential modifying effects of certain water quality parameters (e.g., hardness, alkalinity, pH) on the acute toxicity of boron were tested using a freshwater cladoceran, Ceriodaphnia dubia. By comparison, boron acute toxicity was less affected by water quality characteristics than some metals (e.g., copper and silver). Increases in alkalinity over the range tested did not alter toxicity. Increases in water hardness appeared to have an effect with very hard waters (>500 mg/L as CaCO(3)). Decreased pH had a limited influence on boron acute toxicity in laboratory waters. Increasing chloride concentration did not provide a protective effect. Boron acute toxicity was unaffected by sodium concentrations. Median acute lethal concentrations (LC(50)) in natural water samples collected from three field sites were all greater than in reconstituted laboratory waters that matched natural waters in all respects except for dissolved organic carbon. Water effect ratios in these waters ranged from 1.4 to 1.8. In subsequent studies using a commercially available source of natural organic matter, acute toxicity decreased with increased dissolved organic carbon, suggesting, along with the natural water studies, that dissolved organic carbon should be considered further as a modifier of boron toxicity in natural waters where it exceeds 2 mg/L.

The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goyal, Ashish; Ribeiro, Ruy Miguel; Perelson, Alan S.

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection datamore » together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. Lastly, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.« less

The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans

DOE PAGES

Goyal, Ashish; Ribeiro, Ruy Miguel; Perelson, Alan S.

2017-11-18

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection datamore » together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. Lastly, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.« less

Tissue responses to low protracted doses of high let radiations or photons - Early and late damage relevant to radio-protective countermeasures

NASA Technical Reports Server (NTRS)

Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

1989-01-01

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

Medical Management of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group

DTIC Science & Technology

2004-06-15

Precautions G-CSF or filgrastim Subcutaneous administration of 5 g/kg of body weight per day, continued until ANC 1.0 109 cells/L Subcutaneous...lymphohematopoietic elements. Several studies have indicated that administra- tion of antibiotics reduces mortality rates in irradiated dogs in the LD50/30...hematopoiesis of normal dogs and on hematopoietic recovery after otherwise lethal total body irradiation. Blood. 1989;74:1308-13. [PMID: 2475186] 10. Farese AM

Acute Lethality of Inhaled Hydrogen Cyanide in the Laboratory Rat: Impact of Concentration x Time Profile and Evaluation of the Predictivity of Toxic Load Models

DTIC Science & Technology

2013-05-03

public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions...AVAILABILITY STATEMENT Approved for public release; distribution is unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Toxic load models are mathematical...equal). The Department of Defense (DOD) (2005) publication “Potential Military Chemical/Biological Agents and Compounds” currently uses the toxic load

Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pohjanvirta, Raimo, E-mail: raimo.pohjanvirta@helsinki.fi; Miettinen, Hanna, E-mail: hanna.miettinen@crl.com; Sankari, Satu, E-mail: satu.sankari@helsinki.fi

The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on themore » substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD{sub 50} for TCDD being over 5000 μg/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons. -- Highlights: ► In contrast to rats, male mice are more sensitive to TCDD toxicity than female mice. ► The resistance of female C57BL/6Kuo mice matches or exceeds that of male DBA/2 mice. ► The resistance of female C57BL/6Kuo mice is not based on AHR structure or abundance. ► Both androgens and estrogens appear to influence TCDD sensitivity. ► TCDD sensitivity correlates best with the severity of lesions in the liver.« less

Acute thermal tolerance of tropical estuarine fish occupying a man-made tidal lake, and increased exposure risk with climate change

NASA Astrophysics Data System (ADS)

Waltham, Nathan J.; Sheaves, Marcus

2017-09-01

Understanding acute hyperthermic exposure risk to animals, including fish in tropical estuaries, is increasingly necessary under future climate change. To examine this hypothesis, fish (upper water column species - glassfish, Ambassis vachellii; river mullet, Chelon subviridis; diamond scale mullet, Ellochelon vaigiensis; and ponyfish, Leiognathus equulus; and lower water bottom dwelling species - whiting Sillago analis) were caught in an artificial tidal lake in tropical north Queensland (Australia), and transported to a laboratory tank to acclimate (3wks). After acclimation, fish (between 10 and 17 individuals each time) were transferred to a temperature ramping experimental tank, where a thermoline increased (2.5 °C/hr; which is the average summer water temperature increasing rate measured in the urban lakes) tank water temperature to establish threshold points where each fish species lost equilibrium (defined here as Acute Effect Temperature; AET). The coolest AET among all species was 33.1 °C (S. analis), while the highest was 39.9 °C (A. vachellii). High frequency loggers were deployed (November and March representing Austral summer) in the same urban lake where fish were sourced, to measure continuous (20min) surface (0.15 m) and bottom (0.1 m) temperature to derive thermal frequency curves to examine how often lake temperatures exceed AET thresholds. For most fish species examined, water temperature that could be lethal were exceeded at the surface, but rarely, if ever, at the bottom waters suggesting deep, cooler, water provides thermal refugia for fish. An energy-balance model was used to estimate daily mean lake water temperature with good accuracy (±1 °C; R2 = 0.91, modelled vs lake measured temperature). The model was used to predict climate change effects on lake water temperature, and the exceedance of thermal threshold change. A 2.3 °C climate warming (based on 2100 local climate prediction) raised lake water temperature by 1.3 °C. However, small as this increase might seem, it led to a doubling of time that water temperatures were in excess of AET thresholds at the surface, but also the bottom waters that presently provide thermal refugia for fish.

The Evolving MCART Multimodal Imaging Core: Establishing a protocol for Computed Tomography and Echocardiography in the Rhesus macaque to perform longitudinal analysis of radiation-induced organ injury

PubMed Central

de Faria, Eduardo B.; Barrow, Kory R.; Ruehle, Bradley T.; Parker, Jordan T.; Swartz, Elisa; Taylor-Howell, Cheryl; Kieta, Kaitlyn M.; Lees, Cynthia J.; Sleeper, Meg M.; Dobbin, Travis; Baron, Adam D.; Mohindra, Pranshu; MacVittie, Thomas J.

2015-01-01

Computed Tomography (CT) and Echocardiography (EC) are two imaging modalities that produce critical longitudinal data that can be analyzed for radiation-induced organ-specific injury to the lung and heart. The Medical Countermeasures Against Radiological Threats (MCART) consortium has a well-established animal model research platform that includes nonhuman primate (NHP) models of the acute radiation syndrome and the delayed effects of acute radiation exposure. These models call for a definition of the latency, incidence, severity, duration, and resolution of different organ-specific radiation-induced subsyndromes. The pulmonary subsyndromes and cardiac effects are a pair of inter-dependent syndromes impacted by exposure to potentially lethal doses of radiation. Establishing a connection between these will reveal important information about their interaction and progression of injury and recovery. Herein, we demonstrate the use of CT and EC data in the rhesus macaque models to define delayed organ injury thereby establishing: a) consistent and reliable methodology to assess radiation-induced damage to the lung and heart, b) an extensive database in normal age-matched NHP for key primary and secondary endpoints, c) identified problematic variables in imaging techniques and proposed solutions to maintain data integrity and d) initiated longitudinal analysis of potentially lethal radiation-induced damage to the lung and heart. PMID:26425907

An Antidote for Acute Cocaine Toxicity

PubMed Central

Treweek, Jennifer B.; Janda, Kim D.

2012-01-01

Not only has immunopharmacotherapy grown into a field that addresses the abuse of numerous illicit substances, but also the treatment methodologies within immunopharmacotherapy have expanded from traditional active vaccination to passive immunization with anti-drug monoclonal antibodies, optimized mAb formats, and catalytic drug-degrading antibodies. Many laboratories have focused on transitioning distinct immunopharmacotherapeutics to clinical evaluation, but with respect to the indication of cocaine abuse, only the active vaccine TA-CD, which is modeled after our original cocaine hapten GNC1, has been carried through to human clinical trials.2 The successful application of murine mAb GNC92H2 to the reversal of cocaine overdose in a mouse model prompted investigations of human immunoglobulins with the clinical potential to serve as cocaine antidotes. We now report the therapeutic utility of a superior clone, human mAb GNCgzk (Kd = 0.18 nM), which offers a 10-fold improvement in cocaine binding affinity. The GNCgzk manifold was engineered for rapid cocaine clearance, and administration of the F(ab′)2 and Fab formats even after the appearance of acute behavioral signs of cocaine toxicity granted nearly complete prevention of lethality. Thus, contrary to the immunopharmacotherapeutic treatment of drug self-administration, minimal antibody doses were shown to counteract the lethality of a molar excess of circulating cocaine. Passive vaccination with drug-specific antibodies represents a viable treatment strategy for the human condition of cocaine overdose. PMID:22380623

Acute toxicity of arsenic and oxidative stress responses in the embryonic development of the common South American toad Rhinella arenarum.

PubMed

Mardirosian, Mariana Noelia; Lascano, Cecilia Inés; Ferrari, Ana; Bongiovanni, Guillermina Azucena; Venturino, Andrés

2015-05-01

Arsenic (As), a natural element of ecological relevance, is found in natural water sources throughout Argentina in concentrations between 0.01 mg/L and 15 mg/L. The autochthonous toad Rhinella arenarum was selected to study the acute toxicity of As and the biochemical responses elicited by the exposure to As in water during its embryonic development. The median lethal concentration (LC50) value averaged 24.3 mg/L As and remained constant along the embryonic development. However, As toxicity drastically decreased when embryos were exposed from heartbeat-stage on day 4 of development, suggesting the onset of detoxification mechanisms. Given the environmental concentrations of As in Argentina, there is a probability of exceeding lethal levels at 1% of sites. Arsenic at sublethal concentrations caused a significant decrease in the total antioxidant potential but generated an increase in endogenous glutathione (GSH) content and glutathione S-transferase (GST) activity. This protective response might prevent a deeper decline in the antioxidant system and further oxidative damage. Alternatively, it might be linked to As conjugation with GSH for its excretion. The authors conclude that toad embryos are more sensitive to As during early developmental stages and that relatively high concentrations of this toxic element are required to elicit mortality, but oxidative stress may be an adverse effect at sublethal concentrations. © 2014 SETAC.

Comparison of an Ampelisca abdita growth rate test with other standard amphipod sediment toxicity tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schafer, K.; Weston, D.P.

1995-12-31

Amphipod crustaceans are often used to measure the toxicity of bulk sediments. Acute lethal bioassays are commonly employed, but this study investigated the potential for using a chronic growth bioassay with Ampelisca abdita. A potential advantage of this method is that the growth rate could be a more sensitive measure of contamination than mortality. Growth rates for A. abdita in sediments spiked with cadmium and crude oil were compared to mortality rates in A. abdita, Eohaustorius estuaries, and Rhepoxynius abronius in sediments with the same concentrations of contaminants. A. abdita was more sensitive to cadmium than the other two species.more » For crude oil, there was a significant shift in size distribution from the control even at concentrations as low as 150 mg/kg of oil. The standard acute lethal tests for all species, on the other hand, did not show significant mortality until at least 1,600 mg/kg. The results confirm that growth rates are a more sensitive indicator of toxicity, and to at least the three contaminants tested, A. abdita is as sensitive as E. estuarius and R. abronius. This study also confirmed the reported high mortality rates of E. estuaries in San Francisco Bay sediments. The causes of this high mortality are unknown but give further reason for using A. abdita for toxicity tests in this region.« less

Biochemical and genotoxic response of naphthalene to fingerlings of milkfish Chanos chanos.

PubMed

Palanikumar, L; Kumaraguru, A K; Ramakritinan, C M

2013-09-01

The present study investigated the acute toxicity, sub-lethal toxicity and biochemical response of naphthalene in fingerlings of milkfish Chanos chanos. The 96 h acute toxicity LC50 values for C. chanos exposed to naphthalene was 5.18 μg l(-1). The estimated no observed effect concentration and lowest observed effect concentration values for naphthalene in C. chanos were 0.42 and 0.69 μg l(-1) respectively for 30 days. The estimated maximum allowable toxicant concentration for naphthalene was 0.53 μg l(-1). Biochemical enzyme markers such as lipid peroxidation, catalase, glutathione S transferase and reduced glutathione were measured in gills and liver tissues of C. chanos exposed to sub-lethal concentrations of naphthalene. Fluctuation in lipid peroxidation and catalase level suggests that naphthalene concentrations play a vital role in induction of oxidative stress in fish. Induction of reduced glutathione level and inhibition of glutathione S-transferase level was observed in naphthalene exposed C. chanos suggesting that there may be enhanced oxidative damage due to free radicals. Increasing concentration increases in number of nuclear abnormalities. The formation of micronuclei and binucleated micronuclei induction by naphthalene confirm its genotoxic potential. The highest levels of DNA damage (% tail length) were observed at 1.24 μg l(-1) of naphthalene. The study suggests that biochemical enzymes, nuclear abnormalities and DNA damage index can serve as a biological marker for naphthalene contamination.

