Science.gov

Sample records for acute lethality tests

  1. The lethality test system

    SciTech Connect

    Parsons, W.M.; Sims, J.R.; Parker, J.V.

    1986-11-01

    The Lethality Test System (LTS), presently under construction at Los Alamos, is an electromagnetic launcher facility designed to perform impact experiments at velocities up to 15 km/s. The launcher is a 25 mm round bore, plasma armature railgun extending 22 m in length. Preinjection is accomplished with a two-stage light gas gun capable of 7 km/s. The railgun power supply utilized traction motors, vacuum interrupters, and pulse transformers. The design of these traction motors, vacuum interrupters and pulse transformers are detailed.

  2. Lethality test system

    SciTech Connect

    Parsons, W.M.; Sims, J.R.; Parker, J.V.

    1986-01-01

    The Lethality Test System (LTS), presently under construction at Los Alamos, is an electromagnetic launcher facility designed to perform impact experiments at velocities up to 15 km/s. The launcher is a 25 mm round bore, plasma armature railgun extending 22 m in length. Preinjection is accomplished with a two-stage gas gun capable of 7 km/s. The railgun power supply utilizes traction motors, vacuum interrupters, and pulse transformers. An assembly of 28 traction motors, equipped with flywheels, stores approximately 80 MJ at 92% of full speed and energizes the primary windings of three pulse transformers at a current of 50 kA. At peak current an array of vacuum interrupters disconnects the transformer primary windings and forces the current to flow in the secondary windings. The secondary windings are connected to the railgun, and by staging the vacuum interrupter openings, a 1 MA to 1.3 MA ramped current waveform will be delivered to the railgun.

  3. The Lethality Test System

    NASA Astrophysics Data System (ADS)

    Parsons, W. M.; Sims, J. R.; Parker, J. V.

    1986-11-01

    The Lethality Test System (LTS) under construction at Los Alamos is an electromagnetic launcher facility designed to perform impact experiments at velocities up to 15 km/sec. The launcher is a 25 mm round bore, plasma armature railgun 22 m in length. Preinjection is accomplished with a two-stage light gas gun capable of 7 km/sec. The railgun power supply utilizes traction motors, vacuum interrupters, and pulse transformers. An assembly of 28 traction motors, equipped with flywheels, stores approximately 80 MJ at 92 percent of full speed and energizes the primary windings of three pulse transformers at a current of 50 kA. At peak current an array of vacuum interrupters disconnects the transformer primary windings and forces the current to flow in the secondary windings. The secondary windings are connected to the railgun, and by staging the vacuum interrupter openings, a 1-1.3 MA ramped current waveform will be delivered to the railgun.

  4. Lethality Rate Estimation and Testing Procedures

    DTIC Science & Technology

    1989-09-11

    AUTHOR(S) Steven W. Rust, Paul I. Feder, Frederick R. Todt, Ronald L. Joiner Ila. TYPE OF REPORT 13b, IME .OVFRE 8 14. ATE OF PORT (VeerMontl.vay) 15...GD, and VX Administered Topically to Rabbits " (MREF Protocol 21, May 1985) to compare liquid or powder experimental decontaminants against the dual...chemical surety materick (CSM). The standardized screen is based on a lethality endpoint in laboratory albino rabbits . An essential aspect of this testing

  5. Statistical tests for recessive lethal-carriers.

    PubMed

    Hamilton, M A; Haseman, J K

    1979-08-01

    This paper presents a statistical method for testing whether a male mouse is a recessive lethal-carrier. The analysis is based on a back-cross experiment in which the male mouse is mated with some of his daughters. The numbers of total implantations and intrauterine deaths in each litter are recorded. It is assumed that, conditional on the number of total implantations, the number of intrauterine deaths follows a binomial distribution. Using computer-simulated experimentation it is shown that the proposed statistical method, which is sensitive to the pattern of intrauterine death rates, is more powerful than a test based only on the total number of implant deaths. The proposed test requires relatively simple calculations and can be used for a wide range of values of total implantations and background implant mortality rates. For computer-simulated experiments, there was no practical difference between the empirical error rate and the nominal error rate.

  6. Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines.

    PubMed

    Mordue, D G; Monroy, F; La Regina, M; Dinarello, C A; Sibley, L D

    2001-10-15

    Virulence in Toxoplasma gondii is strongly influenced by the genotype of the parasite. Type I strains uniformly cause rapid death in mice regardless of the host genotype or the challenge dose. In contrast, the outcome of infections with type II strains is highly dependent on the challenge dose and the genotype of the host. To understand the basis of acute virulence in toxoplasmosis, we compared low and high doses of the RH strain (type I) and the ME49/PTG strain (type II) of T. gondii in outbred mice. Differences in virulence were reflected in only modestly different growth rates in vivo, and both strains disseminated widely to different tissues. The key difference in the virulent RH strain was the ability to reach high tissue burdens rapidly following a low dose challenge. Lethal infections caused by type I (RH) or type II (PTG) strain infections were accompanied by extremely elevated levels of Th1 cytokines in the serum, including IFN-gamma, TNF-alpha, IL-12, and IL-18. Extensive liver damage and lymphoid degeneration accompanied the elevated levels of cytokines produced during lethal infection. Increased time of survival following lethal infection with the RH strain was provided by neutralization of IL-18, but not TNF-alpha or IFN-gamma. Nonlethal infections with a low dose of type II PTG strain parasites were characterized by a modest induction of Th1 cytokines that led to control of infection and minimal damage to host tissues. Our findings establish that overstimulation of immune responses that are normally necessary for protection is an important feature of acute toxoplasmosis.

  7. Bioassay technique using seed shrimps for comparative studies regarding the aquatic acute lethality of biodegradable lubricants.

    PubMed

    Tamura, S; Ezoe, S; Sasaki, C

    2011-09-01

    To evaluate the environmental load resulting from the spillage of biodegradable lubricants in aquatic systems, a comparative acute lethality test wherein an oil-water interfacial area could be examined was considered. In this study, oleic acid was employed as a model biodegradable lubricant. Measurements of the pH value and dissolved oxygen (DO) level of water during the exposure tests indicate that water degradation depends on the oil-water interfacial area, exposure duration, and water temperature. Furthermore, 72 h acute lethality tests were performed using two types of freshwater ostracods (seed shrimps) as test organisms: the large species Stenocypris hislopi and the small species Cypretta seurati. The longevity of the small species, which was physically more active, was strongly affected by water pollution. During the exposure test, the DO in water was significantly consumed by the degradation of the lubricant floating on it. Water exposed to a lubricant containing copper (Cu) demonstrated strong toxicity even after the recovery of the pH value and DO level by aging. The decrease in the DO level of water and increase in the concentration of metal compounds are dominant factors responsible for the mortality of aquatic organisms.

  8. Acute and sub-lethal response to mercury in Arctic and boreal calanoid copepods.

    PubMed

    Overjordet, Ida Beathe; Altin, Dag; Berg, Torunn; Jenssen, Bjørn Munro; Gabrielsen, Geir Wing; Hansen, Bjørn Henrik

    2014-10-01

    Acute lethal toxicity, expressed as LC50 values, is a widely used parameter in risk assessment of chemicals, and has been proposed as a tool to assess differences in species sensitivities to chemicals between climatic regions. Arctic Calanus glacialis and boreal Calanus finmarchicus were exposed to mercury (Hg(2+)) under natural environmental conditions including sea temperatures of 2° and 10°C, respectively. Acute lethal toxicity (96 h LC50) and sub-lethal molecular response (GST expression; in this article gene expression is used as a synonym of gene transcription, although it is acknowledged that gene expression is also regulated, e.g., at translation and protein stability level) were studied. The acute lethal toxicity was monitored for 96 h using seven different Hg concentrations. The sub-lethal experiment was set up on the basis of nominal LC50 values for each species using concentrations equivalent to 50, 5 and 0.5% of their 96 h LC50 value. No significant differences were found in acute lethal toxicity between the two species. The sub-lethal molecular response revealed large differences both in response time and the fold induction of GST, where the Arctic species responded both faster and with higher mRNA levels of GST after 48 h exposure. Under the natural exposure conditions applied in the present study, the Arctic species C. glacialis may potentially be more susceptible to mercury exposure on the sub-lethal level.

  9. Cortisol response to acute stress in jundiá Rhamdia quelen acutely exposed to sub-lethal concentrations of agrichemicals.

    PubMed

    Cericato, Leonardo; Neto, Joaquim Gonçalves Machado; Fagundes, Michele; Kreutz, Luiz Carlos; Quevedo, Rosmari Mezzalira; Finco, Jovani; da Rosa, João Gabriel Santos; Koakoski, Gessi; Centenaro, Lucas; Pottker, Emanuele; Anziliero, Deniz; Barcellos, Leonardo José Gil

    2008-09-01

    Exposure to agrichemicals can have deleterious effects on fish, such as disruption of the hypothalamus-pituitary-inter-renal axis (HPI) that could impair the ability of fish to respond to stressors. In this study, fingerlings of the teleost jundiá (Rhamdia quelen) were used to investigate the effects of the commonly used agrichemicals on the fish response to stress. Five common agrichemicals were tested: the fungicide - tebuconazole, the insecticide - methyl-parathion, and the herbicides - atrazine, atrazine+simazine, and glyphosate. Control fishes were not exposed to agrichemicals and standard stressors. In treatments 2-4, the fishes were exposed to sub-lethal concentrations (16.6%, 33.3%, and 50% of the LC(50)) of each agrichemical for 96 h, and at the end of this period, were subjected to an acute stress-handling stimulus by chasing them with a pen net. In treatments 5-7 (16.6%, 33.3%, and 50% of the LC(50)), the fishes were exposed to the same concentrations of the agrichemicals without stress stimulus. Treatment 8 consisted of jundiás not exposed to agrichemicals, but was subjected to an acute stress-handling stimulus. Jundiás exposed to methyl-parathion, atrazine+simazine, and glyphosate presented a decreased capacity in exhibiting an adequate response to cope with stress and in maintaining the homeostasis, with cortisol level lower than that in the control fish (P<0.01). In conclusion, the results of this study clearly demonstrate that the acute exposure to sub-lethal concentrations of methyl-parathion, atrazine+simazine, and glyphosate exert a deleterious effect on the cortisol response to an additional acute stressor in the jundiá fingerlings.

  10. Acute lethal and teratogenic effects of tributyltin chloride and copper chloride on mahi mahi (Coryphaena hippurus) eggs and larvae.

    PubMed

    Adema-Hannes, Rachel; Shenker, Jonathan

    2008-10-01

    Acute and chronic bioassays were used to evaluate the lethal and sublethal effects of copper chloride and tributyltin chloride on mahi mahi (Coryphaena hippurus) embryos, a pelagic life stage often found in the surface microlayer where anthropogenic contaminants can accumulate. Acute bioassay testing determined the median lethal concentration (LC50) for the test organism after 48 h of exposure. Chronic toxicity tests were used to determine the measurement of sublethal parameters, such as developmental abnormalities after 72-h exposures to the toxicants. Embryos were collected 4 h postfertilization and subsequently exposed to 1, 5, 25, 50, and 100 microg/L of copper chloride and 3, 10, 20, 30, and 50 microg/L of tributyltin chloride. Analysis of hatch rate percentage determined that the mean 48-h LC50 of copper chloride and tributyltin chloride was 32.8 and 16.7 microg/L, respectively, based on the pooled data of four experiments with four replicates for each metal. Consistent abnormalities, such as yolk sac swelling, spinal deformities, and decreased hatch rates, were observed for each metal. Teratogenic responses to copper chloride and tributyltin chloride demonstrate the need to investigate further the impacts of pollution in the open oceans to a species indigenous to, and commercially important to, the Florida (USA) coasts. This information could then lead to the future development of a surface microlayer bioassay using mahi mahi embryos.

  11. Calcitonin gene-related peptide inhibits local acute inflammation and protects mice against lethal endotoxemia.

    PubMed

    Gomes, Rachel Novaes; Castro-Faria-Neto, Hugo C; Bozza, Patricia T; Soares, Milena B P; Shoemaker, Charles B; David, John R; Bozza, Marcelo T

    2005-12-01

    Calcitonin gene-related peptide (CGRP), a potent vasodilatory peptide present in central and peripheral neurons, is released at inflammatory sites and inhibits several macrophage, dendritic cell, and lymphocyte functions. In the present study, we investigated the role of CGRP in models of local and systemic acute inflammation and on macrophage activation induced by lipopolysaccharide (LPS). Intraperitoneal pretreatment with synthetic CGRP reduces in approximately 50% the number of neutrophils in the blood and into the peritoneal cavity 4 h after LPS injection. CGRP failed to inhibit neutrophil recruitment induced by the direct chemoattractant platelet-activating factor, whereas it significantly inhibited LPS-induced KC generation, suggesting that the effect of CGRP on neutrophil recruitment is indirect, acting on chemokine production by resident cells. Pretreatment of mice with 1 mug of CGRP protects against a lethal dose of LPS. The CGRP-induced protection is receptor mediated because it is completely reverted by the CGRP receptor antagonist, CGRP 8-37. The protective effect of CGRP correlates with an inhibition of TNF-alpha and an induction of IL-6 and IL-10 in mice sera 90 min after LPS challenge. Finally, CGRP significantly inhibits LPS-induced TNF-alpha released from mouse peritoneal macrophages. These results suggest that activation of the CGRP receptor on macrophages during acute inflammation could be part of the negative feedback mechanism controlling the extension of acute inflammatory responses.

  12. Is Atyaephyra desmarestii a useful candidate for lethal and sub-lethal toxicity tests on pharmaceutical compounds?

    PubMed

    Nieto, Elena; Blasco, Julián; González-Ortegón, Enrique; Drake, Pilar; Hampel, Miriam

    2013-12-15

    Single and mixture toxicity tests on three pharmaceutical compounds, Diclofenac (DF), Ibuprofen (IB) and Carbamazepine (CBZ), were carried out with the freshwater shrimp Atyaephyra desmarestii. Lethal and sublethal responses were analyzed for single compounds. Lethal concentrations (LC50) obtained for each individual compound, after 96 h of exposure, were 6.3 mg L(-1) for DF, 13.3 mg L(-1) for IB and 94.3 mg L(-1) for CBZ. The selected sublethal endpoints of food ingestion, osmoregulatory capacity and respiration rates were not affected by the exposures to environmentally-relevant concentrations. Based on mortality data obtained, the predictive no effect concentration (PNEC) was calculated for each of the compounds, and compared with predicted environmental concentrations (PEC) reported in surface waters. The environmental risk of each compound was estimated as the ratio between PEC/PNEC, and indicated that IB could represent a medium risk in freshwater environments. Additionally, binary and ternary mixture toxicity assays of the selected compounds were carried out. The data obtained was applied to two predictive toxicity models: Concentration Addition (CA) and Independent Action (IA). Finally, risk assessment was estimated using risk quotients (RQ) for the compound mixtures based on EC50 and LC50 values.

  13. Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

    PubMed Central

    Savoy, A C; Lupan, D M; Manalo, P B; Roberts, J S; Schlageter, A M; Weinhold, L C; Kozel, T R

    1997-01-01

    Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with a cryptococcal infection and was reduced or absent in the early and late stages of disease. The clinical course and histopathology were consistent with those for shock. There was considerable variation between mouse strains in susceptibility to toxicity. Swiss Webster mice from the Charles River colony were most susceptible, followed by C3H/He, BALB/c, and C57BL/6 mice. DBA/2 mice and Swiss Webster mice from the Simonsen colony were resistant. Acute toxicity was mimicked by injection of preformed complexes of MAb and purified polysaccharide. The toxic effect was also produced by injection of MAbs into mice that were preloaded with polysaccharide. The toxic effect was not blocked by treatment of mice with chloropheniramine or anti-tumor necrosis factor alpha antibodies or by depletion of complement components via pretreatment with cobra venom factor. Toxicity was reduced by treatment of mice with high doses of epinephrine, dexamethasone, or chlorpromazine. Finally, the toxic effect was completely blocked by treatment of mice with the platelet-activating factor antagonist WEB 2170 BS or by pretreatment of mice with the liposome-encapsulated drug dichloromethylene diphosphonate, a procedure which depletes macrophages from the spleen and liver. PMID:9125564

  14. Lethal acute lung injury and hypoglycemia after subcutaneous administration of monochloroacetic acid.

    PubMed

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

    2006-06-01

    Hypoglycemia is suspected in the acute lethal toxicity induced by cutaneous exposure to monochloroacetic acid (MCA). Although it has been shown that hepato-renal dysfunction is involved, the mechanism and the target organs that directly affect mortality remain to be determined. We suspected respiratory failure as a main cause of death in some reported cases. We investigated dose-response effects, hypoglycemia, and lung injury in rats exposed to MCA. Serum glucose, blood gases, and parameters of alveolar injury in bronchoalveolar lavage fluid (BALF) were analysed 2 and 4 h after subcutaneous administration of MCA (108, 135 or 163 mg/kg). Apparent pulmonary injury and hypoglycemia were not identified 2 h after administration, but lactate dehydrogenase (LDH) and total cells in BALF were dose-dependently increased; and severe hypoglycemia was identified 4 h after administration. Blood gas analysis showed remarkable alveolar gas dysfunction as exchange in the 163 mg/kg group. Thus, hypoglycemia and lung injury appear to cause death in response to MCA exposure.

  15. Prolonged pretreatment of mice with cholera toxin, but not isoproterenol, alleviates acute lethal systemic inflammatory response.

    PubMed

    Wang, Jingyang; Guo, Xiangrui; Cao, Junxia; Zhang, Xueying; Zhang, Jiyan; Sun, Dejun; Wang, Qingyang

    2014-11-01

    Isoproterenol, a synthetic non-selective β-adrenergic agonist, is often used during the immediate postoperative period after open heart surgery for its chronotropic and vasodilatory effects. It has been demonstrated that isoproterenol pretreatment followed by immediate LPS administration leads to reduced tumor necrosis factor-α (TNF-α) response in vivo. However, sepsis never happens immediately after the surgery, but rather severe immune dysfunction occurs at least 24h later. It remains elusive what effects isoproterenol might exert to innate immunity during the period. In this scenario, we investigated the effects of 24-h isoproterenol pretreatment on septic shock induced by experimental endotoxemia and bacterial peritonitis, with cholera toxin as another cAMP elevator. Unexpectedly, we found that isoproterenol and cholera toxin exhibited distinct effects in acute lethal systemic inflammatory response. Isoproterenol worsened liver injury without enhancing NK/NKT activity. Meanwhile, cholera toxin but not isoproterenol showed dramatically reduced TNF-α response in LPS induced septic shock. Our data provide a caution for the clinical use of isoproterenol and suggest that isoproterenol has cAMP-independent functions.

  16. 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.

  17. Tests for induction of presumed dominant-lethal effects in female mice

    SciTech Connect

    Generoso, W.M.; Cain, K.T.; Hughes, L.A.; Braden, P.W.

    1985-01-01

    The two carcinogens, benzo(a)pyrene (BP), and 2-acetylaminofluorene (2AAF), and their respective noncarcinogenic analogs, pyrene (PYR) and 4-acetylaminofluorene (4AAF), were tested for induction of presumed dominant-lethal effects in female mice. Each chemical was administered as a single intraperitoneal injection using the maximum dose that could be given as limited either by toxicity or solubility. The study was conducted in at least two stocks of females and the induction of presumed dominant-lethal response was determined in oocytes in maturing follicles. Among the four compounds studied, only BP induced clear-cut presumed dominant-lethal effects. In addition, it had cytotoxic effects on the oocytes resulting in marked reduction in the reproductive performance of treated females. 11 refs., 1 fig., 4 tabs.

  18. A novel acute lethal liver injury mouse model with visualization of NF-κB activity for treatment of severe acute liver injury

    PubMed Central

    Liao, Huanjin; Cai, Jun; Zhang, Lifang; Peng, Yanxia; Wu, Ping; Xie, Tong; Pan, Qingjun

    2017-01-01

    Acute lethal inflammation, especially that related to liver injury, is an important clinical issue. To date, however, there is no model that can be used to assess this serious condition. This study was designed to establish a novel lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute lethal liver injury model in nuclear factor-κB (NF-κB) transgenic mice. The results show that a high dose of LPS (500 μg/kg) plus D-GalN (800 mg/kg) successfully established a novel mouse model of acute lethal liver injury with a lifespan of 8-10 h. Significantly increased NF-κB activity, detected with an in vivo imaging system (IVIS), peaked at approximately 4 h post-LPS/D-GalN challenge in NF-κB transgenic mice. Moreover, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 were significantly increased and peaked at approximately 4 h post-i.p. injection of LPS/D-GalN. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) also sharply increased. Correlation analyses showed that NF-κB activity was significantly correlated with serum levels of ALT and AST. The mouse model livers showed marked congestion and hemorrhage, and hematoxylin and eosin (H&E) staining confirmed the destruction of the lobular structure and severe hepatocyte necrosis and hemorrhage. None of these changes were observed in the control mice. In summary, a novel LPS/D-GalN-induced acute lethal liver injury model with visualization of NF-κB activity was established in NF-κB transgenic mice. This model will provide the technology for developing new therapeutic strategies for treatment of severe acute liver injury complicated by endotoxemia or septicemia. PMID:28386325

  19. 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.

  20. Beneficial Effect of Dexamethasone in Decreasing the Lethality of Acute T-2 Toxicosis,

    DTIC Science & Technology

    1986-11-07

    lethality of T-2 toxin. Steroidal agents, assessed at equivalent doses for ant i-inf lammatory activity, were all effective, with dexamethasone being more...effective than either mthylprednisolone or hydrocor- tisone. The doses of dexamethasone producing the highest efficacy were 1.0 mg/kg and 12.5 mg/kg for...Bdte-4 2 The mean time to 4eath, mean survival time, and percent lethality were deter- (A amined for untreated and dexamethasone -treated mice injected

  1. Natural sunlight and residual fuel oils are an acutely lethal combination for fish embryos.

    PubMed

    Hatlen, Kristin; Sloan, Catherine A; Burrows, Douglas G; Collier, Tracy K; Scholz, Nathaniel L; Incardona, John P

    2010-08-01

    The majority of studies characterizing the mechanisms of oil toxicity in fish embryos and larvae have focused largely on unrefined crude oil. Few studies have addressed the toxicity of modern bunker fuels, which contain residual oils that are the highly processed and chemically distinct remains of the crude oil refinement process. Here we use zebrafish embryos to investigate potential toxicological differences between unrefined crude and residual fuel oils, and test the effects of sunlight as an additional stressor. Using mechanically dispersed oil preparations, the embryotoxicity of two bunker oils was compared to a standard crude oil from the Alaska North Slope. In the absence of sunlight, all three oils produced the stereotypical cardiac toxicity that has been linked to the fraction of tricyclic aromatic compounds in an oil mixture. However, the cardiotoxicity of bunker oils did not correlate strictly with the concentrations of tricyclic compounds. Moreover, when embryos were sequentially exposed to oil and natural sunlight, the bunker oils produced a rapid onset cell-lethal toxicity not observed with crude oil. To investigate the chemical basis of this differential toxicity, a GC/MS full scan analysis was used to identify a range of compounds that were enriched in the bunker oils. The much higher phototoxic potential of chemically distinct bunker oils observed here suggests that this mode of action should be considered in the assessment of bunker oil spill impacts, and indicates the need for a broader approach to understanding the aquatic toxicity of different oils.

  2. Qsars for photoinduced toxicity: 1. acute lethality of polycyclic aromatic hydrocarbons to daphnia magna'

    SciTech Connect

    Mekenyan, O.G.; Ankley, G.T.; Veith, G.D.; Call, D.J.

    1994-01-01

    Research with a variety of aquatic species has shown that while polycyclic aromatic hydrocarbons (PAHs) are generally not acutely toxic in conventional laboratory tests, many are extremely toxic in the presence of sunlight. In an effort to develop a model for predicting which PAHs may exhibit photo-induced toxicity, Newsted and Giesy (1987) reported a parabolic relationship between the toxicity and the energy of the triplet state of a variety of PAHs. The authors have reexamined these data and propose a more mechanistic explanation for the prediction of photo-induced PAH toxicity. They sought a molecular descriptor which could be computed from structure rather than measured empirically.

  3. Phenotypic analysis of pulmonary perivascular mononuclear infiltrates that occur as a direct result of acute lethal graft-versus-host disease describes the onset of interstitial pneumonitis.

    PubMed Central

    Workman, D. L.; Clancy, J.

    1995-01-01

    We recently determined that the sequential development of interstitial pneumonitis and lymphocytic bronchiolitis/bronchitis occurs as a direct result of acute lethal graft-versus-host disease. Interstitial pneumonitis develops before lymphocytic bronchiolitis/bronchitis primarily from the dissemination of perivascular mononuclear infiltrates. We have used the adult, nonirradiated (DA x LEW) F1 hybrid rat in the absence of chemotherapy, immunosuppression, or overt infection to determine the phenotype of infiltrating perivascular mononuclear cells throughout acute lethal graft-versus-host disease. F1 animals were intravenously injected with 1 x 10(6) DA parental lymphoid cells/g body weight, which produced 100% morbidity and mortality by day 21. Graft-versus-host disease animals were killed on days 3, 7, 10, 14, and 15 to 21 after injection. Whole left lung lobes were frozen, serially sectioned (4 microns), and incubated with a panel of mouse anti-rat monoclonal antibodies. Labeled antibody density was determined by computerized image analysis. Perivascular infiltration was observed first for ED1+, OX8+, and W3/25+ cells, and then OX41+, W3/13+ and OX19/25+ populations. OX6 was expressed in control tissues and at all time points tested. OX12+, OX39+ and MOM/3F12/F2+ cells were not quantifiable. The present study has determined that the process of perivascular infiltration was produced through a biphasic influx of OX6+, T-cell, and macrophage populations. Images Figure 1 Figure 4 PMID:7485398

  4. CD4+ T cells provide protection against acute lethal encephalitis caused by Venezuelan equine encephalitis virus.

    PubMed

    Yun, Nadezhda E; Peng, Bi-Hung; Bertke, Andrea S; Borisevich, Viktoriya; Smith, Jennifer K; Smith, Jeanon N; Poussard, Allison L; Salazar, Milagros; Judy, Barbara M; Zacks, Michele A; Estes, D Mark; Paessler, Slobodan

    2009-06-19

    Studying the mechanisms of host survival resulting from viral encephalitis is critical to the development of vaccines. Here we have shown in several independent studies that high dose treatment with neutralizing antibody prior to intranasal infection with Venezuelan equine encephalitis virus had an antiviral effect in the visceral organs and prolonged survival time of infected mice, even in the absence of alphabeta T cells. Nevertheless, antibody treatment did not prevent the development of lethal encephalitis. On the contrary, the adoptive transfer of primed CD4(+) T cells was necessary to prevent lethal encephalitis in mice lacking alphabeta T cell receptor.

  5. 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.

  6. Blood tests for acute pancreatitis

    PubMed Central

    Basnayake, Chamara; Ratnam, Dilip

    2015-01-01

    Summary The diagnosis of acute pancreatitis requires the presence of at least two of the three diagnostic criteria – characteristic abdominal pain, elevated serum amylase or lipase, and radiological evidence of pancreatitis. Serum concentrations of amylase and lipase rise within hours of the pancreatic injury. A threshold concentration 2–4 times the upper limit of normal is recommended for diagnosis. Serum lipase is now the preferred test due to its improved sensitivity, particularly in alcohol-induced pancreatitis. Its prolonged elevation creates a wider diagnostic window than amylase. Neither enzyme is useful in monitoring or predicting the severity of an episode of pancreatitis in adults. New biomarkers including trypsinogen and elastase have no significant advantage over amylase or lipase. PMID:26648641

  7. The mechanism of development of acute lung injury in lethal endotoxic shock using α-galactosylceramide sensitization

    PubMed Central

    Tumurkhuu, G; Koide, N; Dagvadorj, J; Morikawa, A; Hassan, F; Islam, S; Naiki, Y; Mori, I; Yoshida, T; Yokochi, T

    2008-01-01

    The mechanism underlying acute lung injury in lethal endotoxic shock induced by administration of lipopolysaccharide (LPS) into α-galactosylceramide (α-GalCer)-sensitized mice was studied. Sensitization with α-GalCer resulted in the increase of natural killer T (NK T) cells and the production of interferon (IFN)-γ in the lung. The IFN-γ that was produced induced expression of adhesion molecules, especially vascular cell adhesion molecule-1 (VCAM-1), on vascular endothelial cells in the lung. Anti-IFN-γ antibody inhibited significantly the VCAM-1 expression in α-GalCer-sensitized mice. Very late activating antigen-4-positive cells, as the counterpart of VCAM-1, accumulated in the lung. Anti-VCAM-1 antibody prevented LPS-mediated lethal shock in α-GalCer-sensitized mice. The administration of LPS into α-GalCer-sensitized mice caused local production of excessive proinflammatory mediators, such as tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and nitric oxide. LPS caused microvascular leakage of proteins and cells into bronchoalveolar lavage fluid. Taken together, sensitization with α-GalCer was suggested to induce the expression of VCAM-1 via IFN-γ produced by NK T cells and recruit a number of inflammatory cells into the lung. Further, LPS was suggested to lead to the production of excessive proinflammatory mediators, the elevation of pulmonary permeability and cell death. The putative mechanism of acute lung injury in LPS-mediated lethal shock using α-GalCer sensitization is discussed. PMID:18307519

  8. Blood soluble drag-reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments.

    PubMed

    Kameneva, Marina V; Wu, Zhongjun J; Uraysh, Arkady; Repko, Brandon; Litwak, Kenneth N; Billiar, Timothy R; Fink, Mitchell P; Simmons, Richard L; Griffith, Bartley P; Borovetz, Harvey S

    2004-01-01

    Over the past several decades, blood-soluble drag reducing polymers (DRPs) have been shown to significantly enhance hemodynamics in various animal models when added to blood at nanomolar concentrations. In the present study, the effects of the DRPs on blood circulation were tested in anesthetized rats exposed to acute hemorrhagic shock. The animals were acutely resuscitated either with a 2.5% dextran solution (Control) or using the same solution containing 0.0005% or 5 parts per million (ppm) concentration of one of two blood soluble DRPs: high molecular weight (MW=3500 kDa) polyethylene glycol (PEG-3500) or a DRP extracted from Aloe vera (AVP). An additional group of animals was resuscitated with 0.0075% (75 ppm) polyethylene glycol of molecular weight of 200 kDa (PEG-200), which possesses no drag-reducing ability. All of the animals were observed for two hours following the initiation of fluid resuscitation or until they expired. We found that infusion of the DRP solutions significantly improved tissue perfusion, tissue oxygenation, and two-hour survival rate, the latter from 19% (Control) and 14% (PEG-200) to 100% (AVP) and 100% (PEG-3500). Furthermore, the Control and PEG-200 animals that survived required three times more fluid to maintain their blood pressure than the AVP and PEG-3500 animals. Several hypotheses regarding the mechanisms underlying these observed beneficial hemodynamic effects of DRPs are discussed. Our findings suggest that the drag-reducing polymers warrant further investigation as a potential clinical treatment for hemorrhagic shock and possibly other microcirculatory disorders.

  9. Acute lethal toxicity of some reference chemicals to freshwater fishes of Scandinavia

    SciTech Connect

    Oikari, A.O.J.

    1987-07-01

    Relevance of the choice of a test organism intended to be representative for a given environment seems to be under continual debate in aquatic ecotoxicology. For instance, it is commonly argue that acute toxicity tests with rainbow trout, the species most often recommended as a standard cold water teleost, were not representative for Nordic countries because the species is an alien in local faunas. A comparative study with several freshwater species was therefore initiated to clarify the validity of this assumption. As a first approximation, standard LC 50 assays were conducted. The species used were chosen only on the basis of their local availability, i.e, they randomly represented the fish fauna of Nordic inland waters. Furthermore, inter-species variation of toxicity response was compared with certain other, quantitatively more important, intra-species sources of variability affecting the toxicity of chemicals. Use of reference toxicants has been recommended as a means of standardizing bioassays. Compounds, characteristic of effluents from the pulp and paper industry, were selected for the present study. The toxicity of organic acids such a phenols and resin acids, as well as that of pupmill effluents, strongly depends on water pH. Because of the possibility that species differences could exist in this respect, effects of water acidity on toxicity of these types of substances to a randomly selected local species was investigated. Finally, as an example of the biological source of assay variability, the effect of yolk absorption was studied with a subsequent crisis period due to moderate starvation under laboratory conditions.

  10. Testing of candidate non-lethal sampling methods for detection of Renibacterium salmoninarum in juvenile Chinook salmon Oncorhynchus tshawytscha

    USGS Publications Warehouse

    Elliott, Diane G.; McKibben, Constance L.; Conway, Carla M.; Purcell, Maureen K.; Chase, Dorothy M.; Applegate, Lynn M.