Acute oral toxicities of wildland fire control chemicals to birds

USGS Publications Warehouse

Vyas, N.B.; Spann, J.W.; Hill, E.F.

2009-01-01

Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

Acute poisoning following ingestion of medicines: initial management. How to treat life-threatening complications and to evaluate the risk of delayed effects and psychological distress.

PubMed

2010-12-01

Acute poisoning following ingestion of medications, both intentional and unintentional, is frequent and more or less severe. It is often unclear whether a toxic dose has been ingested. This review examines the initial management of patients with suspected acute poisoning, based on a review of the literature using the standard Prescrire methodology. We examined clinical practice guidelines, which are mostly based on observational, pharmacological and toxicological data, as well as empirical data. Few comparative trials are available. In life-threatening situations, the first priority is to call an emergency response mobile unit and to implement life-support techniques, i.e., resuscitation for cardiorespiratory arrest; respiratory support if necessary; and the left lateral head-down position and glucose injection if the patient is unconscious. Prompt, initial measures may also include: anticonvulsant injection for status epilepticus (diazepam, for example); a sedative for extreme agitation (diazepam or clorazepate if there is no risk of respiratory depression; otherwise haloperidol); atropine for severe bradycardia; elevating the legs for hypotension; and naloxone in case of respiratory depression due to opioids. Drug poisoning can be life-threatening.The extent of the risk should be assessed by questioning the patient and close contacts, examining the immediate environment, and carrying out a clinical examination to identify a major toxic condition. The severity of poisoning is assessed by gathering all information about the patient, the drug(s) ingested, the circumstances of ingestion, and any other substances ingested at the same time. A poison control centre may be called to assist with diagnosis, to predict the clinical consequences, and to guide patient management. Activated charcoal can reduce the gastrointestinal absorption of some drugs. It should be given as soon as possible, preferably within 2 hours after ingestion of a drug known to be adsorbed by activated charcoal, provided the patient is fully conscious and capable of swallowing safely. Gastric lavage carries a risk of serious adverse effects. It is only justified in the rare cases in which the patient's life is at risk following ingestion of a drug that is not adsorbed by activated charcoal. Ipecac syrup should not be used under any circumstances. Purging and gastric lavage are not part of initial management. Few antidotes are suitable for use in the early stages of poisoning. Acetylcysteine can be used for some cases of paracetamol poisoning, and naloxone for some types of opioid poisoning. Paracetamol poisoning can cause life-threatening hepatocellular necrosis. Activated charcoal should be administered as soon as possible. Acetylcysteine protects the liver when administered within 24 hours after paracetamol ingestion. Paracetamol serum assay can be useful for guiding patient management. In practice, acetylcysteine should be given when access to emergency medical intervention is not feasible within 8 to 10 hours after paracetamol ingestion. Intravenous naloxone is useful for respiratory depression due to opioid poisoning, but its duration of action is often shorter than that of opioids, making continuous monitoring necessary. Hospital monitoring is warranted in case of potentially severe poisoning; this includes patients at increased risk, patients having taken a potentially lethal substance at a toxic or unknown dose. Some pharmacological substances and formulations can have delayed effects. In case of self-poisoning, the risk of short-term relapse should be evaluated, even when the patient's condition is not life-threatening. Hospital admission should be proposed, or sometimes imposed, until the acute risk of suicide has subsided. In practice, when faced with acute drug poisoning, the first step is to implement life-support measures, to gather and communicate prognostic information and details of any treatments to the ambulance crew or hospital team.

OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing.

PubMed

Busquet, François; Strecker, Ruben; Rawlings, Jane M; Belanger, Scott E; Braunbeck, Thomas; Carr, Gregory J; Cenijn, Peter; Fochtman, Przemyslaw; Gourmelon, Anne; Hübler, Nicole; Kleensang, André; Knöbel, Melanie; Kussatz, Carola; Legler, Juliette; Lillicrap, Adam; Martínez-Jerónimo, Fernando; Polleichtner, Christian; Rzodeczko, Helena; Salinas, Edward; Schneider, Katharina E; Scholz, Stefan; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Walter-Rohde, Susanne; Weigt, Stefan; Witters, Hilda; Halder, Marlies

2014-08-01

The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV<30%) for most chemicals and laboratories. The reproducibility was lower (CV>30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Examining the Impact of Suicide Attempt Function and Perceived Effectiveness in Predicting Reattempt for Emergency Medicine Patients.

PubMed

O'Connor, Stephen S; Comtois, Katherine Anne; Atkins, David C; Kerbrat, Amanda H

2017-01-01

While previous studies have examined motivational aspects of self-directed violence, few studies have included specific motivations in predictive models for future suicide attempts. The current study utilized a sample of 160 individuals treated in an acute emergency setting following a suicide attempt who completed an interview battery that included an assessment of functional aspects of the index suicide attempt. A follow-up interview was conducted at 6 months to ascertain subsequent suicide attempts. The functional domains of suicide attempts were labeled as reduction-of-distress, communication, perceived better alternative to living, and self-loathing. Above and beyond other known risk factors, including history and highest lethality of previous self-injury, suicide attempts that served a communication function (OR = 0.18, p = .02, CI = 0.04, 0.73) and higher ratings of clinical dysfunction (OR = 3.41, p = .05, CI = 1.02, 11.36) were associated with a significant reduction in likelihood to engage in a suicide attempt during the 6-month follow-up window. Including the perceived effectiveness of the index suicide attempt in getting one's needs met strengthened the overall model predicting a suicide attempt in the follow-up window and was an independent risk factor above and beyond other variables in the model OR = 1.75, p = .04, CI = 1.02, 3.01). Assessment of functional aspects of suicide attempt is feasible and may improve formulation of risk in a population where typical risk factors for suicide are ubiquitous. Copyright © 2016. Published by Elsevier Ltd.

PHOTOACTIVATED POLYCYCLIC AROMATIC HYDROCARBON TOXICITY IN MEDAKA (ORYZIAS LATIPES) EMBRYOS: RELEVANCE TO ENVIRONMENTAL RISK IN CONTAMINATED SITES

EPA Science Inventory

The hazard for photoactivated toxicity of polycyclic aromatic hydrocarbons (PAHs) has been clearly demonstrated; however, to our knowledge, the risk in contaminated systems has not been characterized. To address this question, a median lethal dose (LD50) for fluoranthene photoa...

Evaluation of Time- and Concentration-dependent Toxic Effect Models for use in Aquatic Risk Assessments, Oral Presentation

EPA Science Inventory

Various models have been proposed for describing the time- and concentration-dependence of toxic effects to aquatic organisms, which would improve characterization of risks in natural systems. Selected models were evaluated using results from a study on the lethality of copper t...

78 FR 73726 - Endangered Fish and Wildlife; Final Rule To Remove the Sunset Provision of the Final Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-09

... expanded speed/risk models, one study estimated that the 2008 vessel speed rule reduced the risk of lethal... are completely absent there or that the risk of strikes does not exist. One recent study concluded... the world's most critically endangered large whale species and one of the world's most endangered...

Trophic cascades in rocky shore tide pools: distinguishing lethal and nonlethal effects.

PubMed

Trussell, Geoffrey C; Ewanchuk, Patrick J; Bertness, Mark D; Silliman, Brian R

2004-05-01

The effects of predators on the density of their prey can have positive indirect effects on the abundance of the prey's resource via a trophic cascade. This concept has strongly influenced contemporary views of how communities are structured. However, predators also can transmit indirect effects by inducing changes in prey traits. We show that the mere presence of predator risk cues can initiate a trophic cascade in rocky shore tide pools. In large (mean surface area =9 m2), natural tide pools, we manipulated crab density and their foraging ability to examine the relative importance of lethal (density-mediated) and non-lethal (trait-mediated) predator effects to algal community development. We found that perceived predation risk reduced snail density as much as the direct predation treatment, showing that green crab predation was not an important factor regulating local snail density. Instead, snail emigration away from resident crabs appears to be the most important factor regulating local snail density. As a result, the abundance of ephemeral green algae was similar in the predation risk and direct predation treatments, suggesting that the consumption of snails by crabs plays a minimal role in mediating the trophic cascade. Increased attention to trait-mediated effects that are transmitted by predator-induced changes in prey behavior may change our view of how predators exert their strong influence on community structure.

B cells are not essential for Lactobacillus-mediated protection against lethal pneumovirus infection*

PubMed Central

Percopo, Caroline M.; Dyer, Kimberly D.; Garcia-Crespo, Katia E.; Gabryszewski, Stanislaw J.; Shaffer, Arthur L.; Domachowske, Joseph B.; Rosenberg, Helene F.

2014-01-01

We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice (PVM), a property known as heterologous immunity. Lactobacillus-priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. As B cells have been shown to promote heterologous immunity against respiratory virus pathogens under similar conditions, here we explore the role of B cells in Lactobacillus-mediated protection against acute pneumovirus infection. We found that Lactobacillus-primed mice feature elevated levels of airway immunoglobulins IgG, IgA and IgM and lung tissues with dense, B cell (B220+) enriched peribronchial and perivascular infiltrates with germinal centers consistent with descriptions of bronchus-associated lymphoid tissue. No B cells were detected in lung tissue of Lactobacillus-primed B-cell deficient μMT mice or Jh mice, and Lactobacillus-primed μMT mice had no characteristic infiltrates or airway immunoglobulins. Nonetheless, we observed diminished virus recovery and profound suppression of virus-induced proinflammatory cytokines CCL2, IFN-gamma, and CXCL10 in both wild-type and Lactobacillus-primed μMT mice. Furthermore, L. plantarum-primed, B-cell deficient μMT and Jh mice were fully protected from an otherwise lethal PVM infection, as were their respective wild-types. We conclude that B cells are dispensable for Lactobacillus-mediated heterologous immunity and were not crucial for promoting survival in response to an otherwise lethal pneumovirus infection. PMID:24748495

B cells are not essential for Lactobacillus-mediated protection against lethal pneumovirus infection.

PubMed

Percopo, Caroline M; Dyer, Kimberly D; Garcia-Crespo, Katia E; Gabryszewski, Stanislaw J; Shaffer, Arthur L; Domachowske, Joseph B; Rosenberg, Helene F

2014-06-01

We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice, a property known as heterologous immunity. Lactobacillus priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. Because B cells have been shown to promote heterologous immunity against respiratory virus pathogens under similar conditions, in this study we explore the role of B cells in Lactobacillus-mediated protection against acute pneumovirus infection. We found that Lactobacillus-primed mice feature elevated levels of airway Igs IgG, IgA, and IgM and lung tissues with dense, B cell (B220(+))-enriched peribronchial and perivascular infiltrates with germinal centers consistent with descriptions of BALT. No B cells were detected in lung tissue of Lactobacillus-primed B cell deficient μMT mice or Jh mice, and Lactobacillus-primed μMT mice had no characteristic infiltrates or airway Igs. Nonetheless, we observed diminished virus recovery and profound suppression of virus-induced proinflammatory cytokines CCL2, IFN-γ, and CXCL10 in both wild-type and Lactobacillus-primed μMT mice. Furthermore, Lactobacillus plantarum-primed, B cell-deficient μMT and Jh mice were fully protected from an otherwise lethal pneumonia virus of mice infection, as were their respective wild-types. We conclude that B cells are dispensable for Lactobacillus-mediated heterologous immunity and were not crucial for promoting survival in response to an otherwise lethal pneumovirus infection.

[Underlying Mechanisms of Methamphetamine-Induced Self-Injurious Behavior and Lethal Effects in Mice].

PubMed

Mori, Tomohisa; Sawaguchi, Toshiko

2018-01-01

Relatively high doses of psychostimulants induce neurotoxicity on the dopaminergic system and self-injurious behavior (SIB) in rodents. However the underlying neuronal mechanisms of SIB remains unclear. Dopamine receptor antagonists, N-methyl-D-aspartic acid (NMDA) receptor antagonists, Nitric Oxide Synthase (NOS) inhibitors and free radical scavengers significantly attenuate methamphetamine-induced SIB. These findings indicate that activation of dopamine as well as NMDA receptors followed by radical formation and oxidative stress, especially when mediated by NOS activation, is associated with methamphetamine-induced SIB. On the other hand, an increase in the incidence of polydrug abuse is a major problem worldwide. Coadministered methamphetamine and morphine induced lethality in more than 80% in mice, accompanied by an increase in the number of poly (ADP-ribose) polymerase (PARP)-immunoreactive cells in the heart, kidney and liver. The lethal effect and the increase in the incidence of rupture or PARP-immunoreactive cells induced by the coadministration of methamphetamine and morphine were significantly attenuated by pretreatment with a phospholipase A2 inhibitor or a radical scavenger, or by cooling of body from 30 to 90 min after drug administration. These results suggest that free radicals play an important role in the increased lethality induced by the coadministration of methamphetamine and morphine. Therefore, free radical scavengers and cooling are beneficial for preventing death that is induced by the coadministration of methamphetamine and morphine. These findings may help us better understand for masochistic behavior, which is a clinical phenomenon on SIB, as well as polydrug-abuse-induced acute toxicity.