    2015-01-01

    Non-lethal pathogen testing can be a useful tool for fish disease research and management. Our research objectives were to determine if (1) fin clips, gill snips, surface mucus scrapings, blood draws, or kidney biopsies could be obtained non-lethally from 3 to 15 g Chinook salmon Oncorhynchus tshawytscha, (2) non-lethal samples could accurately discriminate between fish exposed to the bacterial kidney disease agent Renibacterium salmoninarum and non-exposed fish, and (3) non-lethal samples could serve as proxies for lethal kidney samples to assess infection intensity. Blood draws and kidney biopsies caused ≥5% post-sampling mortality (Objective 1) and may be appropriate only for larger fish, but the other sample types were non-lethal. Sampling was performed over 21 wk following R. salmoninarum immersion challenge of fish from 2 stocks (Objectives 2 and 3), and nested PCR (nPCR) and real-time quantitative PCR (qPCR) results from candidate non-lethal samples were compared with kidney tissue analysis by nPCR, qPCR, bacteriological culture, enzyme-linked immunosorbent assay (ELISA), fluorescent antibody test (FAT) and histopathology/immunohistochemistry. R. salmoninarum was detected by PCR in >50% of fin, gill, and mucus samples from challenged fish. Mucus qPCR was the only non-lethal assay exhibiting both diagnostic sensitivity and specificity estimates >90% for distinguishing between R. salmoninarum-exposed and non-exposed fish and was the best candidate for use as an alternative to lethal kidney sample testing. Mucus qPCR R. salmoninarum quantity estimates reflected changes in kidney bacterial load estimates, as evidenced by significant positive correlations with kidney R. salmoninaruminfection intensity scores at all sample times and in both fish stocks, and were not significantly impacted by environmentalR. salmoninarum concentrations.

  11. Acute inhalation toxicity of carbon monoxide and hydrogen cyanide revisited: Comparison of models to disentangle the concentration × time conundrum of lethality and incapacitation.

    PubMed

    Pauluhn, Juergen

    2016-10-01

    Contemporary emergency response planning guidelines are stratified to consider the threshold for serious toxicity and/or impairment of escape, relative to the potentially lethal level above this threshold and the lower level at which individuals should not experience or develop effects more serious than mild irritation. While harmonized testing guidelines and risk assessment paradigms are available for the quantification of thresholds for lethality or establishing no adverse effect levels, the quantification of 'impairment of escape' appears to be a more elusive goal. Approaches were explored in context with CO and HCN in past experimental combustion toxicology studies to estimate the time available for escape. This point of departure (POD) was compared with the non-lethal threshold (LC01) and one third thereof from published recent acute inhalation studies in rats examining the Cxt-matrix of both CO and HCN. The findings from this analysis suggest that the rat delivers the most consistent data. However, it remains challenging yet to bridge the behavioral variables of human behavior typical of escape to any surrogate animal model. For the asphyxiant gases examined, the PODs characterizing 'impairment of escape' were difficult to distinguish from those indicative of impending death. No specific modeled carboxyhemoglobin (COHb) level could be linked to onset of incapacitation. In summary, the higher ventilation of rats (kg body weight adjusted) renders this species even more susceptible than heavy breathing humans. LCt01 × 1/3 values derived from the comprehensive Cxt matrix of rat inhalation studies are considered to be most suitable and robust to estimate the human equivalent threshold (POD) of 'impairment of escape'.

  12. Comparing median lethal concentration values using confidence interval overlap or ratio tests.

    PubMed

    Wheeler, Matthew W; Park, Robert M; Bailer, A John

    2006-05-01

    Experimenters in toxicology often compare the concentration-response relationship between two distinct populations using the median lethal concentration (LC50). This comparison is sometimes done by calculating the 95% confidence interval for the LC50 for each population, concluding that no significant difference exists if the two confidence intervals overlap. A more appropriate test compares the ratio of the LC50s to 1 or the log(LC50 ratio) to 0. In this ratio test, we conclude that no difference exists in LC50s if the confidence interval for the ratio of the LC50s contains 1 or the confidence interval for the log(LC50 ratio) contains 0. A Monte Carlo simulation study was conducted to compare the confidence interval overlap test to the ratio test. The confidence interval overlap test performs substantially below the nominal alpha = 0.05 level, closer to p = 0.005; therefore, it has considerably less power for detecting true differences compared to the ratio test. The ratio-based method exhibited better type I error rates and superior power properties in comparison to the confidence interval overlap test. Thus, a ratio-based statistical procedure is preferred to using simple overlap of two independently derived confidence intervals.

  13. 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

  14. High-resolution identification of mercury in particles in mouse kidney after acute lethal exposure.

    PubMed

    Cunha, Elisabete M; Silva, Daniela P; Aguas, Artur P

    2003-12-01

    Contamination of the food chain by mercury is a major concern of Public Health of our day. Kidney and nervous system are the major targets of mercury toxicity in mammals. We show here that the detailed subcellular in vivo topography of microparticles of mercury in tissues can be achieved by scanning electron microscopy (SEM) coupled with X-ray elemental microanalysis (XRM). SEM-XRM offered the fine topography of mercury in the kidney of BALB/c mice that were submitted to an intraperitoneal lethal injection of mercuric chloride (HgCl2). All of the renal mercury was seen inside blood vessels located in both cortex and medulla of the mouse kidney. This blood-born mercury was organised in spheroid particles of less than 50 nm in diameter (31.4 +/- 14.1 nm). They were seen attached either to aggregates of plasma proteins or to the surface of blood cells. No evidence of internalisation of mercury by blood, endothelial or kidney cells was found. The average kidney density of mercury microspheres was 1920 +/- 1320 particles per mm2. We propose SEM-XRM as an elective approach to further investigations, at the subcellular level, on the quantitative dynamics of mercury particles in the tissues.

  15. Draft Test Guideline: Gammarid Acute Toxicity Test

    EPA Pesticide Factsheets

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  16. Draft Test Guideline: Penaeid Acute Toxicity Test

    EPA Pesticide Factsheets

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  17. Draft Test Guideline: Mysid Acute Toxicity Test

    EPA Pesticide Factsheets

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  18. 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.

  19. Acute Human Lethal Toxicity of Agricultural Pesticides: A Prospective Cohort Study

    PubMed Central

    Senarathna, Lalith; Mohamed, Fahim; Gawarammana, Indika; Bowe, Steven J.; Manuweera, Gamini; Buckley, Nicholas A.

    2010-01-01

    Background Agricultural pesticide poisoning is a major public health problem in the developing world, killing at least 250,000–370,000 people each year. Targeted pesticide restrictions in Sri Lanka over the last 20 years have reduced pesticide deaths by 50% without decreasing agricultural output. However, regulatory decisions have thus far not been based on the human toxicity of formulated agricultural pesticides but on the surrogate of rat toxicity using pure unformulated pesticides. We aimed to determine the relative human toxicity of formulated agricultural pesticides to improve the effectiveness of regulatory policy. Methods and Findings We examined the case fatality of different agricultural pesticides in a prospective cohort of patients presenting with pesticide self-poisoning to two clinical trial centers from April 2002 to November 2008. Identification of the pesticide ingested was based on history or positive identification of the container. A single pesticide was ingested by 9,302 patients. A specific pesticide was identified in 7,461 patients; 1,841 ingested an unknown pesticide. In a subset of 808 patients, the history of ingestion was confirmed by laboratory analysis in 95% of patients. There was a large variation in case fatality between pesticides—from 0% to 42%. This marked variation in lethality was observed for compounds within the same chemical and/or WHO toxicity classification of pesticides and for those used for similar agricultural indications. Conclusion The human data provided toxicity rankings for some pesticides that contrasted strongly with the WHO toxicity classification based on rat toxicity. Basing regulation on human toxicity will make pesticide poisoning less hazardous, preventing hundreds of thousands of deaths globally without compromising agricultural needs. Ongoing monitoring of patterns of use and clinical toxicity for new pesticides is needed to identify highly toxic pesticides in a timely manner. Please see later in the

  20. The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

    PubMed

    MacVittie, Thomas J; Farese, Ann M; Jackson, William

    2015-11-01

    Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total

  1. Dominant lethal and heritable translocation tests with chlorambucil and melphalan in male mice.

    PubMed

    Generoso, W M; Witt, K L; Cain, K T; Hughes, L; Cacheiro, N L; Lockhart, A M; Shelby, M D

    1995-12-01

    Chemicals used in the treatment of cancer include several that are potent mutagens in a range of in vitro and in vivo assays. For some, genetic effects have also been demonstrated in humans, detected as chromosomal aberrations in peripheral lymphocytes. Because (1) many of these agents are confirmed mutagens, (2) humans are exposed to them in relatively high doses, and (3) an increasing number of early cancer victims are surviving to reproductive age, it is important that information be available on the genetic and reproductive hazards associated with exposure to these agents. Chlorambucil and melphalan are structurally related chemicals that are included in our efforts to identify and assess such hazards among cancer chemotherapy agents. To date, both have been reported to induce specific locus mutations in germ cells of male mice (Russell et al., 1989; Russel et al., 1992b) and melphalan is one of very few chemicals shown to induce such mutations in spermatogonial stem cells. More recently, both chemicals were found to have strong reproductive effects in female mice (Bishop and Generoso, 1995, in preparation). In the present studies, these chemicals were tested for the induction of dominant lethal mutations and heritable translocations in male mice. Both chemicals were found to have reproductive effects attributable to cytotoxicity in specific male germ cell stages and to induce dominant lethal mutations and heritable translocations in postmeiotic germ cells, particularly in mid to early stage spermatids. Thus, relatively extensive data are now available for assessing the genetic and reproductive hazards that may result from therapeutic exposures to these chemicals.

  2. Non-lethal, repeated testing, anesthetized canine model for the evaluation of effectiveness of new forms of prophylaxis and therapy for cyanide intoxication

    SciTech Connect

    Von Bredow, J.; Vick, J.; Kaminskis, A.; Brewer, T.

    1993-05-13

    Acute cyanide intoxication has most often been modeled through the bolos intravenous administration of a lethal amount of sodium or potassium cyanide which provides reproducible effects and represents the most severe challenge to any new form of prophylaxis and therapy. Inhalation of cyanide leads to a similar acute onset of toxic signs which is controlled by the rate and depth of respiration. The cyanide induced halt in respiration also halts the continued absorption of cyanide leading to a well defined, consistent end point of the amount of cyanide absorbed. Regardless of the abundance of cyanide in the ambient air, the casualty can only absorb cyanide during respiration. A slow intravenous infusion of cyanide which is continued only until respiratory arrest is achieved should define the same limit of cyanide intoxication. Cyanide intoxication defined by the amount of sodium cyanide infused to induce respiratory arrest (RA) in pentobarbital anesthetized dogs provides the basis for the development of a useful repeated testing animal model. Utilization of the RA yields a surrogate endpoint in the anesthetized dog model and provides a non-traumatic, reproducible procedure to estimate the lethal level of CN in each dog as well defining the protective effect of pretreatments and antidotes.

  3. 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.

  4. 40 CFR 798.5275 - Sex-linked recessive lethal test in drosophila melanogaster.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... phenotypically expressed in males carrying the mutant gene. When the mutation is lethal in the hemizygous... in each group should reflect these defined parameters. The spontaneous mutant frequency observed...

  5. 40 CFR 798.5275 - Sex-linked recessive lethal test in drosophila melanogaster.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... phenotypically expressed in males carrying the mutant gene. When the mutation is lethal in the hemizygous... in each group should reflect these defined parameters. The spontaneous mutant frequency observed...

  6. 40 CFR 798.5275 - Sex-linked recessive lethal test in drosophila melanogaster.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... phenotypically expressed in males carrying the mutant gene. When the mutation is lethal in the hemizygous... in each group should reflect these defined parameters. The spontaneous mutant frequency observed...

  7. 40 CFR 798.5275 - Sex-linked recessive lethal test in drosophila melanogaster.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... phenotypically expressed in males carrying the mutant gene. When the mutation is lethal in the hemizygous... in each group should reflect these defined parameters. The spontaneous mutant frequency observed...

  8. Temporal changes in tissue repair permit survival of diet-restricted rats from an acute lethal dose of thioacetamide.

    PubMed

    Ramaiah, S K; Bucci, T J; Warbritton, A; Soni, M G; Mehendale, H M

    1998-10-01

    Although, diet restriction (DR) has been shown to substantially increase longevity while reducing or delaying the onset of age-related diseases, little is known about the mechanisms underlying the beneficial effects of DR on acute toxic outcomes. An earlier study (S. K. Ramaiah et al., 1998, Toxicol. Appl. Pharmacol. 150, 12-21) revealed that a 35% DR compared to ad libitum (AL) feeding leads to a substantial increase in liver injury of thioacetamide (TA) at a low dose (50 mg/kg, i.p.). Higher liver injury was accompanied by enhanced survival. A prompt and enhanced tissue repair response in DR rats at the low dose (sixfold higher liver injury) occurred, whereas at equitoxic doses (50 mg/kg in DR and 600 mg/kg in AL rats) tissue repair in AL rats was substantially diminished and delayed. The extent of liver injury did not appear to be closely related to the extent of stimulated tissue repair response. The purpose of the present study was to investigate the time course (0-120 h) of liver injury and liver tissue repair at the high dose (600 mg TA/kg, i.p., lethal in AL rats) in AL and DR rats. Male Sprague-Dawley rats (225-275 g) were 35% diet restricted compared to their AL cohorts for 21 days and on day 22 they received a single dose of TA (600 mg/kg, i.p.). Liver injury was assessed by plasma ALT and by histopathological examination of liver sections. Tissue repair was assessed by [3H]thymidine incorporation into hepatonuclear DNA and proliferating cell nuclear antigen (PCNA) immunohistochemistry during 0-120 h after TA injection. In AL-fed rats hepatic necrosis was evident at 12 h, peaked at 60 h, and persisted thereafter until mortality (3 to 6 days). Peak liver injury was approximately twofold higher in DR rats compared to that seen in AL rats. Hepatic necrosis was evident at 36 h, peaked at 48 h, persisted until 96 h, and returned to normal by 120 h. Light microscopy of liver sections revealed progression of hepatic injury in AL rats whereas injury regressed

  9. A new test for evaluating Eighth Amendment challenges to lethal injections.

    PubMed

    2007-03-01

    An explosion of Eighth Amendment challenges to lethal injection protocols has struck the federal courts. The Supreme Court's recent decision in Hill v. McDonough,1 which empowered prisoners to bring challenges to lethal injection procedures under 42 U.S.C. para. 1983, has facilitated a flood of new lethal injection cases. In response, several courts have ordered states to alter their protocols, spurring other capital inmates to litigate such challenges. Distressingly, the courts evaluating these claims have almost no law to guide them. The last Supreme Court decision applying the Eighth Amendment to a method of execution was written in 1947; that case, Louisiana ex rel. Francis v. Resweber,2 occurred before the Eighth Amendment was applied to the states and resulted in a 4-1-4 split. Although lower courts have heard numerous challenges to execution methods, few have analyzed the constitutional validity of a method of execution in detail. Making matters worse, courts that find Eighth Amendment violations must craft equitable remedies that often amount to entirely new execution protocols. No clear precedent exists to guide courts in formulating such remedies. This Note proposes a legal standard for the administration of Eighth Amendment method-of-execution claims, focusing on lethal injection cases. Part I describes lethal injection procedures and summarizes recent litigation. Part II discusses the difficulty of evaluating lethal injection claims, analyzing both general difficulties in interpreting the Eighth Amendment and specific difficulties associated with lethal injection cases. Part III proposes a standard for addressing method-of-execution claims that attempts to balance a prisoner's interest in a painless execution with a state's interest in conducting executions efficiently. Part IV discusses remedies for unconstitutional procedures. Part V concludes.

  10. Sediment acute toxicity testing utilizing short-term bioassays

    SciTech Connect

    Campbell, M.G.

    1991-01-01

    The purpose of this study was to investigate the usefulness of two new bioassays for acute toxicity assessments of sediments. A bacterial bioassay based on inhibition of alpha-glucosidase biosynthesis in Bacillus licheniformis and a 48-hour lethality bioassay employing the benthic cladoceran, Chydorus sphaericus. were evaluated by direct comparisons with standard bioassays, using sediment samples collected from various sites in Florida. This study showed that the bioassay based on inhibition of alpha-glucosidase biosynthesis in Bacillus licheniformis was useful in the acute toxicity screening of sediment elutriates. In regards to Escambia County, Florida samples, the assay was comparable with the Microtox assay and was especially sensitive for samples containing metals. To determine an appropriate procedure for assessing hydrophobic contaminants of sediments in the B. licheniformis bioassay, two extracting procedures were compared. Based on the responses in the Microtox bioassay, shaking sediment samples in methylene chloride produced extracts that were significantly higher in toxicity than extracts obtained by sonication for eight of the ten sediment samples tested. Comparisons of methanol and dimethyl sulfoxide (DMSO) as exchange solvents revealed that there was generally no significant difference between these solvents in terms of toxicity in the Microtox assay. Solvent extracts prepared by shaking and exchanged into methanol showed lower toxicity in the B. licheniformis bioassay than in the Microtox assay. Observed sediment toxicity in both bioassays was expressed in terms of the equivalent dry weight concentration of sediment causing 50% inhibition of the assay organism.

  11. Reassessment of the lethal London fog of 1952: novel indicators of acute and chronic consequences of acute exposure to air pollution.

    PubMed

    Bell, M L; Davis, D L

    2001-06-01

    This article develops and assesses novel indicators of respiratory and other morbidity and mortality following London's lethal smog in the winter of 1952. Public health insurance claims, hospital admission rates for cardiac and respiratory disease, pneumonia cases, mortality records, influenza reports, temperature, and air pollutant concentrations are analyzed for December-February 1952-1953 and compared with those for the previous year or years. Mortality rates for the smog episode from December 1952 to February 1953 were 50-300% higher than the previous year. Claims that the smog only elevated health risks during and immediately following the peak fog 5-9 December 1952 and that an influenza epidemic accounted fully for persisting mortality increases in the first 2 months of 1953 are rejected. We estimate about 12,000 excess deaths occurred from December 1952 through February 1953 because of acute and persisting effects of the 1952 London smog. Pollution levels during the London smog were 5-19 times above current regulatory standards and guidelines and approximate current levels in some rapidly developing regions. Ambient pollution in many regions poses serious risks to public health.

  12. Relative toxicity testing of spacecraft materials. 1: Spacecraft materials. [lethality of pyrolysates

    NASA Technical Reports Server (NTRS)

    Lawrence, W. H.

    1980-01-01

    In chamber thermodegradation procedures were used to access the lethality to rats of the pyrolysis/combustion products of three foams, an adhesive backed metallic tape and RTV silicone rubber adhesive sealant used in spacecraft construction. The role of carbon monoxide in the overall pyrolysate toxicity was also investigated. Post exposure observation of the rats, histological evaluation of selected organs, carbon monoxide concentration in the chamber atmosphere during exposure and the percent carboxyhemoglobin in the animals expiring in the chamber are discussed. Thermogravimetric analysis and dosage response results are given. The lethal effect of the RTV silicon appears to be due to physical obstruction of the respiratory system by particulate matter from pyrolysis.

  13. Ethylene oxide dose and dose-rate effects in the mouse dominant-lethal test

    SciTech Connect

    Generoso, W.M.; Cain, K.T.; Hughes, L.A.; Sega, G.A.; Braden, P.W.; Gosslee, D.G.; Shelby, M.D.

    1986-01-01

    In the dose-response study, male mice were exposed by inhalation to ethylene oxide (EtO) for 4 consecutive days. Mice were exposed for 6 hr per day to 300 ppm, 400 ppm, or 500 ppm EtO for a daily total of 1800, 2400, or 3000 ppm X hr (total exposures of 7200, 9600 and 12,000 ppm X hr), respectively. In the dose-rate study, mice were given a total exposure of 1800 ppm X hr per day, also for 4 consecutive days, delivered either at 300 ppm in 6 hr, 600 ppm in 3 hr, or 1200 ppm in 1.5 hr. Quantitation of dominant-lethal responses was made on matings involving sperm exposed as late spermatids and early spermatozoa, the most sensitive stages to EtO. In the dose-response study, a dose-related increase in dominant-lethal mutations was observed, the dose-response curve proved to be nonlinear. In the dose-rate study, increasing the exposure concentrations resulted in increased dominant-lethal responses.

  14. Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

    USGS Publications Warehouse

    Vyas, Nimish B.; Rattner, Barnett A.

    2012-01-01

    Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

  15. Chemical mutagenesis testing in Drosophila. I. Comparison of positive and negative control data for sex-linked recessive lethal mutations and reciprocal translocations in three laboratories

    SciTech Connect

    Woodruff, R.C.; Mason, J.M.; Valencia, R.; Zimmering, S.

    1984-01-01

    As part of the validation phase of the Drosophila melanogaster segment of the National Toxicology Program, a comparison has been made of positive and negative controls for sex-linked recessive lethal mutations and reciprocal translocations from three laboratories. This comparison involves approximately 700,000 spontaneous recessive lethal mutation tests, 70,000 spontaneous translocation tests, and screens for genetic damage induced by N-nitrosodimethylamine and ..beta..-propiolactone. Spontaneous frequencies for lethal mutations and translocations were homogeneous in the laboratories regardless of solvent or broods sampled. Inhomogeneity was observed in induced frequencies among laboratories, but the variation was no greater than that found within a laboratory.

  16. Genetic studies: dominant lethal study, sex linked recessive lethal, ames mutagenicity, and heritable translocation test of thermal processed, frozen, electron irradiated, and gamma irradiated chicken. Final report Jun 76-Aug 83

    SciTech Connect

    Sullivan, D.; Lusskin, R.M.; Thomson, G.M.; Kuzdas, C.D.; Ronning, D.C.

    1983-01-01

    Four samples of chicken meat identified as the frozen control, thermally processed, gamma sterilized (5.9 Mrad), and electron sterilized (5.9 MeV), along with negative and positive controls, were evaluated for genetic activity. The samples were evaluated for ability to induce dominant lethal mutations in spermatid and spermatozoan stages of spermatogenesis in mice fed 35 percent chicken meat. The test meat samples were not observed to have an effect on the incidence of the dominant lethal mutations. However, the positive control failed to give a positive response. The meat samples were investigated for mutagenic activity employing Drosophila melanogaster in the sex linked recessive lethal test. The samples were determined to be nonmutagenic in this test and the positive control gave a significant response. Reduced production of offspring in cultures of Drosophila reared on gamma irradiated chicken which could not be overcome by the addition of vitamins was observed. Pre-incubation tests with and without added mutagens revealed that in no case was a positive result observed in the Ames test from chicken meat without an added mutagen. The manner in which chicken meat was processed had no effect upon the response to the Ames test. A heritable translocation test in mice failed to reveal any cytological evidence of translocation heterozygosity in any of the chicken-containing diets.

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

    PubMed Central

    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. PMID:26367124

  18. 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.

  19. Use of OpdA, an Organophosphorus (OP) Hydrolase, Prevents Lethality in an African Green Monkey Model of Acute OP Poisoning

    PubMed Central

    Jackson, Colin J; Carville, Angela; Ward, Jeanine; Mansfield, Keith; Ollis, David L.; Khurana, Tejvir; Bird, Steven B.

    2014-01-01

    Organophosphorus (OP) pesticides are a diverse class of acetylcholinesterase (AChE) inhibitors that are responsible for tremendous morbidity and mortality worldwide, killing approximately 300,000 people annually. Enzymatic hydrolysis of OPs is a potential therapy for acute poisoning. OpdA, an OP hydrolase isolated from Agrobacterium radiobacter, has been shown to decrease lethality in rodent models of OP poisoning. This study investigated the effects of OpdA on AChE activity, plasma concentrations of OP, and signs of toxicity after administration of dichlorvos to nonhuman primates. A dose of 75 mg/kg dichlorvos given orally caused apnea within 10 minutes with a progressive decrease in heart rate. Blood AChE activity decreased to zero within ten minutes. Respirations and AChE activity did not recover. The mean dichlorvos concentration rose to a peak of 0.66 μg/ml. Treated monkeys received 1.2 mg/kg OpdA iv immediately after poisoning with dichlorvos. In Opda-treated animals, heart and respiratory rates were unchanged from baseline over a 240-minute observation period. AChE activity slowly declined, but remained above 25% of baseline for the entire duration. Dichlorvos concentrations reached a mean peak of 0.19 μg/ml at 40 minutes after poisoning and decreased to a mean of 0.05 μg/ml at 240 minutes. These results show that OpdA hydrolyzes dichlorvos in an African Green Monkey model of lethal poisoning, delays AChE inhibition, and prevents lethality. PMID:24447378

  20. 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

  1. Laboratory Test Surveillance following Acute Kidney Injury

    PubMed Central

    Matheny, Michael E.; Peterson, Josh F.; Eden, Svetlana K.; Hung, Adriana M.; Speroff, Theodore; Abdel-Kader, Khaled; Parr, Sharidan K.; Ikizler, T. Alp; Siew, Edward D.

    2014-01-01

    Background Patients with hospitalized acute kidney injury (AKI) are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort. Methods We acquired clinical data from the Electronic health record (EHR) of 5 Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR) ≥60 L/min/1.73 m2. Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH) monitoring recommended for chronic kidney disease (CKD) patients. Results A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients. Conclusions Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease. PMID:25117447

  2. 40 CFR 798.5275 - Sex-linked recessive lethal test in drosophila melanogaster.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... historical control data. (5) Test chemicals—(i) Vehicle. Test chemicals should be dissolved in water. Compounds which are insoluble in water may be dissolved or suspended in appropriate vehicles (e.g., a mixture of ethanol and Tween-60 or 80) and then diluted in water or saline prior to...

  3. Dominant lethal mutation test in male mice exposed to 900MHz radiofrequency fields.

    PubMed

    Zhu, Shunxing; Zhang, Jie; Liu, Chun; He, Qina; Vijayalaxmi; Prihoda, Thomas J; Tong, Jian; Cao, Yi

    2015-10-01

    Adult male ICR mice were exposed to continuous wave 900MHz radiofrequency fields (RF) at 1.6mW/cm(2) power intensity (whole body average specific absorption rate of 0.731W/kg) for 4 hour/day for 15 days. At the end of exposure, each mouse was caged with 3 mature virgin female mice for mating. After 7 days, each male mouse was transferred to a fresh cage and mated with a second batch of 3 females. This process was repeated for a total of 4 consecutive weeks. Sham exposed male mice and those subjected to an acute 2Gy γ-irradiation (GR) were handled similarly and used as un-exposed and positive controls, respectively. All females were sacrificed on the 18th day of gestation and presumptive mating and, the contents in their uteri were examined. The overall observations during the 4 weeks of mating indicated that the un-exposed female mice mated to RF-exposed male mice showed no significant differences in the percentage of pregnancies, total implants, live implants and dead implants when compared with those mated with sham-exposed mice. In contrast, female mice mated with GR-exposed males showed a consistent pattern of significant differences in the above indices in each and all 4 weeks of mating. Thus, the data indicated an absence of mutagenic potential of RF exposure in the germ cells of male mice.

  4. Core body temperature as adjunct to endpoint determination in murine median lethal dose testing of rattlesnake venom.

    PubMed

    Cates, Charles C; McCabe, James G; Lawson, Gregory W; Couto, Marcelo A

    2014-12-01

    Median lethal dose (LD50) testing in mice is the 'gold standard' for evaluating the lethality of snake venoms and the effectiveness of interventions. As part of a study to determine the murine LD50 of the venom of 3 species of rattlesnake, temperature data were collected in an attempt to more precisely define humane endpoints. We used an 'up-and-down' methodology of estimating the LD50 that involved serial intraperitoneal injection of predetermined concentrations of venom. By using a rectal thermistor probe, body temperature was taken once before administration and at various times after venom exposure. All but one mouse showed a marked, immediate, dose-dependent drop in temperature of approximately 2 to 6°C at 15 to 45 min after administration. The lowest temperature sustained by any surviving mouse was 33.2°C. Surviving mice generally returned to near-baseline temperatures within 2 h after venom administration, whereas mice that did not survive continued to show a gradual decline in temperature until death or euthanasia. Logistic regression modeling controlling for the effects of baseline core body temperature and venom type showed that core body temperature was a significant predictor of survival. Linear regression of the interaction of time and survival was used to estimate temperatures predictive of death at the earliest time point and demonstrated that venom type had a significant influence on temperature values. Overall, our data suggest that core body temperature is a useful adjunct to monitoring for endpoints in LD50 studies and may be a valuable predictor of survival in venom studies.

  5. 40 CFR 797.1050 - Algal acute toxicity test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... acute toxicity of chemical substances and mixtures (“chemicals”) subject to environmental effects test... per volume of nutrient medium or test solution in a specified period of time. (5) Static system means a test container in which the test solution is not renewed during the period of the test. (c)...

  6. Effectiveness Testing and Evaluation of Non-Lethal Weapons for Crowd Management

    DTIC Science & Technology

    2014-06-01

    Distribution A : Approved for Public Release Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of...provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid...experimentation are a demonstration of the depth of analyses that result from these laboratory methods for the testing and evaluation of NLWs. To our

  7. Complexity-Measure-Based Sequential Hypothesis Testing for Real-Time Detection of Lethal Cardiac Arrhythmias

    NASA Astrophysics Data System (ADS)

    Chen, Szi-Wen

    2006-12-01

    A novel approach that employs a complexity-based sequential hypothesis testing (SHT) technique for real-time detection of ventricular fibrillation (VF) and ventricular tachycardia (VT) is presented. A dataset consisting of a number of VF and VT electrocardiogram (ECG) recordings drawn from the MIT-BIH database was adopted for such an analysis. It was split into two smaller datasets for algorithm training and testing, respectively. Each ECG recording was measured in a 10-second interval. For each recording, a number of overlapping windowed ECG data segments were obtained by shifting a 5-second window by a step of 1 second. During the windowing process, the complexity measure (CM) value was calculated for each windowed segment and the task of pattern recognition was then sequentially performed by the SHT procedure. A preliminary test conducted using the database produced optimal overall predictive accuracy of[InlineEquation not available: see fulltext.]. The algorithm was also implemented on a commercial embedded DSP controller, permitting a hardware realization of real-time ventricular arrhythmia detection.

  8. 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 Central

    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.

    2014-01-01

    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

  9. Judged Lethality

    DTIC Science & Technology

    1980-12-01

    75 High Blood Pressure 535 89 17 538 76 Drug Abuse 1,020 1,371 19 95 80 Bronchitis 162 19 43 2,111 85 Pregnancy 67 24 13 787 250 Diabetes 487 101 52...Diseases 4 Mumps 3 Dental Problems 1 Always Overestimated High Blood Pressure 9 Alcoholism 6 Influenza 2 Note: Measles (8), tuberculosis (13), auto...statis- tical lethality rate and total number of people killed (cancer, strokes, heart attacks, emphysema, high blood pressure ) were rather accurately

  10. Lethal combat over limited resources: testing the importance of competitors and kin.

    PubMed

    Innocent, Tabitha M; West, Stuart A; Sanderson, Jennifer L; Hyrkkanen, Nita; Reece, Sarah E

    2011-09-01

    Although most animals employ strategies to avoid costly escalation of conflict, the limitation of critical resources may lead to extreme contests and fatal fighting. Evolutionary theories predict that the occurrence and intensity of fights can be explained by resource value and the density and relatedness of competitors. However, the interaction between these factors and their relative importance often remains unclear; moreover, few systems allow all variables to be experimentally investigated, making tests of these theoretical predictions rare. Here, we use the parasitoid wasp Melittobia to test the importance of all these factors. In contrast to predictions, variation in contested resource value (female mates) and the relatedness of competitors do not influence levels of aggression. However, as predicted, fight intensity increased with competitor density and was not influenced by the greater cost of fighting at high density. Our results suggest that in the absence of kin recognition, indirectly altruistic behavior (spite) is unlikely to evolve, and in such circumstances, the scale of competition will strongly influence the amount of kin discrimination in the form of level of aggression as observed in Melittobia species.

  11. Acute, lethal, natural killer cell-resistant myeloproliferative disease induced by polyomavirus in severe combined immunodeficient mice.

    PubMed Central

    Szomolanyi-Tsuda, E.; Dundon, P. L.; Joris, I.; Shultz, L. D.; Woda, B. A.; Welsh, R. M.

    1994-01-01

    Infection of severe combined immunodeficient mice, which lack T and B lymphocytes, with polyomavirus (PyV) induced an acute hematological disorder leading to the death of the mice by 2 weeks postinfection. The disease was characterized by a dramatic decrease in megakaryocytes, multiple hemorrhages, anemia, thrombocytopenia, splenomegaly, a massive myeloproliferation and splenic erythroproliferation with a defect in maturation of the myeloid elements similar to that in acute leukemia. This pathology in severe combined immunodeficient mice is very different from that of the well-characterized tumor profiles induced by PyV in normal newborn or nude mice. Viral T and capsid (VP1) antigens and viral genome were detected in some cells in the spleen, but not in the majority of the proliferating myeloid cells. This suggests that the myeloproliferation is induced by some indirect mechanism, such as secretion of growth factors or cytokines by virus-infected cells, rather than by direct transformation by PyV. Neither the spread of PyV, its replication in different organs, nor the pathogenesis or the time of death were altered by depleting natural killer cells in vivo by anti-natural killer cell antibodies. Analysis of the spleen leukocyte population indicated that the cells expressed high levels of class I major histocompatibility complex antigens and were resistant to lysis by activated natural killer cells. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8311119

  12. Acute parietal and chief cell changes induced by a lethal dose of lipopolysaccharide in mouse stomach before thrombus formation.

    PubMed

    Ito, K; Ishida, K; Shishido, T; Tabata, H; Miura, H; Okamiya, H; Hanada, T

    2000-01-01

    The common lipopolysaccharide (LPS)-induced gastric lesions, such as erosions or ulcers, have been investigated in depth. Little is known, however, about the acute gastric lesions following a high dose of LPS. In a time-course study, ICR female mice were given a high subcutaneous dose of LPS (50 mg/kg). Mice were sacrificed at 4, 6, 12, and 24 hours after dosing and were assessed histopathologically for acute gastric lesions. The major gastric changes were seen in the fundic region and included vacuolar degeneration of parietal cells and apoptosis of chief cells. The vacuole in parietal cells was apparent as early as 4 hours postinjection (PI), and apoptosis of chief cells was apparent at 12 hours PI. Thrombus formation, in contrast, was not seen until 24 hours PI. No erosion, ulcer, or hemorrhage was seen in any gastric region in any of the treated animals at 24 hours PI. These results indicate that a subcutaneous high dose of LPS in mice causes vacuolar degeneration of parietal cells and apoptosis of chief cells before thrombus formation or subsequent ulcerative lesions.

  13. Comparative study of the assay of Artemia salina L. and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts.

    PubMed

    Logarto Parra, A; Silva Yhebra, R; Guerra Sardiñas, I; Iglesias Buela, L

    2001-09-01

    Artemia salina L. (Artemiidae), the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemical and natural products. In this study the Medium Lethal Concentrations (LC50 value) of 20 plant extracts, Aloe vera (L.) Burm. F. (Aloeaceae), Artemisia absinthium L. (Asteraceae); Citrus aurantium L. (Rutaceae); Cymbopogon citratus (DC. Ex Nees) Stapf (Poaceae); Datura stramonium L. (Solanaceae); Justicia pectoralis Jacq. (Acanthaceae); Musa x paradisiaca L. (Musaceae); Ocimum basilicum L.; O. gratissimum L.; O. tenuiflorum L. (Lamiaceae); Pimenta dioica (L.) Merr. (Myrtaceae); Piper auritum Kunth (Piperaceae); Plantago major L. (Plantaginaceae); Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Ruta graveolens L. (Rutaceae); Senna alata (L.) Roxb. (Fabaceae); Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae); and Thuja occidentalis L. (Cupressaceae), were determined using Artemia salina L. (Artemiidae), with the objective of relating the results to the LD50 values reported in mice (tested at three concentrations: 10, 100, and 1000 microg/mL, for each extract). We found good correlation between the in vivo and the in vitro tests (r = 0.85 p < 0.05), and this method is a useful tool for predicting oral acute toxicity in plant extracts.

  14. [Dynamics of pre-hospital lethality in acute coronary insufficiency and myocardial infarct in Krasnoyarsk during 1963-1975].

    PubMed

    Opaleva-Stegantseva, V A; Rybkin, I A; Protopopova, A N; Litvintseva, G A; Ratovskaia, V I

    1978-05-01

    The data on the dynamics of prehospital mortality in acute coronary failure (ACF) and myocardial infarction (MI) depending on the improvement in medical service in the prehospital stage of treatment are presented. The research showed that prehospital mortality in ACF and MI accounts for 75% of the total mortality. Among deaths registered in the prehospital stage 73.7% were sudden. As the result of improvements in prehospital medical service due to the training of physicians of the emergency medical service, the organization of cardiologic emergency aid teams, clinico-pathologic conferences held at the emergency medical service stations, etc. extrahospital mortality dropped from 45.6% (1963) to 26.2% (1975) with simultaneous drop in total mortality from 61.9% (1963) to 37.4% (1975).

  15. Metagenomic detection of viral pathogens in Spanish honeybees: co-infection by Aphid Lethal Paralysis, Israel Acute Paralysis and Lake Sinai Viruses.

    PubMed

    Granberg, Fredrik; Vicente-Rubiano, Marina; Rubio-Guerri, Consuelo; Karlsson, Oskar E; Kukielka, Deborah; Belák, Sándor; Sánchez-Vizcaíno, José Manuel

    2013-01-01

    The situation in Europe concerning honeybees has in recent years become increasingly aggravated with steady decline in populations and/or catastrophic winter losses. This has largely been attributed to the occurrence of a variety of known and "unknown", emerging novel diseases. Previous studies have demonstrated that colonies often can harbour more than one pathogen, making identification of etiological agents with classical methods difficult. By employing an unbiased metagenomic approach, which allows the detection of both unexpected and previously unknown infectious agents, the detection of three viruses, Aphid Lethal Paralysis Virus (ALPV), Israel Acute Paralysis Virus (IAPV), and Lake Sinai Virus (LSV), in honeybees from Spain is reported in this article. The existence of a subgroup of ALPV with the ability to infect bees was only recently reported and this is the first identification of such a strain in Europe. Similarly, LSV appear to be a still unclassified group of viruses with unclear impact on colony health and these viruses have not previously been identified outside of the United States. Furthermore, our study also reveals that these bees carried a plant virus, Turnip Ringspot Virus (TuRSV), potentially serving as important vector organisms. Taken together, these results demonstrate the new possibilities opened up by high-throughput sequencing and metagenomic analysis to study emerging new diseases in domestic and wild animal populations, including honeybees.

  16. Hydrocortisone in culture protects the blast cells in acute myeloblastic leukemia from the lethal effects of cytosine arabinoside

    SciTech Connect

    Yang, G.S.; Wang, C.; Minkin, S.; Minden, M.D.; McCulloch, E.A. )

    1991-07-01

    The blast cells in acute myeloblastic leukemia (AML) respond to many of the same regulatory mechanisms that control normal hemopoiesis. These include the growth factors that bind to membrane receptors and steroid hormones or vitamins that have intracellular receptors. The authors report the effects in culture of the steroid glucocorticoid hydrocortisone on freshly explanted AML blasts from patients and on two continuous AML cell lines. Only small changes in clonogenic cell numbers in suspension cultures were seen in the presence of hydrocortisone. The most striking effect of the hormone was on the sensitivity of blasts cells to cytosine arabinoside (ara-C). In contrast to the response of AML blast cells to retinoic acid, a ligand for intracellular steroid receptors that sensitizes some blast populations to ara-C, hydrocortisone reduced the toxic effects of the drug. The protective action of hydrocortisone was not mediated through the cell cycle since exposure of blasts to hydrocortisone did not affect the percentage of cells in DNA synthesis as measured with the tritiated thymidine (3HTdR) suicide technique. The hydrocortisone effect could be demonstrated using a pulse (20 min) exposure protocol. Blasts pulsed with increasing specific activities of 3HTdR showed the usual response pattern with an initial loss in plating efficiency to about 50% of control, followed by a plateau, regardless of whether the cells had been exposed to hydrocortisone. Control blasts exposed to increasing ara-C concentrations gave very similar dose-response curves; in striking contrast, blast cells cultured in hydrocortisone, then pulsed with ara-C did not lose colony-forming ability even though the same population was sensitive to 3HTdR.

  17. 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.

  18. Resolving some practical questions about Daphnia acute toxicity tests

    SciTech Connect

    Barera, Y.; Adams, W.J.

    1981-10-01

    Acute toxicity tests were performed with six age groups of Daphnia magna, ranging from less than or equal to6 h to 216 h, and with five chemicals, selected on the basis of their physical and chemical properties as well as their acute toxicity to D. magna. The age of the daphnids did not significantly alter the 48-h EC/sub 50/ values for the chemicals tested. The maximum difference observed in the 48-h EC/sub 50/ values between the 6-h and 216-h age groups was a factor of 3.9 for linear alkylbenzene sulfonate (LAS). For purposes of standardization, it appears that D. magna up to 48 h of age at the beginning of the test can be used to conduct acute toxicity tests with most chemicals. The results of static acute toxicity tests conducted with butylbenzyl phthalate (BBP) and D. magna in the presence and absence of several commonly used solvents indicate that the acute toxicity of this chemical is not altered by the use of a solvent carrier. The 48-h EC/sub 50/ value for BBP without a solvent was 1.0 mg/L, compared with a range of 1.6 to 2.2 mg/L when acetone, dimethylformamide, ethanol, or triethylene glycol were used as solvent carriers. The acute toxicities of the solvents in the absence of BBP were also determined for D. magna. The values ranged from 9.3 to 52.4 g/L. The results of static acute tests performed with D. magna and BBP in the presence of various concentrations of daphnid foods (algae or trout chow), indicate that the 48-h EC/sub 50/ values increase proportionally with an increase in food concentrations. These results suggest that acute toxicity tests with D. magna should be conducted in the presence of food with chemicals with a high Ksigma if the results are to be used to select the test concentrations for a chronic study with daphnids. The type of food and the concentration used in the acute test should be the same as those used in a chronic test.

  19. Comparison of sublethal and lethal criteria for nine different chemicals in standardized toxicity tests using the earthworm Eisenia andrei

    SciTech Connect

    Van Gestel, C.A.; Dirven-Van Breemen, E.M.; Baerselman, R.; Emans, H.J.; Janssen, J.A.; Postuma, R.; Van Vliet, P.J. )

    1992-04-01

    In this study, the effects of nine different chemicals on the survival, growth, and reproduction of the earthworm species Eisenia andrei were determined using a recently developed method. Earthworms were exposed for 3 weeks to the test chemicals in an artificial soil substrate. Additional data on the acute toxicity of these chemicals were derived from the literature. For some chemicals, cocoon production was the most sensitive parameter (cadmium, chromium, paraquat, fentin, benomyl, phenmedipham), while for others cocoon hatchability was most sensitive (pentachlorophenol, parathion, carbendazim). In the case of parathion, growth of the worms seemed to be even more sensitive than reproduction. As an overall parameter for the effect on earthworm reproduction, the total number of juveniles produced per worm appeared to be a useful parameter. Differences between (acute) LC50 values and the lowest NOEC value for effects on growth and reproduction were different for each chemical. Difference was greatest for cadmium (a factor of greater than 100) and smallest for fentin, benomyl, and pentachlorophenol (a factor of 5-6).

  20. Distinct effects of acute pretreatment with lipophilic and hydrophilic statins on myocardial stunning, arrhythmias and lethal injury in the rat heart subjected to ischemia/reperfusion.

    PubMed

    Čarnická, S; Adameová, A; Nemčeková, M; Matejíková, J; Pancza, D; Ravingerová, T

    2011-01-01

    Although both lipophilic and more hydrophilic statins share the same pathway of the inhibition of HMG-CoA reductase, their pleiotropic cardioprotective effects associated with the ability to cross cellular membranes, including membranes of heart cells, may differ. To test this hypothesis, isolated rat hearts were Langendorff-perfused either with simvastatin (S, 10 micromol/l) or pravastatin (P, 30 micromol/l), 15 min prior to ischemia. Control untreated hearts (C) were perfused with perfusion medium only. Postischemic contractile dysfunction, reperfusion-induced ventricular arrhythmias and infarct size were investigated after exposure of the hearts to 30-min global ischemia and 2-h reperfusion. Both lipophilic S and hydrophilic P reduced the severity of ventricular arrhythmias (arrhythmia score) from 4.3 +/- 0.2 in C to 3.0 +/- 0 and 2.7 +/- 0.2 in S and P, respectively, (both P < 0.05), decreased the duration of ventricular tachycardia and suppressed ventricular fibrillation. Likewise, the extent of lethal injury (infarct size) determined by tetrazolium staining and expressed in percentage of risk area, was significantly lower in both treated groups, moreover, the effect of P was more pronounced (27 +/- 2 % and 10 +/- 2 % in S and P groups, respectively, vs. 42 +/- 1 % in C; P < 0.05). In contrast, only S, but not P, was able to improve postischemic recovery of left ventricular developed pressure (LVDP; 48 +/- 12 % of preischemic values vs. 25 +/- 4 % in C and 21 +/ -7 % in P groups; P < 0.05). Our results suggest that differences in water solubility of statins indicating a different ability to cross cardiac membranes may underlie their distinct cardioprotective effects on myocardial stunning and lethal injury induced by ischemia/reperfusion.

  1. Use of butterflies as nontarget insect test species and the acute toxicity and hazard of mosquito control insecticides.

    PubMed

    Hoang, Tham C; Pryor, Rachel L; Rand, Gary M; Frakes, Robert A

    2011-04-01

    Honeybees are the standard insect test species used for toxicity testing of pesticides on nontarget insects for the U.S. Environmental Protection Agency (U.S. EPA) under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). Butterflies are another important insect order and a valued ecological resource in pollination. The current study conducted acute toxicity tests with naled, permethrin, and dichlorvos on fifth larval instar (caterpillars) and adults of different native Florida, USA, butterfly species to determine median lethal doses (24-h LD50), because limited acute toxicity data are available with this major insect group. Thorax- and wing-only applications of each insecticide were conducted. Based on LD50s, thorax and wing application exposures were acutely toxic to both caterpillars and adults. Permethrin was the most acutely toxic insecticide after thorax exposure to fifth instars and adult butterflies. However, no generalization on acute toxicity (sensitivity) of the insecticides could be concluded based on exposures to fifth instars versus adult butterflies or on thorax versus wing exposures of adult butterflies. A comparison of LD50s of the butterflies from this study (caterpillars and adults) with honeybee LD50s for the adult mosquito insecticides on a µg/organism or µg/g basis indicates that several butterfly species are more sensitive to these insecticides than are honeybees. A comparison of species sensitivity distributions for all three insecticides shows that permethrin had the lowest 10th percentile. Using a hazard quotient approach indicates that both permethrin and naled applications in the field may present potential acute hazards to butterflies, whereas no acute hazard of dichlorvos is apparent in butterflies. Butterflies should be considered as potential test organisms when nontarget insect testing of pesticides is suggested under FIFRA.

  2. Combined administration of anisodamine and neostigmine rescued acute lethal crush syndrome through α7nAChR-dependent JAK2-STAT3 signaling

    PubMed Central

    Xu, Zhe-Qi; Shao, Bo-Zong; Ke, Ping; Liu, Jian-Guo; Liu, Guo-Ku; Chen, Xiong-Wen; Su, Ding-Feng; Liu, Chong

    2016-01-01

    Previously we showed that Ani (anisodamine)/Neo (neostigmine) combination produced anti-shock effect via activating α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we aim to investigate the therapeutic effect and underlying mechanisms of Ani/Neo combination in acute lethal crush syndrome (CS). In rat and rabbit CS models, Ani/Neo combination increased the 24 h survival rates, improved hemodynamics and decreased the levels of creatine kinase, MB isoenzyme of creatine kinase, blood urea nitrogen, creatinine, K+ in serum. It also decreased the levels of H2O2, myeloperoxidase (MPO) and nitric oxide (NO) in serum and compressed muscle in rat CS model. In wild-type (WT) mice with CS, Ani/Neo combination increased 24 h survival rate and decreased the levels of H2O2, MPO, NO, TNFα, IL-6 and IL-10 in compressed muscle. These effects were attenuated by α7nAChR knockout (KO). Moreover, Ani/Neo combination prevented the decrease of phosphorylation of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3) induced by CS. These effects of Ani/Neo in CS mice were cancelled by methyllycaconitine (α7nAChR antagonist) and α7nAChR KO. Collectively, our results demonstrate that Ani/Neo combination could produce therapeutic effects in CS. The underlying mechanism involves the activation of α7nAChR-dependent JAK2-STAT3 signaling pathway. PMID:27874086

  3. Comparison of standard acute toxicity tests with rapid-screening toxicity tests

    SciTech Connect

    Toussaint, M.W.; Shedd, T.R.; VanDerSchal, W.H.; Leather, G.R.

    1995-10-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus ccalyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photo bacterium phosphoreum - Microtox test, and a mixture of bacterial species - the polytox test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriadaphnta dubia), green algae (Setenastrum capricarnutum), fathead minnows (Pimephalespromelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC5O/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  4. A comparison of standard acute toxicity tests with rapid-screening toxicity tests

    SciTech Connect

    Toussaint, M.W.; Shedd, T.R.; Schalie, W.H. van der; Leather, G.R.

    1995-05-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus calyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photobacterium phosphoreum--Microtox{reg_sign} test, and a mixture of bacterial species--the Polytox{reg_sign} test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriodaphnia dubia), green algae (Selenastrum capricornutum), fathead minnows (Pimephales promelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC50/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  5. Heterogeneity of Lethals in a "Simple" Lethal Complementation Group

    PubMed Central

    Janca, Frank C.; Woloshyn, Effie P.; Nash, David

    1986-01-01

    Of 24 ethyl methanesulphonate-induced, recessive-lethal mutations in the region 9E1-9F13 of the X chromosome of Drosophila melanogaster , eight fall into a typically homogeneous lethal complementation group associated with the raspberry (ras) locus. Mutations in this group have previously been shown to be pleiotropic, affecting not only ras but also two other genetic entities, gua1 and pur1, which yield auxotrophic mutations.—The eight new mutations have been characterized phenotypically in double heterozygotes with gua1, pur1 and ras mutations. Despite their homogeneity in lethal complementation tests, the mutations prove quite diverse. For example, two mutations have little or no effect on eye color in double heterozygotes with ras2 . The differences between the lethals are allele-specific and cannot be explained as a trivial outcome of a hypomorphic series.—Taken alone, the lethal complementation studies mask the complexity of the locus and the diversity of its recessive lethal alleles. By extension, we argue that the general use of lethal saturation studies provides an unduly simplified image of genetic organization. We suggest that the reason why recessive lethal mutations rarely present complex complementation patterns is that complex loci tend to produce mutations that affect several subfunctions. PMID:3080355

  6. Procalcitonin Strip Test as an Independent Predictor in Acute Pancreatitis.

    PubMed

    Dias, Brendan Hermenigildo; Rozario, Anthony Prakash; Olakkengil, Santosh Antony; V, Anirudh

    2015-12-01

    Plasma procalcitonin (PCT) is a highly specific marker for the diagnosis of bacterial infection and sepsis. Studies have demonstrated its role in the setting of sepsis and acute pancreatitis. This study aims to analyze and compare the prognostic efficacy of plasma procalcitonin strip test in acute pancreatitis. A prospective study was conducted in the department of general surgery from June 2012 to June 2013. Plasma procalcitonin was estimated by the semiquantitative strip test. The study included a total of 50 patients diagnosed to have acute pancreatitis. Data was collected and statistically analyzed using SPSS version 17. Thirty-nine out of the 50 patients (78 %) were males with a mean age of 46.8 years (range, 25-78 years) and 25 patients (50 %) had ethanol-induced pancreatitis, while 13 patients (26 %) had gall stone pancreatitis. Plasma PCT values were found to correlate better than CRP levels and total leukocyte count with the total duration of hospitalization, ITU, and ICU stay, as well as with the progression to severe acute pancreatitis. A cut off for plasma PCT of >2 ng/mL was found to be 100 % sensitive and 100 % specific and a cut off for CRP of >19 mg/dL was 70 % sensitive and 65 % specific for predicting the progression to severe acute pancreatitis. Plasma PCT also correlated well with antibiotic requirement. A cut off value of >0.5 ng/mL for plasma PCT was 100 % sensitive and 80 % specific and a cut off value of >18 mg/dL for CRP was 86 % sensitive and 63 % specific for predicting antibiotic requirement. Plasma procalcitonin is an early and reliable prognostic indicator in acute pancreatitis. The procalcitonin strip test is a rapid test which is useful in analyzing prognosis in patients with acute pancreatitis.

  7. Draft Test Guideline: Oyster Acute Toxicity Test (Shell Deposition)

    EPA Pesticide Factsheets

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  8. Draft Test Guideline: Fish Acute Toxicity Test, Freshwater And Marine

    EPA Pesticide Factsheets

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  9. Draft Test Guideline: Bivalve Acute Toxicity Test (Embryo Larval)

    EPA Pesticide Factsheets

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  10. Draft Test Guideline: Aquatic Invetebrate Acute Toxicity, Test, Freshwater Daphnids

    EPA Pesticide Factsheets

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  11. Neutral red uptake cytotoxicity tests for estimating starting doses for acute oral toxicity tests.

    PubMed

    Stokes, William S; Casati, Silvia; Strickland, Judy; Paris, Michael

    2008-05-01

    In vitro cytotoxicity assays can be used as alternative toxicity tests to reduce the total number of animals needed for acute oral toxicity tests. This unit describes two methods for determining the in vitro cytotoxicity of test substances using neutral red uptake (NRU) and using the in vitro data to determine starting doses for in vivo acute oral systemic toxicity tests, e.g., the up-and-down procedure or the acute toxic class method. The use of the NRU methods to determine starting doses for acute oral toxicity tests may reduce the number of animals required, and for relatively toxic substances, this approach may also reduce the number of animals that die or require humane euthanasia due to severe toxicity. An interlaboratory validation study has demonstrated that the methods are useful and reproducible for these purposes. Two standardized protocols provide details for performing NRU tests with rodent and human cells.

  12. Development of a general baseline toxicity QSAR model for the fish embryo acute toxicity test.

    PubMed

    Klüver, Nils; Vogs, Carolina; Altenburger, Rolf; Escher, Beate I; Scholz, Stefan

    2016-12-01

    Fish embryos have become a popular model in ecotoxicology and toxicology. The fish embryo acute toxicity test (FET) with the zebrafish embryo was recently adopted by the OECD as technical guideline TG 236 and a large database of concentrations causing 50% lethality (LC50) is available in the literature. Quantitative Structure-Activity Relationships (QSARs) of baseline toxicity (also called narcosis) are helpful to estimate the minimum toxicity of chemicals to be tested and to identify excess toxicity in existing data sets. Here, we analyzed an existing fish embryo toxicity database and established a QSAR for fish embryo LC50 using chemicals that were independently classified to act according to the non-specific mode of action of baseline toxicity. The octanol-water partition coefficient Kow is commonly applied to discriminate between non-polar and polar narcotics. Replacing the Kow by the liposome-water partition coefficient Klipw yielded a common QSAR for polar and non-polar baseline toxicants. This developed baseline toxicity QSAR was applied to compare the final mode of action (MOA) assignment of 132 chemicals. Further, we included the analysis of internal lethal concentration (ILC50) and chemical activity (La50) as complementary approaches to evaluate the robustness of the FET baseline toxicity. The analysis of the FET dataset revealed that specifically acting and reactive chemicals converged towards the baseline toxicity QSAR with increasing hydrophobicity. The developed FET baseline toxicity QSAR can be used to identify specifically acting or reactive compounds by determination of the toxic ratio and in combination with appropriate endpoints to infer the MOA for chemicals.

  13. Dose–response tests and semi-field evaluation of lethal and sub-lethal effects of slow release pyriproxyfen granules (Sumilarv®0.5G) for the control of the malaria vectors Anopheles gambiae sensu lato

    PubMed Central

    2013-01-01

    Background Recently research has shown that larviciding can be an effective tool for integrated malaria vector control. Nevertheless, the uptake of this intervention has been hampered by the need to re-apply larvicides frequently. There is a need to explore persistent, environmentally friendly larvicides for malaria vector control to reduce intervention efforts and costs by reducing the frequency of application. In this study, the efficacy of a 0.5% pyriproxyfen granule (Surmilarv®0.5G, Sumitomo Chemicals) was assessed for the control of Anopheles gambiae sensu stricto and Anopheles arabiensis, the major malaria vectors in sub-Saharan Africa. Methods Dose–response and standardized field tests were implemented following standard procedures of the World Health Organization’s Pesticide Evaluation Scheme to determine: (i) the susceptibility of vectors to this formulation; (ii) the residual activity and appropriate retreatment schedule for field application; and, (iii) sub-lethal impacts on the number and viability of eggs laid by adults after exposure to Sumilarv®0.5G during larval development. Results Anopheles gambiae s.s. and An. arabiensis were highly susceptible to Sumilarv®0.5G. Estimated emergence inhibition (EI) values were very low and similar for both species. The minimum dosage that completely inhibited adult emergence was between 0.01-0.03 parts per million (ppm) active ingredient (ai). Compared to the untreated control, an application of 0.018 ppm ai prevented 85% (95% confidence interval (CI) 82%-88%) of adult emergence over six weeks under standardized field conditions. A fivefold increase in dosage of 0.09 ppm ai prevented 97% (95% CI 94%-98%) emergence. Significant sub-lethal effects were observed in the standardized field tests. Female An. gambiae s.s. that were exposed to 0.018 ppm ai as larvae laid 47% less eggs, and females exposed to 0.09 ppm ai laid 74% less eggs than females that were unexposed to the treatment. Furthermore, 77

  14. ANA testing in the presence of acute and chronic infections.

    PubMed

    Litwin, Christine M; Binder, Steven R

    2016-01-01

    Autoantibody testing is performed to help diagnose patients who have clinical symptoms suggestive of possible autoimmune diseases. Antinuclear antibodies (ANA) are present in many systemic autoimmune conditions such as systemic lupus erythematosus (SLE). However, a positive ANA test may also be seen with non-autoimmune inflammatory diseases, including both acute and chronic infections. When the ANA test is used as an initial screen in patients with non-specific clinical symptoms, such as fever, joint pain, myalgias, fatigue, rash, or anemia, the likelihood of a positive result due to infection will increase, especially in children. This article identifies acute and chronic infectious diseases that are likely to produce a positive ANA result and summarizes recent literature addressing both the causes and consequences of these findings.

  15. In vitro cytotoxicity testing for prediction of acute human toxicity.

    PubMed

    Barile, F A; Dierickx, P J; Kristen, U

    1994-06-01

    This study was designed to compare the cytotoxic concentrations of chemicals, determined with three independent in vitro cytotoxicity testing protocols, with each other and with established animal LD50 values, and against human toxic concentrations for the same chemicals. Ultimately, these comparisons allow us to evaluate the potential of in vitro cell culture methods for the ability to screen a variety of chemicals for prediction of human toxicity. Each laboratory independently tested 50 chemicals with known human lethal plasma concentrations and LD50 values. Two of the methods used monolayer cell cultures to measure the incorporation of radiolabeled amino acids into newly synthesized proteins and cellular protein content, while the third technique used the pollen tube growth test. The latter is based on the photometric quantification of pollen tube mass production in suspension culture. Experiments were performed in the absence or presence of increasing doses of the test chemical, during an 18- to 24-h incubation. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Comparison of the cytotoxic concentrations confirms previous independent findings that the experimental IC50 values are more accurate predictors of human toxicity than equivalent toxic blood concentrations (HETC values) derived from rodent LD50s. In addition, there were no conclusive statistical differences among the methods. It is anticipated that, together, these procedures can be used as a battery of tests to supplement or replace currently used animal protocols for human risk assessment.

  16. An Evaluation of Select Test Variables Potentially Affecting Acute Oil Toxicity.

    PubMed

    Echols, Brandi S; Smith, A; Gardinali, P; Rand, G

    2016-02-01

    In the wake of the Deepwater Horizon incident (2010) in the Gulf of Mexico, an abundance of research studies have been performed, but the methodologies used have varied making comparisons and replication difficult. In this study, acute toxicity tests with mysids and inland silversides were performed to examine the effect of different variables on test results. The toxicity test variables evaluated in this study included (1) open versus closed static test chambers, (2) natural versus artificial diluent, (3) aerated versus nonaerated test solution, and (4) low versus medium energy water-accommodated (WAF) mixing energies. The use of tests using natural or artificial diluent showed no difference in either toxicity test or analytical chemistry results. Based on median lethal concentrations (LC50) of WAFs of unweathered oil (MASS), mysid tests performed in closed chambers were approximately 41 % lower than LC50 values from open-chamber studies, possibly a result of the presence of low-molecular weight volatile aromatics (i.e., naphthalenes). This research also showed that using a medium-energy WAF (with a 20–25 % vortex) increases the number of chemical components compared with low-energy WAF, thus affecting the composition of the exposure media and increasing toxicity. The comparison of toxic units as a measure of the potential toxicity of fresh and weathered oils showed that weathered oils (e.g., Juniper, CTC) are less toxic than the unweathered MASS oil. In the event of future oil spills, these variables should be considered to ensure that data regarding the potential toxicity and environmental risk are of good quality and reproducible.

  17. Non-animal Replacements for Acute Toxicity Testing.

    PubMed

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

    2015-07-01

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

  18. 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

    Van Molle, W; Hochepied, T; Brouckaert, P; Libert, C

    2000-09-01

    The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) 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 SAP(0/0) mice generated by gene targeting. We studied the lethal response of SAP(0/0) 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-1beta (IL-1beta) for desensitization and clearly involving a liver protein, the other by tolerizing mice for 5 days using small doses of human TNF-alpha. Although after IL-1beta or after tolerization the SAP levels in the serum had risen fourfold in the control mice and not in the SAP(0/0) 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-alpha was not altered in SAP(0/0) mice. We conclude that the presence or absence of SAP has no influence on the sensitivity of mice to TNF-alpha-induced hepatitis, SIRS, and hemorrhagic necrosis or on the endogenous protective mechanisms of desensitization or tolerization.

  19. The Gottingen minipig is a model of the hematopoietic acute radiation syndrome: G-CSF stimulates hematopoiesis and enhances survival from lethal total-body gamma-irradiation

    PubMed Central

    Moroni, Maria; Ngudiankama, Barbara F.; Christensen, Christine; Olsen, Cara H.; Owens, Rossitsa; Lombardini, Eric D.; Holt, Rebecca K.; Whitnall, Mark H.

    2013-01-01

    Purpose We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the Acute Radiation Syndrome (ARS), to enhance discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematological parameters and dynamics of cell loss/recovery following irradiation provide a convenient means to compare efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials Male Gottingen minipigs, 4–5 months old and weighing 9–11 kg were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen®, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body gamma-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results Results indicate G-CSF enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusion These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing numbers of circulating granulocytes. PMID:23845847

  20. Acute toxicity testing in cultures of mouse neuroblastoma cells.

    PubMed

    Walum, E; Peterson, A

    1983-01-01

    Cultured mouse neuroblastoma cells (C1300) may be used as models for nerve cells since they have a number of properties in common with their normal counterparts in vivo. In order to test the possibility of using C1300 cells as alternative to experimental animals when testing for acute toxicity, cells (clone 41A3) were exposed to a number of common chemicals (CH3HgCl, CdCl2,HgCl2 ppDDT, n-butanol, benzene, dioxan, n-propanol, aceton and t-butanol). The toxic effect was quantified by measuring the degree of cell detachment in the cultures. The concentrations of chemicals that caused 25% of the total cell number to detach (TD25) were used for comparison with LD50 values. In spite of the very simplified situation in culture, where the toxicity of a substance is little or not at all influenced by factors like penetration, storage, metabolism and excretion a good correlation (corr. coeff. 0,98) was obtained between TD25 values and LD50 values. Good correlations between in vitro and in vivo tests have also been reported by others. One possible explanation to these findings could be simplified in vivo toxicokinetics of these substances when tested in high doses for general effects like animal death. If so, simple in vitro tests may be used for predicting acute toxicity of certain groups of substances.

  1. Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests.

    PubMed

    Ito, Tomohiro; Ono, Tomoko; Sato, Atsuya; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Maeda, Takahiro

    2014-03-01

    The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement.

  2. Effects of acute salbutamol intake during a Wingate test.

    PubMed

    Collomp, K; Le Panse, B; Portier, H; Lecoq, A-M; Jaffre, C; Beaupied, H; Richard, O; Benhamou, L; Courteix, D; De Ceaurriz, J

    2005-09-01

    To investigate the impact of acute salbutamol intake on performance and selected hormonal and metabolic variables during supramaximal exercise, 13 recreational male athletes performed two 30-second Wingate tests after either placebo (PLA, lactose) or salbutamol (SAL, 4 mg) oral administration, according to a double-blind and randomized protocol. Blood samples collected at rest, end of the Wingate test, recovery (5, 10, 15 min) were tested for growth hormone (GH), insulin (INS), blood glucose (GLU), and lactate determination. We found the peak and mean power performed significantly increased after SAL vs. PLA (PPSAL: 896 +/- 46; PPPLA: 819 +/- 57 W; MPSAL: 585 +/- 27; MPPLA: 534 +/- 35 W, p < 0.05), whereas no change was observed in the fatigue index. Blood glucose and INS were significantly increased by SAL at rest, at the end of the Wingate test, and during the 5 first minutes of recovery (p < 0.05). Plasma GH was significantly decreased by SAL (p < 0.05) during the recovery whereas end-exercise and recovery blood lactate tended but were not significantly increased after SAL vs. PLA. From these data, acute salbutamol intake at therapeutical dosage did appear to improve peak power and mean power during a supramaximal exercise, but the mechanisms involved need further investigation.