Lethal/sublethal responses of Daphnia magna to acute norfloxacin contamination and changes in phytoplankton-zooplankton interactions induced by this antibiotic

NASA Astrophysics Data System (ADS)

Pan, Ying; Yan, Shi-Wei; Li, Ruo-Zhu; Hu, Yi-Wen; Chang, Xue-Xiu

2017-01-01

Although the well-known antibiotic norfloxacin (NOR) is recognized as an important environmental pollutant, little is known about its impacts on ecological processes, particularly on species interactions. In this paper, we quantified Daphnia magna (Crustacea, Cladocera) responses in mortality rate at lethal NOR concentrations (0, 25, 50, 100, 200, 300 and 400 mg L-1), and in heartbeat rate, swimming behavior and feeding rate (on the green alga Chlorella pyrenoidosa) at sublethal NOR concentrations (0, 25, 50 and 100 mg L-1) to determine the effects of this antibiotic in plankton systems. In 96-h-long lethal experiment, mortality rates of D. magna increased significantly with increasing NOR concentration and exposure time. In sublethal experiments, heartbeat rate decreased, while time ratio of vertical to horizontal swimming (TVH) and the duration of quiescence increased in D. magna individuals exposed to increasing NOR concentrations after 4 and 12 h of exposure. These collectively led to decreases in both average swimming ability and feeding rate, consistent with the positive relationship between average swimming ability and feeding rate. Overall, results indicate that, by affecting zooplankton heartbeat rate and behavior, NOR decreased feeding efficiency of D. magna even at low doses, therefore, it might seriously compromise ecosystem health and function.

TUBERCULOSIS AND LETHAL AS WELL AS SUBLETHAL WHOLE-BODY X-RAY IRRADIATION OF GUINEA PIGS (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gabler, E.

1964-02-01

Lethally total-body-x-ray-irradiated (550 r) and simultaneously Tb- infected guinea pigs died earlier (1.5 to 3.2 days) than lethally irradiated control animals. A tuberculous focus formation could not be found microscopically or macroscopically in these guinea pigs or in sublethally irradiated and simultaneously infected animals. However, in tubcrculous control animals, which were killed at this time, specific foci could be found in liver, spleen, and lungs. Using sublethal irradiation (300 r) and simultaneous Tb inoculation half of the animals died a radiation death and the rest died of tuberculosis. It was found that 86.4% of the animals die a radiation deathmore » and 13.5% because of tuberculosis when irradiated sublethally 30 days after infection. The greatest tuberculosis foci in these animais appeared in lungs, spleen, and especially in the liver ( destroyed iiver''). Tuberculous giant cells of the Langhans-type were missing in case of irradiation and simultaneous tuberculosis. They appeared again about 20 to 30 days after irradiation. The native resistance to tuberculosis was very reduced in cases of simultaneous exposure; radioinduced cell shortage and cell damage permit tuberculous focus formation only after overcoming the acute radiation syndrome in case of sublethal irradiations. (auth)« less

Acute, Sub-lethal Cyanide Poisoning in Mice is Ameliorated by Nitrite Alone: Complications Arising from Concomitant Administration of Nitrite and Thiosulfate as an Antidotal Combination

PubMed Central

Cambal, Leah K.; Swanson, Megan R.; Yuan, Quan; Weitz, Andrew C.; Li, Hui-Hua; Pitt, Bruce R.; Pearce, Linda L.; Peterson, Jim

2011-01-01

Sodium nitrite alone is shown to ameliorate sub-lethal cyanide toxicity in mice when given from ~1 hour before until 20 minutes after the toxic dose as demonstrated by the recovery of righting ability. An optimum dose (12 mg/kg) was determined to significantly relieve cyanide toxicity (5.0 mg/kg) when administered to mice intraperitoneally. Nitrite so administered was shown to rapidly produce NO in the bloodsteam as judged by the dose dependent appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin. It is argued that antagonism of cyanide inhibition of cytochrome c oxidase by NO is the crucial antidotal activity rather than the methemoglobin-forming action of nitrite. Concomitant addition of sodium thiosulfate to nitrite-treated blood resulted in the detection of sulfidomethemoblobin by EPR spectroscopy. Sulfide is a product of thiosulfate hydrolysis and, like cyanide, is known to be a potent inhibitor of cytochrome c oxidase; the effects of the two inhibitors being essentially additive under standard assay conditions, rather than dominated by either one. The findings afford a plausible explanation for an observed detrimental effect in mice associated with the use of the standard nitrite-thiosulfate combination therapy at sub-lethal levels of cyanide intoxication. PMID:21534623

The non-target impact of spinosyns on beneficial arthropods.

PubMed

Biondi, Antonio; Mommaerts, Veerle; Smagghe, Guy; Viñuela, Elisa; Zappalà, Lucia; Desneux, Nicolas

2012-12-01

Spinosyn-based products, mostly spinosad, have been widely recommended by extension specialists and agribusiness companies; consequently, they have been used to control various pests in many different cropping systems. Following the worldwide adoption of spinosad-based products for integrated and organic farming, an increasing number of ecotoxicological studies have been published in the past 10 years. These studies are primarily related to the risk assessment of spinosad towards beneficial arthropods. This review takes into account recent data with the aim of (i) highlighting potentially adverse effects of spinosyns on beneficial arthropods (and hence on ecosystem services that they provide in agroecosystems), (ii) clarifying the range of methods used to address spinosyn side effects on biocontrol agents and pollinators in order to provide new insights for the development of more accurate bioassays, (iii) identifying pitfalls when analysing laboratory results to assess field risks and (iv) gaining increasing knowledge on side effects when using spinosad for integrated pest management (IPM) programmes and organic farming. For the first time, a thorough review of possible risks of spinosad and novel spinosyns (such as spinetoram) to beneficial arthropods (notably natural enemies and pollinators) is provided. The acute lethal effect and multiple sublethal effects have been identified in almost all arthropod groups studied. This review will help to optimise the future use of spinosad and new spinosyns in IPM programmes and for organic farming, notably by preventing the possible side effects of spinosyns on beneficial arthropods. Copyright © 2012 Society of Chemical Industry.

Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

PubMed

Roell, Wilhelm; Klein, Alexandra M; Breitbach, Martin; Becker, Torsten S; Parikh, Ashish; Lee, Jane; Zimmermann, Katrin; Reining, Shaun; Gabris, Beth; Ottersbach, Annika; Doran, Robert; Engelbrecht, Britta; Schiffer, Miriam; Kimura, Kenichi; Freitag, Patricia; Carls, Esther; Geisen, Caroline; Duerr, Georg D; Sasse, Philipp; Welz, Armin; Pfeifer, Alexander; Salama, Guy; Kotlikoff, Michael; Fleischmann, Bernd K

2018-05-08

Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45 + cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.

Impacts of metal and metal oxide nanoparticles on marine organisms.

PubMed

Baker, Tony J; Tyler, Charles R; Galloway, Tamara S

2014-03-01

Increasing use of metal and metal oxide nanoparticles [Me(O)NPs] in products means many will inevitably find their way into marine systems. Their likely fate here is sedimentation following hetero-aggregation with natural organic matter and/or free anions, putting benthic, sediment-dwelling and filter feeding organisms most at risk. In marine systems, Me(O)NPs can absorb to micro-organisms with potential for trophic transfer following consumption. Filter feeders, especially bivalves, accumulate Me(O)NPs through trapping them in mucus prior to ingestion. Benthic in-fauna may directly ingest sedimented Me(O)NPs. In fish, uptake is principally via the gut following drinking, whilst Me(O)NPs caught in gill mucus may affect respiratory processes and ion transport. Currently, environmentally-realistic Me(O)NP concentrations are unlikely to cause significant adverse acute health problems, however sub-lethal effects e.g. oxidative stresses have been noted in many organisms, often deriving from dissolution of Ag, Cu or Zn ions, and this could result in chronic health impacts. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Modulation of bilirubin neurotoxicity by the Abcb1 transporter in the Ugt1-/- lethal mouse model of neonatal hyperbilirubinemia.

PubMed

Bockor, Luka; Bortolussi, Giulia; Vodret, Simone; Iaconcig, Alessandra; Jašprová, Jana; Zelenka, Jaroslav; Vitek, Libor; Tiribelli, Claudio; Muro, Andrés F

2017-01-01

Moderate neonatal jaundice is the most common clinical condition during newborn life. However, a combination of factors may result in acute hyperbilirubinemia, placing infants at risk of developing bilirubin encephalopathy and death by kernicterus. While most risk factors are known, the mechanisms acting to reduce susceptibility to bilirubin neurotoxicity remain unclear. The presence of modifier genes modulating the risk of developing bilirubin-induced brain damage is increasingly being recognised. The Abcb1 and Abcc1 members of the ABC family of transporters have been suggested to have an active role in exporting unconjugated bilirubin from the central nervous system into plasma. However, their role in reducing the risk of developing neurological damage and death during neonatal development is still unknown.To this end, we mated Abcb1a/b-/- and Abcc1-/- strains with Ugt1-/- mice, which develop severe neonatal hyperbilirubinemia. While about 60% of Ugt1-/- mice survived after temporary phototherapy, all Abcb1a/b-/-/Ugt1-/- mice died before postnatal day 21, showing higher cerebellar levels of unconjugated bilirubin. Interestingly, Abcc1 role appeared to be less important.In the cerebellum of Ugt1-/- mice, hyperbilirubinemia induced the expression of Car and Pxr nuclear receptors, known regulators of genes involved in the genotoxic response.We demonstrated a critical role of Abcb1 in protecting the cerebellum from bilirubin toxicity during neonatal development, the most clinically relevant phase for human babies, providing further understanding of the mechanisms regulating bilirubin neurotoxicity in vivo. Pharmacological treatments aimed to increase Abcb1 and Abcc1 expression, could represent a therapeutic option to reduce the risk of bilirubin neurotoxicity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Aggression-impulsivity, mental pain, and communication difficulties in medically serious and medically non-serious suicide attempters.

PubMed

Gvion, Yari; Horresh, Netta; Levi-Belz, Yossi; Fischel, Tsvi; Treves, Ilan; Weiser, Mark; David, Haim Shem; Stein-Reizer, Orit; Apter, Alan

2014-01-01

Unbearable mental pain, depression, and hopelessness have been associated with suicidal behavior in general, while difficulties with social communication and loneliness have been associated with highly lethal suicide attempts in particular. The literature also links aggression and impulsivity with suicidal behavior but raises questions about their influence on the lethality and outcome of the suicide attempt. To evaluate the relative effects of aggression and impulsivity on the lethality of suicide attempts we hypothesized that impulsivity and aggression differentiate between suicide attempters and non-attempters and between medically serious and medically non-serious suicide attempters. The study group included 196 participants divided into four groups: 43 medically serious suicide attempters; 49 medically non-serious suicide attempters, 47 psychiatric patients who had never attempted suicide; and 57 healthy control subjects. Data on sociodemographic parameters, clinical history, and details of the suicide attempts were collected. Participants completed a battery of instruments for assessment of aggression-impulsivity, mental pain, and communication difficulties. The medically serious and medically non-serious suicide attempters scored significantly higher than both control groups on mental pain, depression, and hopelessness (p<.001 for all) and on anger-in, anger-out, violence, and impulsivity (p<.05 for all), with no significant difference between the two suicide attempter groups. Medically serious suicide attempters had significantly lower self-disclosure (p<.05) and more schizoid tendencies (p<.001) than the other three groups and significantly more feelings of loneliness than the medically non-serious suicide attempters and nonsuicidal psychiatric patients (p<.05). Analysis of aggression-impulsivity, mental pain, and communication variables with suicide lethality yielded significant correlations for self-disclosure, schizoid tendency, and loneliness. The interaction between mental pain and schizoid traits explained some of the variance in suicide lethality, over and above the contribution of each component alone. Aggression-impulsivity and mental pain are risk factors for suicide attempts. However, only difficulties in communication differentiate medically serious from medically non-serious suicide attempters. The combination of unbearable mental pain and difficulties in communication has a magnifying effect on the risk of lethal suicidal behavior. © 2014.

Head injury assessment of non-lethal projectile impacts: A combined experimental/computational method.

PubMed

Sahoo, Debasis; Robbe, Cyril; Deck, Caroline; Meyer, Frank; Papy, Alexandre; Willinger, Remy

2016-11-01

The main objective of this study is to develop a methodology to assess this risk based on experimental tests versus numerical predictive head injury simulations. A total of 16 non-lethal projectiles (NLP) impacts were conducted with rigid force plate at three different ranges of impact velocity (120, 72 and 55m/s) and the force/deformation-time data were used for the validation of finite element (FE) NLP. A good accordance between experimental and simulation data were obtained during validation of FE NLP with high correlation value (>0.98) and peak force discrepancy of less than 3%. A state-of-the art finite element head model with enhanced brain and skull material laws and specific head injury criteria was used for numerical computation of NLP impacts. Frontal and lateral FE NLP impacts to the head model at different velocities were performed under LS-DYNA. It is the very first time that the lethality of NLP is assessed by axonal strain computation to predict diffuse axonal injury (DAI) in NLP impacts to head. In case of temporo-parietal impact the min-max risk of DAI is 0-86%. With a velocity above 99.2m/s there is greater than 50% risk of DAI for temporo-parietal impacts. All the medium- and high-velocity impacts are susceptible to skull fracture, with a percentage risk higher than 90%. This study provides tool for a realistic injury (DAI and skull fracture) assessment during NLP impacts to the human head. Copyright © 2016 Elsevier Ltd. All rights reserved.