  3. Acute toxicity and inactivation tests of CO2 on invertebrates in drinking water treatment systems.

    PubMed

    Yin, Wen-Chao; Zhang, Jin-Song; Liu, Li-Jun; Zhao, Jian-Shu; Li, Tuo

    2011-01-01

    In addition to the esthetic problem caused by invertebrates, researchers are recently starting to be more aware of their potential importance in terms of public health. However, the inactivation methods of invertebrates which could proliferate in drinking water treatment systems are not well developed. The objective of this study is to assess the acute toxicity and inactivation effects of CO2 on familiar invertebrates in water treatment processes. The results of this study revealed that CO2 has a definite toxicity to familiar invertebrates. The values of 24-h LC50 (median lethal concentration) were calculated for each test with six groups of invertebrates. The toxicity of CO2 was higher with increasing concentrations in solution but was lower with the increase in size of the invertebrates. Above the concentration of 1,000 mg/L for the CO2 solution, the 100% inactivation time of all the invertebrates was less than 5 s, and in 15 min, the inactivation ratio showed a gradient descent with a decline in concentration. As seen for Mesocyclops thermocyclopoides, by dosing with a sodium bicarbonate solution first and adding a dilute hydrochloric acid solution 5 min later, it is possible to obtain a satisfactory inactivation effect in the GAC (granular activated carbon) filters.

  4. Measurable residual disease testing in acute myeloid leukaemia.

    PubMed

    Hourigan, C S; Gale, R P; Gormley, N J; Ossenkoppele, G J; Walter, R B

    2017-04-07

    There is considerable interest in developing techniques to detect and/or quantify remaining leukaemia cells termed measurable or, less precisely, minimal residual disease (MRD) in persons with acute myeloid leukaemia (AML) in complete remission defined by cytomorphological criteria. An important reason for AML MRD testing is the possibility of estimating the likelihood (and timing) of leukaemia relapse. A perfect MRD-test would precisely quantify leukaemia cells biologically able and likely to cause leukaemia relapse within a defined interval. AML is genetically diverse and there is currently no uniform approach to detecting such cells. Several technologies focused on immune phenotype or cytogenetic and/or molecular abnormalities have been developed, each with advantages and disadvantages. Many studies report a positive MRD-test at diverse time points during AML therapy identifies persons with a higher risk of leukaemia relapse compared with those with a negative MRD-test even after adjusting for other prognostic and predictive variables. No MRD-test in AML has perfect sensitivity and specificity for relapse prediction at the cohort- or subject-levels and there are substantial rates of false-positive and -negative tests. Despite these limitations, correlations between MRD-test results and relapse risk have generated interest in MRD-test result directed therapy interventions. However, convincing proof that a specific intervention will reduce relapse risk in persons with a positive MRD-test is lacking and needs testing in randomized trials. Routine clinical use of MRD-testing requires further refinements and standardization/harmonization of assay platforms and results reporting. Such data are needed to determine whether results of MRD-testing can be used as a surrogate endpoint in AML therapy trials. This could make drug-testing more efficient and accelerate regulatory approvals. Although MRD-testing in AML has advanced substantially, much remains to be done

  5. 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

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

    PubMed

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

    2017-02-24

    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.

  7. Developmental toxicity, acute toxicity and mutagenicity testing in freshwater snails Biomphalaria glabrata (Mollusca: Gastropoda) exposed to chromium and water samples.

    PubMed

    Tallarico, Lenita de Freitas; Borrely, Sueli Ivone; Hamada, Natália; Grazeffe, Vanessa Siqueira; Ohlweiler, Fernanda Pires; Okazaki, Kayo; Granatelli, Amanda Tosatte; Pereira, Ivana Wuo; Pereira, Carlos Alberto de Bragança; Nakano, Eliana

    2014-12-01

    A protocol combining acute toxicity, developmental toxicity and mutagenicity analysis in freshwater snail Biomphalaria glabrata for application in ecotoxicological studies is described. For acute toxicity testing, LC50 and EC50 values were determined; dominant lethal mutations induction was the endpoint for mutagenicity analysis. Reference toxicant potassium dichromate (K2Cr2O7) was used to characterize B. glabrata sensitivity for toxicity and cyclophosphamide to mutagenicity testing purposes. Compared to other relevant freshwater species, B. glabrata showed high sensitivity: the lowest EC50 value was obtained with embryos at veliger stage (5.76mg/L). To assess the model applicability for environmental studies, influent and effluent water samples from a wastewater treatment plant were evaluated. Gastropod sensitivity was assessed in comparison to the standardized bioassay with Daphnia similis exposed to the same water samples. Sampling sites identified as toxic to daphnids were also detected by snails, showing a qualitatively similar sensitivity suggesting that B. glabrata is a suitable test species for freshwater monitoring. Holding procedures and protocols implemented for toxicity and developmental bioassays showed to be in compliance with international standards for intra-laboratory precision. Thereby, we are proposing this system for application in ecotoxicological studies.

  8. Lethal/sublethal responses of Daphnia magna to acute norfloxacin contamination and changes in phytoplankton-zooplankton interactions induced by this antibiotic

    PubMed Central

    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. PMID:28079143

  9. 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.

  10. Mutagenic Potential of 4-Nitrophenyl Methyl (Phenyl) Phosphinate Using the Drosophila melanogaster Sex-Linked Recessive Lethal Test.

    DTIC Science & Technology

    1983-04-01

    inst ability of (TWq I) when prepared in an aqueous system, a mixture of Tween 80 R, ethanol, citrate buffer and water were prepared to stabilize the...concentrations of the test chemical formulated with Tween 80 , ethanol, citrate buffer, water and 1% fructose. These m0es formed the test groups. Concurrent...exposure of the Tween 80 , ethanol, citrate buffer, water and 1% fructose (250 ul) for CS males to feed upon were designated as negative control

  11. Measurements of vaccinia virus dissemination using whole body imaging: approaches for predicting of lethality in challenge models and testing of vaccines and antiviral treatments.

    PubMed

    Zaitseva, Marina; Kapnick, Senta; Golding, Hana

    2012-01-01

    Preclinical evaluation of novel anti-smallpox vaccines and antiviral treatments often rely on mouse -challenge models using pathogenic vaccinia virus, such as Western Reserve (WR) strain or other orthopoxviruses. Traditionally, efficacy of treatment is evaluated using various readouts, such as lethality (rare), measurements of body weight loss, pox lesion scoring, and determination of viral loads in internal organs by enumerating plaques in sensitive cell lines. These methodologies provide valuable information about the contribution of the treatment to protection from infection, yet all have similar limitations: they do not evaluate dissemination of the virus within the same animal and require large numbers of animals. These two problems prompted us to turn to a recently developed whole body imaging technology, where replication of recombinant vaccinia virus expressing luciferase enzyme (WRvFire) is sensed by detecting light emitted by the enzyme in the presence of D: -luciferin substrate administered to infected animal. Bioluminescence signals from infected organs in live animals are registered by the charge-coupled device camera in IVIS instrument developed by Caliper, and are converted into numerical values. This chapter describes whole body bioimaging methodology used to determine viral loads in normal live BALB/c mice infected with recombinant WRvFire vaccinia virus. Using Dryvax vaccination as a model, we show how bioluminescence data can be used to determine efficacy of treatment. In addition, we illustrate how bioluminescence and survival outcome can be combined in Receiver Operating Characteristic curve -analysis to develop predictive models of lethality that can be applied for testing of new therapeutics and second-generation vaccines.

  12. Myocardial rupture associated with bolus injection of contrast medium during computed tomographic study in a patient with acute myocardial infarction: a rare but lethal complication.

    PubMed

    Lai, Vincent; Hau, K C; Lau, H Y; Chan, W C

    2009-08-01

    Well-documented potential cardiovascular complications associated with the use of contrast media include bradycardia, hypotension, arrhythmia, and conduction disturbances. Rupture of the myocardium after acute myocardial infarction is a known cause of death, but has yet to be recognised as a potential complication of the use of a bolus injection of contrast medium. On the contrary, contrast-enhanced computed tomographic studies have been performed widely for the diagnosis and evaluation of myocardial infarction. We report a case of complicated myocardial rupture after a single bolus injection of contrast medium during a computed tomographic study in an elderly woman with acute myocardial infarction, which led to cardiac tamponade and rapid death. Although rare, this should alert us to the need for cautious use of contrast medium in patients with acute myocardial infarction.

  13. The Mutagenic Potential of: 4-Nitrophenyl Diphenyl Phosphinate Using the Drosophila melanogaster Sex-Linked Recessive Lethal Test.

    DTIC Science & Technology

    1983-03-01

    an aqueous system, a mixture of Tween 80 , ethanol (100%), citrate buffer, (5.0 mM) and distilled water were prepared to stabilize the test Powers-4...chemical fromulated with TWeen 80 , ethanol (100%), citrate buffer (5.0 mM), distilled water, and 1% fructose. These males formed the test Tgroups...Concurrent exposure, 250 ul of a mixture of Tween 80 , ethanol (100%), citrate buffer (5.0 mM), distilled water, and 1% fructose for CS males to feed upon

  14. Serial Testing of Postural Control After Acute Lateral Ankle Sprain

    PubMed Central

    Buckley, W. E.; Denegar, Craig R.

    2001-01-01

    Objective: To identify subjects' changes in postural control during single-leg stance in the 4 weeks after acute lateral ankle sprain. Design and Setting: We used a 2 × 2 × 3 (side-by-plane-by-session) within-subjects design with repeated measures on all 3 factors. All tests were performed in a university laboratory. Subjects: Seventeen young adults (9 men, 8 women; age, 21.8 ± 5.9 years; mass, 74.9 ± 10.5 kg; height, 176.9 ± 7.1 cm) who had sustained unilateral acute mild or moderate lateral ankle sprains. Measurements: Measures of center-of-pressure excursion length, root mean square velocity of center-of-pressure excursions (VEL), and range of center-of-pressure excursions (RANGE) were calculated separately in the frontal and sagittal planes during 5-second trials of static single-leg stance. Results: We noted significant side-by-plane-by-session interactions for magnitude of center-of-pressure excursions in a given trial (PSL) (P = .004), VEL (P = .011), and RANGE (P = .009). Both PSL and VEL in the frontal plane were greater in the injured limbs compared with the uninjured limbs on day 1 and during week 2 but not during week 4, whereas sagittal-plane differences existed during all 3 testing sessions. Injured-limb, frontal-plane RANGE scores were greater than uninjured values at day 1 but not during weeks 2 or 4. No significant differences in sagittal-plane RANGE scores were seen. Conclusions: Postural control was significantly impaired in the injured limbs at day 1 and during week 2 after lateral ankle sprain but not during week 4. Consistent improvement in postural control measures on both injured and uninjured limbs was seen throughout the 4 weeks after ankle sprain. PMID:12937477

  15. Mutagenic Potential of 4-Nitrophenyl Monochloromethyl (Phenyl) Phosphinate Using the Drosophila melanogaster Sex-Linked Recessive Lethal Test.

    DTIC Science & Technology

    1983-08-01

    11CiNO P 0 !12-C1 Molecular Weight: 311.67 Vehicle Due to the instability o ,TAO09 when prepared in an aqueous system, a mixture of Tween 80 , ethanol...variousToncentrations of the test chemical formulated with Tween 80 , ethanol (100%), citrate buffer (5.0 mM), water and 1% fructose. These males Im...a mixture of Tween 80 , ethanol (100%), citrate buffer (5.0 .M), and 1% fructose for CS males to feed upon (250 ul) were designated as negative

  16. Design and Testing of Novel Lethal Ovitrap to Reduce Populations of Aedes Mosquitoes: Community-Based Participatory Research between Industry, Academia and Communities in Peru and Thailand

    PubMed Central

    Yukich, Josh; Soonthorndhada, Amara; Giron, Maziel; Apperson, Charles S.; Ponnusamy, Loganathan; Schal, Coby; Morrison, Amy C.; Keating, Joseph; Wesson, Dawn M.

    2016-01-01

    Background Dengue virus (and Chikungunya and Zika viruses) is transmitted by Aedes aegypti and Aedes albopictus mosquitoes and causes considerable human morbidity and mortality. As there is currently no vaccine or chemoprophylaxis to protect people from dengue virus infection, vector control is the only viable option for disease prevention. The purpose of this paper is to illustrate the design and placement process for an attractive lethal ovitrap to reduce vector populations and to describe lessons learned in the development of the trap. Methods This study was conducted in 2010 in Iquitos, Peru and Lopburi Province, Thailand and used an iterative community-based participatory approach to adjust design specifications of the trap, based on community members’ perceptions and feedback, entomological findings in the lab, and design and research team observations. Multiple focus group discussions (FGD) were held over a 6 month period, stratified by age, sex and motherhood status, to inform the design process. Trap testing transitioned from the lab to within households. Results Through an iterative process of working with specifications from the research team, findings from the laboratory testing, and feedback from FGD, the design team narrowed trap design options from 22 to 6. Comments from the FGD centered on safety for children and pets interacting with traps, durability, maintenance issues, and aesthetics. Testing in the laboratory involved releasing groups of 50 gravid Ae. aegypti in walk-in rooms and assessing what percentage were caught in traps of different colors, with different trap cover sizes, and placed under lighter or darker locations. Two final trap models were mocked up and tested in homes for a week; one model was the top choice in both Iquitos and Lopburi. Discussion The community-based participatory process was essential for the development of novel traps that provided effective vector control, but also met the needs and concerns of community

  17. Victoria Symptom Validity Test performance in acute severe traumatic brain injury: implications for test interpretation.

    PubMed

    Macciocchi, Stephen N; Seel, Ronald T; Alderson, Amy; Godsall, Robert

    2006-08-01

    Effort testing has become commonplace in clinical practice. Recent research has shown that performance on effort tests is highly correlated with performance on neuropsychological measures. Clinical application of effort testing is highly dependent on research derived interpretive guidelines. The Victoria Symptom Validity Test (VSVT) is one of many measures currently used in clinical practice. The VSVT has recommended interpretive guidelines published in the test manual, but the samples used in developing interpretive guidelines are small and heterogeneous and concern has been expressed regarding high false negative rates. In this study, a homogeneous sample of acute, severely brain injured persons were used to assess the sensitivity of the VSVT. Results confirmed that acute, severely brain injured persons (N=71) perform very well on the VSVT. The severe brain injury population is 99% likely to have between 44.1 and 46.8 correct VSVT Combined Score responses. While the VSVT was insensitive to memory dysfunction, the presence of severe visual perceptual (Benton Visual Form Discrimination Score<21) and verbal fluency (Controlled Oral Word Association Score<15) deficits predicted poor performance on the VSVT. These results provide further evidence that performance expectations currently incorporated in the VSVT manual interpretative criteria are too conservative. Empirically based alternative criteria for interpreting VSVT Combined Scores in the TBI population are presented.

  18. Acute toxicity of some synthetic cyanogens in rats: time-dependent cyanide generation and cytochrome oxidase inhibition in soft tissues after sub-lethal oral intoxication.

    PubMed

    Rao, Pooja; Singh, Poonam; Yadav, Shiv Kumar; Gujar, Niranjan L; Bhattacharya, Rahul

    2013-09-01

    Cyanogens include complex nitrile-containing compounds that can generate free cyanide of toxicological significance. Acute toxicity, time-dependent cyanide generation and cytochrome oxidase (CYTOX) inhibition in soft tissues, and urinary thiocyanate levels were measured after acute cyanogen intoxication in rats. Order of cyanogens in terms of LD₅₀ was: malononitrile (MCN)>propionitrile (PCN)≈sodium nitroprusside (SNP)>acrylonitrile (ACN)>succinonitrile (SCN)>acetonitrile (ATCN) for oral, and SNP>MCN>ACN>PCN>SCN>ATCN for intraperitoneal and subcutaneous routes. MCN was most toxic by oral (LD₅₀=66.4 mg/kg) and SNP by intraperitoneal (LD₅₀=16.7 mg/kg) and subcutaneous (LD₅₀=11.9 mg/kg) routes. Minimum survival time (25 min) was recorded after 4.0 LD₅₀ ATCN. Order of cyanogens (0.75 LD₅₀; oral) on the basis of maximum blood cyanide and time of peak cyanide generation were: ATCN>SNP>SCN>PCN>MCN>ACN, and MCN (30 min)

  19. Acute vasoreactivity testing with nicardipine in patients with pulmonary arterial hypertension.

    PubMed

    Saito, Yukihiro; Nakamura, Kazufumi; Miyaji, Katsumasa; Akagi, Satoshi; Mizoguchi, Hiroki; Ogawa, Aiko; Fuke, Soichiro; Fujio, Hideki; Kiyooka, Takahiko; Nagase, Satoshi; Kohno, Kunihisa; Morita, Hiroshi; Kusano, Kengo F; Matsubara, Hiromi; Ohe, Tohru; Ito, Hiroshi

    2012-01-01

    Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 μg·kg⁻¹·min⁻¹ for 5 min and 2 μg·kg⁻¹·min⁻¹ for 5 min) followed by bolus injection (5 μg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients.

  20. Lethal and sublethal toxicity of didecyldimethylammonium chloride in early life stages of white sturgeon, Acipenser transmontanus.

    PubMed

    Teh, Swee Joo; Wong, Cecilia; Furtula, Vesna; Teh, Foo-Ching

    2003-09-01

    This study was conducted to describe the acute lethality and latent toxicity of didecyldimethylammonium chloride (DDAC) on early life stages of white sturgeon (Acipenser transmontanus). Fish responses to 0, 10, 50, 100, 250, 500 microg/L concentrations of DDAC were determined using a 96-h standard static renewal method for acute toxicity testing, with three replicates per concentration. Twenty fish per replicate were tested for 3, 11, and 42-d-old larvae, and 7 fish per replicate were tested for 78-d-old juveniles. Following exposure, survival and growth were evaluated in exposed fish raised in clean water for 2 weeks. The 96-h median lethal concentration (LC50) values for DDAC were 10.0 to 50.0, 58.5, and 99.7 microg/L for 3, 11, and 42-d-old larvae and 100 to 250 microg/L for 78-d-old juveniles. Significant decreases in larval growth and survival were noted at all tested concentrations and in all sturgeon age groups. Results of this study reveal age- and concentration-dependent responses to DDAC. Among the age groups tested, the 3-d-old larvae were the most sensitive group. Results also revealed that 96-h lethality testing alone is not adequate for determining the toxicity of DDAC to white sturgeon.

  1. Protective effect of p-methoxyl-diphenyl diselenide in lethal acute liver failure induced by lipopolysaccharide and D-galactosamine in mice.

    PubMed

    Wilhelm, E A; Jesse, C R; Nogueira, C W

    2009-12-01

    Organoselenium compounds display important antioxidant activity and many biological activities interesting from pharmacological point of view. The aim of this study was to evaluate the hepatoprotective effect of p-methoxyl-diphenyl diselenide, a disubstituted diaryl diselenide, on acute liver injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in mice. The animals received p-methoxyl-diphenyl diselenide (10, 50 and 100 mg/kg; per oral, p.o.) and 1 h after d-GalN (500 mg/kg) and LPS (50 microg/kg) were administered by intraperitoneal route (i.p.). Twenty-four hours after LPS/d-GalN exposure the animals were euthanized to the biochemical and histological analysis. Pretreatment with p-methoxyl-diphenyl diselenide (50 and 100 mg/kg; p.o.) protected against the increase in aspartate aminotransferase (AST) activity induced by LPS/d-GalN exposure in mice. p-Methoxyl-diphenyl diselenide at the doses of 50 and 100 mg/kg protected against the increase in alanine aminotransferase (ALT) activity induced by LPS/D-GalN exposure. In this study, no alteration in ascorbic acid levels was observed in livers of mice exposed to LPS/D-GalN. Glutathione-S-transferase (GST) activity was stimulated by LPS/D-GalN exposure and p-methoxyl-diphenyl diselenide, at all doses, protected against this alteration. p-Methoxyl-diphenyl diselenide was effective in ameliorating inhibition of catalase activity induced by LPS/d-GalN exposure. Histological data showed that sections of livers from LPS/D-GalN-treated mice presented massive hemorrhage, inflammatory cells and necrosis. p-Methoxyl-diphenyl diselenide significantly attenuated LPS/D-GalN-induced hepatic histopathological alterations. Based on the results, we suggest the hepatoprotective effect of p-methoxyl-diphenyl diselenide on acute liver injury induced by LPS/d-GalN exposure in mice.

  2. Risk estimators for radiation-induced bone marrow syndrome lethality in humans

    SciTech Connect

    Scott, B.R.; Hahn, F.F.; McClellan, R.O.; Seiler, F.A.

    1988-09-01

    This manuscript provides risk estimators for acute lethality from radiation-induced injury to the bone marrow of humans after uniform total-body exposure to low linear energy transfer (LET) radiation. The risk estimators are needed for nuclear disaster risk assessment. The approach used is based on the dose X, in units of D50 (i.e., the dose required for 50% lethality). Using animal data, it is demonstrated that the use of dose in units of D50 eliminates most of the variability associated with mammalian species, type of low-LET radiation, and low-LET dose rate. Animal data are used to determine the shape of the dose-effect curve for marrow-syndrome lethality in man and to develop a functional relationship for the dependence of the D50 on dose rate. The functional relationship is used, along with the Weibull model, to develop acute lethality risk estimators for complex temporal patterns of continuous exposure to low-LET radiation. Animal data are used to test model predictions.

  3. 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.

  4. Calcium/calmodulin-dependent protein kinase IV mediates acute nicotine-induced antinociception in acute thermal pain tests.

    PubMed

    Jackson, Kia J; Damaj, Mohamad I

    2013-12-01

    Calcium-activated second messengers such as calcium/calmodulin-dependent protein kinase II have been implicated in drug-induced antinociception. The less abundant calcium-activated second messenger, calcium/calmodulin-dependent protein kinase IV (CaMKIV), mediates emotional responses to pain and tolerance to morphine analgesia but its role in nicotine-mediated antinociception is currently unknown. The goal of this study was to evaluate the role of CaMKIV in the acute effects of nicotine, primarily acute nicotine-induced antinociception. CaMKIV knockout (-/-), heterozygote (+/-), and wild-type (+/+) mice were injected with various doses of nicotine and evaluated in a battery of tests, including the tail-flick and hot-plate tests for antinociception, body temperature, and locomotor activity. Our results show a genotype-dependent reduction in tail-flick and hot-plate latency in CaMKIV (+/-) and (-/-) mice after acute nicotine treatment, whereas no difference was observed between genotypes in the body temperature and locomotor activity assessments. The results of this study support a role for CaMKIV in acute nicotine-induced spinal and supraspinal pain mechanisms, and further implicate involvement of calcium-dependent mechanisms in drug-induced antinociception.

  5. Prediction of Acute Mountain Sickness using a Blood-Based Test

    DTIC Science & Technology

    2015-01-01

    Award Number: W81XWH-11-2-0034 TITLE: Prediction of Acute Mountain Sickness using a Blood-Based Test PRINCIPAL INVESTIGATOR: Robert Roach...Acute Mountain Sickness using a Blood-Based Test 5a. CONTRACT NUMBER: 5b. GRANT NUMBER W81XWH-11-2-0034 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR... mountain sickness or who was AMS resistant. In Phase II, results suggest a completely independent sample was equally effective in predicting AMS

  6. Implementing Lecane quadridentata acute toxicity tests to assess the toxic effects of selected metals (Al, Fe and Zn).

    PubMed

    Guzmán, Félix Torres; González, Francisco Javier Avelar; Martínez, Roberto Rico

    2010-03-01

    An environmental study revealed that three metals (Al, Fe and Zn) are common in the San Pedro River (SPR) (Aguascalientes, Mexico). Regrettably, in many samples the concentrations of these metals exceeded the maximum allowed toxicant concentrations levels as defined in by Mexican legislation. The highest concentrations of the three metals were found during the 2005 dry season, with elevated Al concentrations present along the entire river. Not surprisingly, the highest concentrations for all three metals came from locations adjacent to industrial areas. Estimates of the contribution of these metals to total toxicity revealed that these three metals are important contaminants of the river and responsible for most of the lethal toxicity found in environmental samples. To assess the importance of these reports, we conducted acute toxicity tests to determine LC50 for Al, Fe and Zn on the freshwater rotifer Lecane quadridentata. This permitted us to estimate the contribution of these metals to total toxicity during 2005-2006. Based on LC50 values, all three metals should be considered very toxic, with the zinc LC50 value (0.12 mg L(-1)) making it the most toxic metal for L. quadridentata. This approach can be applied to other sites with similar concentrations of these metals.

  7. Lethal multiple pterygium syndrome

    PubMed Central

    Joshi, Tulika; Noor, Nazia Nagori; Kural, Moolraj; Tripathi, Amita

    2016-01-01

    The multiple pterygium syndrome is consist of wide range of fetal malformations which have a genetic linkage. A defect in embryonic acetylcholine receptor which can be inherited as autosomal recessive, autosomal dominant, or X-linked fashion is the cause of this syndrome. We present a sporadic case of lethal multiple pterygium syndrome. PMID:27843868

  8. Can Artemia Hatching Assay Be a (Sensitive) Alternative Tool to Acute Toxicity Test?

    PubMed

    Rotini, A; Manfra, L; Canepa, S; Tornambè, A; Migliore, L

    2015-12-01

    Artemia sp. is extensively used in ecotoxicity testing, despite criticisms inherent to both acute and long-term tests. Alternative endpoints and procedures should be considered to support the use of this biological model. The hatching process comprises several developmental steps and the cyst hatchability seems acceptable as endpoint criterion. In this study, we assessed the reliability of the hatching assay on A. franciscana by comparing with acute and long-term mortality tests, using two chemicals: Diethylene Glycol (DEG), Sodium Dodecyl Sulphate (SDS). Both DEG and SDS tests demonstrated a dose dependent hatching inhibition. The hatching test resulted more sensitive than acute mortality test and less sensitive than the long-term one. Results demonstrate the reliability and high sensitivity of this hatching assay on a short time lag and support its useful application in first-tier risk assessment procedures.

  9. Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

    PubMed Central

    Seidle, Troy; Robinson, Sally; Holmes, Tom; Creton, Stuart; Prieto, Pilar; Scheel, Julia; Chlebus, Magda

    2010-01-01

    Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area. PMID:20484382

  10. On-site availability of Legionella testing in acute care hospitals, United States.

    PubMed

    Garrison, Laurel E; Shaw, Kristin M S; McCollum, Jeffrey T; Dexter, Carol; Vagnone, Paula M Snippes; Thompson, Jamie H; Giambrone, Gregory; White, Benjamin; Thomas, Stepy; Carpenter, L Rand; Nichols, Megin; Parker, Erin; Petit, Susan; Hicks, Lauri A; Langley, Gayle E

    2014-07-01

    We surveyed 399 US acute care hospitals regarding availability of on-site Legionella testing; 300 (75.2%) did not offer Legionella testing on site. Availability varied according to hospital size and geographic location. On-site access to testing may improve detection of Legionnaires disease and inform patient management and prevention efforts.

  11. Acute toxicity assessment of Polish (waste) water with a microplate-based Hydra attenuata assay: a comparison with the Microtox test.

    PubMed

    Pardos, M; Benninghoff, C; Guéguen, C; Thomas, R; Dobrowolski, J; Dominik, J

    1999-12-15

    The use of Hydra attenuata in acute toxicity assessment is a potentially useful tool in (waste) water biomonitoring. The purpose of this study was to compare the sensitivity of H. attenuata with the extensively used Microtox test on 14 (waste) water samples from the Kraków region (South Poland). To this end, specific morphological changes displayed by the freshwater cnidarian Hydra attenuata (lethal LC50s and sublethal EC50s effects) and bioluminescence of the marine bacteria Vibrio fisheri (Microtox) were compared. Clearly, the Hydra assay was the more sensitive indicator of toxicity. No relationship was found among Hydra toxicological responses and water levels of As, Cd, Co, Cu, Pb and Zn. However, it appeared that toxicity to Hydra might be due to ammonia levels. Additional studies to better circumscribe the tolerance of H. attenuata to 'natural' water characteristics are needed.

  12. Field accuracy of fourth-generation rapid diagnostic tests for acute HIV-1: a systematic review

    PubMed Central

    Lewis, Joseph M.; Macpherson, Peter; Adams, Emily R.; Ochodo, Eleanor; Sands, Anita; Taegtmeyer, Miriam

    2015-01-01

    Introduction: Fourth-generation HIV-1 rapid diagnostic tests (RDTs) detect HIV-1 p24 antigen to screen for acute HIV-1. However, diagnostic accuracy during clinical use may be suboptimal. Methods: Clinical sensitivity and specificity of fourth-generation RDTs for acute HIV-1 were collated from field evaluation studies in adults identified by a systematic literature search. Results: Four studies with 17 381 participants from Australia, Swaziland, the United Kingdom and Malawi were identified. All reported 0% sensitivity of the HIV-1 p24 component for acute HIV-1 diagnosis; 26 acute infections were missed. Specificity ranged from 98.3 to 99.9%. Conclusion: Fourth-generation RDTs are currently unsuitable for the detection of acute HIV-1. PMID:26558545

  13. 40 CFR 797.1930 - Mysid shrimp acute toxicity test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... chambers shall be loosely covered to reduce the loss of test solution or dilution water due to evaporation...” means a continuous or an intermittent passage of test solution or dilution water through a test chamber... test organisms and eliminating loss of organisms in outflow water. (6) “Static system” means a...

  14. 40 CFR 797.1050 - Algal acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... seq.). This guideline prescribes test procedures and conditions using freshwater and marine algae to... definitions also apply to this guideline: (1) Algicidal means having the property of killing algae. (2... volumes of nutrient medium and/or test solution. Start the test by introducing algae into the test...

  15. 40 CFR 797.1050 - Algal acute toxicity test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... seq.). This guideline prescribes test procedures and conditions using freshwater and marine algae to... definitions also apply to this guideline: (1) Algicidal means having the property of killing algae. (2... volumes of nutrient medium and/or test solution. Start the test by introducing algae into the test...

  16. 40 CFR 797.1050 - Algal acute toxicity test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... seq.). This guideline prescribes test procedures and conditions using freshwater and marine algae to... definitions also apply to this guideline: (1) Algicidal means having the property of killing algae. (2... volumes of nutrient medium and/or test solution. Start the test by introducing algae into the test...

  17. 40 CFR 797.1050 - Algal acute toxicity test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... seq.). This guideline prescribes test procedures and conditions using freshwater and marine algae to... definitions also apply to this guideline: (1) Algicidal means having the property of killing algae. (2... volumes of nutrient medium and/or test solution. Start the test by introducing algae into the test...

  18. Draft Test Guideline: Whole Sediment Acute Toxicity Invertebrates, Marine

    EPA Pesticide Factsheets

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  19. Draft Test Guideline: Fish Acute Toxicity Mitigated By Humic Acid

    EPA Pesticide Factsheets

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  20. Draft Test Guideline: Whole Sediment Acute Toxicity Invertebrates, Freshwater

    EPA Pesticide Factsheets

    The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

  1. Sensitivity of Danio rerio (Teleostei, Cyprinidae) during two stages of development based on acute toxicity tests.

    PubMed

    Freiry, R; Stelzer, J A A; Maltchik, L; Arenzon, A

    2014-10-01

    The sensitivity of Danio rerio to three chemicals was compared at two growth stages [larval (10 ± 2 after hatching) and post-larval (60 ± 4 days after hatching)] based on acute toxicity tests. Thirty-nine 48 h acute toxicity tests were performed with the substances CuSO4, NaCl and KCl. The 48 h LC50 values at the two growth stages were compared by independent samples t-tests. The results showed a clear decrease in sensitivity when post-larval organisms were used. Since acute toxicity test methods for D. rerio that recommend using post-larval stage fish do not represent the most sensitive stage of the test organism, our study suggests a revision of the methods to use larval fish.

  2. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    PubMed

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-01-06

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants.