Croton grewioides Baill. (Euphorbiaceae) Shows Antidiarrheal Activity in Mice

PubMed Central

da Silva, Anne Dayse Soares; de Melo e Silva, Karoline; Neto, José Clementino; Costa, Vicente Carlos de Oliveira; Pessôa, Hilzeth de Luna F.; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Cavalcante, Fabiana de Andrade

2016-01-01

Based on chemotaxonomy, we decided to investigate the possible antidiarrheal activity in mice of a crude ethanolic extract obtained from aerial parts of Croton grewioides (CG-EtOH). We tested for any possible toxicity in rat erythrocytes and acute toxicity in mice. Antidiarrheal activity was assessed by determining the effect of CG-EtOH on defecation frequency, liquid stool, intestinal motility and intestinal fluid accumulation. CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females. CG-EtOH produced a significant and equipotent antidiarrheal activity, both in defecation frequency (ED50 = 106.0 ± 8.1 mg/kg) and liquid stools (ED50 = 105.0 ± 9.2 mg/kg). However, CG-EtOH (125 mg/kg) decreased intestinal motility by only 22.7% ± 4.4%. Moreover, extract markedly inhibited the castor oil-induced intestinal contents (ED50 = 34.6 ± 5.4 mg/kg). We thus conclude that CG-EtOH is not orally lethal and contains active principles with antidiarrheal activity, and this effect seems to involve mostly changes in intestinal secretion. SUMMARY CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females.CG-EtOH probably contains active metabolites with antidiarrheal activity.CG-EtOH reduced the frequency and number of liquid stools.Metabolites presents in the CG-EtOH act mainly by reducing intestinal fluid and, to a lesser extent, reducing intestinal motility. Abbreviations Used: CG-EtOH: crude ethanolic extract obtained from the aerial parts of C. grewioides; WHO: World Health Organization; ED50: dose of a drug that produces 50% of its maximum effect; Emax: maximum effect PMID:27365990

Both epsilon-toxin and beta-toxin are important for the lethal properties of Clostridium perfringens type B isolates in the mouse intravenous injection model.

PubMed

Fernandez-Miyakawa, Mariano E; Fisher, Derek J; Poon, Rachael; Sayeed, Sameera; Adams, Vicki; Rood, Julian I; McClane, Bruce A; Uzal, Francisco A

2007-03-01

Clostridium perfringens is capable of producing up to 15 toxins, including alpha-toxin (CPA), beta-toxin (CPB), epsilon-toxin (ETX), enterotoxin, beta2-toxin (CPB2), and perfringolysin O. Type B isolates, which must produce CPA, CPB, and ETX, are associated with animal illnesses characterized by sudden death or acute neurological signs, with or without intestinal damage. Type B pathogenesis in ruminants is poorly understood, with some animals showing lesions and clinical signs similar to those caused by either type C or type D infections. It is unknown whether host or environmental conditions are dominant for determining the outcome of type B disease or if disease outcomes are determined by variable characteristics of type B isolates. To help clarify this issue, 19 type B isolates were evaluated for toxin production during late-log-phase growth via quantitative Western blotting and by biological activity assays. Most type B isolates produced CPB levels similar to those produced by type C isolates in vitro and have the potential to produce genotype C-like disease. The lethality of type B isolate supernatants administered intravenously to mice was evaluated with or without prior trypsin treatment, and monoclonal antibody neutralization studies also were performed. Correlation analyses comparing toxin levels in type B supernatants versus lethality and neutralization studies both found that the main contributor to lethality without pretreatment with trypsin was CPB, whereas neutralization studies indicated that CPB and ETX were both important after trypsin pretreatment. At least part of the CPB produced by type B isolates remained active after trypsin treatment. However, the overall lethalities of most supernatants were lower after trypsin pretreatment. Also, there was a significant association between ETX, CPB2, and CPA production in vitro among type B isolates. However, our results suggest that both CPB and ETX are likely the most important contributors to the pathogenesis of C. perfringens type B infections in domestic animals.

Acute Cyanide Poisoning: Hydroxocobalamin and Sodium Thiosulfate Treatments with Two Outcomes following One Exposure Event.

PubMed

Meillier, Andrew; Heller, Cara

2015-01-01

Cyanide is rapidly reacting and causes arrest of aerobic metabolism. The symptoms are diffuse and lethal and require high clinical suspicion. Remediation of symptoms and mortality is highly dependent on quick treatment with a cyanide antidote. Presently, there are two widely accepted antidotes: sodium thiosulfate and hydroxocobalamin. These treatments act on different components of cyanide's metabolism. Here, we present two cases resulting from the same source of cyanide poisoning and the use of both antidotes separately used with differing outcomes.

Development of methodologies to assess the relative hazards from thermal decomposition products of polymeric materials.

PubMed

Barrow, C S; Lucia, H; Stock, M F; Alarie, Y

1979-05-01

The physiological stress imposed upon mice due to the irritating properties of thermal decomposition products of polymeric materials was evaluated. Acute lethality and histopathological evaluation were included in the study. The rankings of the polymeric materials studied from most to least hazardous was concluded to be polytetrafluoroethylene greater than polyvinyl chloride greater than Douglas Fir and flexible polyurethane foam greater than fiber glass reinforced polyester greater than copper coated wire with mineral insulation.

Spontaneous thrombosis of congenital extrahepatic portosystemic shunt (Abernethy malformation) simulating inguinal hernia incarceration.

PubMed

Afzal, Samara; Nair, Amit; Grainger, Jennie; Latif, Sherif; Rehman, Atiq-ur

2010-08-01

Tender lumps in the inguinal region are often explored emergently to treat suspected hernial strangulation. We discuss the case of an adult male who presented acutely with a tender inguinal swelling and raised inflammatory markers and was therefore deemed as requiring surgical exploration. However preoperative abdominal computerized tomography (CT) revealed an extensive thrombosing congenital venous malformation of portosystemic origin with extension into the symptomatic inguinal canal. A potentially lethal exsanguination from surgery was thus avoided.

Median Lethal Doses Associated with Intravenous Exposure to the Optically Pure Enantiomers of VX in Guinea Pigs

DTIC Science & Technology

2017-03-01

highly toxic based on the U.S. Environmental Protection Agency’s Acute Toxicity Categories for Pesticide Products . 15. SUBJECT TERMS Guinea pig ...in Guinea Pigs 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Wright, Linnzi K. M.; Forster, Jeffry S...intravenous exposure of adult, male guinea pigs to the individual VX enantiomers, and we compared those potencies to that for a racemic mixture. The P

Acute toxicity of emamectin benzoate and its desmethyl metabolite to Eohaustorius estuarius.

PubMed

Kuo, Jen-Ni; Buday, Craig; van Aggelen, Graham; Ikonomou, Michael George; Pasternak, John

2010-08-01

Emamectin benzoate is one of the active ingredients of the anti-sealice drug SLICE. Ten-day acute sediment lethal tests (10-d LC50) of emamectin benzoate and its desmethyl metabolite (AB1) were conducted to determine LC50 values using a sensitive representative West Coast amphipod crustacean, Eohaustorius estuarius. The 10-d LC50s of emamectin benzoate and AB1 to E. estuarius were 0.185 and 0.019 mg/kg wet weight sediment (0.146 and 0.015 mg/kg dry wt), respectively. The degradation properties of emamectin benzoate and AB1 during the 10-d period were also measured and described. No obvious decay patterns were observed for either emamectin benzoate and AB1 over the 10-d period. Copyright 2010 SETAC

THE COURSE OF ACUTE INTESTINAL INFECTIONS IN MONKEYS DURING THE ACTION OF IONISING RADIATION (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stasilevich, Z.K.

1963-04-01

The influence of sublethal x irradiation on the susceptibility of monkeys to acute intestinal infections (paratyphoid B fever, Heidelberg's salmonellosis and colienteritis) was studied. Experiments were carried out on 46 macaque monkeys, aged 2 1/2 to 3 yr. In monkeys subjected to a dose of 300 r there was an elevated susceptibility to paratyphoid B fever; however, the infectious process was not aggravated. Irradiation of animals with a similar dose aggravated the infectious process in Heidelberg's salmonellosis. In monkeys with colienteritis the above dose did not influence the natural immunity of animals to this disease. A clinically marked disease (colienteritis),more » with a lethal outcome was induced in monkeys irradiated with a dose of 445 r. (auth)« less

Pivotal advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection.

PubMed

Raué, Hans-Peter; Slifka, Mark K

2007-05-01

Previous studies have shown that T cells, which are genetically deficient in CTLA-4/CD152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical role in the negative regulation of effector T cell function. In contrast to expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus or vaccinia virus infection. When compared with CTLA-4- T cells directly ex vivo, CTLA-4+ T cells also exhibited normal antiviral effector functions following stimulation with peptide-coated cells, virus-infected cells, plate-bound anti-CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that CTLA-4 does not directly inhibit antiviral T cell expansion or T cell effector functions, at least not under the normal physiological conditions associated with either of these two acute viral infections.

Sudden oronasal bleeding in a young child.

PubMed

Hey, Edmund

2008-10-01

Sudden severe upper-airway obstruction occurring in a hospital setting can sometimes precipitate an episode of acute haemorrhagic pulmonary oedema. A review of 197 published case reports shows that the presenting feature is almost always the sudden appearance of blood stained fluid coming up through the larynx or out through the mouth and nose of an adult or child in obvious respiratory distress. Such overt features are seen in 10-15% of cases of sudden severe, but sub-lethal, upper-airway obstruction. Signs normally appear within minutes once the obstruction is relieved but are occasionally only recognized after 1-4 h. All signs and symptoms usually resolve within 12-24 h. Other causes of acute pulmonary haemorrhage are rare in young children. If what looks like blood is seen in, or coming from, the mouth or nose of a previously healthy young child who has suddenly become distressed and started to struggle for breath, that child has most probably suffered an episode of acute pulmonary oedema, and the commonest precipitating cause is sudden upper-airway obstruction.

Acute toxicity of peracetic acid (PAA) formulations to Ichthyophthirius multifiliis theronts.

PubMed

Straus, David L; Meinelt, Thomas

2009-04-01

Peracetic acid (PAA) is an antimicrobial disinfectant used in agriculture, food processing, and medical facilities. It has recently been suggested as a means to control infestations of Ichthyophthirius multifiliis. The purpose of this study was to determine the acute toxicity of two products containing 4.5% and 40% PAA to I. multifiliis theronts from two geographically separate isolates. Theronts were exposed to concentrations of PAA in 96-well plates containing groundwater at 23 degrees C. Acute toxicity was observed over a 4-h period. No significant difference in the median lethal concentration (LC(50)) estimates was evident between the two isolates at 4 h with the 4.5% PAA product (0.146 versus 0.108 mg/l PAA), while there was a statistical difference between the 4 h LC(50) with the 40% PAA product (0.274 versus 0.158 mg/l PAA). These results suggest that PAA is toxic to I. multifiliis theronts at low concentrations and that one of the isolates was more resistant to this compound.

Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression.

PubMed

Ahearn, Thomas U; Tchrakian, Nairi; Wilson, Kathryn M; Lis, Rosina; Nuttall, Elizabeth; Sesso, Howard D; Loda, Massimo; Giovannucci, Edward; Mucci, Lorelei A; Finn, Stephen; Shui, Irene M

2016-06-01

Prostate cancer metastases preferentially target bone, and the calcium-sensing receptor (CaSR) may play a role in promoting this metastatic progression. We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer. A validated CaSR immunohistochemistry assay was performed on tumor tissue microarrays. Vitamin D receptor (VDR) expression and phosphatase and tensin homolog tumor status were previously assessed in a subset of cases by immunohistochemistry. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and pathological tumor node metastasis stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer. The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study. We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009. Participants were followed up or cancer-specific mortality or development of metastatic disease. On average, men were followed up 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathological variables (HR 2.0; 95% CI 1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR 3.2; 95% CI 1.4-7.3) but not in cases with high tumor VDR expression (HR 0.8; 95% CI 0.2-3.0). Tumor CaSR expression is associated with an increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.

A School-Based Suicide Risk Assessment Protocol

ERIC Educational Resources Information Center

Boccio, Dana E.

2015-01-01

Suicide remains the third leading cause of death among young people in the United States. Considering that youth who contemplate suicide generally exhibit warning signs before engaging in lethal self-harm, school-based mental health professionals can play a vital role in identifying students who are at risk for suicidal behavior. Nevertheless, the…

Acute aquatic toxicity and biodegradation potential of biodiesel fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haws, R.A.; Zhang, X.; Marshall, E.A.