  3. Imaging tests for accurate diagnosis of acute biliary pancreatitis.

    PubMed

    Şurlin, Valeriu; Săftoiu, Adrian; Dumitrescu, Daniela

    2014-11-28

    Gallstones represent the most frequent aetiology of acute pancreatitis in many statistics all over the world, estimated between 40%-60%. Accurate diagnosis of acute biliary pancreatitis (ABP) is of outmost importance because clearance of lithiasis [gallbladder and common bile duct (CBD)] rules out recurrences. Confirmation of biliary lithiasis is done by imaging. The sensitivity of the ultrasonography (US) in the detection of gallstones is over 95% in uncomplicated cases, but in ABP, sensitivity for gallstone detection is lower, being less than 80% due to the ileus and bowel distension. Sensitivity of transabdominal ultrasonography (TUS) for choledocolithiasis varies between 50%-80%, but the specificity is high, reaching 95%. Diameter of the bile duct may be orientative for diagnosis. Endoscopic ultrasonography (EUS) seems to be a more effective tool to diagnose ABP rather than endoscopic retrograde cholangiopancreatography (ERCP), which should be performed only for therapeutic purposes. As the sensitivity and specificity of computerized tomography are lower as compared to state-of-the-art magnetic resonance cholangiopancreatography (MRCP) or EUS, especially for small stones and small diameter of CBD, the later techniques are nowadays preferred for the evaluation of ABP patients. ERCP has the highest accuracy for the diagnosis of choledocholithiasis and is used as a reference standard in many studies, especially after sphincterotomy and balloon extraction of CBD stones. Laparoscopic ultrasonography is a useful tool for the intraoperative diagnosis of choledocholithiasis. Routine exploration of the CBD in cases of patients scheduled for cholecystectomy after an attack of ABP was not proven useful. A significant rate of the so-called idiopathic pancreatitis is actually caused by microlithiasis and/or biliary sludge. In conclusion, the general algorithm for CBD stone detection starts with anamnesis, serum biochemistry and then TUS, followed by EUS or MRCP. In the end

  4. Apparent lethal concentrations of pyrolysis products of some polymeric materials

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Marcussen, W. H.; Furst, A.; Kourtides, D. A.; Parker, J. A.

    1976-01-01

    Thirty-nine samples of polymeric materials were evaluated to determine the apparent lethal concentrations of their pyrolysis products. The materials were compared on the basis of the apparent lethal concentration for 50 percent of the test animals. Relative toxicity rankings based o apparent lethal concentration values can differ significantly depending on whether they are based on weight of sample charged or weight of sample pyrolyzed. The ranking of polyphenylene sulfide is particularly sensitive to this difference.

  5. On the performance of acute toxicity tests using the National Reference Toxicant Database

    SciTech Connect

    Zaidhk, B.

    1995-12-31

    The US National Reference Toxicant Database was used to compile data from 158 Ceriodaphnia dubia, and 187 fathead minnow acute toxicity tests. The data are analyzed using the EPA flow-chart for acute toxicity tests to determine the distribution of test methods selected. The data are reanalyzed using maximum likelihood estimation assuming probit, logit and Gompertz tolerance distributions and non-parametrically using the Spearman-Karber method with and without trimming. The results of these analyses are compared with respect to mean square error for the parametric methods and confidence intervals for the point estimate for all analyses.

  6. Evaluation of a Western Blot Test in an Outbreak of Acute Pulmonary Histoplasmosis

    PubMed Central

    Pizzini, Claudia V.; Zancopé-Oliveira, Rosely M.; Reiss, Errol; Hajjeh, Rana; Kaufman, Leo; Peralta, José Mauro

    1999-01-01

    A western blot (WB) test was evaluated for detection of antibodies against native glycosylated and chemically deglycosylated M and H antigens of Histoplasma capsulatum in serum obtained from patients during the acute phase of pulmonary histoplasmosis that occurred during an outbreak. Of 275 serum samples tested by immunodiffusion and complement fixation (CF) samples from 40 patients affected during this outbreak and from 37 negative controls were tested by WB test. A group of patients whose sera were negative for CF antibodies and precipitins early in the acute stage of histoplasmosis but who all seroconverted during convalescence 6 weeks later were tested with the WB test. Antibodies against untreated H and M antigens were detected at a 1:100 dilution by WB test in 45% of the 20 acute-phase serum samples and in all 20 of the convalescent-phase specimens. The WB test’s sensitivity for acute-phase specimens increased to 90% (18 of 20 specimens) when H and M antigens were treated by periodate oxidation to inactivate susceptible carbohydrate epitopes. When native glycosylated antigens were used in the WB test, positive reactions were observed in negative control serum specimens (3 of 37 specimens; 8%) and in serum specimens obtained from asymptomatic persons screened as part of the outbreak investigation (13 of 20 specimens; 65%). These positive reactions were also attributed to glycosidic epitopes since the specificity of the WB test increased from 78 to 100% when periodate-treated H and M antigens were used. WB test with deglycosylated H and M antigens of histoplasmin provides a rapid, sensitive, and specific test to diagnose acute pulmonary histoplasmosis before precipitins can be detected. PMID:9874658

  7. Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

    USGS Publications Warehouse

    Johnson, W. Waynon; Finley, Mack T.

    1980-01-01

    Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates.The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies.Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a).The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity data

  8. 40 CFR 797.1400 - Fish acute toxicity test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... particulate matter of the dilution water should be measured at the beginning of each static test and at the..., acclimation and test periods. (C) Apparatus for straining particulate matter, removing gas bubbles, or insufficient dissolved oxygen, respectively. (D) Apparatus for providing a 16-hour light and 8-hour...

  9. 40 CFR 797.1400 - Fish acute toxicity test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... particulate matter of the dilution water should be measured at the beginning of each static test and at the..., acclimation and test periods. (C) Apparatus for straining particulate matter, removing gas bubbles, or insufficient dissolved oxygen, respectively. (D) Apparatus for providing a 16-hour light and 8-hour...

  10. 40 CFR 797.1400 - Fish acute toxicity test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... particulate matter of the dilution water should be measured at the beginning of each static test and at the..., acclimation and test periods. (C) Apparatus for straining particulate matter, removing gas bubbles, or insufficient dissolved oxygen, respectively. (D) Apparatus for providing a 16-hour light and 8-hour...

  11. 40 CFR 797.1400 - Fish acute toxicity test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... particulate matter of the dilution water should be measured at the beginning of each static test and at the..., acclimation and test periods. (C) Apparatus for straining particulate matter, removing gas bubbles, or insufficient dissolved oxygen, respectively. (D) Apparatus for providing a 16-hour light and 8-hour...

  12. 40 CFR 797.1400 - Fish acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... particulate matter of the dilution water should be measured at the beginning of each static test and at the..., acclimation and test periods. (C) Apparatus for straining particulate matter, removing gas bubbles, or insufficient dissolved oxygen, respectively. (D) Apparatus for providing a 16-hour light and 8-hour...

  13. Lethal entanglement in baleen whales.

    PubMed

    Cassoff, Rachel M; Moore, Kathleen M; McLellan, William A; Barco, Susan G; Rotsteins, David S; Moore, Michael J

    2011-10-06

    Understanding the scenarios whereby fishing gear entanglement of large whales induces mortality is important for the development of mitigation strategies. Here we present a series of 21 cases involving 4 species of baleen whales in the NW Atlantic, describing the available sighting history, necropsy observations, and subsequent data analyses that enabled the compilation of the manners in which entanglement can be lethal. The single acute cause of entanglement mortality identified was drowning from entanglement involving multiple body parts, with the animal's inability to surface. More protracted causes of death included impaired foraging during entanglement, resulting in starvation after many months; systemic infection arising from open, unresolved entanglement wounds; and hemorrhage or debilitation due to severe gear-related damage to tissues. Serious gear-induced injury can include laceration of large vessels, occlusion of the nares, embedding of line in growing bone, and massive periosteal proliferation of new bone in an attempt to wall off constricting, encircling lines. These data show that baleen whale entanglement is not only a major issue for the conservation of some baleen whale populations, but is also a major concern for the welfare of each affected individual.

  14. 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.

  15. 40 CFR 797.1300 - Daphnid acute toxicity test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., acclimation, and test periods; (3) apparatus for straining particulate matter, removing gas bubbles, or aerating the water as necessary; and (4) an apparatus for providing a 16-hour light and 8-hour dark... concentration Particulate matter 20 mg/liter. Total organic carbon or 2 mg/liter. Chemical oxygen demand 5...

  16. 40 CFR 795.120 - Gammarid acute toxicity test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., conductivity, TOC or COD, and particulate matter of the dilution water shall be measured at the beginning of..., acclimation and test periods; (4) Apparatus for straining particulate matter, removing gas bubbles, or... dark photoperiod with a 15- to 30-minute transition period. (B) Facilities should be well...

  17. 40 CFR 797.1300 - Daphnid acute toxicity test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., acclimation, and test periods; (3) apparatus for straining particulate matter, removing gas bubbles, or aerating the water as necessary; and (4) an apparatus for providing a 16-hour light and 8-hour dark... concentration Particulate matter 20 mg/liter. Total organic carbon or 2 mg/liter. Chemical oxygen demand 5...

  18. 40 CFR 797.1300 - Daphnid acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., acclimation, and test periods; (3) apparatus for straining particulate matter, removing gas bubbles, or aerating the water as necessary; and (4) an apparatus for providing a 16-hour light and 8-hour dark... concentration Particulate matter 20 mg/liter. Total organic carbon or 2 mg/liter. Chemical oxygen demand 5...

  19. 40 CFR 797.1300 - Daphnid acute toxicity test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., acclimation, and test periods; (3) apparatus for straining particulate matter, removing gas bubbles, or aerating the water as necessary; and (4) an apparatus for providing a 16-hour light and 8-hour dark... concentration Particulate matter 20 mg/liter. Total organic carbon or 2 mg/liter. Chemical oxygen demand 5...

  20. 40 CFR 795.120 - Gammarid acute toxicity test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., conductivity, TOC or COD, and particulate matter of the dilution water shall be measured at the beginning of..., acclimation and test periods; (4) Apparatus for straining particulate matter, removing gas bubbles, or... dark photoperiod with a 15- to 30-minute transition period. (B) Facilities should be well...

  1. 40 CFR 795.120 - Gammarid acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., conductivity, TOC or COD, and particulate matter of the dilution water shall be measured at the beginning of..., acclimation and test periods; (4) Apparatus for straining particulate matter, removing gas bubbles, or... dark photoperiod with a 15- to 30-minute transition period. (B) Facilities should be well...

  2. 40 CFR 797.1300 - Daphnid acute toxicity test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., acclimation, and test periods; (3) apparatus for straining particulate matter, removing gas bubbles, or aerating the water as necessary; and (4) an apparatus for providing a 16-hour light and 8-hour dark... concentration Particulate matter 20 mg/liter. Total organic carbon or 2 mg/liter. Chemical oxygen demand 5...

  3. 40 CFR 795.120 - Gammarid acute toxicity test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., conductivity, TOC or COD, and particulate matter of the dilution water shall be measured at the beginning of..., acclimation and test periods; (4) Apparatus for straining particulate matter, removing gas bubbles, or... dark photoperiod with a 15- to 30-minute transition period. (B) Facilities should be well...

  4. 40 CFR 795.120 - Gammarid acute toxicity test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., conductivity, TOC or COD, and particulate matter of the dilution water shall be measured at the beginning of..., acclimation and test periods; (4) Apparatus for straining particulate matter, removing gas bubbles, or... dark photoperiod with a 15- to 30-minute transition period. (B) Facilities should be well...

  5. 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.

  6. Evaluation of a rapid IgM detection test for diagnosis of acute leptospirosis in dogs.

    PubMed

    Lizer, J; Grahlmann, M; Hapke, H; Velineni, S; Lin, D; Kohn, B

    2017-02-24

    Recently, a lateral flow assay (LFA) for detection of Leptospira-specific IgM in canine sera became commercially available in Europe. The present study aims to evaluate the diagnostic performance of this assay using canine sera from a collection of diagnostic accessions. Diagnostic sensitivity was assessed by testing 37 acute-phase and 9 corresponding convalescent-phase sera from dogs with a confirmed diagnosis of leptospirosis. Specificity was determined by testing sera from sick dogs with non-leptospiral infections (n=15) and healthy dogs with incomplete history of vaccination (n=45). During acute phase of illness, LFA scored positive for 28/37 sera with a sensitivity of 75.7 per cent while only 9/37 (24.3 per cent) samples were positive on microscopic agglutination test. The specificity of the LFA was 98.3 per cent (59/60). This test showed 89.7 and 100 per cent overall agreements with clinical diagnosis for acute-phase and convalescent-phase sera, respectively. The impact of vaccination on the LFA was also determined and vaccine-stimulated IgM responses were negative in 19/25 (76 per cent) dogs at 12 weeks post vaccination. In conclusion, the LFA is a rapid and reliable test for early detection of Leptospira-specific IgM during acute phase of canine leptospirosis. However, interpretation of a positive result must be made in the context of clinical signs and vaccination history.

  7. Maintaining the Constant Exposure Condition for an Acute Caenorhabditis elegans Mortality Test Using Passive Dosing

    PubMed Central

    Kwon, Hyuck-Chul; Roh, Ji-Yeon; Lim, Dongyoung; Choi, Jinhee

    2011-01-01

    Objectives Maintaining the constant exposure to hydrophobic organic compouds in acute toxicity tests is one of the most difficult issues in the evaluation of their toxicity and corresponding risks. Passive dosing is an emerging tool to keep constant aqueous concentration because of the overwhelming mass loaded in the dosing phase. The primary objectives of this study were to develop the constant exposure condition for an acute mortality test and to compare the performance of the passive dosing method with the conventional spiking with co-solvent. Methods A custom cut polydimethylsiloxane (PDMS) tubing loaded with benzyl butyl phthalate (BBP) was placed in each well of a 24-well plate containing assay medium. The rate of the release of BBP from PDMS was evaluated by measuring the change in the concentration of BBP in the assay medium. The efficiency of maintaining constant exposure condition was also evaluated using a simple two-compartment mass transport model employing a film-diffusion theory. An acute mortality test using 10 C. elegans in each well was conducted for the evaluation of the validity of passive dosing and the comparative evaluation of the passive dosing method and the conventional spiking method. Results Free concentration in the assay medium reached 95% steady state value within 2.2 hours without test organisms, indicating that this passive dosing method is useful for an acute toxicity test in 24 hours. The measured concentration after the mortality test agreed well with the estimated values from partitioning between PDMS and the assay medium. However, the difference between the nominal and the free concentration became larger as the spiked concentration approached water solubility, indicating the instability of the conventional spiking with a co-solvent. Conclusions The results in this study support that passive dosing provides a stable exposure condition for an acute toxicity test. Thus, it is likely that more reliable toxicity assessment can be

  8. Use of life tables and LC50 tests to evaluate chronic and acute toxicity effects of copper on the marine copepod Tisbe furcata (Baird)

    SciTech Connect

    Bechmann, R.K. . Dept. of Marine Zoology and Marine Chemistry)

    1994-09-01

    Cohorts of the epiphytic marine copepod Tisbe furcata were chronically exposed to copper in life-table experiments to test whether ecologically relevant impacts can occur at sublethal concentrations. Data on fecundity, longevity, and rate of development were used to calculate r[sub m]--the intrinsic rate of natural increase. Acute toxicity tests were done to compare the concentrations of copper affecting individual lethality and population biology. The LC50 value for Tisbe furcata nauplii was 2.8 [mu]M copper. The results from the life-table experiments show that 0.9 [mu]M copper can cause significant negative effects on demographic parameters (total production of nauplii, life span, and reproductive period for fertile females) and reduce the percentage of fertile females leading to a 61% reduction of r[sub m]. However, r[sub m] was still positive at 0.9 [mu]M copper, and the net reproductive rate (R[sub 0]) indicated a fivefold increase in population size from one generation to the next. Although there were no significant effects of copper at 0.5 [mu]M, there was a negative trend in almost all the demographic parameters, indicating that the observed 10% reduction of r[sub m] at this concentration was an effect of copper. For the substances tested so far with both acute LC50 tests and life-table experiments, r[sub m] was not reduced at concentrations below LC50/10. When life-table experiments are used as part of environmental hazard assessments, concentrations below LC50/10 should be tested to detect substances that are potentially harmful to the environment at sublethal concentrations, rather than testing concentrations close to LC50.

  9. Hydroxychloroquine-induced acute generalized exanthematous pustulosis with positive patch-testing.

    PubMed

    Charfi, Ons; Kastalli, Sarrah; Sahnoun, Rym; Lakhoua, Ghozlane

    2015-01-01

    Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction, mostly induced by drugs. Hydroxychloroquine have been rarely reported in literature as a causative drug of this reaction. We report a case of AGEP induced by hydroxychloroquine with systemic involvement and confirmed by positive patch testing.

  10. Carbon monoxide and lethal arrhythmias

    SciTech Connect

    Farber, J.P.; Schwartz, P.J.; Vanoli, E.; Stramba-Badiale, M.; De Ferrari, G.M. )

    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 are 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)

  11. Results of acute and chronic toxicity tests conducted at SRS NPDES outfalls, July--October 1991

    SciTech Connect

    Specht, W.L.

    1992-01-01

    Acute (48 hour LC50) and chronic (7-day reproductive impairment) toxicity tests were conducted on Ceriodaphnia dubia in water collected from 53 NPDES outfalls. All tests were conducted at the in-stream waste concentration. only 12 of the 53 outfalls showed no evidence of toxicity. Twenty-eight of the outfalls were acutely toxic, often producing 100% mortality during the first day of exposure. Fourteen outfalls had no discharge at the time of sampling and could not be tested. Three outfalls were not tested because their toxicity has been adequately characterized in other investigations. Elevated concentrations of total residual chlorine are suspected to be responsible for the observed toxicity of many NPDES outfalls, particularly the sanitary wastewater treatment plants. Chemical data from previous studies indicate that metals may also be present in toxic concentrations at many outfalls. Toxicity identification and reduction options are discussed.

  12. [Are urgent imaging tests indicated in the management of acute pancreatitis?].

    PubMed

    Fornell Pérez, R; Lozano Rodríguez, A

    2016-01-01

    Acute pancreatitis is a common emergency within abdominal disease. It is accepted that two of three conditions must be fulfilled for its diagnosis: characteristic clinical presentation, characteristic laboratory findings, and/or characteristic diagnostic imaging findings. The first two conditions are the most often used, probably for reasons of efficiency and frequency. Nevertheless, the need for imaging studies is sometimes a source of conflict. For this reason, we decided to review the current evidence regarding the indication of urgent imaging tests in the management of acute pancreatitis.

  13. The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

    SciTech Connect

    Moroni, Maria; Ngudiankama, Barbara F.; Christensen, Christine; Olsen, Cara H.; Owens, Rossitsa; Lombardini, Eric D.; Holt, Rebecca K.; Whitnall, Mark H.

    2013-08-01

    Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes.

  14. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity

    PubMed Central

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination. PMID:27110562

  15. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity.

    PubMed

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination.

  16. How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing.

    PubMed

    McCue, Marshall D; Guzman, R Marena; Passement, Celeste A; Davidowitz, Goggy

    2015-01-01

    Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint. In this study we raised populations of five species of insects (adult grasshoppers, crickets, cockroaches, and larval beetles and moths) on diets labeled with either 13C-palmitic acid or 13C-leucine to isotopically enrich the lipids or the proteins in their bodies, respectively. The insects were allowed to become postabsorptive and then starved. We periodically measured the δ13C of the exhaled breath to characterize how each species adjusted their reliance on endogenous lipids and proteins as energy sources. We found that starving insects employ a wide range of strategies for regulating lipid and protein oxidation. All of the insects except for the beetle larvae were capable of sharply reducing reliance on protein oxidation; however, this protein sparing strategy was usually unsustainable during the entire starvation period. All insects increased their reliance on lipid oxidation, but while some species (grasshoppers, cockroaches, and beetle larvae) were still relying extensively on lipids at the time of death, other species (crickets and moth larvae) allowed rates of lipid oxidation to return to prestarvation levels. Although lipids and proteins are critical metabolic fuels for both vertebrates and insects, insects apparently exhibit a much wider range of strategies for rationing these limited resources during starvation.

  17. How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing

    PubMed Central

    McCue, Marshall D.; Guzman, R. Marena; Passement, Celeste A.; Davidowitz, Goggy

    2015-01-01

    Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint. In this study we raised populations of five species of insects (adult grasshoppers, crickets, cockroaches, and larval beetles and moths) on diets labeled with either 13C-palmitic acid or 13C-leucine to isotopically enrich the lipids or the proteins in their bodies, respectively. The insects were allowed to become postabsorptive and then starved. We periodically measured the δ13C of the exhaled breath to characterize how each species adjusted their reliance on endogenous lipids and proteins as energy sources. We found that starving insects employ a wide range of strategies for regulating lipid and protein oxidation. All of the insects except for the beetle larvae were capable of sharply reducing reliance on protein oxidation; however, this protein sparing strategy was usually unsustainable during the entire starvation period. All insects increased their reliance on lipid oxidation, but while some species (grasshoppers, cockroaches, and beetle larvae) were still relying extensively on lipids at the time of death, other species (crickets and moth larvae) allowed rates of lipid oxidation to return to prestarvation levels. Although lipids and proteins are critical metabolic fuels for both vertebrates and insects, insects apparently exhibit a much wider range of strategies for rationing these limited resources during starvation. PMID:26465334

  18. Systematic review of acute levodopa and apomorphine challenge tests in the diagnosis of idiopathic Parkinson's disease

    PubMed Central

    Clarke, C; Davies, P

    2000-01-01

    OBJECTIVES—To perform a systematic review of studies examining the diagnostic accuracy of acute challenge tests with levodopa and/or apomorphine in parkinsonian syndromes to assess their value in the diagnosis of idiopathic Parkinson's disease.
METHODS—A literature search including Medline and the Cochrane Library was performed for studies published in any language comparing acute levodopa and/or apomorphine response with chronic levodopa therapy in parkinsonian syndromes. Abstracted sensitivity and specificity data were summarised using variance weighting and conditional logistic regression for studies comparing two challenge tests.
RESULTS—Thirteen studies were located: four examining de novo patients and nine examining patients with well established idiopathic Parkinson's disease and non-parkinsonian conditions. Despite the significant heterogeneity in the methodologies employed, the comparable results suggest that this had little effect on the accuracy of the tests. The sensitivity for the diagnosis of established idiopathic Parkinson's disease was: apomorphine 0.86 (95% confidence interval (95% CI) 0.78-0.94), acute levodopa 0.75 (95% CI 0.64-0.85), and chronic levodopa therapy 0.91 (95% CI 0.85-0.99). The specificity for the diagnosis of established idiopathic Parkinson's disease was: apomorphine 0.85 (95% CI 0.74-0.96), acute levodopa 0.87(95% CI 0.77-0.97), and chronic levodopa therapy 0.77 (95% CI 0.61-0.93). The number of patients positive for each test divided by the number with clinically diagnosed de novo disease was: apomorphine 0.63 (95% CI 0.56-0.70), acute levodopa 0.69 (95% CI 0.59-0.80), and chronic levodopa therapy 0.76 (95% CI 0.70-0.82).
CONCLUSIONS—The accuracy of the acute levodopa and apomorphine challenge tests is similar to, but not superior than, that of chronic levodopa therapy in the diagnosis of idiopathic Parkinson's disease. As most patients will be given chronic dopamimetic therapy, these tests add nothing while

  19. Evaluation of lethal and non-lethal sampling methods for the detection of white sturgeon iridovirus infection in white sturgeon, Acipenser transmontanus (Richardson).

    PubMed

    Drennan, J D; Lapatra, S E; Samson, C A; Ireland, S; Eversman, K F; Cain, K D

    2007-06-01

    Pectoral fin tissue of white sturgeon was investigated as a potential non-lethal sample source for the detection of white sturgeon iridovirus (WSIV) infection. Histopathology and polymerase chain reaction (PCR) results using fin tissue were compared with the standard lethal histopathology sampling method that utilizes head tissue. Tissues for each of the three sampling methods were collected weekly for 8 weeks from individual sturgeon undergoing an experimental cohabitation challenge with fish infected with the Abernathy isolate of WSIV. Non-lethal fin histopathological evaluation did not reveal infection during the first 3 weeks of sampling, while non-lethal PCR and the lethal method were variable. However, all three sampling methods were equally capable of identifying infection from 4 to 8 weeks post-exposure. Of the survivors tested, all were negative by PCR and the lethal method, and only one fish was identified as being positive by non-lethal fin histopathology. In another experiment, all three sampling methods were applied to asymptomatic WSIV carriers in a case study conducted at the Kootenai Tribal Sturgeon Conservation Hatchery. Results showed that both lethal and non-lethal fin histopathology were equally effective in detecting infection, but PCR was unable to identify this strain of WSIV. Depending on the virus isolate, these results suggest that non-lethal sampling of fin tissue (histopathology or PCR) is comparable with the lethal sampling method at identifying WSIV infection once infection is established, and under certain circumstances may provide an alternative to lethal sampling.

  20. Certification testing as an acute naturalistic stressor for disaster dog handlers.

    PubMed

    Lit, L; Boehm, D; Marzke, S; Schweitzer, J; Oberbauer, A M

    2010-09-01

    USA Federal Disaster Canine Teams, consisting of a handler and a dog, are essential for locating survivors following a disaster. Certification, required by the Federal Emergency Management Agency Urban Search and Rescue organization, requires two successful mock searches. Confirmation of the certification testing process as an acute stressor might offer further opportunities to consider stress effects on handlers and dogs in a controlled environment. This study used a pretest-posttest design to evaluate relationships between salivary hormone concentrations (cortisol and testosterone) and subjective stress ratings in handlers and controls, handler assessments of stress in their dogs, and posttest temperature and pulse rate in dogs. Posttest, both subjective stress ratings and salivary cortisol concentration were higher in handlers than controls with both correlated to handlers' assessment of stress in their dogs. Handlers' posttest salivary cortisol concentration was associated with posttest dog pulse and temperature. Posttest cortisol concentration was lower in handlers who were successfully certified compared with those who failed, and was also lower in handlers whose primary occupation was "firefighter". Salivary testosterone concentrations increased from pretest to posttest in handlers but decreased in controls, and higher posttest handler testosterone concentration was negatively associated with posttest dog pulse rate. These findings confirm certification testing as an acute stressor, suggest a relationship between stress and performance moderated by occupation, and demonstrate an interaction between handler stress and dog physiological responses. This certification testing offers a controlled environment for targeted evaluation of effects of an acute naturalistic stressor on disaster dog handlers and dogs.

  1. Acute toxicity assessment of ANAMMOX substrates and antibiotics by luminescent bacteria test.

    PubMed

    Ding, Shuang; Wu, Junwei; Zhang, Meng; Lu, Huifeng; Mahmood, Qaisar; Zheng, Ping

    2015-12-01

    Acute toxicities of anaerobic ammonia oxidation (ANAMMOX) substrates and four antibiotics from pharmaceutical wastewaters on ANAMMOX process were reported. Individual and joint acute toxicity assays were performed using 50% inhibitory concentration (IC50). Results showed that IC50 values and their 95% confidence interval of ammonium chloride (A), sodium nitrite (B), penicillin G-Na (C), polymyxin B sulfate (D), chloramphenicol (E) and kanamycin sulfate (F) were 2708.9 (2247.9-3169.9), 1475.4 (1269.9-1680.9), 5114.4 (4946.4-5282.4), 10.2 (1.8-18.6), 409.9 (333.7-486.1) and 5254.1 (3934.4-6573.8) mgL(-1) respectively, suggesting toxicities were in the order of D>E>B>A>C>F. Joint acute toxicities of bicomponent mixtures A and B, C and D, C and F, D and F were independent; D and E, E and F were additive while C and E were synergistic. Joint acute toxicities of multicomponent mixtures were synergistic or additive. Luminescent bacteria test is an easy and robust method for forecasting the feasibility of ANAMMOX process for pharmaceutical wastewater treatment.

  2. The effect of acute hypoxia at low altitude and acute normoxia at high altitude on performance during a 30-s Wingate test in children.

    PubMed

    Blonc, S; Falgairette, G; Bedu, M; Fellmann, N; Spielvogel, H; Coudert, J

    1994-10-01

    The effect of acute hypoxia (FIO2 = 0.137 +/- 0.001) at Low Altitude (LA: Clermont-Ferrand, 330 m) and acute normoxia (FIO2 = 0.306 +/- 0.006) at High Altitude (HA: La Paz, 3600 m) on performance during a 30-s Wingate test has been investigated in prepubertal children (Tanner stage 1). Twenty five boys (LA, n = 10; HA, n = 15) aged from 10.6 to 12.7 years performed two Wingate tests at random: at LA, one in normoxia (ambient air) and one in acute hypoxia and at HA, one in chronic hypoxia (ambient air) and one in acute normoxia. The subjects performed the two tests using the same calibrated cycle ergometer. Peak Power (PP), Mean Power (MP), O2 uptake during the 30 s (VO2) and blood lactate accumulation (delta [L]s) were measured. Compared to normoxia, acute hypoxia at LA did not alter PP (8.0 +/- 1.1 vs 7.9 +/- 1.3 W.kg-1 BW) and MP (6.1 +/- 0.7 vs 6.1 +/- 1.1 W.kg-1 BW). Similarly, compared to chronic hypoxia, acute normoxia at HA did not modify these parameters (PP: 7.4 +/- 1.5 vs 7.3 +/- 1.8; MP: 5.4 +/- 1.2 vs 5.5 +/- 1.1; W.kg-1 BW). VO2 and delta [L]s were neither significantly changed by acute hypoxia at LA (520 +/- 50 vs 550 +/- 60 ml O2; 5.3 +/- 1.7 vs 4.8 +/- 1.7 mmol.l-1) nor by acute normoxia at HA (530 +/- 110 vs 500 +/- 90 ml O2; 3.4 +/- 1.3 vs 3.3 +/- 1.0 mmol.l-1).(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Pegfilgrastim Improves Survival of Lethally Irradiated Nonhuman Primates.

    PubMed

    Hankey, Kim G; Farese, Ann M; Blaauw, Erica C; Gibbs, Allison M; Smith, Cassandra P; Katz, Barry P; Tong, Yan; Prado, Karl L; MacVittie, Thomas J

    2015-06-01

    Leukocyte growth factors (LGF), such as filgrastim, pegfilgrastim and sargramostim, have been used to mitigate the hematologic symptoms of acute radiation syndrome (ARS) after radiation accidents. Although these pharmaceuticals are currently approved for treatment of chemotherapy-induced myelosuppression, such approval has not been granted for myelosuppression resulting from acute radiation exposure. Regulatory approval of drugs used to treat radiological or nuclear exposure injuries requires their development and testing in accordance with the Animal Efficacy Rule, set forth by the U.S. Food and Drug Administration. To date, filgrastim is the only LGF that has undergone efficacy assessment conducted under the Animal Efficacy Rule. To confirm the efficacy of another LGF with a shorter dosing regimen compared to filgrastim, we evaluated the use of pegfilgrastim (Neulasta(®)) in a lethal nonhuman primate (NHP) model of hematopoietic acute radiation syndrome (H-ARS). Rhesus macaques were exposed to 7.50 Gy total-body irradiation (the LD(50/60)), delivered at 0.80 Gy/min using linear accelerator 6 MV photons. Pegfilgrastim (300 μg/kg, n = 23) or 5% dextrose in water (n = 23) was administered on day 1 and 8 postirradiation and all animals received medical management. Hematologic and physiologic parameters were evaluated for 60 days postirradiation. The primary, clinically relevant end point was survival to day 60; secondary end points included hematologic-related parameters. Pegfilgrastim significantly (P = 0.0014) increased 60 day survival to 91.3% (21/23) from 47.8% (11/23) in the control. Relative to the controls, pegfilgrastim also significantly: 1. decreased the median duration of neutropenia and thrombocytopenia; 2. improved the median time to recovery of absolute neutrophil count (ANC) ≥500/μL, ANC ≥1,000/μL and platelet (PLT) count ≥20,000/μL; 3. increased the mean ANC at nadir; and 4. decreased the incidence of Gram-negative bacteremia. These data

  4. Progress Towards the Development of a Fathead Minnow Embryo Test and Comparison to the Zebrafish Embryo Test for Assessing Acute Fish Toxicity

    EPA Science Inventory

    The Zebrafish Embryo Test (ZFET) for acute fish toxicity is a well developed method nearing adoption as an OECD Test Guideline. Early drafts of the test guideline (TG) envisioned a suite of potential test species to be covered including zebrafish, fathead minnow, Japanese Medaka...