1995-12-31

Recent studies on the biodegradation potential and aquatic toxicity of biodiesel fuels are reviewed. Biodegradation data were obtained using the shaker flask method observing the appearance of CO{sub 2} and by observing the disappearance of test substance with gas chromatography. Additional BOD{sub 5} and COD data were obtained. The results indicate the ready biodegradability of biodiesel fuels as well as the enhanced co-metabolic biodegradation of biodiesel and petroleum diesel fuel mixtures. The study examined reference diesel, neat soy oil, neat rape oil, and the methyl and ethyl esters of these vegetable oils as well as various fuel blends. Acute toxicitymore » tests on biodiesel fuels and blends were performed using Oncorhynchus mykiss (Rainbow Trout) in a static non-renewal system and in a proportional dilution flow replacement system. The study is intended to develop data on the acute aquatic toxicity of biodiesel fuels and blends under US EPA Good Laboratory Practice Standards. The test procedure is designed from the guidelines outlined in Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms and the Fish Acute Aquatic Toxicity Test guideline used to develop aquatic toxicity data for substances subject to environmental effects test regulations under TSCA. The acute aquatic toxicity is estimated by an LC50, a lethal concentration effecting mortality in 50% of the test population.« less

Acute toxicity of chlorantraniliprole to non-target crayfish (Procambarus clarkii) associated with rice-crayfish cropping systems.

PubMed

Barbee, Gary C; McClain, W Ray; Lanka, Srinivas K; Stout, Michael J

2010-09-01

Chlorantraniliprole, a novel anthranilic diamide insecticide, was recently introduced into the United States where rice-crayfish crop rotations are practiced to control rice water weevil (Lissorhoptrus oryzophilus Kuschel) infestations. Chlorantraniliprole has high margins of mammalian safety and excellent insecticidal efficacy, but its toxicity to non-target crayfish is uncertain. In this study, the acute toxicity of chlorantraniliprole to the red swamp crayfish Procambarus clarkii Girard was determined using aquatic and feeding assays. The aquatic 96 h median lethal toxicity (LC(50)) data indicate that technical-grade chlorantraniliprole is highly toxic (US EPA category) to crayfish with an LC(50) of 951 microg L(-1) (95% CL = 741-1118 microg L(-1)). A no observed effect concentration (NOEC) of 480 microg L(-1) was recorded. Neither the 36 day chronic feeding study, where crayfish fed on chlorantraniliprole-treated rice seed in aquaria, nor the 144 h acute feeding test, where crayfish fed on rice seeds treated with chlorantraniliprole, produced mortality or abnormal behavior. Chlorantraniliprole is three orders of magnitude less acutely toxic to P. clarkii than lambda-cyhalothrin and etofenprox, two pyrethroid insecticides also used in rice, and is less likely to cause acute crayfish toxicity in rice pond ecosystems. Based on acute toxicity data, the use of chlorantraniliprole should be more compatible with rice-crayfish crop rotations than pyrethroids. (c) 2010 Society of Chemical Industry.

Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action.

PubMed

Sanderson, Hans; Thomsen, Marianne

2009-06-01

Pharmaceuticals have been reported to be ubiquitously present in surface waters prompting concerns of effects of these bioactive substances. Meanwhile, there is a general scarcity of publicly available ecotoxicological data concerning pharmaceuticals. The aim of this paper was to compile a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68% of the pharmaceuticals have a non-specific MOA. Additionally, the acute-to-chronic ratio (ACR) for 70% of the analyzed pharmaceuticals was below 25 further suggesting a non-specific MOA. Sub-lethal receptor-mediated effects may however have a more specific MOA.

Distinctive emotional responses of clinicians to suicide-attempting patients - a comparative study

PubMed Central

2013-01-01

Background Clinician responses to patients have been recognized as an important factor in treatment outcome. Clinician responses to suicidal patients have received little attention in the literature however, and no quantitative studies have been published. Further, although patients with high versus low lethality suicidal behaviors have been speculated to represent two distinct populations, clinicians’ emotional responses to them have not been examined. Methods Clinicians’ responses to their patients when last seeing them prior to patients’ suicide attempt or death were assessed retrospectively with the Therapist Response/Countertransference Questionnaire, administered anonymously via an Internet survey service. Scores on individual items and subscale scores were compared between groups, and linear discriminant analysis was applied to determine the combination of items that best discriminated between groups. Results Clinicians reported on patients who completed suicide, made high-lethality attempts, low-lethality attempts, or died unexpected non-suicidal deaths in a total of 82 cases. We found that clinicians treating imminently suicidal patients had less positive feelings towards these patients than for non-suicidal patients, but had higher hopes for their treatment, while finding themselves notably more overwhelmed, distressed by, and to some degree avoidant of them. Further, we found that the specific paradoxical combination of hopefulness and distress/avoidance was a significant discriminator between suicidal patients and those who died unexpected non-suicidal deaths with 90% sensitivity and 56% specificity. In addition, we identified one questionnaire item that discriminated significantly between high- and low-lethality suicide patients. Conclusions Clinicians’ emotional responses to patients at risk versus not at risk for imminent suicide attempt may be distinct in ways consistent with responses theorized by Maltsberger and Buie in 1974. Prospective replication is needed to confirm these results, however. Our findings demonstrate the feasibility of using quantitative self-report methodologies for investigation of the relationship between clinicians’ emotional responses to suicidal patients and suicide risk. PMID:24053664

Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

NASA Astrophysics Data System (ADS)

Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

2015-03-01

Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

PubMed Central

Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

2013-01-01

ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

Interaction Effects of Acute Kidney Injury, Acute Respiratory Failure, and Sepsis on 30-Day Postoperative Mortality in Patients Undergoing High-Risk Intraabdominal General Surgical Procedures.

PubMed

Kim, Minjae; Brady, Joanne E; Li, Guohua

2015-12-01

Acute kidney injury (AKI), acute respiratory failure, and sepsis are distinct but related pathophysiologic processes. We hypothesized that these 3 processes may interact to synergistically increase the risk of short-term perioperative mortality in patients undergoing high-risk intraabdominal general surgery procedures. We performed a retrospective, observational cohort study of data (2005-2011) from the American College of Surgeons-National Surgical Quality Improvement Program, a high-quality surgical outcomes data set. High-risk procedures were those with a risk of AKI, acute respiratory failure, or sepsis greater than the average risk in all intraabdominal general surgery procedures. The effects of AKI, acute respiratory failure, and sepsis on 30-day mortality were assessed using a Cox proportional hazards model. Additive interactions were assessed with the relative excess risk due to interaction. Of 217,994 patients, AKI, acute respiratory failure, and sepsis developed in 1.3%, 3.7%, and 6.8%, respectively. The 30-day mortality risk with sepsis, acute respiratory failure, and AKI were 11.4%, 24.1%, and 25.1%, respectively, compared with 0.85% without these complications. The adjusted hazard ratios and 95% confidence intervals for a single complication (versus no complication) on mortality were 7.24 (6.46-8.11), 10.8 (8.56-13.6), and 14.2 (12.8-15.7) for sepsis, AKI, and acute respiratory failure, respectively. For 2 complications, the adjusted hazard ratios were 30.8 (28.0-33.9), 42.6 (34.3-52.9), and 65.2 (53.9-78.8) for acute respiratory failure/sepsis, AKI/sepsis, and acute respiratory failure/AKI, respectively. Finally, the adjusted hazard ratio for all 3 complications was 105 (92.8-118). Positive additive interactions, indicating synergism, were found for each combination of 2 complications. The relative excess risk due to interaction for all 3 complications was not statistically significant. In high-risk general surgery patients, the development of AKI, acute respiratory failure, or sepsis is independently associated with an increase in 30-day mortality. In addition, the development of 2 complications shows significant positive additive interactions to further increase the risk of mortality. Our findings suggest that interactions between these 3 perioperative complications increase the risk of mortality more than would be expected by the independent effects of each complication alone.

Lethal and behavioral impacts of diesel and fuel oil on the Antarctic amphipod Paramoera walkeri.

PubMed

Brown, Kathryn E; King, Catherine K; Harrison, Peter L

2017-09-01

Toxicity testing with Antarctic species is required for risk assessment of fuel spills in Antarctic coastal waters. The lethal and sublethal (movement behavior) sensitivities of adults and juveniles of the Antarctic amphipod Paramoera walkeri to the water accommodated fractions (WAFs) of 3 fuels were estimated in extended-duration tests at -1 °C to 21 d. Response of P. walkeri for lethal hydrocarbon concentrations was slow, with 50% lethal concentrations (LC50s) first able to be estimated at 7 d for adults exposed to Special Antarctic Blend diesel (SAB), which had the highest hydrocarbon concentrations of the 3 fuel WAFs. Juveniles showed greater response to marine gas oil (MGO) and intermediate residual fuel oil (IFO 180) at longer exposure durations and were most sensitive at 21 d to IFO 180 (LC50 = 12 μg/L). Adults were initially more sensitive than juveniles; at 21 d, however, juveniles were more than twice as sensitive as adults to SAB (LC50 = 153 μg/L and 377 μg/L, respectively). Significant effects on movement behavior were evident at earlier time points and lower concentrations than was mortality in all 3 fuel WAFs, and juveniles were highly sensitive to sublethal effects of MGO. These first estimates of Antarctic amphipod sensitivity to diesel and fuel oils in seawater contribute to the development of ecologically relevant risk assessments for management of hydrocarbon contamination in the region. Environ Toxicol Chem 2017;36:2444-2455. © 2017 SETAC. © 2017 SETAC.

Expression of hsp 27, hsp 60, hsc 70, and hsp 70 stress response genes in cultured human urothelial cells (UROtsa) exposed to lethal and sublethal concentrations of sodium arsenite.

PubMed

Rossi, Michael R; Somji, Seema; Garrett, Scott H; Sens, Mary Ann; Nath, Joginder; Sens, Donald A

2002-12-01

The stress response is one mechanism that the bladder urothelium could potentially employ to protect itself from cellular damage after exposure to arsenic and, in so doing, influence the shape of the dose-response curve at low concentrations of exposure to this environmental pollutant. In the present study, we used the cultured human urothelial cell line UROtsa, a model of human urothelium, to determine the expression of heat shock proteins hsp 27, hsp 60, hsc 70, and hsp 70 after acute and extended exposure of the cells to lethal and sublethal levels of sodium arsenite (NaAsO2). Acute exposure was modeled by exposing confluent cultures of UROtsa cells to 100 micro M NaAsO2 for 4 hr followed by a 48-hr recovery period. Extended exposure was modeled by exposing confluent UROtsa cells to 1, 4, and 8 micro M NaAsO2 for 16 days, with the highest concentration producing cell death by 4 days of exposure. The expression of hsp 27, hsp 60, hsc 70, and hsp 70 mRNA and protein was determined by reverse-transcription polymerase chain reaction and Western analysis. Cell viability was determined by the MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The results demonstrated that the expression of hsp 27, hsp 60, and hsc 70 mRNA and protein were not consistently increased by either acute or extended exposure to NaAsO2. In contrast, hsp 70 expression was induced by NaAsO2 after both acute and extended exposure. The degree and duration of the induction of the hsp 70 protein in the extended time course of exposure to NaAsO2 correlated directly with UROtsa cell cytotoxicity. The substantial level of basal expression of hsp 27, hsp 60, and hsc 70 shown previously in human bladder urothelium, coupled with the inducible expression of hsp 70, could provide the human urothelium with a mechanism to withstand and recover from a low level of arsenite exposure.

Lymphatic involution and early mortality in the young chicken produced by 2.2 GeV protons

NASA Technical Reports Server (NTRS)

Montour, J. L.; Shellabarger, C. J.

1972-01-01

Young single-comb white Leghorn cockerels were subjected to single acute doses of either 2.2 GeV protons or 250 kVp X-rays. Since young chickens exposed in the lethal range die within 48 hours of exposure, an hourly tabulation of deaths was recorded for this length of time after exposure. Animals which were exposed to sublethal doses were killed five days after exposure and their major lymphatic organs, (thymus, bursa, and spleen), removed and weighed. In the lethal range, animals exposed to 2.2 GeV protons died sooner than those receiving similar doses of X-rays, but total mortality was similar in each case at similar dose levels. The 48 hour LD sub 50 was determined to be 710 rad. Measured five days after exposure, 50% depression ED sub 50 for lymphatic organs occurred as follows: (1) thymus, 350 rad; (2) pursa, 500 rad, and (3) spleen, 450 rad. In all case R.B.E. values were not different from unity.

Effects of low-molecular-weight organic acids on the acute lethality, accumulation, and enzyme activity of cadmium in Eisenia fetida in a simulated soil solution.

PubMed

Liu, Hai-Long; Wang, Yu-Jun; Xuan, Liang; Dang, Fei; Zhou, Dong-Mei

2017-04-01

In the present study, the effects of low-molecular-weight organic acids (LMWOAs) on the toxicity of cadmium (Cd) to Eisenia fetida were investigated in a simulated soil solution. The LMWOAs protected E. fetida from Cd toxicity, as indicated by the increased median lethal concentration (LC50) values and the increased activity of superoxide dismutase. In addition, Cd concentrations in E. fetida decreased dramatically in the presence of LMWOAs. These results were likely because of the complexation between Cd and LMWOAs, which decreased the bioavailability and consequential toxicity of Cd to E. fetida. Notably, LMWOAs reduced Cd toxicity in decreasing order (ethylenediamine tetraacetic acid [EDTA] > citric acid > oxalic acid > malic acid > acetic acid), which was consistent with the decreasing complexation constants between LMWOAs and Cd. These results advance our understanding of the interactions between Cd and LMWOAs in soil. Environ Toxicol Chem 2017;36:1005-1011. © 2016 SETAC. © 2016 SETAC.

Superantigens Are Critical for Staphylococcus aureus Infective Endocarditis, Sepsis, and Acute Kidney Injury

PubMed Central

Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R.; Merriman, Joseph A.; Stach, Christopher S.; Horswill, Alexander R.; Peterson, Marnie L.; Schlievert, Patrick M.

2013-01-01

ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. PMID:23963178

Studying the effect of CO2-induced acidification on sediment toxicity using acute amphipod toxicity test.

PubMed

Basallote, M Dolores; De Orte, Manoela R; DelValls, T Ángel; Riba, Inmaculada

2014-01-01

Carbon capture and storage is increasingly being considered one of the most efficient approaches to mitigate the increase of CO2 in the atmosphere associated with anthropogenic emissions. However, the environmental effects of potential CO2 leaks remain largely unknown. The amphipod Ampelisca brevicornis was exposed to environmental sediments collected in different areas of the Gulf of Cádiz and subjected to several pH treatments to study the effects of CO2-induced acidification on sediment toxicity. After 10 days of exposure, the results obtained indicated that high lethal effects were associated with the lowest pH treatments, except for the Ría of Huelva sediment test. The mobility of metals from sediment to the overlying seawater was correlated to a pH decrease. The data obtained revealed that CO2-related acidification would lead to lethal effects on amphipods as well as the mobility of metals, which could increase sediment toxicity.

The use of bacteria for detecting toxic effects of pollutants in soil and water

NASA Astrophysics Data System (ADS)

Obiakor, Maximilian; Wilson, Susan; Tighe, Matthew; Pereg, Lily

2017-04-01

Microbial abundance and diversity are essential for sustaining soil structure and function and have been strongly linked to human health and wellbeing. Antimony (Sb) in the environment can present an ecological hazard and depending on concentration can be lethal. The toxic effects of Sb(III) and Sb(V) on the model soil bacterium Azospirillum brasilense Sp7 were assessed in exposure-dose-response assays and water samples from an Sb contaminated creek were analyzed for bacterial mortality. In both cases, Sb(III) and Sb(V) greatly affected the survival of A. brasilense Sp7 cells. The Sb(III) had a greater toxic effect than Sb(V) at all concentrations tested. Critical concentrations of Sb also caused variant colonies to appear, indicating both acute and sub-lethal effects, which were dose and time dependent. This work demonstrates the usefulness of A. brasilense as an indicator species to detect harmful effects of an environmental pollutant of emerging concern.

Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability.

PubMed

Brooks, Marjory B; Turk, James R; Guerrero, Abraham; Narayanan, Padma K; Nolan, John P; Besteman, Elizabeth G; Wilson, Dennis W; Thomas, Roberta A; Fishman, Cindy E; Thompson, Karol L; Ellinger-Ziegelbauer, Heidrun; Pierson, Jennifer B; Paulman, April; Chiang, Alan Y; Schultze, Albert E

2017-01-01

Systemic inflammation co-activates coagulation, which unchecked culminates in a lethal syndrome of multi-organ microvascular thrombosis known as disseminated intravascular coagulation (DIC). We studied an endotoxin-induced inflammatory state in rats to identify biomarkers of hemostatic imbalance favoring hypercoagulability. Intraperitoneal injection of LPS at 15 mg/kg body weight resulted in peripheral leukopenia and widespread neutrophilic sequestration characteristic of an acute systemic inflammatory response. Early indicators of hemostatic pathway activation developed within 4 hours, including increased circulating concentrations of procoagulant extracellular vesicles (EVs), EVs expressing endothelial cell and platelet membrane markers, and high concentration of soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1), and D-dimers. Inflammation persisted throughout the 48-hour observation period; however, increases were found in a subset of serum microRNA (miRNA) that coincided with gradual resolution of hemostatic protein abnormalities and reduction in EV counts. Dose-adjusted LPS treatment in rats provides a time-course model to develop biomarker profiles reflecting procoagulant imbalance and rebalance under inflammatory conditions.

Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.

PubMed

Mucker, Eric M; Chapman, Jennifer; Huzella, Louis M; Huggins, John W; Shamblin, Joshua; Robinson, Camenzind G; Hensley, Lisa E

2015-01-01

Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.

Haem peroxidase activity in Daphnia magna: a biomarker for sub-lethal toxicity assessments of kerosene-contaminated groundwater.

PubMed

Connon, Richard; Dewhurst, Rachel E; Crane, Mark; Callaghan, Amanda

2003-10-01

A novel biomarker was developed in Daphnia magna to detect organic pollution in groundwater. The haem peroxidase assay, which is an indirect means of measuring oxidase activity, was particularly sensitive to kerosene contamination. Exposure to sub-lethal concentrations of kerosene-contaminated groundwater resulted in a haem peroxidase activity increase by dose with a two-fold activity peak at 25%. Reproduction in D. magna remained unimpaired when exposed to concentrations below 25% for 21 days, and a decline in fecundity was only observed at concentrations above the peak in enzyme activity. The measurement of haem peroxidase activity in D. magna detected sublethal effects of kerosene in just 24 h, whilst offering information on the health status of the organisms. The biomarker may be useful in determining concentrations above which detrimental effects would occur from long-term exposure for fuel hydrocarbons. Moreover, this novel assay detects exposure to chemicals in samples that would normally be classified as non-toxic by acute toxicity tests.

Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease

PubMed Central

Mucker, Eric M.; Chapman, Jennifer; Huzella, Louis M.; Huggins, John W.; Shamblin, Joshua; Robinson, Camenzind G.; Hensley, Lisa E.

2015-01-01

Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox. PMID:26147658

Relationship Between Acute Benzodiazepine Poisoning and Acute Pancreatitis Risk

PubMed Central

Liaw, Geng-Wang; Hung, Dong-Zong; Chen, Wei-Kung; Lin, Cheng-Li; Lin, I-Ching; Kao, Chia-Hung

2015-01-01

Abstract We designed a population-based retrospective cohort study to investigate the association between the event of benzodiazepine (BZD) poisoning and the risk of acute pancreatitis. In the present study, 12,893 patients with BZD poisoning during 2000 to 2011 were enrolled and matched with 4 comparison patients according to mean age and sex. We determined the cumulative incidences and adjusted hazard ratios of acute pancreatitis. A significant association was observed between BZD poisoning and acute pancreatitis. After adjustment for potential risk factors, the patients with BZD poisoning had a 5.33-fold increased risk of acute pancreatitis compared with the controls without BZD poisoning (HR = 5.33, 95% CI = 2.26–12.60). The results revealed that acute pancreatitis in patients with BZD poisoning occurred in a follow-up time of ≤1 month (HR = 50.0, P < .001), and the risk of acute pancreatitis was no different between the patients with and without BZD poisoning when the follow-up time was >1 month (HR = 1.07, P > .05). This population-based study revealed the positive correlation between the event of BZD poisoning and an increased risk of acute pancreatitis. The findings warrant further large-scale and in-depth investigation. PMID:26717383

High surface adsorption properties of carbon-based nanomaterials are responsible for mortality, swimming inhibition, and biochemical responses in Artemia salina larvae.

PubMed

Mesarič, Tina; Gambardella, Chiara; Milivojević, Tamara; Faimali, Marco; Drobne, Damjana; Falugi, Carla; Makovec, Darko; Jemec, Anita; Sepčić, Kristina

2015-06-01

We investigated the effects of three different carbon-based nanomaterials on brine shrimp (Artemia salina) larvae. The larvae were exposed to different concentrations of carbon black, graphene oxide, and multiwall carbon nanotubes for 48 h, and observed using phase contrast and scanning electron microscopy. Acute (mortality) and behavioural (swimming speed alteration) responses and cholinesterase, glutathione-S-transferase and catalase enzyme activities were evaluated. These nanomaterials were ingested and concentrated in the gut, and attached onto the body surface of the A. salina larvae. This attachment was responsible for concentration-dependent inhibition of larval swimming, and partly for alterations in the enzyme activities, that differed according to the type of tested nanomaterials. No lethal effects were observed up to 0.5mg/mL carbon black and 0.1mg/mL multiwall carbon nanotubes, while graphene oxide showed a threshold whereby it had no effects at 0.6 mg/mL, and more than 90% mortality at 0.7 mg/mL. Risk quotients calculated on the basis of predicted environmental concentrations indicate that carbon black and multiwall carbon nanotubes currently do not pose a serious risk to the marine environment, however if uncontrolled release of nanomaterials continues, this scenario can rapidly change. Copyright © 2015 Elsevier B.V. All rights reserved.

Virulence, pathology, and pathogenesis of Pteropine orthoreovirus (PRV) in BALB/c mice: Development of an animal infection model for PRV.

PubMed

Egawa, Kazutaka; Shimojima, Masayuki; Taniguchi, Satoshi; Nagata, Noriyo; Tani, Hideki; Yoshikawa, Tomoki; Kurosu, Takeshi; Watanabe, Shumpei; Fukushi, Shuetsu; Saijo, Masayuki

2017-12-01

Cases of acute respiratory tract infection caused by Pteropine orthoreovirus (PRV) of the genus Orthoreovirus (family: Reoviridae) have been reported in Southeast Asia, where it was isolated from humans and bats. It is possible that PRV-associated respiratory infections might be prevalent in Southeast Asia. The clinical course of PRV is not fully elucidated. The virulence, pathology, and pathogenesis of two PRV strains, a human-borne PRV strain (isolated from a patient, who returned to Japan from Bali, Indonesia in 2007) and a bat-borne PRV (isolated from a bat [Eonycteris spelaea] in the Philippines in 2013) were investigated in BALB/c mice using virological, pathological, and immunological study methods. The intranasal inoculation of BALB/c mice with human-borne PRV caused respiratory infection. In addition, all mice with immunity induced by pre-inoculation with a non-lethal dose of PRV were completely protected against lethal PRV infection. Mice treated with antiserum with neutralizing antibody activity after inoculation with a lethal dose of PRV showed a reduced fatality rate. In this mouse model, bat-borne PRV caused respiratory infection similar to human-borne PRV. PRV caused lethal respiratory disease in an animal model of PRV infection, in which BALB/c mice were used. The BALB/c mouse model might help to accelerate research on the virulence of PRV and be useful for evaluating the efficacy of therapeutic agents and vaccines for the treatment and prevention of PRV infection. PRV was shown for the first time to be a causative virus of respiratory disease on the basis of Koch's postulations by the additional demonstration that PRV caused respiratory disease in mice through their intranasal inoculation with PRV.

Emergency planning and the acute toxic potency of inhaled ammonia.

PubMed Central

Michaels, R A

1999-01-01

Ammonia is present in agriculture and commerce in many if not most communities. This report evaluates the toxic potency of ammonia, based on three types of data: anecdotal data, in some cases predating World War 1, reconstructions of contemporary industrial accidents, and animal bioassays. Standards and guidelines for human exposure have been driven largely by the anecdotal data, suggesting that ammonia at 5,000-10,000 parts per million, volume/volume (ppm-v), might be lethal within 5-10 min. However, contemporary accident reconstructions suggest that ammonia lethality requires higher concentrations. For example, 33,737 ppm-v was a 5-min zero-mortality value in a major ammonia release in 1973 in South Africa. Comparisons of secondary reports of ammonia lethality with original sources revealed discrepancies in contemporary sources, apparently resulting from failure to examine old documents or accurately translate foreign documents. The present investigation revealed that contemporary accident reconstructions yield ammonia lethality levels comparable to those in dozens of reports of animal bioassays, after adjustment of concentrations to human equivalent concentrations via U.S. Environmental Protection Agency (EPA) procedures. Ammonia levels potentially causing irreversible injury or impairing the ability of exposed people to escape from further exposure or from coincident perils similarly have been biased downwardly in contemporary sources. The EPA has identified ammonia as one of 366 extremely hazardous substances subject to community right-to-know provisions of the Superfund Act and emergency planning provisions of the Clean Air Act. The Clean Air Act defines emergency planning zones (EPZs) around industrial facilities exceeding a threshold quantity of ammonia on-site. This study suggests that EPZ areas around ammonia facilities can be reduced, thereby also reducing emergency planning costs, which will vary roughly with the EPZ radius squared. Images Figure 1 Figure 2 PMID:10417358

[A fatal case series of Rocky Mountain spotted fever in Sonora, México].