  5. Pulmonary function test findings in patients with acute inhalation injury caused by smoke bombs

    PubMed Central

    Cao, Lu; Zhang, Xin-Gang; Wang, Jian-Guo; Wang, Han-Bin; Chen, Yi-Bing; Zhao, Da-Hui; Shi, Wen-Fang

    2016-01-01

    Background This study aimed to determine the effects of smoke bomb-induced acute inhalation injury on pulmonary function at different stages of lung injury. Methods We performed pulmonary function tests (PFTs) in 15 patients with acute inhalation injury from days 3 to 180 after smoke inhalation. We measured the trace element zinc in whole blood on days 4 and 17, and correlations of zinc levels with PFTs were performed. Results In the acute stage of lung injury (day 3), 3 of 11 patients with mild symptoms had normal pulmonary function and 8 patients with restrictive ventilatory dysfunction and reduced diffusing capacity. Some patients also had mild obstructive ventilatory dysfunction (5 patients) and a decline in small airway function (6 patients). For patients with severe symptoms, PFT results showed moderate to severe restrictive ventilatory dysfunction and reduced diffusing capacity. PaCO2 was significantly higher (P=0.047) in patients with reduced small airway function compared with those with normal small airway function. Whole blood zinc levels in the convalescence stage (day 17) were significantly lower than those in the acute stage (day 4). Zinc in the acute stage was negatively correlated with DLCO/VA on days 3, 10, and 46 (r=−0.633, −0.676, and −0.675 respectively, P<0.05). Conclusions Smoke inhalation injury mainly causes restrictive ventilatory dysfunction and reduced diffusing capacity, and causes mild obstructive ventilatory dysfunction and small airway function decline in some patients. Zinc is negatively correlated with DLCO/VA. Zinc levels may be able to predict prognosis and indicate the degree of lung injury. PMID:28066595

  6. Relative sensitivity of one freshwater and two marine acute toxicity tests as determined by testing 30 offshore E & P chemicals.

    PubMed

    Sverdrup, Line E; Fürst, Charlotte S; Weideborg, Mona; Vik, Eilen A; Stenersen, Jørgen

    2002-01-01

    Acute toxicity of 30 offshore E & P (Exploration and Production) chemicals was measured using the three standard test organisms Daphnia magna (freshwater cladoceran), Acartia tonsa (marine copepod) and Skeletonema costatum (marine diatom alga). Test chemicals included 20 water-soluble and 10 (partially) non-soluble products. For 22 out of the 30 chemicals, the difference in sensitivity between the three tests varied within one order of magnitude. A very good correlation was found between the two marine tests (r = 0.96, P < 0.01, n = 30), and a correlation coefficient of r = 0.78 (P < 0.01, n = 30) was found between D. magna and both A. tonsa and S. costatum, individually. When the comparison of D. magna and A. tonsa sensitivity was based only on the water-soluble chemicals, a significantly higher correlation was obtained (r = 0.84, n = 20), indicating that the sample preparation method used for the (partially) non-soluble chemicals (the water accommodated fraction (WAF) method) induces additional variation between tests performed with different test media. (Partially) non-soluble chemicals are characterised by phase separation or precipitation at the concentrations used for testing. In a WAF-based test, each test concentration/exposure level is prepared separately, and following mixing and separation, only the water phase is used for testing. Toxicity is related to the amount of substance originally added to the mixing vessels. For 25 of the 30 chemicals, D. magna was found to be less sensitive than the marine copepod by a factor >2. The generally higher sensitivity of the marine toxicity tests compared to the Daphnia test emphasise the importance of using marine data for environmental hazard classification as well as for environmental risk assessment purposes.

  7. Vitamin D Levels and Monospot Tests in Military Personnel with Acute Pharyngitis: A Retrospective Chart Review

    PubMed Central

    Maloney, Sean R.; Almarines, David; Goolkasian, Paula

    2014-01-01

    Some recent studies have proposed an important role for vitamin D in reducing the risk of infection by assisting in the suppression of viruses and by controlling the inflammatory response. A low vitamin D state may have a detrimental effect on the immune system’s ability to produce activated CD8+ T cells, and it may increase the inflammatory reaction to Epstein Barr virus. The aim of this chart review was to see if serum 25 OH vitamin D3 levels in service members with acute pharyngitis were lower in those who had positive rather than negative monospot tests. A retrospective chart review was conducted on the medical records of service members who presented to sick call at Camp Lejeune, NC with acute pharyngitis from October 8, 2010 until June 30, 2011. Serum 25 OH vitamin D3 levels were compared between those with positive and negative monospot test results. Of the 25 records that were reviewed, there were 9 (36%) service members with positive results, and they were found to have lower vitamin D levels (Median = 20.80 ng/ml, Interquartile range = 10.15) than those with negative test results (Median = 30.35 ng/ml, Interquartile range = 17.05), Mann-Whitney U = 41, p = .039. Only 1 of the 9 with positive test results had a normal serum 25 OH vitamin D3 level (30 ng/ml or greater) compared with 9 of the 16 with negative test results. Optimal vitamin D stores may play a significant role in reducing the risk of developing acute mononucleosis but larger, prospective studies will be needed to verify these findings. PMID:25009977

  8. Vitamin D levels and monospot tests in military personnel with acute pharyngitis: a retrospective chart review.

    PubMed

    Maloney, Sean R; Almarines, David; Goolkasian, Paula

    2014-01-01

    Some recent studies have proposed an important role for vitamin D in reducing the risk of infection by assisting in the suppression of viruses and by controlling the inflammatory response. A low vitamin D state may have a detrimental effect on the immune system's ability to produce activated CD8+ T cells, and it may increase the inflammatory reaction to Epstein Barr virus. The aim of this chart review was to see if serum 25 OH vitamin D3 levels in service members with acute pharyngitis were lower in those who had positive rather than negative monospot tests. A retrospective chart review was conducted on the medical records of service members who presented to sick call at Camp Lejeune, NC with acute pharyngitis from October 8, 2010 until June 30, 2011. Serum 25 OH vitamin D3 levels were compared between those with positive and negative monospot test results. Of the 25 records that were reviewed, there were 9 (36%) service members with positive results, and they were found to have lower vitamin D levels (Median = 20.80 ng/ml, Interquartile range = 10.15) than those with negative test results (Median = 30.35 ng/ml, Interquartile range = 17.05), Mann-Whitney U = 41, p = .039. Only 1 of the 9 with positive test results had a normal serum 25 OH vitamin D3 level (30 ng/ml or greater) compared with 9 of the 16 with negative test results. Optimal vitamin D stores may play a significant role in reducing the risk of developing acute mononucleosis but larger, prospective studies will be needed to verify these findings.

  9. Design of a testing strategy using non-animal based test methods: lessons learnt from the ACuteTox project.

    PubMed

    Kopp-Schneider, Annette; Prieto, Pilar; Kinsner-Ovaskainen, Agnieszka; Stanzel, Sven

    2013-06-01

    In the framework of toxicology, a testing strategy can be viewed as a series of steps which are taken to come to a final prediction about a characteristic of a compound under study. The testing strategy is performed as a single-step procedure, usually called a test battery, using simultaneously all information collected on different endpoints, or as tiered approach in which a decision tree is followed. Design of a testing strategy involves statistical considerations, such as the development of a statistical prediction model. During the EU FP6 ACuteTox project, several prediction models were proposed on the basis of statistical classification algorithms which we illustrate here. The final choice of testing strategies was not based on statistical considerations alone. However, without thorough statistical evaluations a testing strategy cannot be identified. We present here a number of observations made from the statistical viewpoint which relate to the development of testing strategies. The points we make were derived from problems we had to deal with during the evaluation of this large research project. A central issue during the development of a prediction model is the danger of overfitting. Procedures are presented to deal with this challenge.

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

    USGS Publications Warehouse

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

    2007-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  12. Establishing Genetic Interactions by a Synthetic Dosage Lethality Phenotype

    PubMed Central

    Kroll, E. S.; Hyland, K. M.; Hieter, P.; Li, J. J.

    1996-01-01

    We have devised a genetic screen, termed synthetic dosage lethality, in which a cloned ``reference'' gene is inducibly overexpressed in a set of mutant strains carrying potential ``target'' mutations. To test the specificity of the method, two reference genes, CTF13, encoding a centromere binding protein, and ORC6, encoding a subunit of the origin of replication binding complex, were overexpressed in a large collection of mutants defective in either chromosome segregation or replication. CTF13 overexpression caused synthetic dosage lethality in combination with ctf14-42 (cbf2, ndc10), ctf17-61 (chl4), ctf19-58 and ctf19-26. ORC6 overexpression caused synthetic dosage lethality in combination with cdc2-1, cdc6-1, cdc14-1, cdc16-1 and cdc46-1. These relationships reflect specific interactions, as overexpression of CTF13 caused lethality in kinetochore mutants and overexpression of ORC6 caused lethality in replication mutants. In contrast, only one case of dosage suppression was observed. We suggest that synthetic dosage lethality identifies a broad spectrum of interacting mutations and is of general utility in detecting specific genetic interactions using a cloned wild-type gene as a starting point. Furthermore, synthetic dosage lethality is easily adapted to the study of cloned genes in other organisms. PMID:8722765

  13. Antecedent acute cycling exercise affects attention control: an ERP study using attention network test.

    PubMed

    Chang, Yu-Kai; Pesce, Caterina; Chiang, Yi-Te; Kuo, Cheng-Yuh; Fong, Dong-Yang

    2015-01-01

    The purpose of this study was to investigate the after-effects of an acute bout of moderate intensity aerobic cycling exercise on neuroelectric and behavioral indices of efficiency of three attentional networks: alerting, orienting, and executive (conflict) control. Thirty young, highly fit amateur basketball players performed a multifunctional attentional reaction time task, the attention network test (ANT), with a two-group randomized experimental design after an acute bout of moderate intensity spinning wheel exercise or without antecedent exercise. The ANT combined warning signals prior to targets, spatial cueing of potential target locations and target stimuli surrounded by congruent or incongruent flankers, which were provided to assess three attentional networks. Event-related brain potentials and task performance were measured during the ANT. Exercise resulted in a larger P3 amplitude in the alerting and executive control subtasks across frontal, central and parietal midline sites that was paralleled by an enhanced reaction speed only on trials with incongruent flankers of the executive control network. The P3 latency and response accuracy were not affected by exercise. These findings suggest that after spinning, more resources are allocated to task-relevant stimuli in tasks that rely on the alerting and executive control networks. However, the improvement in performance was observed in only the executively challenging conflict condition, suggesting that whether the brain resources that are rendered available immediately after acute exercise translate into better attention performance depends on the cognitive task complexity.

  14. Content validity of a clinical problem solving test for use in recruitment to the acute specialties.

    PubMed

    Crossingham, Gemma; Gale, Thomas; Roberts, Martin; Carr, Alison; Langton, Jeremy; Anderson, Ian

    2011-02-01

    Clinical problem solving tests (CPSTs) have been shown to be reliable and valid for recruitment to general practice (GP) training programmes. This article presents the results from a Department of Health-funded pilot into the use of a CPST designed for recruitment to the acute specialties (AS). The pilot paper consisted of 99 items from the validated GP question bank and 40 new items aimed specifically at topics of relevance to AS training. The CPST successfully differentiated between applicants. The overall test and the GP section showed high internal reliability, whereas the AS pilot section performed less well. A detailed item analysis revealed that the AS pilot items were, on average, more difficult and of poorer quality than the GP items. Important issues that need to be addressed in the early development phase of a test used for high stakes selection to specialty training programmes are discussed.

  15. Acute and chronic toxicity testing of bisphenol A with aquatic invertebrates and plants.

    PubMed

    Mihaich, Ellen M; Friederich, Urs; Caspers, Norbert; Hall, A Tilghman; Klecka, Gary M; Dimond, Stephen S; Staples, Charles A; Ortego, Lisa S; Hentges, Steven G

    2009-07-01

    Bisphenol A (BPA, 4,4'-isopropylidine diphenol) is a commercially important chemical used primarily as an intermediate in the production of polycarbonate plastic and epoxy resins. Extensive effect data are currently available, including long-term studies with BPA on fish, amphibians, crustaceans, and mollusks. The aim of this study was to perform additional tests with a number of aquatic invertebrates and an aquatic plant. These studies include acute tests with the midge (Chironomus tentans) and the snail (Marisa cornuarietis), and chronic studies with rotifers (Brachionus calyciflorus), amphipods (Hyalella azteca), and plants (Lemna gibba). The effect data on different aquatic invertebrate and plant species presented in this paper correspond well with the effect and no-effect concentrations (NOECs) available from invertebrate studies in the published literature and are within the range found for other aquatic species tested with BPA.

  16. Lethal Amanita species in China.

    PubMed

    Cai, Qing; Cui, Yang-Yang; Yang, Zhu L

    2016-09-01

    Lethal amanitas (Amanita sect. Phalloideae) cause many casualties worldwide. Recent molecular phylogenetic studies revealed diverse lethal Amanita spp. in China. Here a 5-gene phylogeny (nuc rDNA region encompassing the internal transcribed spacers 1 and 2 with the 5.8S rDNA, the D1-D3 domains of nuc 28S rDNA, and partial RNA polymerase II second largest subunit, translation elongation factor 1-α and β-tubulin genes) is used to investigate the phylogenetic lineages and species delimitation in this section. Thirteen species are recognized, including four new species, namely A. griseorosea, A. molliuscula, A. parviexitialis, and A. subfuliginea They are documented with morphological, multigene phylogenetic, and ecological evidence, line drawings, and photographs and compared with similar species. A key to the Chinese lethal Amanita species is provided.

  17. Development of miniaturized acute toxicity tests for Daphnia magna and Pimephales promelas

    SciTech Connect

    Powell, R.L.; Kimerle, R.A.; Moser, E.M.; McKee, M.J.

    1995-12-31

    Standard EPA methods for conducting static, 48-hour, acute toxicity tests using Daphnia magna and Pimephales promelas (fathead minnows) can be miniaturized to successfully yield accurate LC50/EC50 values. The screening procedure involves exposing the test organisms to 1 mL of test solution, in test chambers which consist of the wells on 48-well microliter plates. Toxicity of the microliter plates and solvent, DO concentration, organism biomass to test solution ratio, partitioning of the chemicals and dilution of the test solution during transfer of the test organisms were examined. Survival and exposure were not significantly altered using non-standard test chambers. Toxicity of linear alkylbenzene sulfonate (LAS), pentachlorophenol (PCP), kepone, and sodium lauryl sulfate (SLS) was determined using D. magna and fathead minnows. Serial dilutions were made and 1 mL aliquots pipetted into the wells. Daphnia magna, < 24 hours old, and newly hatched fathead minnows, were transferred into the wells, twenty individuals per concentration, one per well. Dose-response curves were established for all test compounds. LC50/EC50`s values obtained using miniaturized methods strongly correlated with those obtained using standard EPA procedures. The tests were repeated a number of times with coefficient of variances for D. magna ranging from 10% with kepone to 64% with SLS. For fathead minnows CVs ranged from 0% with PCP to 23% with kepone. It was concluded that current methods can be miniaturized, yet still provide accurate information regarding toxicity for compounds in limited supply. This method may also be amenable to effluent testing i.e. TIE fractions. Other benefits include reducing the amount of equipment and space needed to conduct a test and the time involved.

  18. 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.

  19. The submitochondrial particle assay as a screening test for acute aquatic toxicity of surfactant molecules

    SciTech Connect

    Bookland, E.A.; Bettermann, A.D.

    1995-12-31

    Two complementary protocols of the submitochondrial particle assay (SMP) were evaluated as screening tools for predicting the acute aquatic toxicity of various classes and chain lengths of surfactant molecules. SMP contain the functionally intact mitochondrial enzyme systems responsible for electron transport and oxidative phosphorylation. Both the Electron Transfer Assay (ETR) and the Reverse Electron Transfer Assay (RET) have been shown in prior work to generally be sensitive to agents capable of membrane and protein interactions, both suspected mechanisms of action for surfactants. The toxicity of ten compounds; four anionic surfactants, C{sub 12} alkyl sulfate (C{sub 12}AS), C{sub 12} and C{sub 15} alkyl ethoxy sulfate (C{sub 12}E{sub 4}S, C{sub 15}E{sub 4}S), linear alkyl benzene sulfonate (C{sub 12.3}LAS); one nonionic surfactant, alkyl ethoxylate (C{sub 12}E{sub 3}); three cationic surfactants, C{sub 8}, C{sub 12}, and C{sub 16} alkyl trimethyl ammonium chloride (C{sub 8}TMAC, C{sub 12}TMAC, C{sub 16}TMAC); an alcohol (C{sub 12}OH); and an amine, alkyl dimethylamine (C{sub 12}DMA); was determined. In all cases, both the ETR and the RET gave results showing equal or greater sensitivity than previously reported acute fish and invertebrate LC{sub 50}`s. In addition, increasing toxicity with increasing alkyl chain length was observed. As a rapid screening tool, the SMP bioassay avoids exposure concerns such as degradation of test material, a common concern for acute in vivo toxicity testing with rapidly degradable materials. Results indicate that the SMP bioassay can be useful as a predictive screening tool for the aquatic toxicity of surfactants.

  20. A field test and comparison of acute and chronic sediment toxicity tests with the estuarine amphipod Leptocheirus plumulosus in Chesapeake Bay, USA.

    PubMed

    McGee, Beth L; Fisher, Daniel J; Wright, David A; Yonkos, Lance T; Ziegler, Gregory P; Turley, Steven D; Farrar, J Daniel; Moore, David W; Bridges, Todd S

    2004-07-01

    A 28-d partial life-cycle test with the estuarine amphipod Leptocheirus plumulosus was developed in response to the need for an assay to mimic chronic exposure to sediment-associated contaminants. To ensure that toxicity tests have environmental relevance, it is essential to evaluate the relationship between laboratory responses and field measures of contamination. Consequently, one objective of the study was to compare the results of the chronic sediment toxicity test with L. plumulosus to gradients of sediment contamination and the in situ benthic community in its native Chesapeake Bay. Chronic tests were conducted by two laboratories, the Army Corps of Engineers Waterways Experiment Station ([WES]; Vicksburg, MS, USA) and the University of Maryland ([UM] College Park, MD, USA) using different feeding regimes, providing the opportunity to evaluate the effect of this variable on response sensitivity. A second objective was to compare the relative sensitivity of acute and chronic tests with L. plumulosus with field-collected sediments. Overall, there was good agreement between the toxicological response of acute and chronic tests with L. plumulosus and field measures of contamination. Survival in the acute test and chronic test conducted by WES was negatively correlated with concentrations of sediment-associated contaminants. Survival in acute exposures was significantly reduced in sediments from 8 of 11 stations. Indigenous L. plumulosus were found only at two of the three stations that did not exhibit acute toxicity. An unexpected finding was the difference in responsiveness of the two chronic tests. Survival in tests conducted by UM and WES was significantly reduced in sediments from 4 and 6 of 11 stations, respectively. No additional sublethal toxicity was detected in the UM chronic test, but the WES test detected reproductive effects at two additional stations. We believe the observed differences were related to the test diet used. Partly as a result of our

  1. Comparison of feeding strategies in acute toxicity tests of crude oil and commercial bioremediation agents

    SciTech Connect

    Cavender, R.C.; Cherry, D.S.; Yeager, M.M.; Bidwell, J.R.

    1995-12-31

    Proposed modifications to the National Oil and Hazardous Substance Pollution Contingency Plan have prompted examinations of the methodology used in toxicity testing of the water soluble fraction (WSF) of oil, commercial bioremediation agents (CBA), and a combination of the two. The organisms currently used in acute (96 hr) testing of these agents are the inland silverside, Menidia beryllina, and an estuarine mysid, Mysidopsis bahia. The mysid is a carnivorous species that must be fed during a test in order to prevent predation within the test chambers. Currently proposed methodology for silverside testing also includes feeding. The high oxygen demand of CBAs and the WSF of oil causes dissolved oxygen to be a factor in toxicity. This effect can be intensified by the addition of brine shrimp (Artemia sp.) to the test chambers. The purpose of this study was to compare the toxicity of CBAs in combination with the WSF of oil to silversides with and without the addition of food. Tests were conducted using both 24-hour and 14-day spinning times for the CBA/WSF mixture. With the 24-hour spinning time, LC50 values from each day of the 4-day test were consistently lower in the Artemia fed test (47.8--22.6%) as compared to the unfed test (72.1--43.0%). A similar trend was seen in the 24 and 48 hour LC50`s in the 14-day spinning time. Overall, low dissolved oxygen was found to be most relevant at the highest CBA/WSF concentrations where D.O. dropped below 2 mg/l in Artemia fed tests.

  2. The effect of food on the acute toxicity of silver nitrate to four freshwater test species and acute-to-chronic ratios.

    PubMed

    Naddy, Rami B; McNerney, Gina R; Gorsuch, Joseph W; Bell, Russell A; Kramer, James R; Wu, Kuen B; Paquin, Paul R

    2011-11-01

    Acute silver toxicity studies were conducted with and without food for four common freshwater test species: Daphnia magna, Ceriodaphnia dubia, Pimephales promelas (fathead minnow-FHM), and Oncorhynchus mykiss (rainbow trout-RBT) in order to generate acute-to-chronic ratios (ACR). The studies were conducted similarly (i.e., static-renewal or flow-through) to chronic/early-life stage studies that were previously performed in this laboratory. The acute toxicity (EC/LC50 values) of silver without food ranged from 0.57 μg dissolved Ag/l for C.dubia to 9.15 μg dissolved Ag/l for RBT. The presence of food resulted in an increase in EC/LC50 values from 1.25× for RBT to 22.4× for C. dubia. Invertebrate food type was also shown to effect acute silver toxicity. Food did not affect EC/LC50s or ACRs as greatly in fish studies as in invertebrate studies. ACRs for both invertebrate species were <1.0 when using acute studies without food but were 1.22 and 1.33 when using acute studies with food. ACRs for FHMs ranged from 4.06 to 7.19, while RBT ACRs ranged from 28.6 to 35.8 depending on whether food was present in acute studies. The data generated from this research program should be useful in re-determining a final ACR for silver in freshwater as well as in risk assessments.

  3. Intimate partner homicide: new insights for understanding lethality and risks.

    PubMed

    Sheehan, Brynn E; Murphy, Sharon B; Moynihan, Mary M; Dudley-Fennessey, Erin; Stapleton, Jane G

    2015-02-01

    Research on covictims, family members, and close friends who have lost loved ones to intimate partner homicide (IPH) is a neglected area of study. We conducted phenomenological interviews with covictims to gain insights into risk and lethality, examined affidavits from criminal case files, and reviewed news releases. The data uncovered acute risk factors prior to the homicide, identified changes in the perpetrators' behavior and the perpetrators' perceived loss of control over the victim, and described barriers that victims faced when attempting to gain safety. Findings suggest that recognizing acute risk factors is an important area for future IPH research.

  4. Acute toxicity testing with the tropical marine copepod Acartia sinjiensis: optimisation and application.

    PubMed

    Gissi, F; Binet, M T; Adams, M S

    2013-11-01

    Globally there is limited toxicity data for tropical marine species, and there has been a call for further research and development in the area of tropical marine ecotoxicology. An increase in developmental pressures in northern tropical Australia is causing a higher demand for toxicity test protocols with ecologically relevant species. Copepods are a diverse group of zooplankton that are major components of marine food webs. The calanoid copepod Acartia sinjiensis is widely distributed across tropical and sub-tropical brackish to marine waters of Australia and was identified in a recent comprehensive review of marine tropical toxicity testing in Australia as a suitable test organism. Through a number of optimisation steps including feeding trials, changes to culture and test conditions; a 48-h acute toxicity test with A. sinjiensis was modified to become a highly reliable and reproducible standard test protocol. Control mobility was improved significantly, and the sensitivity of A. sinjiensis to copper (EC50 of 33µg/L), ammonia (EC50 of 10mg/L) and phenol (EC50 of 13mg/L) fell within the ranges of those reported previously, indicating that the modifications did not alter its sensitivity. In a comprehensive literature search we found that this species was the most sensitive to copper out of a range of marine copepods. The test was also successfully applied in toxicity assessments of four environmental samples: two produced formations waters (PFWs) and two mine tailing liquors (MTLs). The toxicity assessments utilised toxicity data from a suite of marine organisms (bacteria, microalgae, copepods, sea urchins, oysters, prawns, and fish). For the PFWs, which were predominantly contaminated with organic chemicals, A. sinjiensis was the most sensitive species (EC50 value 2-17 times lower than for any other test species). For the predominantly metal-contaminated mine tailing liquors, its sensitivity was similar to that of other test species used. The modified 48-h acute

  5. Field and laboratory tests on acute toxicity of cadmium to freshwater crayfish

    SciTech Connect

    Not Available

    1986-09-01

    Environmental regulatory standards for cadmium (EPA 1980), like those for most pollutants, are based on acute, laboratory toxicity tests of single species. Such tests can be conducted rapidly and inexpensively in comparison to acute or chronic field studies, but their validity has often been questioned. Laboratory-based criteria are subject to two criticisms: (1) chemical and physical conditions differ greatly in degree and variability from laboratory to field, and (2) species are not isolated, but live in an ecosystem of interacting taxa and biofeedback. To investigate the validity of basing field toxicity standards on laboratory data, the authors subjected the freshwater crayfish Orconectes immunis for 96 h to various levels of cadmium in laboratory aquaria and experimental ponds. The study was designed to evaluate in part the first criticism of lab-based criteria. The studies were conducted concurrently with similar short-term experiments on the fathead minnow, Pimephales promelas, and coincided with studies of chronic cadmium stress on fathead minnows in experimental ponds.

  6. Acute toxicity testing of some herbicides-, alkaloids-, and antibiotics-metabolizing soil bacteria in the rat.

    PubMed

    Kaiser, A; Classen, H G; Eberspächer, J; Lingens, F

    1981-01-01

    Seven strains of soil bacteria with the ability to metabolize herbicides, alkaloids or antibiotics were tested in rats for acute toxicity. 1. Upon oral administration of 9.0 x 10(8) to 6.6 x 10(10) cells daily during 7 d no adverse reactions were observed. 2. Exposure by air did not lead to specific pulmonary changes. 3. Intracutaneous injection of 7.5 x 10(6) to 1.4 x 10(8) cells did not lead to adverse skin reactions. 4. Intraperitoneal injections up to 10(8) cells per animal did not kill rats although bacteria entered blood. At higher concentrations some mortality occurred partly due to unspecific stress reactions. 5. Animal data and observations on 20 humans being exposed to these strains for 2 months up to 15 years support the view that the bacteria tested are essentially harmless for health.

  7. Acute Bronchitis

    MedlinePlus

    ... can also cause acute bronchitis. To diagnose acute bronchitis, your health care provider will ask about your symptoms and listen to your breathing. You may also have other tests. Treatments include rest, fluids, and aspirin (for adults) or ...

  8. CerioFAST{trademark}: An acute toxicity test based on Ceriodaphnia dubia feeding behavior

    SciTech Connect

    Bitton, G.; Rhodes, K.; Koopman, B.

    1996-02-01

    The authors have developed a rapid acute toxicity test (CerioFAST{trademark}) based on suppression of feeding activity of Ceriodaphnia dubia in the presence of toxicants. The bioassay consists of a 1-h exposure period to a given toxicant. Yeast cells, stained with a fluorescent dye, are added 20 min before the end of the exposure period. Response to a toxic sample is indicated by the absence of fluorescence in the gut of the daphnids. CerioFAST was compared to the standard 48-h C. dubia acute bioassay, using heavy metals and organic compounds.CerioFAST EC50s of Cd, Cu, Pb, Ag, Zn, and carbofuran were in the 0.01--0.1-mg/L range, whereas EC50s of hexachloroethane, pentachlorophenol, trichlorophenol, and lindane were in the 1--10-mg/L range. CerioFAST EC50s of the heavy metals and organics were well correlated with Ec50s obtained with the 48-h C. dubia bioassay.

  9. How test vessel properties affect the fate of silver nitrate and sterically stabilized silver nanoparticles in two different test designs used for acute tests with Daphnia magna.

    PubMed

    Sakka, Yvonne; Koeser, Jan; Filser, Juliane

    2017-01-01

    The relation between test conditions such as medium composition or pH on silver nanoparticle (AgNP) behavior and its link to toxicity is one of the major topics in nanoecotoxicological research in the last years. In addition, the adaptation of the ecotoxicological standard tests for nanomaterials is intensely discussed to increase comparability and reliability of results. Due to the limitation of test material production volumes and the need for high-throughput screening, miniaturization has been proposed for several test designs. In the present study, the effect of a miniaturization of the acute Daphnia immobilization test on AgNP behavior was investigated. For this purpose, available, adsorbed, and dissolved silver fractions were measured using AgNP and silver nitrate in the following two test designs: a standard test (ST) design and a miniaturized test (MT) design with reduced test volume and less animals. Despite the increase in surface area in relation to the test volume in MT, more AgNP attached to the ST vessel surface, so that in this case, exposure concentrations were significantly lower compared to the MT assessment. Ionic silver concentrations resulting from AgNP dissolution were similar in both test designs. The same was observed for ionic silver concentrations in silver nitrate (AgNO3) treatments, but adsorbed silver was also higher in ST treatments. Assessing the structure-activity relationships revealed that surface properties such as hydrophobicity, potential binding sites, or surface roughness were of higher importance than surface:volume ratios for both test substances.

  10. Decision support for acute problems: the role of the standardized patient in usability testing.

    PubMed

    Linder, Jeffrey A; Rose, Alan F; Palchuk, Matvey B; Chang, Frank; Schnipper, Jeffrey L; Chan, Joseph C; Middleton, Blackford

    2006-12-01

    For applications that require clinician use while interacting with patients, usability testing with standardized patients has the potential to approximate actual patient care in a controlled setting. We used hypothetical scenarios and a standardized patient to collect quantitative and qualitative results in testing an early prototype of a new application, the Acute Respiratory Infection (ARI) Smart Form. The standardized patient fit well into the usability testing sessions. Clinicians had a positive response to the standardized patients and behaved as they normally would during a clinical encounter. Positive findings of the ARI Smart Form included that users thought it had impressive functionality and the potential to save time. Criticism focused on the visual design, which could be streamlined, and navigation, which was difficult in some areas. Based on these results, we are modifying the ARI Smart Form in preparation for use in actual patient care. Standardized patients should be considered for usability testing, especially if an application is to be used during the patient interview.

  11. Acute and Chronic Effects of Alcohol on Trail Making Test Performance Among Underage Drinkers in a Field Setting

    PubMed Central

    Day, Anne M.; Lisman, Stephen A.; Johansen, Gerard E.; Spear, Linda P.

    2013-01-01

    Objective: Alcohol’s effects on executive functioning are well documented. Research in this area has provided much information on both the acute and chronic effects of alcohol on processes such as working memory and mental flexibility. However, most research on the acute effects of alcohol is conducted with individuals older than 21 years of age. Using field recruitment methods can provide unique empirical data on the acute effects of alcohol on an underage population. Method: The current study examined the independent effects of acute alcohol intoxication (measured by breath alcohol content) and chronic alcohol use (measured by years drinking) on a test of visuomotor performance and mental flexibility (Trail Making Test) among 91 drinkers ages 18–20 years recruited from a field setting. Results: Results show that breath alcohol predicts performance on Trails B, but not on Trails A, and that years drinking, above and beyond acute intoxication, predicts poorer performance on both Trails A and B. Conclusions: These data suggest that, independent of the acute effects of alcohol, chronic alcohol consumption has deleterious effects on executive functioning processes among underage drinkers. Our discussion focuses on the importance of these data in describing the effect of alcohol on adolescents and the potential for engaging in risky behavior while intoxicated. PMID:23739029

  12. The Acute toxicity of alpha-branched phenylsulfonyl acetates in Photobacterium phosphoreum test.

    PubMed

    Liu, X; Wu, C; Han, S; Wang, L; Zhang, Z

    2001-07-01

    The acute toxicity (15-min EC(50)) of 20 alpha-substituted phenylsulfonyl acetates was measured using the Microtox test with Photobacterium phosphoreum. On the basis of TLSER, quantitative structure-activity relationships (QSARs) were calculated for the inhibition of bioluminescence. With the parameters molecular volume (V(mc)), dipolarity/polarizability (pi*), and the covalent contribution to Lewis basicity (epsilon(b)), a squared correlation coefficient (r(2)(adj)) of 0.868 and standard error of 0.094 for log EC(50) were obtained. By introducing a structural indicator variable (I), the regressive quality was improved (correlation coefficient of 0.948 and standard error of 0.059); the descriptors V(mc), pi*, and the electrostatic basicity contribution (q(-)) were significant. -NO(2)-- and -SO(2)--groups are active centers of these compounds. The strong hydrogen bonding effects between the compound active centers and FMNH(2) play an important role in the greater toxicity of these chemicals.

  13. Rapid antimicrobial susceptibility testing with electrokinetics enhanced biosensors for diagnosis of acute bacterial infections.