PubMed

Delgado-De la Mora, Jesús; Licona-Enríquez, Jesús David; Leyva-Gastélum, Marcia; Delgado-De la Mora, David; Rascón-Alcantar, Adela; Álvarez-Hernández, Gerardo

2018-03-15

Rocky Mountain spotted fever is a highly lethal infectious disease, particularly if specific treatment with doxycycline is given belatedly. To describe the clinical profile of fatal Rocky Mountain spotted fever cases in hospitalized patients in the state of Sonora, México. We conducted a cross-sectional study on a series of 47 deaths caused by Rickettsia rickettsii from 2013 to 2016. The diagnosis of Rocky Mountain spotted fever was confirmed in a single blood sample by polymerase chain reaction (PCR) or by a four-fold increase in immunoglobulin G measured in paired samples analyzed by indirect immunofluorescence. Clinical and laboratory characteristics were compared stratifying subjects into two groups: pediatric and adult. There were no differences in clinical characteristics between groups; petechial rash was the most frequent sign (96%), followed by headache (70%) and myalgia (67%). Although that doxycycline was administered before the fifth day from the onset of symptoms, death occurred in 55% of patients. In clinical laboratory, thrombocytopenia, and biomarkers of liver acute failure and acute kidney failure were the most frequent. Rocky Mountain spotted fever remains as one of the most lethal infectious diseases, which may be related not only to the lack of diagnostic suspicion and delayed administration of doxycycline, but to genotypic characteristics of Rickettsia rickettsii that may play a role in the variability of the fatality rate that has been reported in other geographical regions where the disease is endemic.

Accelerated hematopoietic toxicity by high energy (56)Fe radiation.

PubMed

Datta, Kamal; Suman, Shubhankar; Trani, Daniela; Doiron, Kathryn; Rotolo, Jimmy A; Kallakury, Bhaskar V S; Kolesnick, Richard; Cole, Michael F; Fornace, Albert J

2012-03-01

There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to γ or X-rays, and the general assumption based on in vitro studies has been that acute toxicity is substantially greater. C57BL/6J mice were irradiated with (56)Fe ions (1 GeV/nucleon), and acute (within 30 d) toxicity compared to that of γ rays or protons (1 GeV). To assess relative hematopoietic and gastrointestinal toxicity, the effects of (56)Fe ions were compared to γ rays using complete blood count (CBC), bone marrow granulocyte-macrophage colony forming unit (GM-CFU), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis in bone marrow, and intestinal crypt survival. Although onset was more rapid, (56)Fe ions were only slightly more toxic than γ rays or protons with lethal dose (LD)(50/30) (a radiation dose at which 50% lethality occurs at 30-day) values of 5.8, 7.25, and 6.8 Gy, respectively, with relative biologic effectiveness for (56)Fe ions of 1.25 and 1.06 for protons. (56)Fe radiation caused accelerated and more severe hematopoietic toxicity. Early mortality correlated with more profound leukopenia and subsequent sepsis. Results indicate that there is selective enhanced toxicity to bone marrow progenitor cells, which are typically resistant to γ rays, and bone marrow stem cells, because intestinal crypt cells did not show increased HZE toxicity.

Lethal and Sublethal Effects of the Herbicide Atrazine in the Early Stages of Development of Physalaemus gracilis (Anura: Leptodactylidae).

PubMed

Rutkoski, Camila F; Macagnan, Natani; Kolcenti, Cassiane; Vanzetto, Guilherme V; Sturza, Paola F; Hartmann, Paulo A; Hartmann, Marilia T

2018-05-01

Water sources used as reproductive sites by crying frog, Physalaemus gracilis, are extensively associated with agroecosystems in which the herbicide atrazine is employed. To evaluate the lethal and sublethal effects of atrazine commercial formulation, acute and chronic toxicity tests were performed in the embryonic phase and the beginning of the larval phase of P. gracilis. Tests were started on stage 19 of Gosner (Herpetologica 16:183-190, 1960) and performed in 24-well cell culture plates. Acute tests had a duration of 96 h with embryo mortality monitoring every 24 h. Chronic assays contemplated the transition from the embryonic to larval stages and lasted 168 h. Every 24 h the embryos/larvae were observed for mortality, mobility, and malformations. The LC50 of atrazine determined for P. gracilis embryos was 229.34 mg L -1 . The sublethal concentrations did not affect the development of the larvae but were observed effects on mobility and malformations, such as spasmodic contractions, reduced mobility, malformations in mouth and intestine, and edema arising. From 1 mg L -1 atrazine, the exposed larvae began to have changes in mobility and malformations. The atrazine commercial formulation has caused early life effects of P. gracilis that may compromise the survival of this species but at higher concentrations than recorded in the environment, so P. gracilis can be considered tolerant to this herbicide at environmentally relevant concentrations.

Inhibition of nuclear factor of activated T cells (NFAT) c3 activation attenuates acute lung injury and pulmonary edema in murine models of sepsis

PubMed Central

Karpurapu, Manjula; Lee, Yong Gyu; Qian, Ziqing; Wen, Jin; Ballinger, Megan N.; Rusu, Luiza; Chung, Sangwoon; Deng, Jing; Qian, Feng; Reader, Brenda F.; Nirujogi, Teja Srinivas; Park, Gye Young; Pei, Dehua; Christman, John W.

2018-01-01

Specific therapies targeting cellular and molecular events of sepsis induced Acute Lung Injury (ALI) pathogenesis are lacking. We have reported a pivotal role for Nuclear Factors of Activated T cells (NFATc3) in regulating macrophage phenotype during sepsis induced ALI and subsequent studies demonstrate that NFATc3 transcriptionally regulates macrophage CCR2 and TNFα gene expression. Mouse pulmonary microvascular endothelial cell monolayer maintained a tighter barrier function when co-cultured with LPS stimulated NFATc3 deficient macrophages whereas wild type macrophages caused leaky monolayer barrier. More importantly, NFATc3 deficient mice showed decreased neutrophilic lung inflammation, improved alveolar capillary barrier function, arterial oxygen saturation and survival benefit in lethal CLP sepsis mouse models. In addition, survival of wild type mice subjected to the lethal CLP sepsis was not improved with broad-spectrum antibiotics, whereas the survival of NFATc3 deficient mice was improved to 40–60% when treated with imipenem. Passive adoptive transfer of NFATc3 deficient macrophages conferred protection against LPS induced ALI in wild type mice. Furthermore, CP9-ZIZIT, a highly potent, cell-permeable peptide inhibitor of Calcineurin inhibited NFATc3 activation. CP9-ZIZIT effectively reduced sepsis induced inflammatory cytokines and pulmonary edema in mice. Thus, this study demonstrates that inhibition of NFATc3 activation by CP9-ZIZIT provides a potential therapeutic option for attenuating sepsis induced ALI/pulmonary edema. PMID:29535830

Accelerated Hematopoietic Toxicity by High Energy 56Fe Radiation

PubMed Central

Datta, Kamal; Suman, Shubhankar; Trani, Daniela; Doiron, Kathryn; Rotolo, Jimmy A.; Kallakury, Bhaskar V. S.; Kolesnick, Richard; Cole, Michael F.; Fornace, Albert J.

2013-01-01

Purpose There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to γ or x-rays, and the general assumption based on in vitro studies has been that acute toxicity is substantially greater. Methods C57BL/6J mice were irradiated with 56Fe ions (1 GeV/nucleon), and acute (within 30 d) toxicity compared to that of γ rays or protons (1 GeV). To assess relative hematopoietic and gastrointestinal toxicity, the effects of 56Fe ions were compared to γ rays using complete blood count (CBC), bone marrow granulocyte-macrophage colony forming unit (GM-CFU), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis in bone marrow, and intestinal crypt survival. Results Although onset was more rapid, 56Fe ions were only slightly more toxic than γ rays or protons with lethal dose (LD)50/30 (a radiation dose at which 50% lethality occurs at 30-day) values of 5.8, 7.25, and 6.8 Gy respectively with relative biologic effectiveness for 56Fe ions of 1.25 and 1.06 for protons. Conclusions 56Fe radiation caused accelerated and more severe hematopoietic toxicity. Early mortality correlated with more profound leukopenia and subsequent sepsis. Results indicate that there is selective enhanced toxicity to bone marrow progenitor cells, which are typically resistant to γ rays, and bone marrow stem cells, because intestinal crypt cells did not show increased HZE toxicity. PMID:22077279

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

PubMed

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

2015-08-01

Green stormwater infrastructure (GSI), or low impact development, encompasses a diverse and expanding portfolio of strategies to reduce the impacts of stormwater runoff on natural systems. Benchmarks for GSI success are usually framed in terms of hydrology and water chemistry, with reduced flow and loadings of toxic chemical contaminants as primary metrics. Despite the central goal of protecting aquatic species abundance and diversity, the effectiveness of GSI treatments in maintaining diverse assemblages of sensitive aquatic taxa has not been widely evaluated. In the present study we characterized the baseline toxicity of untreated urban runoff from a highway in Seattle, WA, across six storm events. For all storms, first flush runoff was toxic to the daphniid Ceriodaphnia dubia, causing up to 100% mortality or impairing reproduction among survivors. We then evaluated whether soil media used in bioretention, a conventional GSI method, could reduce or eliminate toxicity to juvenile coho salmon (Oncorhynchus kisutch) as well as their macroinvertebrate prey, including cultured C. dubia and wild-collected mayfly nymphs (Baetis spp.). Untreated highway runoff was generally lethal to salmon and invertebrates, and this acute mortality was eliminated when the runoff was filtered through soil media in bioretention columns. Soil treatment also protected against sublethal reproductive toxicity in C. dubia. Thus, a relatively inexpensive GSI technology can be highly effective at reversing the acutely lethal and sublethal effects of urban runoff on multiple aquatic species. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Inhibiting Bruton's Tyrosine Kinase Rescues Mice from Lethal Influenza Induced Acute Lung Injury.

PubMed

Florence, Jon M; Krupa, Agnieszka; Booshehri, Laela M; Davis, Sandra A; Matthay, Michael A; Kurdowska, Anna K

2018-03-08

Infection with seasonal influenza A virus (IAV) leads to lung inflammation and respiratory failure, a main cause of death in influenza infected patients. Previous experiments in our laboratory indicated that Bruton's tyrosine kinase (Btk) plays a substantial role in regulating inflammation in the respiratory region during acute lung injury (ALI) in mice, therefore we sought to determine if blocking Btk activity had a protective effect in the lung during influenza induced inflammation. A Btk inhibitor (Btk Inh.) Ibrutinib (also known as PCI-32765) was administered intranasally to mice starting 72h after lethal infection with IAV. Our data indicates that treatment with the Btk inhibitor not only reduced weight loss and led to survival, but had a dramatic effect on morphological changes to the lungs of IAV infected mice. Attenuation of lung inflammation indicative of ALI such as alveolar hemorrhage, interstitial thickening, and the presence of alveolar exudate, together with reduced levels of inflammatory mediators TNFα, IL-1β, IL-6, KC, and MCP-1 strongly suggest amelioration of the pathological immune response in the lungs to promote resolution of the infection. Finally, we observed that blocking Btk specifically in the alveolar compartment led to significant attenuation of neutrophil extracellular traps (NET)s released into the lung in vivo, and NET formation in vitro. Our innovative findings suggest that Btk may be a new drug target for influenza induced lung injury, and in general immunomodulatory treatment may be key in treating lung dysfunction driven by excessive inflammation.

Representing and Retrieving Patients' Falls Risk Factors and Risk for Falls among Adults in Acute Care through the Electronic Health Record

ERIC Educational Resources Information Center

Pfaff, Jann

2013-01-01

Defining fall risk factors and predicting fall risk status among patients in acute care has been a topic of research for decades. With increasing pressure on hospitals to provide quality care and prevent hospital-acquired conditions, the search for effective fall prevention interventions continues. Hundreds of risk factors for falls in acute care…

Chiropractic care and risk for acute lumbar disc herniation: a population-based self-controlled case series study.

PubMed

Hincapié, Cesar A; Tomlinson, George A; Côté, Pierre; Rampersaud, Y Raja; Jadad, Alejandro R; Cassidy, J David

2017-10-16

Chiropractic care is popular for low back pain, but may increase the risk for acute lumbar disc herniation (LDH). Low back pain is a common early (prodromal) symptom of LDH and commonly precedes LDH diagnosis. Our objective was to investigate the association between chiropractic care and acute LDH with early surgical intervention, and contrast this with the association between primary care physician (PCP) care and acute LDH with early surgery. Using a self-controlled case series design and population-based healthcare databases in Ontario, Canada, we investigated all adults with acute LDH requiring emergency department (ED) visit and early surgical intervention from April 1994 to December 2004. The relative incidence of acute LDH with early surgery in exposed periods after chiropractic visits relative to unexposed periods was estimated within individuals, and compared with the relative incidence of acute LDH with early surgery following PCP visits. 195 cases of acute LDH with early surgery (within 8 weeks) were identified in a population of more than 100 million person-years. Strong positive associations were found between acute LDH and both chiropractic and PCP visits. The risk for acute LDH with early surgery associated with chiropractic visits was no higher than the risk associated with PCP visits. Both chiropractic and primary medical care were associated with an increased risk for acute LDH requiring ED visit and early surgery. Our analysis suggests that patients with prodromal back pain from a developing disc herniation likely seek healthcare from both chiropractors and PCPs before full clinical expression of acute LDH. We found no evidence of excess risk for acute LDH with early surgery associated with chiropractic compared with primary medical care.

Analysis of Phone Calls Regarding Fluoride Exposure made to New Jersey Poison Control Center from 2010 to 2012.

PubMed

Shah, Sneha; Quek, Samuel; Ruck, Bruce

2016-02-01

The American Association of Poison Control Center's annual reports demonstrate that acute fluoride exposure is not an uncommon occurrence. Despite its prevalence, there has been little published research on the topic in the last 10 years. The purpose of this study was to calculate the incidence of acute fluoride toxicity and lethality as it occurs in New Jersey and provide a descriptive epidemiology of acute fluoride exposures. The study design was retrospective in nature. Records of phone calls made by individuals reporting excessive fluoride exposure (in an amount greater than directed/prescribed) to New Jersey's poison control center, known as Poison Information and Education System from the years 2010 through 2012, were extracted from Toxicall® (Computer Automatic Systems, Inc.) database. A total of 2,476 human-only exposure records met the inclusion criteria and were analyzed. Incidence rates were calculated, and population characteristics, circumstances and medical outcomes of acute fluoride exposure cases were assessed and categorized. A total of 2,476 phone call records met the inclusion criteria. The fluoride exposures reported were from toothpaste with fluoride (49%, n=1,214), mouth rinse with fluoride (21.6%, n=536), multivitamin with fluoride (21.4%, n=530) and pure fluoride (0.08%, n=199). Medically speaking, 94.75% of calls were asymptomatic cases (n=2,346), 4.24% were symptomatic (n=105) and 1.01% were informational inquiries (n=25). Adverse symptoms reported were mostly minor (83.9% of symptomatic cases, n=88) and moderate (16.1% of symptomatic cases, n=17). The age group 18 months to 3 years of age showed the highest incidence of acute fluoride exposure (53.2%, n=1,317). There was a slightly higher incidence of acute fluoride exposures among males (n=1,317) vs. females (n=1,159). Most incidences occurred in the home (93.1% of records, n=2,305) and occurred unintentionally (96.7%, n=2,394). Calls were mainly made by the subject's mother (67.5%, n=1,671). Based on the data, there were no reports of lethality or toxicity due to acute fluoride exposure in New Jersey from 2010 through 2012. Symptomatic reports and informational inquiries were few. All adverse outcomes due to excessive fluoride intake were remedied with calcium as the antidote. Dental hygienists should educate patients on safety measures of fluoride-containing products and evaluate overall fluoride exposure prior to making recommendations. However, findings in this study suggest that levels of fluoride in available commercial products will not produce life-threatening events, even if taken in doses higher than recommended. Copyright © 2016 The American Dental Hygienists’ Association.

Impact on the Japanese atomic bomb survivors of radiation received from the bombs.

PubMed

Cullings, Harry M

2014-02-01

The Radiation Effects Research Foundation (RERF) studies various cohorts of Japanese atomic bomb survivors, the largest being the Life Span Study (LSS), which includes 93,741 persons who were in Hiroshima or Nagasaki at the times of the bombings; there are also cohorts of persons who were exposed in utero and survivors' children. This presentation attempts to summarize the total impact of the radiation from the bombs on the survivors from both an individual perspective (both age-specific and integrated lifetime risk, along with a measure of life expectancy that describes how the risk affects the individual given age at exposure) and a group perspective (estimated numbers of excess occurrences in the cohort), including both early and late effects. As survivors' doses ranged well into the acutely lethal range at closer distances, some of them experienced acute signs and symptoms of radiation exposure in addition to being at risk of late effects. Although cancer has always been a primary concern among late effects, estimated numbers of excess cancers and hematopoietic malignancies in the LSS are a small fraction of the total due to the highly skewed dose distribution, with most survivors receiving small doses. For example, in the latest report on cancer incidence, 853 of 17,448 incident solid cancers were estimated to be attributable to radiation from the bombs. RERF research indicates that risk of radiation-associated cancer varies among sites and that some benign tumors such as uterine myoma are also associated with radiation. Noncancer late effects appear to be in excess in proportion to radiation dose but with an excess relative risk about one-third that of solid cancer and a correspondingly small overall fraction of cases attributable to radiation. Specific risks were found for some subcategories, particularly circulatory disease, including stroke and precedent conditions such as hypertension. Radiation-related cataract in the atomic bomb survivors is well known, with evidence in recent years of risk at lower dose levels than previously appreciated. In addition to somatic effects, survivors experienced psychosocial effects such as uncertainty, social stigma, or rejection, and other social pressures. Developmental deficits associated with in utero exposure, notably cognitive impairment, have also been described. Interaction of radiation with other risk factors has been demonstrated in relation to both cancer and noncancer diseases. Current research interests include whether radiation increases risk of diabetes or conditions of the eye apart from cataract, and there continues to be keen interest as to whether there are heritable effects in survivors' children, despite negative findings to date. Introduction of Impact on the Japanese Atomic- Bomb Survivors (Video 1:52, http://links.lww.com/HP/A29).

Patterns of Partners' Abusive Behaviors as Reported by Latina and Non-Latina Survivors

ERIC Educational Resources Information Center

Glass, Nancy; Perrin, Nancy; Hanson, Ginger; Mankowski, Eric; Bloom, Tina; Campbell, Jacquelyn

2009-01-01

This study builds on the existing knowledge of risk factors for lethal intimate partner violence (IPV) and typologies of IPV abusers by exploring patterns of abusive partners' behaviors among known risk factors for intimate partner femicide (i.e., murder of women) and determines if groups of survivors with similar patterns of abusive behaviors…

Defining High-Risk Precursor Signaling to Advance Breast Cancer Risk Assessment and Prevention

DTIC Science & Technology

2016-03-01

the incidence and lethality of breast cancer will require a detailed understanding of the earliest tissue changes that ultimately drive the process of...Changes/Problems 12-14 6. Products ...as stated in the approved SOW. If the application listed milestones/target dates for important activities or phases of the project, identify these

Assessment of acute toxicity of carbofuran in Macrobrachium olfersii (Wiegmann, 1836) at different temperature levels.

PubMed

Barbieri, Edison; Moreira, Priscila; Luchini, Luiz Alberto; Hidalgo, Karla Ruiz; Muñoz, Alejandro

2016-01-01

Carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate; C12H15NO3) is one of the most toxic carbamate pesticides. For acute toxicity of carbofuran, juveniles of Macrobrachium olfersii were exposed to different concentrations of carbofuran using the static renewal method at different temperature levels (15, 20 and 25°C) at pH 7.0. The main purpose of the present study was to detect the acute toxicity of carbofuran to M. olfersii and investigate its effects on oxygen consumption and ammonium excretion; these tests have not been carried out in this species before. First, the acute toxicity - median lethal concentration - of carbofuran to M. olfersii for 24, 48, 72 and 96 h was examined, which resulted in the following values: 1.64, 1.22, 0.86 and 0.42 mg L(-1), respectively. Furthermore, we also found that carbofuran caused an inhibition in oxygen consumption of 60.6, 65.3 and 66.2% with respect to the control. In addition, after separate exposures to carbofuran, elevations in ammonium excretion were more than 500% with respect to the control. © The Author(s) 2013.

Pathogenesis of graft-versus-host disease: innate immunity amplifying acute alloimmune responses.

PubMed

Maeda, Yoshinobu

2013-09-01

In addition to reduced-intensity conditioning, which has expanded the eligibility for hematopoietic cell transplantation (HCT) to older patients, increased availability of alternative donors, including HLA-mismatched unrelated donors, has increased access to allogeneic HCT for more patients. However, acute graft-versus-host disease (GVHD) remains a lethal complication, even in HLA-matched donor-recipient pairs. The pathophysiology of GVHD depends on aspects of adaptive immunity and interactions between donor T-cells and host dendritic cells (DCs). Recent work has revealed that the role of other immune cells and endothelial cells and components of the innate immune response are also important. Tissue damage caused by the conditioning regimen leads to the release of exogenous and endogenous "danger signals". Exogenous danger signals called pathogen-associated molecular patterns and endogenous noninfectious molecules known as damage-associated molecular patterns (DAMPs) are responsible for initiating or amplifying acute GVHD by enhancing DC maturation and alloreactive T-cell responses. A significant association of innate immune receptor polymorphisms with outcomes, including GVHD severity, was observed in patients receiving allogeneic HCT. Understanding of the role of innate immunity in acute GVHD might offer new therapeutic approaches.

Mechanistic modeling of insecticide risks to breeding birds in North American agroecosystems

PubMed Central

Garber, Kristina; Odenkirchen, Edward

2017-01-01

Insecticide usage in the United States is ubiquitous in urban, suburban, and rural environments. There is accumulating evidence that insecticides adversely affect non-target wildlife species, including birds, causing mortality, reproductive impairment, and indirect effects through loss of prey base, and the type and magnitude of such effects differs by chemical class, or mode of action. In evaluating data for an insecticide registration application and for registration review, scientists at the United States Environmental Protection Agency (USEPA) assess the fate of the insecticide and the risk the insecticide poses to the environment and non-target wildlife. Current USEPA risk assessments for pesticides generally rely on endpoints from laboratory based toxicity studies focused on groups of individuals and do not directly assess population-level endpoints. In this paper, we present a mechanistic model, which allows risk assessors to estimate the effects of insecticide exposure on the survival and seasonal productivity of birds known to forage in agricultural fields during their breeding season. This model relies on individual-based toxicity data and translates effects into endpoints meaningful at the population level (i.e., magnitude of mortality and reproductive impairment). The model was created from two existing USEPA avian risk assessment models, the Terrestrial Investigation Model (TIM v.3.0) and the Markov Chain Nest Productivity model (MCnest). The integrated TIM/MCnest model was used to assess the relative risk of 12 insecticides applied via aerial spray to control corn pests on a suite of 31 avian species known to forage in cornfields in agroecosystems of the Midwest, USA. We found extensive differences in risk to birds among insecticides, with chlorpyrifos and malathion (organophosphates) generally posing the greatest risk, and bifenthrin and λ-cyhalothrin (pyrethroids) posing the least risk. Comparative sensitivity analysis across the 31 species showed that ecological trait parameters related to the timing of breeding and reproductive output per nest attempt offered the greatest explanatory power for predicting the magnitude of risk. An important advantage of TIM/MCnest is that it allows risk assessors to rationally combine both acute (lethal) and chronic (reproductive) effects into a single unified measure of risk. PMID:28467479

Mechanistic modeling of insecticide risks to breeding birds in North American agroecosystems.

PubMed

Etterson, Matthew; Garber, Kristina; Odenkirchen, Edward

2017-01-01

Insecticide usage in the United States is ubiquitous in urban, suburban, and rural environments. There is accumulating evidence that insecticides adversely affect non-target wildlife species, including birds, causing mortality, reproductive impairment, and indirect effects through loss of prey base, and the type and magnitude of such effects differs by chemical class, or mode of action. In evaluating data for an insecticide registration application and for registration review, scientists at the United States Environmental Protection Agency (USEPA) assess the fate of the insecticide and the risk the insecticide poses to the environment and non-target wildlife. Current USEPA risk assessments for pesticides generally rely on endpoints from laboratory based toxicity studies focused on groups of individuals and do not directly assess population-level endpoints. In this paper, we present a mechanistic model, which allows risk assessors to estimate the effects of insecticide exposure on the survival and seasonal productivity of birds known to forage in agricultural fields during their breeding season. This model relies on individual-based toxicity data and translates effects into endpoints meaningful at the population level (i.e., magnitude of mortality and reproductive impairment). The model was created from two existing USEPA avian risk assessment models, the Terrestrial Investigation Model (TIM v.3.0) and the Markov Chain Nest Productivity model (MCnest). The integrated TIM/MCnest model was used to assess the relative risk of 12 insecticides applied via aerial spray to control corn pests on a suite of 31 avian species known to forage in cornfields in agroecosystems of the Midwest, USA. We found extensive differences in risk to birds among insecticides, with chlorpyrifos and malathion (organophosphates) generally posing the greatest risk, and bifenthrin and λ-cyhalothrin (pyrethroids) posing the least risk. Comparative sensitivity analysis across the 31 species showed that ecological trait parameters related to the timing of breeding and reproductive output per nest attempt offered the greatest explanatory power for predicting the magnitude of risk. An important advantage of TIM/MCnest is that it allows risk assessors to rationally combine both acute (lethal) and chronic (reproductive) effects into a single unified measure of risk.