    PubMed

    Liu, Tingting; Lu, Yi; Gau, Vincent; Liao, Joseph C; Wong, Pak Kin

    2014-11-01

    Rapid pathogen detection and antimicrobial susceptibility testing (AST) are required in diagnosis of acute bacterial infections to determine the appropriate antibiotic treatment. Molecular approaches for AST are often based on the detection of known antibiotic resistance genes. Phenotypic culture analysis requires several days from sample collection to result reporting. Toward rapid diagnosis of bacterial infection in non-traditional healthcare settings, we have developed a rapid AST approach that combines phenotypic culture of bacterial pathogens in physiological samples and electrochemical sensing of bacterial 16S rRNA. The assay determines the susceptibility of pathogens by detecting bacterial growth under various antibiotic conditions. AC electrokinetic fluid motion and Joule heating induced temperature elevation are optimized to enhance the sensor signal and minimize the matrix effect, which improve the overall sensitivity of the assay. The electrokinetics enhanced biosensor directly detects the bacterial pathogens in blood culture without prior purification. Rapid determination of the antibiotic resistance profile of Escherichia coli clinical isolates is demonstrated.

  14. [Development and clinical testing of the Russian version of the Acute Cystitis Symptom Score - ACSS].

    PubMed

    Alidjanov, J F; Abdufattaev, U A; Makhmudov, D Kh; Mirkhamidov, D Kh; Khadzhikhanov, F A; Azgamov, A V; Pilatz, A; Naber, K G; Wagenlehner, F M; Akilov, F A

    2014-01-01

    The Acute Cystitis Symptom Score - ACSS was originally developed in the Uzbek language and has demonstrated high reliability and validity. The study was aimed to develop a Russian version of the ACSS questionnaire and evaluate its psychometric properties. Translation and adaptation of the ACSS questionnaire containing 18 questions, 6 of them - for the typical symptoms of acute cystitis (AC), 4 - for the differential diagnosis; 3 - for the quality of life, and 5 - for the conditions that may affect the choice of treatment, were performed according to the recommendations developed by the Mapi Research Institute. Study involved 83 Russian-speaking women (mean age, 35.6 ±13.7 years); 38 (45.8%) patients were in the main group (patients with AC), and 45 (54.2%) - in the control group (without AC). Medical examination and appropriate treatment of the respondents were conducted in accordance with approved standards. After completing the course of therapy, 19 (50%) patients of the main group came for the control examination. There was statistically significant difference in the scores obtained in the two groups. Score profiles positively correlated with the results of laboratory tests (rho = 0.26-0.48). Cronbach's alpha for the Russian version of the questionnaire was 0.86 (95% CI, 0.81-0.91), area under the curve in the ROC analysis was 0.96. The results of testing the Russian version correspond to those of the original version. The Russian version of the ACSS questionnaire has high. reliability and validity, and can be recommended for clinical research and diagnosis of primary AC, and dynamic monitoring of the effectiveness of the treatment of the Russian-speaking population of patients.

  15. Lethal and sub-lethal effects of spinosad on bumble bees (Bombus impatiens Cresson).

    PubMed

    Morandin, Lora A; Winston, Mark L; Franklin, Michelle T; Abbott, Virginia A

    2005-07-01

    Recent developments of new families of pesticides and growing awareness of the importance of wild pollinators for crop pollination have stimulated interest in potential effects of novel pesticides on wild bees. Yet pesticide toxicity studies on wild bees remain rare, and few studies have included long-term monitoring of bumble bee colonies or testing of foraging ability after pesticide exposure. Larval bees feeding on exogenous pollen and exposed to pesticides during development may result in lethal or sub-lethal effects during the adult stage. We tested the effects of a naturally derived biopesticide, spinosad, on bumble bee (Bombus impatiens Cresson) colony health, including adult mortality, brood development, weights of emerging bees and foraging efficiency of adults that underwent larval development during exposure to spinosad. We monitored colonies from an early stage, over a 10-week period, and fed spinosad to colonies in pollen at four levels: control, 0.2, 0.8 and 8.0 mg kg(-1), during weeks 2 through 5 of the experiment. At concentrations that bees would likely encounter in pollen in the wild (0.2-0.8 mg kg(-1)) we detected minimal negative effects to bumble bee colonies. Brood and adult mortality was high at 8.0 mg kg(-1) spinosad, about twice the level that bees would be exposed to in a 'worst case' field scenario, resulting in colony death two to four weeks after initial pesticide exposure. At more realistic concentrations there were potentially important sub-lethal effects. Adult worker bees exposed to spinosad during larval development at 0.8 mg kg(-1) were slower foragers on artificial complex flower arrays than bees from low or no spinosad treated colonies. Inclusion of similar sub-lethal assays to detect effects of pesticides on pollinators would aid in development of environmentally responsible pest management strategies.

  16. Derivation of Human Lethal Doses

    DTIC Science & Technology

    2006-01-19

    emergency medicine, pharmacology, forensic medicine, and industrial chemical toxicology, in addition to a poison information center. The authors presented...Meditsinskaya Ekspeertiza. Forensic Medical Examination, 26(2), 48, 1983 (as cited in Sax’s). This reference is not available for review. Rat – LD50...mg/kg No LDLo, MLD, or lethal dose for humans Rat – LD50 (Bulletin of the Entomological Society of America, 1969) (as cited in Sax’s). This

  17. Biosafety of an entomopathogenic fungus Isaria fumosorosea in an acute dermal test in rabbits.

    PubMed

    Brunner-Mendoza, Carolina; Navarro-Barranco, Hortensia; León-Mancilla, Benjamín; Pérez-Torres, Armando; Toriello, Conchita

    2017-03-01

    Isaria fumosorosea (formerly Paecilomyces fumosoroseus) is an entomopathogenic fungus that has been proposed as a low risk environmental alternative to the use of chemical insecticides to control agricultural pests and disease vectors. Although there are some mycoinsecticides already being marketed in many countries, not all their biosafety protocols have been published. The acute dermal toxicity test in an animal model is one in a series of biosafety protocols that must be developed, in order to provide information on health hazards, while taking into consideration the periods that the workers are in direct contact with the microbial agent when applied for the control of pests. For this test, we used I. fumosorosea monospore culture EH-506/3, isolated in Mexico from the Bemisia tabaci whitefly, applying a dose of 2 g/kg of animal body weight, on the shaved skin of 16 New Zealand rabbits, with an exposure time of 24 h. Clinical observations were conducted to evaluate the presence of erythema, edema and other alterations in the skin, as well as the behavior and health of the animals, for a period of 14 days. None of the rabbits showed clinical signs of any disease and their body weight corresponded to the expected weight for a healthy rabbit. The test showed no inflammatory reactions in the skin, supporting the safety of a single dose of this fungus in dermal exposure. Therefore, these data support the safety of I. fumosorosea EH-506/3 when applied to the skin.

  18. Diagnosing Stroke in Acute Vertigo: The HINTS Family of Eye Movement Tests and the Future of the "Eye ECG".

    PubMed

    Newman-Toker, David E; Curthoys, Ian S; Halmagyi, G Michael

    2015-10-01

    Patients who present to the emergency department with symptoms of acute vertigo or dizziness are frequently misdiagnosed. Missed opportunities to promptly treat dangerous strokes can result in poor clinical outcomes. Inappropriate testing and incorrect treatments for those with benign peripheral vestibular disorders leads to patient harm and unnecessary costs. Over the past decade, novel bedside approaches to diagnose patients with the acute vestibular syndrome have been developed and refined. A battery of three bedside tests of ocular motor physiology known as "HINTS" (head impulse, nystagmus, test of skew) has been shown to identify acute strokes more accurately than even magnetic resonance imaging with diffusion-weighted imaging (MRI-DWI) when applied in the early acute period by eye-movement specialists. Recent advances in lightweight, high-speed video-oculography (VOG) technology have made possible a future in which HINTS might be applied by nonspecialists in frontline care settings using portable VOG. Use of technology to measure eye movements (VOG-HINTS) to diagnose stroke in the acute vestibular syndrome is analogous to the use of electrocardiography (ECG) to diagnose myocardial infarction in acute chest pain. This "eye ECG" approach could transform care for patients with acute vertigo and dizziness around the world. In the United States alone, successful implementation would likely result in improved quality of emergency care for hundreds of thousands of peripheral vestibular patients and tens of thousands of stroke patients, as well as an estimated national health care savings of roughly $1 billion per year. In this article, the authors review the origins of the HINTS approach, empiric evidence and pathophysiologic principles supporting its use, and possible uses for the eye ECG in teleconsultation, teaching, and triage.

  19. Estuarine sediment acute toxicity testing with the European amphipod Corophium multisetosum Stock, 1952.

    PubMed

    Ré, Ana; Freitas, Rosa; Sampaio, Leandro; Rodrigues, Ana Maria; Quintino, Victor

    2009-09-01

    This study assessed the use of the European amphipod Corophium multisetosum Stock [Stock, J.H., 1952. Some notes on the taxonomy, the distribution and the ecology of four species of the genus Corophium (Crustacea, Malacostraca). Beaufortia 21, 1-10] in estuarine sediment acute toxicity testing. The sensitivity of adults to the reference toxicant CdCl(2) was determined in water-only 96 h exposures in salinity 2. LC(50) values ranged from 0.33mgCd(2+)L(-1) at 22 degrees C to 0.57mgCd(2+)L(-1) at 15 degrees C. Adult survival was studied in control sediment with water salinity from 0 to 36 and with fine particles content (<63 microm) from 2% to 97% of total sediment, dry weight. Experiments were conducted at 15, 18 and 22 degrees C and the results indicate that the species can be used under the full salinity range although higher mortality was observed at the lower salinity in the higher water temperature, and at the higher salinity in the lower water temperature. The species also tolerated the studied range of sediment fines content and showed the highest sensitivity at intermediate values of fines, especially at the higher temperature, thus advising that tests which have to accommodate sediments with a wide range in fines content should preferably be conducted at 15 degrees C rather than at 22 degrees C. The response in natural sediments was studied in samples collected yearly from 1997 to 2006, at a site located off the Tagus Estuary, western Portugal. A major flood event in winter 2000-2001 induced detectable alterations in sediment baseline descriptors (grain-size, redox potential and total volatile solids), organic contaminants (PAHs, PCBs, DDT metabolites and gamma-HCH) and the macrofauna benthic community. Mortality of the amphipod diminished significantly from the before to the after flood period, in close agreement with diminishing sediment contamination and increasing benthic fauna diversity, in the same time period. C. multisetosum is suitable to conduct

  20. Use of various acute, sublethal and early life-stage tests to evaluate the toxicity of refinery effluents

    SciTech Connect

    Sherry, J.; Scott, B.; Dutka, B.

    1997-11-01

    The toxicities of effluents from three Ontario, Canada, refineries were assessed with microbes, plants, invertebrates, and fish. Acute toxicity was assessed by the Microtox test, an assay based on electron transport activity in submitochondrial particles, and Daphnia magna (water flea); growth of Selenastrum capricornutum (alga); growth of Lemna minor (aquatic plant); germination of Lactuca sativa (nonaquatic plant); survival, growth, and maturation of Panagrellus redivivus (nematode); and genotoxicity in the SOS-Chromotest. Only the Microtox test and the submitochondrial particle test detected acute toxicity in the effluent samples. Reduced survival and sublethal responses were caused by some effluents, but not all effluents were toxic, and none caused a response in all of the tests applied. The results suggest that the effluent treatment systems used at Ontario refineries have largely eliminated acute toxicity to the organisms in their test battery. Although reduced survival and sublethal effects were detected in some of the effluents, the effects were minor. Some of the tests provided evidence, albeit weak, of variations in the responses of the test organisms to a temporal series of effluent samples. Not unexpectedly, there were also minor differences in the responses of the tests to effluents from the three refineries. The fathead minnow test seems to be a sensitive indicator of the sublethal toxicity of Ontario refinery effluents.

  1. A Miniature Bioassay for Testing the Acute Phytotoxicity of Photosystem II Herbicides on Seagrass

    PubMed Central

    Wilkinson, Adam D.; Collier, Catherine J.; Flores, Florita; Mercurio, Phil; O’Brien, Jake; Ralph, Peter J.; Negri, Andrew P.

    2015-01-01

    Photosystem II (PSII) herbicides have been detected in nearshore tropical waters such as those of the Great Barrier Reef and may add to the pressure posed by runoff containing sediments and nutrients to threatened seagrass habitats. There is a growing number of studies into the potential effects of herbicides on seagrass, generally using large experimental setups with potted plants. Here we describe the successful development of an acute 12-well plate phytotoxicity assay for the PSII herbicide Diuron using isolated Halophila ovalis leaves. Fluorescence images demonstrated Diuron affected the entire leaf surface evenly and responses were not influenced by isolating leaves from the plant. The optimum exposure duration was 24 h, by which time the inhibition of effective quantum yield of PSII (∆F/Fm’) was highest and no deterioration of photosystems was evident in control leaves. The inhibition of ∆F/Fm’ by Diuron in isolated H. ovalis leaves was identical to both potted and hydroponically grown plants (with leaves remaining attached to rhizomes), indicating similar reductions in photosynthetic activity in these acute well-plate assays. The sensitivity of the assay was not influenced by irradiance (range tested 40 to 400 μmol photons m-2 s-1). High irradiance, however, caused photo-oxidative stress in H. ovalis and this generally impacted in an additive or sub-additive way with Diuron to damage PSII. The bioassay using isolated leaves is more rapid, uses far less biological material and does not rely on specialised aquarium facilities in comparison with assays using potted plants. The development and validation of this sensitive bioassay will be useful to reliably screen and monitor the phytotoxicity of existing and emerging PSII herbicides and contribute to risk assessments and water quality guideline development in the future. PMID:25674791

  2. Urinalysis in Acute Care of Adults: Pitfalls in Testing and Interpreting Results

    PubMed Central

    Pallin, Daniel J.; Ronan, Clare; Montazeri, Kamaneh; Wai, Katherine; Gold, Allen; Parmar, Siddharth; Schuur, Jeremiah D.

    2014-01-01

    Background.  Rapid urine tests for infection (urinalysis, dipstick) have low up-front costs. However, many false positives occur, with important downstream consequences, including unnecessary antibiotics. We studied indications, collection technique, and results of urinalyses in acute care. Methods.  This research was a prospective observational study of a convenience sample of emergency department (ED) patients who had urinalysis performed between June 1, 2012 and February 15, 2013 at an urban teaching hospital. Analyses were conducted via t tests, χ2 tests, and multivariable logistic regression. Results.  Of 195 cases included in the study, the median age was 56 and 70% of participants were female. There were specific symptoms or signs of urinary tract infection (UTI) in 74 cases (38%; 95% confidence interval [CI], 31%–45%), nonspecific symptoms or signs in 83 cases (43%; 95% CI, 36%–50%), and no symptoms or signs of UTI in 38 cases (19%; 95% CI, 14%–25%). The median age was 51 (specific symptoms), 58 (nonspecific symptoms), and 61 (no symptoms), respectively (P = .005). Of 137 patients who produced the specimen without assistance, 78 (57%; 95% CI, 48%–65%) received no instructions on urine collection. Correct midstream clean-catch technique was used in 8 of 137 cases (6%). Presence of symptoms or signs was not associated with a new antibiotic prescription, but positive urinalysis (OR, 4.9; 95% CI, 1.7–14) and positive urine culture (OR, 3.6; 95% CI, 1.1–12) were. Of 36 patients receiving antibiotics, 10 (28%; 95% CI, 13%–43%) had no symptoms or nonspecific symptoms. Conclusion.  In this sample at an urban teaching hospital ED, urine testing was not driven by symptoms. Improving practice may lower costs, improve efficiency of care, decrease unnecessary data that can distract providers and impair patient safety, decrease misdiagnosis, and decrease unnecessary antibiotics. PMID:25734092

  3. Optimizing laboratory test utilization in long-term acute care hospitals

    PubMed Central

    Krug, Brian S.; Grigonis, Antony M.; Dawson, Amanda; Jing, Yuqing; Hammerman, Samuel I.

    2017-01-01

    Laboratory tests can be considered inappropriate if overused or when repeated, unnecessary “routine” testing occurs. For chronically critically ill patients treated in long-term acute care hospitals (LTACHs), inappropriate testing may result in unnecessary blood draws that could potentially harm patients or increase infections. A quality improvement initiative was designed to increase physician awareness of their patterns of lab utilization in the LTACH environment. Within a large network of LTACHs, 9 hospitals were identified as having higher patterns of lab utilization than other LTACHs. Meetings were held with administrative staff and physicians, who designed and implemented hospital-specific strategies to address lab utilization. Lab utilization was measured in units of lab tests ordered per inpatient day (lab UPPD) for 8 months prior to the initial meeting and 7 months after the meeting. A repeated measures mixed model determined that postintervention lab utilization improved, on average and adjusted by case mix index, by 0.37 lab UPPD (t = −3.61, 95% CI 0.17 to 0.58) compared to the preintervention period. Overall, the case mix index 8 months prior to the intervention was no different than it was 7 months after the initial meeting (t[8] = −0.96, P = 0.37). Patient safety and outcome measures, including percentage of patients weaned from a ventilator, readmission rates, central catheter utilization rates, and the incidence of methicillin-resistant Staphylococcus aureus and other multidrug resistant organisms, showed no significant change. Hospital staff meetings focused on lab utilization and the development and deployment of tailored lab utilization strategies were associated with LTACHs achieving significantly lower lab utilization without negatively impacting quality outcomes. PMID:28127124

  4. Acute response test to adaptive servo-ventilation, a possible modality to assessing the reversibility of pulmonary vascular resistance.

    PubMed

    Hieda, Michinari; Seguchi, Osamu; Mutara, Yoshihiro; Sunami, Haruki; Sato, Takuma; Yanase, Masanobu; Hiroki, Hata; Fujita, Tomoyuki; Nakatani, Takeshi

    2015-09-01

    Since pulmonary hypertension (PH) due to left-sided heart failure (HF) with elevated pulmonary vascular resistance (PVR) is contraindication for heart transplantation (HTx), correct evaluation of reversibility in PVR is essential for adequate therapeutic decision-making. However, guidelines or recommended protocols for pharmacological testing to evaluate the reversibility of PVR have not been established yet. In this report, we presented a 34-year-old male with advanced HF complicated by severe PH with high PVR [5.93 Wood units (WU)] who was deemed eligible for HTx. To evaluate his HTx candidacy, oxygen inhalation test was applied during right heart catheterization (RHC) and PVR was drastically decreased to 2.29 WU. At that time, acute response test to adaptive servo-ventilation (ASV) was also applied and use of ASV temporarily but substantially decreased PVR to 2.15 WU. From the results of both oxygen inhalation test and acute response test to ASV, reversibility of PVR in this patient was confirmed, and the patient was approved as HTx candidate and received left ventricular assist device (LVAD) implantation for bridge to transplant. After LVAD implantation, PVR substantially and persistently decreased to 2.4 WU. These findings indicate that acute response test to ASV during RHC may be a possible modality to evaluate the reversibility of PVR in HF patients with PH complicated by elevated PVR.

  5. Improving on Army Field Gauze for Lethal Vascular Injuries: Challenges in Dressing Development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accounting for half of all deaths, uncontrolled hemorrhage remains the leading cause of death on the battlefield. Gaining hemostatic control of lethal vascular injuries sustained in combat using topical agents remains a challenge. Recent animal testing using a lethal arterial injury model compared a...

  6. The Danger Assessment: Validation of a Lethality Risk Assessment Instrument for Intimate Partner Femicide

    ERIC Educational Resources Information Center

    Campbell, Jacquelyn C.; Webster, Daniel W.; Glass, Nancy

    2009-01-01

    The Danger Assessment (DA) is an instrument designed to assess the likelihood of lethality or near lethality occurring in a case of intimate partner violence. This article describes the development, psychometric validation, and suggestions for use of the DA. An 11-city study of intimate partner femicide used multivariate analysis to test the…

  7. Electroshock weapons can be lethal!

    NASA Astrophysics Data System (ADS)

    Lundquist, Marjorie

    2008-03-01

    Electroshock weapons (EWs)-stun guns, tasers, riot shields-are electroconductive devices designed to safely incapacitate healthy men neuromuscularly, so they are called nonlethal or less-lethal. EW firms seeking large nonmilitary markets targeted law enforcement and corrections personnel, who began using EWs in prisons/jails and on public patrol in 1980 in the USA. This shifted the EW-shocked population from healthy soldiers to a heterogeneous mix of both sexes, ages 6-92, in a wide variety of health conditions! An EW operates by disrupting normal physiological processes, producing transient effects in healthy people. But if a person's health is sufficiently compromised, the margin of safety can be lost, resulting in death or permanent health problems. 325 people have died after EW shock since 1980. Did the EW cause these deaths? Evidence indicates that EWs do play a causal role in most such deaths. EWs can be lethal for people in diabetic shock^1 (hypoglycemia), which may be why Robert Dziekanski-a Polish immigrant to Canada-died so quickly after he was tasered at Vancouver Airport: not having eaten for over 10 hours, he likely was severely hypoglycemic. The EW death rate in North America is 30 times higher than need be, because EW users have not been properly trained to use EWs on a heterogeneous population safely! ^1J. Clinical Engineering 30(3):111(2005).

  8. Artemia salina as test organism for assessment of acute toxicity of leachate water from landfills.

    PubMed

    Svensson, B M; Mathiasson, L; Mårtensson, L; Bergström, S

    2005-03-01

    Artemia salina has, for the first time, been used as test organism for acute toxicity of leachate water from three landfills (the municipal landfills at Kristianstad, Sweden and Siauliai, Lithuania, and an industrial landfill at Stena fragmenting AB, Halmstad, as well as for leachate from Kristianstad treated in different ways in a pilot plan). Artemia can tolerate the high concentrations of chloride ions found in such waters. Large differences in toxicities were found, the leachate from Siauliai being the most toxic one. To increase the selectivity in the measurements, a fractionation was done by using ion exchange to separate ammonium/ammonia and metal ions from the leachate, and activated carbon adsorbents for organic pollutants. The influence of some metals and phenol compounds on the toxicity was investigated separately. It was found that most of the toxicity emanated from the ammonium/ammonia components in the leachate. However, there was also a significant contribution n from organic pollutants, other than phenol compounds, since separate experiments had in this latter case indicated negligible impact. The concentrations of metals were at a level, shown by separate experiments, where only small contribution to the toxicity could be expected.

  9. A Five-Gene Peripheral Blood Diagnostic Test for Acute Rejection in Renal Transplantation

    PubMed Central

    Li, Li; Khatri, Purveshkumar; Sigdel, Tara K.; Tran, Tim; Ying, Lihua; Vitalone, Matthew; Chen, Amery; Hsieh, Szu-chuan; Dai, Hong; Zhang, Meixia; Naesens, Maarten; Zarkhin, Valeriya; Sansanwal, Poonam; Chen, Rong; Mindrinos, Michael; Xiao, Wenzhong; Benfield, Mark; Ettenger, Robert; Dharnidharka, Vikas; Mathias, Robert; Portale, Anthony; McDonald, Ruth; Harmon, William; Kershaw, David; Vehaskari, V. Matti; Kamil, Elaine; Baluarte, H. Jorge; Warady, Brad; Davis, Ron; Butte, Atul J.; Salvatierra, Oscar; Sarwal, Minnie

    2012-01-01

    Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in gthe NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n=47) and validated on independent test-set (n=198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool. PMID:23009139

  10. Acute effects of three different stretching protocols on the wingate test performance.

    PubMed

    Franco, Bruno L; Signorelli, Gabriel R; Trajano, Gabriel S; Costa, Pablo B; de Oliveira, Carlos G

    2012-01-01

    The purpose of this study was to examine the acute effects of different stretching exercises on the performance of the traditional Wingate test (WT). Fifteen male participants performed five WT; one for familiarization (FT), and the remaining four after no stretching (NS), static stretching (SS), dynamic stretching (DS), and proprioceptive neuromuscular facilitation (PNF). Stretches were targeted for the hamstrings, quadriceps, and calf muscles. Peak power (PP), mean power (MP), and the time to reach PP (TP) were calculated. The MP was significantly lower when comparing the DS (7.7 ± 0.9 W/kg) to the PNF (7.3 ± 0.9 W/kg) condition (p < 0.05). For PP, significant differences were observed between more comparisons, with PNF stretching providing the lowest result. A consistent increase of TP was observed after all stretching exercises when compared to NS. The results suggest the type of stretching, or no stretching, should be considered by those who seek higher performance and practice sports that use maximal anaerobic power.

  11. A peripheral blood diagnostic test for acute rejection in renal transplantation.

    PubMed

    Li, L; Khatri, P; Sigdel, T K; Tran, T; Ying, L; Vitalone, M J; Chen, A; Hsieh, S; Dai, H; Zhang, M; Naesens, M; Zarkhin, V; Sansanwal, P; Chen, R; Mindrinos, M; Xiao, W; Benfield, M; Ettenger, R B; Dharnidharka, V; Mathias, R; Portale, A; McDonald, R; Harmon, W; Kershaw, D; Vehaskari, V M; Kamil, E; Baluarte, H J; Warady, B; Davis, R; Butte, A J; Salvatierra, O; Sarwal, M M

    2012-10-01

    Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n = 47) and validated on independent test-set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool.

  12. [Usefulness of natriuretic peptide testing and Doppler echocardiography at bedside in the diagnosis of acute heart failure].

    PubMed

    Arques, S; Roux, E

    2016-11-01

    Acute heart failure is a common condition that leads to hospital admission, with important mortality and readmission rates. A prompt and accurate diagnosis of this condition by hospitalists is essential for an early and tailored medical management. The use of natriuretic peptide testing (BNP and NT-proBNP) through a two cut-point strategy is currently recommended as the first-line diagnostic complement to the initial clinical evaluation in the acute care setting. Transthoracic Doppler echocardiography is an other noninvasive method that can be used at bedside, especially in patients with intermediate, inconclusive natriuretic peptides levels. In this regard, left ventricular ejection fraction and several simple Doppler indexes (restrictive mitral filling pattern, spectral tissue Doppler E/e' ratio), have been validated in the emergency diagnosis of acute heart failure. The aim of the present review is to overview the respective contribution of natriuretic peptides and Doppler echocardiography at bedside to the diagnosis of acute heart failure in the acute care setting.

  13. Development of synthetic lethality anticancer therapeutics.

    PubMed

    Fang, Bingliang

    2014-10-09

    The concept of synthetic lethality (the creation of a lethal phenotype from the combined effects of mutations in two or more genes) has recently been exploited in various efforts to develop new genotype-selective anticancer therapeutics. These efforts include screening for novel anticancer agents, identifying novel therapeutic targets, characterizing mechanisms of resistance to targeted therapy, and improving efficacies through the rational design of combination therapy. This review discusses recent developments in synthetic lethality anticancer therapeutics, including poly ADP-ribose polymerase inhibitors for BRCA1- and BRCA2-mutant cancers, checkpoint inhibitors for p53 mutant cancers, and small molecule agents targeting RAS gene mutant cancers. Because cancers are caused by mutations in multiple genes and abnormalities in multiple signaling pathways, synthetic lethality for a specific tumor suppressor gene or oncogene is likely cell context-dependent. Delineation of the mechanisms underlying synthetic lethality and identification of treatment response biomarkers will be critical for the success of synthetic lethality anticancer therapy.

  14. [An acute toxicity study of bromantane].

    PubMed

    Bugaeva, L I; Verovskiĭ, V E; Iezhitsa, I N; Spasov, A A

    2000-01-01

    The toxicity of bromantan was evaluated by conventional acute tests (according to Belen'kiĭ) and by the behavioral activity data (according to Irvin). A method of integral graphical representation of the behavioral activity data is suggested, according to which the results are plotted as a "dose trajectory." Using the dose trajectory constructed for bromantan, the levels of therapeutic, toxic, and lethal doses were calculated. It was established that catecholaminergic effects account for the mechanism of therapeutic action of bromantan, while cholinergic effects determine the drug action in toxic doses.

  15. 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

  16. Non-lethal heat shock increases tolerance to metal exposure in brine shrimp.

    PubMed

    Pestana, João L T; Novais, Sara C; Norouzitallab, Parisa; Vandegehuchte, Michiel B; Bossier, Peter; De Schamphelaere, Karel A C

    2016-11-01

    Pollution and temperature increase are two of the most important stressors that aquatic organisms are facing. Exposure to elevated temperatures and metal contamination both induce heat shock proteins (HSPs), which may thus be involved in the induced cross-tolerance in various organisms. This study aimed to test the hypothesis that exposure to a non-lethal heat shock (NLHS) causes an increased tolerance to subsequent metal exposure. Using gnotobiotic cultures of the brine shrimp Artemia franciscana, the tolerance to Cd and Zn acute exposures was tested after a prior NLHS treatment (30min exposure to 37°C). The effects of NLHS and metal exposure were also assessed by measuring 70kDa-HSPs production, along with the analysis of epigenetic markers such as DNA methylation and histone H3 and histone H4 acetylation. Our results showed that heat-shocked Artemia had increased acute tolerance to Cd and Zn. However, different patterns of HSPs were observed between the two metal compounds and no epigenetic alterations were observed in response to heat shock or metal exposure. These results suggest that HSP production is a phenotypically plastic trait with a potential role in temperature-induced tolerance to metal exposure.

  17. Clinical Study of Acute Vasoreactivity Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension

    PubMed Central

    Xu, Qi-Xia; Yang, Yuan-Hua; Geng, Jie; Zhai, Zhen-Guo; Gong, Juan-Ni; Li, Ji-Feng; Tang, Xiao; Wang, Chen

    2017-01-01

    Background: The clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls. Methods: We analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test. Results: The rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s−1·m−5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT

  18. False positive dengue NS1 antigen test in a traveller with an acute Zika virus infection imported into Switzerland.

    PubMed

    Gyurech, Danielle; Schilling, Julian; Schmidt-Chanasit, Jonas; Cassinotti, Pascal; Kaeppeli, Franz; Dobec, Marinko

    2016-01-01

    We report the first case of an acute Zika virus infection imported into Switzerland by a traveller returning from Canoa Quebrada, Ceará state, in the north-eastern part of Brazil. Due to a false positive dengue virus NS1 antigen test, IgG antibody seroconversion and a suggestive clinical picture,an acute dengue fever was initially considered. However, because of lack of specific IgM-antibodies, stationary IgG antibody titre and a negative dengue virus PCR test result, a dengue virus infection was excluded and a cross-reaction with other, causative flaviviruses was postulated. Based on recent reports of Zika fever cases in the north-eastern parts of Brazil, an acute Zika virus infection was suspected. Because of a lack of commercially available Zika virus diagnostic tests, the case was confirmed in the WHO reference laboratory. As the clinical presentation of Zika virus infection can be confused with dengue fever and chikungunya fever, and because of possible public health implications, all patients returning from affected areas should be additionally tested for Zika virus. This case illustrates the urgent medical need for a broadly available assay capable of differentiating Zika from Dengue infections.

  19. Evaluation of lethality estimates for combustion gases in military scenarios.

    PubMed

    Smith, S M; Stuhmiller, J H; Januszkiewicz, A J

    1996-12-31

    To meet the military objective of determining criteria for incapacitation and lethality from toxic gas exposures, a series of small animal tests and data analyses were conducted. Carbon monoxide (CO), a narcotic gas and nitrogen dioxide (NO2), an irritant gas, along with carbon dioxide (CO2) were tested individually and in the following mixtures: (CO + CO2), (NO2 + CO2) and (NO2 + CO + CO2). A group of six animals was exposed to each of the gases and their combinations, lethality and biophysical data were collected. We conclude that our observations of lethality from single toxic gases can be correlated with a fractional effective dose (FED) description, in which external concentrations are corrected for minute volume changes. Multiple gas exposures clearly demonstrate synergistic effects because lethality rates greatly exceed those expected from statistically independent causes. Simple addition of the FED values, however, overstates the effect and implies a competition between the narcotic and irritant gas effects. The N-Gas model, while being an additive FED model, does not appear to be in a form that could guide the setting of military exposure standards.

  20. Empirical Complexities in the Genetic Foundations of Lethal Mutagenesis

    PubMed Central

    Bull, James J.; Joyce, Paul; Gladstone, Eric; Molineux, Ian J.

    2013-01-01

    From population genetics theory, elevating the mutation rate of a large population should progressively reduce average fitness. If the fitness decline is large enough, the population will go extinct in a process known as lethal mutagenesis. Lethal mutagenesis has been endorsed in the virology literature as a promising approach to viral treatment, and several in vitro studies have forced viral extinction with high doses of mutagenic drugs. Yet only one empirical study has tested the genetic models underlying lethal mutagenesis, and the theory failed on even a qualitative level. Here we provide a new level of analysis of lethal mutagenesis by developing and evaluating models specifically tailored to empirical systems that may be used to test the theory. We first quantify a bias in the estimation of a critical parameter and consider whether that bias underlies the previously observed lack of concordance between theory and experiment. We then consider a seemingly ideal protocol that avoids this bias—mutagenesis of virions—but find that it is hampered by other problems. Finally, results that reveal difficulties in the mere interpretation of mutations assayed from double-strand genomes are derived. Our analyses expose unanticipated complexities in testing the theory. Nevertheless, the previous failure of the theory to predict experimental outcomes appears to reside in evolutionary mechanisms neglected by the theory (e.g., beneficial mutations) rather than from a mismatch between the empirical setup and model assumptions. This interpretation raises the specter that naive attempts at lethal mutagenesis may augment adaptation rather than retard it. PMID:23934886

  1. Cocaethylene is more potent than cocaine in mediating lethality.

    PubMed

    Hearn, W L; Rose, S; Wagner, J; Ciarleglio, A; Mash, D C

    1991-06-01

    Cocaethylene is a pharmacologically active cocaine metabolite that is formed in the presence of ethanol by the activity of liver enzymes. The pharmacology of cocaethylene has not been extensively investigated and its acute toxicity is unknown. The acute toxicity of cocaethylene was compared to cocaine in Swiss-Webster mice. The LD50 of cocaethylene was 60.7 mg/kg and 63.8 mg/kg in female and male mice, respectively. In comparison, the LD50 of cocaine was 93.0 mg/kg in both female and male mice. These studies demonstrate that the cocaine-alcohol metabolite, cocathylene, is more potent in mediating lethality than the parent drug.

  2. False-positive synovial fluid alpha-defensin test in a patient with acute gout affecting a prosthetic knee.

    PubMed

    Partridge, D G; Gordon, A; Townsend, R

    2017-03-17

    The alpha-defensin test has demonstrated promising results in studies evaluating it for the diagnosis of prosthetic joint infection. There are limited data in the literature regarding its use in patients with other inflammatory joint conditions, but a high specificity for infection has been reported. We describe a patient with a prosthetic knee joint, who had a positive alpha-defensin lateral flow assay but in whom subsequent results confirmed a diagnosis of acute gout with no evidence of infection.

  3. Alcohol Consumption and Nearly Lethal Suicide Attempts.

    ERIC Educational Resources Information Center

    Powell, Kenneth E.; Kresnow, Marcie-jo; Mercy, James A.; Potter, Lloyd B.; Swann, Alan C.; Frankowski, Ralph F.; Lee, Roberta K.; Bayer, Timothy L.

    2002-01-01

    Presents a case-control study of the association between nearly lethal suicide attempts and facets of alcohol consumption; namely, drinking frequency, drinking quantity, binge drinking, alcoholism, drinking within 3 hours of suicide attempt, and age began drinking. In bivariate analyses, all measures were associated with nearly lethal suicide…

  4. The acute phase inflammatory response to maximal exercise testing in children and young adults with sickle cell anaemia.

    PubMed

    Liem, Robert I; Onyejekwe, Kasiemobi; Olszewski, Marie; Nchekwube, Chisalu; Zaldivar, Frank P; Radom-Aizik, Shlomit; Rodeghier, Mark J; Thompson, Alexis A

    2015-12-01

    Although individuals with sickle cell anaemia (SCA) have elevated baseline inflammation and endothelial activation, the acute phase response to maximal exercise has not been evaluated among children with SCA. We measured the acute phase response to maximal exercise testing for soluble vascular cell adhesion molecule (sVCAM) as well as interleukin 6 (IL6), total white blood cell (WBC) count, C-reactive protein (CRP) and D-dimer in a cohort of children with SCA and matched controls at baseline, immediately after, and 30, 60 and 120 min following exercise. Despite higher baseline levels of all biomarkers except CRP, the acute phase response from baseline to immediately after exercise was significantly greater in subjects versus controls for CRP (2·1 vs. 0·2 mg/l, P = 0·02) and D-dimer (160 vs. 10 μg/l, P < 0·01) only. Similar between-group trends were observed over time for all biomarkers, including sVCAM, IL6, total WBC, CRP and D-dimer. Lower fitness, defined by peak oxygen consumption (VO2 ), was independently associated with greater acute phase responses to exercise for sVCAM. Our results suggest maximal exercise may not be associated with any greater escalation of endothelial activation or inflammation in SCA and provide preliminary biomarker evidence for the safety of brief, high-intensity physical exertion in children with SCA.

  5. Reproducibility of the six-minute walk test and Glittre ADL-test in patients hospitalized for acute and exacerbated chronic lung disease

    PubMed Central

    José, Anderson; Dal Corso, Simone

    2015-01-01

    Background: The 6-minute walk test (6MWT) and the Glittre ADL-test (GT) are used to assess functional capacity and exercise tolerance; however, the reproducibility of these tests needs further study in patients with acute lung diseases. Objectives: The aim of this study was to investigate the reproducibility of the 6MWT and GT performed in patients hospitalized for acute and exacerbated chronic lung diseases. Method: 48 h after hospitalization, 81 patients (50 males, age: 52±18 years, FEV1: 58±20% of the predicted value) performed two 6MWTs and two GTs in random order on different days. Results: There was no difference between the first and second 6MWT (median 349 m [284-419] and 363 m [288-432], respectively) (ICC: 0.97; P<0.0001). A difference between the first and second tests was found in GT (median 286 s [220-378] and 244 s [197-323] respectively; P<0.001) (ICC: 0.91; P<0.0001). Conclusion: Although both the 6MWT and GT were reproducible, the best results occurred in the second test, demonstrating a learning effect. These results indicate that at least two tests are necessary to obtain reliable assessments. PMID:26039036

  6. Acute toxicity of selected crude and refined shale oil derived and petroleum-derived substances

    SciTech Connect

    Smith, L.H.; Haschek, W.M.; Witschi, H.

    1980-01-01

    General information was obtained on the toxicity of selected samples of crude Paraho shale oil and some of its derivatives, some crude petroleums, and 3 refined petroleum products. Five tests were used to determine the acute toxicity of these substances: acute lethality in mice following oral or intraperitoneal administration of a single dose; acute dermal toxicity of a single dose in rats; delayed-type allergic contact hypersensitivity in guinea pigs; primary eye irritation and primary skin irritation of a single dose in rabbits. Histopathologic changes induced in mice following intraperitoneal injection of a single large dose of crude shale oil and two of its hydrotreated derivatives were examined. Studies also have been initiated to examine the tumor inducing potential of selected samples. The test system used was the mouse lung adenoma bioassay. The present report describes our findings and shows that all compounds tested have very low or no acute toxic effects in laboratory animals.

  7. Acute and chronic bioassays with New Zealand freshwater copepods using pentachlorophenol

    SciTech Connect

    Willis, K.J.

    1999-11-01

    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. 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.

  8. An Analysis of Viral Testing in non-Acetaminophen (non-APAP) Pediatric Acute Liver Failure (PALF)

    PubMed Central

    Schwarz, Kathleen B.; Olio, Dominic Dell; Lobritto, Steven J.; Lopez, M James; Rodriguez-Baez, Norberto; Yazigi, Nada A.; Belle, Steven H.; Zhang, Song; Squires, Robert H.

    2014-01-01

    Objective Viral infections are often suspected to cause pediatric acute liver failure (PALF) but large-scale studies have not been performed. We analyzed results of viral testing among non-acetaminophen (non APAP) PALF study participants. Methods Participants were enrolled in the PALF registry. Diagnostic evaluation and final diagnosis were determined by the site investigator and methods for viral testing by local standard of care. Viruses were classified as either Causative Viruses (CV) or Associated Viruses (AV). Supplemental testing for CV was performed if not done clinically and serum was available. Final diagnoses included “Viral”, “Indeterminate” and “Other”. Results Of 860 participants, 820 had at least one test result for a CV or AV. A positive viral test was found in 166/820 (20.2%) participants and distributed among “Viral” [66/80 (82.5%)], “Indeterminate” [52/420 (12.4%)] and “Other” [48/320 (15.0%)] diagnoses. CV accounted for 81/166 (48.8%) positive tests. Herpes Simplex Virus (HSV) was positive in 39/335 (11.6%) who were tested: 26/103 (25.2%) and 13/232 (5.6%) among infants 0 - 6 months and over 6 months, respectively. HSV was not tested in 61.0% and 53% of the over-all cohort and those 0 - 6 months, respectively. Supplemental testing yielded 17 positive, including 5 HSV. Conclusions Viral testing in PALF occurs frequently but is often incomplete. Evidence for acute viral infection was found in 20.2% of those tested for viruses. HSV is an important viral cause for PALF in all age groups. The etiopathogenic role of CV and AV in PALF requires further investigation. PMID:25079486

  9. Lethal photosensitization of Helicobacter species

    NASA Astrophysics Data System (ADS)

    Millson, Charles E.; Wilson, Michael; MacRobert, Alexander J.; Thurrell, Wendy; Mlkvy, Peter; Davies, Claire; Bown, Stephen G.

    1995-01-01

    Helicobacter pylori (H. pylori) is associated with a large number of gastroduodenal disorders. Clearance of the bacteria has been shown to benefit patients with duodenal ulcers, gastric ulcers, and certain rare types of gastric tumors. Broad-spectrum antibiotics are the mainstay of current treatment strategies but side-effects, poor compliance, and drug resistance limit their usefulness. We sensitized H. pylori with toluidine blue, haematoporphyrin derivative, aluminum disulphonated phthalocyanine, methylene blue or protoporphyrin IX prior to exposure to low-power laser light from either a gallium aluminum arsenide laser or a helium neon gas laser. All 5 sensitizers caused reductions of greater than 1000-fold in the number of viable bacteria. Light alone had no effect and only HpD caused a significant decrease in bacterial numbers without laser light. Next, we sensitized H. mustelae on explanted ferret gastric mucosa (ex vivo) with the same sensitizers and exposed them to light from a copper vapor pumped dye laser tuned appropriately. MB caused significant reductions in bacterial counts. Successful lethal photosensitization of Helicobacter pylori both in vitro and ex vivo raises the possibility of a local method for eradicating the bacteria, especially as the bacteria are only found in those parts of the upper gastrointestinal tract that are accessible to the endoscope.

  10. Cerebellar haemorrhage mimicking acute peripheral vestibulopathy: the role of the video head impulse test in differential diagnosis.

    PubMed

    Armato, E; Ferri, E; Pinzani, A; Ulmer, E

    2014-08-01

    Dizziness and vertigo without neurological signs are typically due to a peripheral vestibular disease. Although the most common causes are benign, differential diagnosis must include potentially life-threatening central diseases such as cerebrovascular pathologies. A systemic clinical approach needs a careful work-up, bedside examination and appropriate instrumental investigation. The head impulse test (HIT) allows qualitative clinical assessment of canalar function; it has some limitations such as subjective evaluation, mainly in patients with a spontaneous nystagmus. A new device has been recently developed consisting of an infrared video camera (video-HIT) to provide quantitative instrumental assessment of the high-frequency vestibular-ocular reflex (VOR) gain. By reporting a case of cerebellar haemorrhage mimicking an acute peripheral vestibulopathy, the authors suggest that video-HIT may be considered a useful tool in differential diagnosis between vestibular neuritis and cerebellar vascular disease in patients with severe acute vertigo without central signs.

  11. Methods to assess the reliability of the interRAI Acute Care: a framework to guide clinimetric testing. Part II.

    PubMed

    Wellens, Nathalie I H; Milisen, Koen; Flamaing, Johan; Moons, Philip

    2012-08-01

    The interRAI Acute Care is a comprehensive geriatric assessment tool that provides a holistic picture of complex and frail hospitalized older persons. It is designed to support holistic care planning and to transfer patient data across settings. Its usefulness in clinical decision making depends on the extent to which clinicians can rely on the patient data as accurate and meaningful indicators of patients functioning. But its multidimensional character implies challenges for clinimetric testing as some of the traditional analyses techniques cannot be unconditionally applied. The objective was to present an overview of methods to examine the reliability of the interRAI Acute Care. For each line of evidence, examples of hypotheses and research questions are listed.

  12. Acute aquatic toxicity and biodegradation potential of biodiesel fuels

    SciTech Connect

    Haws, R.A.; Zhang, X.; Marshall, E.A.; Reese, D.L.; Peterson, C.L.; Moeller, G.

    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 toxicity 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.

  13. Multispecific T cell response and negative HCV RNA tests during acute HCV infection are early prognostic factors of spontaneous clearance

    PubMed Central

    Spada, E; Mele, A; Berton, A; Ruggeri, L; Ferrigno, L; Garbuglia, A R; Perrone, M P; Girelli, G; Del Porto, P; Piccolella, E; Mondelli, M U; Amoroso, P; Cortese, R; Nicosia, A; Vitelli, A; Folgori, A

    2004-01-01

    Background/Aims: Hepatitis C virus (HCV) infection results in a high frequency of chronic disease. The aim of this study was to identify early prognostic markers of disease resolution by performing a comprehensive analysis of viral and host factors during the natural course of acute HCV infection. Methods: The clinical course of acute hepatitis C was determined in 34 consecutive patients. Epidemiological and virological parameters, as well as cell mediated immunity (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed. Results: Ten out of 34 patients experienced self-limiting infection, with most resolving patients showing fast kinetics of viral clearance: at least one negative HCV RNA test during this phase predicted a favourable outcome. Among other clinical epidemiological parameters measured, the self-limiting course was significantly associated with higher median peak bilirubin levels at the onset of disease, and with the female sex, but only the latter parameter was independently associated after multivariate analysis. No significant differences between self-limiting or chronic course were observed for the distribution of DRB1 and DQB1 alleles. HCV specific T cell response was more frequently detected during acute HCV infection, than in patients with chronic HCV disease. A significantly broader T cell response was found in patients with self-limiting infection than in those with chronic evolving acute hepatitis C. Conclusion: The results suggest that host related factors, in particular sex and CMI, play a crucial role in the spontaneous clearance of this virus. Most importantly, a negative HCV RNA test and broad CMI within the first month after onset of the symptoms represent very efficacious predictors of viral clearance and could thus be used as criteria in selecting candidates for early antiviral treatment. PMID:15479691

  14. Simian Retrovirus 4 Induces Lethal Acute Thrombocytopenia in Japanese Macaques

    PubMed Central

    Yoshikawa, Rokusuke; Sakaguchi, Shoichi; Nakagawa, So; Miura, Tomoyuki; Hirai, Hirohisa

    2015-01-01

    ABSTRACT In 2001-2002, six of seven Japanese macaques (Macaca fuscata) died after developing hemorrhagic syndrome at the Kyoto University Primate Research Institute (KUPRI). While the cause of death was unknown at the time, we detected simian retrovirus 4 (SRV-4) in samples obtained from a similar outbreak in 2008-2011, during which 42 of 43 Japanese macaques died after exhibiting hemorrhagic syndrome. In this study, we isolated SRV-4 strain PRI-172 from a Japanese macaque showing severe thrombocytopenia. When inoculated into four Japanese macaques, the isolate induced severe thrombocytopenia in all within 37 days. We then constructed an infectious molecular clone of strain PRI-172, termed pSR415, and inoculated the clone-derived virus into two Japanese macaques. These animals also developed severe thrombocytopenia in just 31 days after inoculation, and the virus was reisolated from blood, bone marrow, and stool. At necropsy, we observed bleeding from the gingivae and subcutaneous bleeding in all animals. SRV-4 infected a variety of tissues, especially in digestive organs, including colon and stomach, as determined by real-time reverse transcription-PCR (RT-PCR) and immunohistochemical staining. Furthermore, we identified the SRV-4 receptor as ASCT2, a neutral amino acid transporter. ASCT2 mRNA was expressed in a variety of tissues, and the distribution of SRV-4 proviruses in infected Japanese macaques correlated well with the expression levels of ASCT2 mRNA. From these results, we conclude that the causative agent of hemorrhagic syndrome in KUPRI Japanese macaques was SRV-4, and its receptor is ASCT2. IMPORTANCE During two separate outbreaks at the KUPRI, in 2001-2002 and 2008-2011, 96% of Japanese macaques (JM) that developed an unknown hemorrhagic syndrome died. Here, we isolated SRV-4 from a JM developing thrombocytopenia. The SRV-4 isolate and a molecularly cloned SRV-4 induced severe thrombocytopenia in virus-inoculated JMs within 37 days. At necropsy, we observed bleeding from gingivae and subcutaneous bleeding in all affected JMs and reisolated SRV-4 from blood, bone marrow, and stool. The distribution of SRV-4 proviruses in tissues correlated with the mRNA expression levels of ASCT2, which we identified as the SRV-4 receptor. From these results, we conclude that SRV-4 was the causative agent of hemorrhagic syndrome in JMs in KUPRI. PMID:25609821

  15. Methods to assess the validity of the interRAI Acute Care: a framework to guide clinimetric testing.

    PubMed

    Wellens, Nathalie I H; Milisen, Koen; Flamaing, Johan; Moons, Philip

    2012-04-01

    The objective was to present an overview of methods to examine the validity of the minimum data set of the interRAI Acute Care (interRAI AC). Because of the multidimensional character of this comprehensive geriatric assessment tool, clinimetric testing of the interRAI AC can be more complex than that of one-dimensional instruments. Thus to facilitate testing of the interRAI AC, we translated this complexity into a structured methodological framework that outlines procedures to assess various lines of evidence. Our framework combined traditional clinimetric techniques and the standards of psychological testing. For each line of evidence, examples of hypotheses and research questions were summarized. Future clinimetric testing can use these guidelines as a basis to obtain and provide a wide and diverse body of evidence.

  16. Two cases of lethal nitrazepam poisoning.

    PubMed

    Brødsgaard, I; Hansen, A C; Vesterby, A

    1995-06-01

    This case report describes two cases of lethal poisoning caused by a combination of advanced chronic disease and an overdose of nitrazepam. In both cases, a relatively small blood concentration of nitrazepam was found postmortem.

  17. Lethality and Autonomous Robots: An Ethical Stance

    DTIC Science & Technology

    2007-01-01

    Lethality and Autonomous Robots : An Ethical Stance Ronald C. Arkin and Lilia Moshkina College of Computing Georgia Institute of Technology Atlanta... autonomous robots that maintain an ethical infrastructure to govern their behavior will be referred to as humane-oids. 2. Understanding the Ethical...2007 4. TITLE AND SUBTITLE Lethality and Autonomous Robots : An Ethical Stance 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER

  18. Non-Lethal Weapons (NLW) Reference Book

    DTIC Science & Technology

    2012-01-01

    v Section A COUNTER-PERSONNEL (CP) FIELDED NLW Non-Lethal Capability Sets ( NLCS ) 1 Escalation of Force-Mission Modules (EoF-MM) 1...Weapons, 27 September 1999. Policy References Section A CP Fielded NLW 1 Non-Lethal Capability Sets ( NLCS ). A versatile package of commercial...and government off-the-shelf mission enhancing equipment and munitions. NLCS provide the warfighter with a variety of acoustic, optical distraction

  19. A conservative method of testing whether combination analgesics produce additive or synergistic effects using evidence from acute pain and migraine.

    PubMed

    Moore, R A; Derry, C J; Derry, S; Straube, S; McQuay, H J

    2012-04-01

    Fixed-dose combination analgesics are used widely, and available both on prescription and over-the-counter. Combination drugs should provide more analgesia than with any single drug in the combination, but there is no evidence in humans about whether oral combinations have just additive effects, or are synergistic or even subadditive. We suggest that the measured result for the combination would be the summation of the absolute benefit increase (effect of active drug minus effect of placebo) of each component of a combination if effects were (merely) additive, and greater than the sum of the absolute benefits if they were synergistic. We tested measured effects of combination analgesics against the sum of the absolute benefits in acute pain and migraine using meta-analysis where individual components and combinations were tested against placebo in the same trials, and verified the result with meta-analyses where individual components and combinations were tested against placebo in different trials. Results showed that expected numbers needed to treat (NNT) for additive effects were generally within the 95% confidence interval of measured NNTs. This was true for combinations of paracetamol plus ibuprofen and paracetamol plus opioids in acute pain, and naproxen plus sumatriptan in migraine, but not where efficacy was very low or very high, nor combinations of paracetamol plus dextropropoxyphene. There was no evidence of synergy, defined as supra-additive effects.

  20. Highly predictive support vector machine (SVM) models for anthrax toxin lethal factor (LF) inhibitors.

    PubMed

    Zhang, Xia; Amin, Elizabeth Ambrose

    2016-01-01

    Anthrax is a highly lethal, acute infectious disease caused by the rod-shaped, Gram-positive bacterium Bacillus anthracis. The anthrax toxin lethal factor (LF), a zinc metalloprotease secreted by the bacilli, plays a key role in anthrax pathogenesis and is chiefly responsible for anthrax-related toxemia and host death, partly via inactivation of mitogen-activated protein kinase kinase (MAPKK) enzymes and consequent disruption of key cellular signaling pathways. Antibiotics such as fluoroquinolones are capable of clearing the bacilli but have no effect on LF-mediated toxemia; LF itself therefore remains the preferred target for toxin inactivation. However, currently no LF inhibitor is available on the market as a therapeutic, partly due to the insufficiency of existing LF inhibitor scaffolds in terms of efficacy, selectivity, and toxicity. In the current work, we present novel support vector machine (SVM) models with high prediction accuracy that are designed to rapidly identify potential novel, structurally diverse LF inhibitor chemical matter from compound libraries. These SVM models were trained and validated using 508 compounds with published LF biological activity data and 847 inactive compounds deposited in the Pub Chem BioAssay database. One model, M1, demonstrated particularly favorable selectivity toward highly active compounds by correctly predicting 39 (95.12%) out of 41 nanomolar-level LF inhibitors, 46 (93.88%) out of 49 inactives, and 844 (99.65%) out of 847 Pub Chem inactives in external, unbiased test sets. These models are expected to facilitate the prediction of LF inhibitory activity for existing molecules, as well as identification of novel potential LF inhibitors from large datasets.

  1. Comparative assessment of the acute skin irritation potential of detergent formulations using a novel human 4-h patch test method.

    PubMed

    Robinson, Michael K; Kruszewski, Francis H; Al-Atrash, Jenan; Blazka, Mark E; Gingell, Ralph; Heitfeld, Fred A; Mallon, David; Snyder, Neil K; Swanson, Judith E; Casterton, Phillip L

    2005-12-01

    Predictive skin irritation test methods, which do not require use of animals, are needed for the pre-market assessment of detergent formulations. The utility of a novel and ethical human acute skin irritation patch test method, originally developed for chemical skin irritation assessment, was evaluated. In this IRB-approved method, subjects were patched under occlusion for increasing periods of time up to 4h in duration. The total incidence of positive skin reactions for test products was compared to a positive control (20% aqueous sodium dodecyl sulfate [SDS]). Acutely irritating formulas were defined as those showing a significantly increased or equal incidence of positive responders compared with that of SDS. The time of exposure required for 50% of subjects to show a positive skin reaction (TR50 value) was calculated for each product and enabled test product comparisons within and between studies. Using this approach, 24 detergent formulations of various types were tested in seven individual studies. The skin irritation profiles were generally consistent within product types, which could be categorized as follows (by decreasing irritancy): mold/mildew removers (average TR50 = 0.37 h) > disinfectants/sanitizers (0.64 h) > fabric softener concentrate (1.09 h) = aluminum wash (1.20 h) > 20% SDS (1.81 h) > liquid laundry detergents (3.48 h) > liquid dish detergents (4.16 h) = liquid fabric softeners (4.56 h) = liquid hand soaps (4.58 h) = shampoos (5.40 h) = hard surface cleaners (6.34 h) > powder automatic dish detergents (>16 h) = powder laundry detergents (>16 h). In addition to formulation effects, some seasonal effects were noted; particularly greater winter-time reactivity to 20% SDS and the hard surface cleaner and liquid laundry formulations. These results demonstrate the utility of this patch test method for the comparative skin irritation assessment of these different product types.

  2. [Acute Toxicity of Coptis chinensis Rhizome Extracts to Daphnia carinata].

    PubMed

    Chen, Ya-nan; Yuan, Ling

    2015-10-01

    Coptis chinensis rhizome and preparations were widely used for the treatment of fish diseases in aquaculture. the acute toxicological effect of CRE on lethal, movement and phototaxis was studied on Daphnia carinata monoclone as a test animal in the present experiment. The results showed that CRE was acute toxic to this animal and alkaloids berberine concentrations in CRE changed in the following sequence: half lethal > half inhibitory > limitable, which led to a significant change in phototaxis index of Daphnia carinata. The concentration of CRE for the significant change in phototaxis index was 4.27 mg x L(-1), which was lower than the concentration in water to cure the fish diseases and this conclusion indicated an ecological risk of this antibiotic to Daphnia carinata in aquaculture. In addition, the concentration of CRE in phototaxis index was changed from 30.62 times at 48th hour to 36.51 times at 24th hour that were lower than half lethal concentration. Detecting phototaxis index was easy and only 3 hours was required, so utilizing the quickly change of Daphnia carinata phototaxis can be an effective method to monitor the toxicity effect of CRE on Daphnia carinata. The abuse of rhizome or preparations in aquaculture might destroy the aquatic food chain, resulting in an imbalance of aquatic ecosystems.

  3. 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).

  4. 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

  5. Prophylactic strategies for acute hemolysis secondary to plasma-incompatible platelet transfusions: correlation between qualitative hemolysin test and isohemagglutinin titration

    PubMed Central

    Landim, Cinthia Silvestre; Gomes, Francisco Carlos Almeida; Zeza, Bernardete Martin; Mendrone-Júnior, Alfredo; Dinardo, Carla Luana

    2015-01-01

    Objective Brazilian legislation has recently suggested the use of the qualitative hemolysin test instead of isohemagglutinin titers as prophylaxis for acute hemolysis related to plasma-incompatible platelet transfusions. The efficacy of this test in preventing hemolytic reactions has never been evaluated while isohemagglutinin titers have been extensively studied. The main objective of this study was to evaluate the correlation between the results of these two tests. The impact of each type of prophylaxis on the platelet inventory management and the ability of the qualitative hemolysin test to prevent red cell sensitization after the transfusion of incompatible units were also studied. Methods A total of 246 donor blood samples were evaluated using both isohemagglutinin titers and the qualitative hemolysin test, and the results were statistically compared. Subsequently, 600 platelet units were tested using the hemolysin assay and the percentage of units unsuitable for transfusion was compared to historical data using isohemagglutinin titers (cut-off: 100). Moreover, ten patients who received units with minor ABO incompatibilities that were negative for hemolysis according to the qualitative hemolysin test were evaluated regarding the development of hemolysis and red cell sensitization (anti-A or anti-B). Results Isohemagglutinin titration and the results of qualitative hemolysin test did not correlate. The routine implementation of the qualitative hemolysin test significantly increased the percentage of platelet units found unsuitable for transfusions (15–65%; p-value <0.001). Furthermore the qualitative hemolysin test did not prevent red blood cell sensitization in a small exploratory analysis. Conclusion Qualitative hemolysin test results do not correlate to those of isohemagglutinin titers and its implementation as the prophylaxis of choice for hemolysis associated with plasma-incompatible platelet transfusions lacks clinical support of safety and

  6. Littoral Combat Ship: Knowledge of Survivability and Lethality Capabilities Needed Prior to Making Major Funding Decisions

    DTIC Science & Technology

    2015-12-01

    its business case for LCS and conduct a number of operational test events on both variants prior to making a decision to contract for more ships...of Survivability and Lethality Capabilities Needed Prior to Making Major Funding Decisions Why GAO Did This Study GAO has reported extensively on...Survivability and Lethality Capabilities Needed Prior to Making Major Funding Decisions , GAO-15-361C (Washington, D.C.: July 7, 2015) (S//NF). 5H.R. Rep

  7. An outbreak of lethal adenovirus infection among different otariid species.

    PubMed

    Inoshima, Yasuo; Murakami, Tomoaki; Ishiguro, Naotaka; Hasegawa, Kazuhiro; Kasamatsu, Masahiko

    2013-08-30

    An outbreak of fatal fulminant hepatitis at a Japanese aquarium involved 3 otariids: a California sea lion (Zalophus californianus), a South African fur seal (Arctocephalus pusillus) and a South American sea lion (Otaria flavescens). In a span of about a week in February 2012, 3 otariids showed diarrhea and were acutely low-spirited; subsequently, all three animals died within a period of 3 days. Markedly increased aspartate amino transferase and alanine amino transferase activities were observed. Necrotic hepatitis and eosinophilic intranuclear inclusion bodies in liver hepatocytes and intestinal epithelial cells were observed in the South American sea lion on histological examination. Otarine adenovirus DNA was detected from the livers of all three animals by polymerase chain reaction and determination of the sequences showed that all were identical. These results suggest that a single otarine adenovirus strain may have been the etiological agent of this outbreak of fatal fulminant hepatitis among the different otariid species, and it may be a lethal threat to wild and captive otariids. This is the first evidence of an outbreak of lethal adenovirus infection among different otariid species.

  8. Histopathological changes in snail, Pomacea canaliculata, exposed to sub-lethal copper sulfate concentrations.

    PubMed

    Dummee, Vipawee; Tanhan, Phanwimol; Kruatrachue, Maleeya; Damrongphol, Praneet; Pokethitiyook, Prayad

    2015-12-01

    The acute toxicity test of Cu including range-finding and definitive test, was performed on golden apple snails, Pomacea canaliculata. The median lethal concentrations (LC50) of Cu at exposure times of 24, 48, 72 and 96 h were 330, 223, 177 and 146 µg/L, respectively. P. canaliculata were exposed to Cu at 146 µg/L for 96 h to study bioaccumulation and histopathological alterations in various organs. Snails accumulated elevated levels of Cu in gill, and lesser amounts in the digestive tract, muscle, and digestive gland. Histopathological investigation revealed several alterations in the epithelia of gill, digestive tract (esophagus, intestine, rectum), and digestive gland. The most striking changes were observed in the epithelium of the gill in which there was loss of cilia, an increase in number of mucus cells, and degeneration of columnar cells. Similar changes occurred in digestive tract epithelium. The digestive gland showed moderate alterations, vacuolization and degeneration of cells and an increase in the number of basophilic cells. We concluded that, P. canaliculata has a great potential as a bioindicator for Cu, and a biomarker for monitoring Cu contamination in aquatic environment.

  9. Lethal and Sublethal Effects of Insecticides on the Egg Parasitoid Telenomus podisi (Hymenoptera: Platygastridae).

    PubMed

    Turchen, L M; Golin, V; Butnariu, A R; Guedes, R N C; Pereira, M J B

    2016-02-01

    Insecticide use remains controversial, and subjected to increasing environmental and health concerns, even when recent insecticide groups are considered. Neonicotinoids and even bioinsecticides are in the forefront of discussions regarding their nontarget safety. The ubiquitous focus on the lethal effects of insecticides on nontarget species has been expanding to sublethal effects, as sublethal exposure extends for a longer time and affects a broader range of (nontarget) species. Here we explored the lethal and sublethal effects of a lambda-cyhalothrin + thiamethoxan mixture, the neonicotinoid imidacloprid, and the bioinsecticide azadirachtin on the egg parasitoid Telenomus podisi Ashmead, an important parasitoid of stink bug Euschistus heros (F.), a key soybean pest in neotropical America. Contact with dry insecticide residue on glass surface and (parasitized and healthy) host egg immersion exposure bioassays were performed, assessing their acute lethal effects, and their potential sublethal impairment of parasitism, adult emergence, and fertility of the egg parasitoid. Both imidacloprid and the insecticide mixture exhibited high acute lethal activity toward the parasitoid under contact with dry insecticide residue. These insecticides compromised parasitism and wasp emergence when exposure took place before parasitism. In contrast, azadirachtin did not affect adult survival. However, this bioinsecticide compromised parasitism and progeny production, impairing the female parasitoid reproductive potential. Our results indicate strong negative effects of imidacloprid, and specially of the mixture lambda-cyhalthrin + thiamethoxan. However, even azadirachtin, which exhibited low acute lethality, exhibited significant negative sublethal effects on parasitism and population growth of egg parasitoid, cautioning against their use and the need of semifield and field assessments to confirm such an impact.

  10. 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 Central

    Sarathy, Vanessa V.; White, Mellodee; Li, Li; Gorder, Summer R.; Pyles, Richard B.; Campbell, Gerald A.; Milligan, Gregg N.

    2014-01-01

    ABSTRACT 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. IMPORTANCE 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

  11. 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

  12. There is need for antigen-based rapid diagnostic tests to identify common acute tropical illnesses.

    PubMed

    Wilde, Henry; Suankratay, Chusana

    2007-01-01

    Enteric fever, typhus, leptospirosis, dengue, melioidosis, and tuberculous meningitis present urgent diagnostic problems that require experience and clinical judgment to make early evidence-based management decisions. Basic and applied research dealing with reliable antigen-based diagnostics has been published and confirmed for several of these infections. This should have initiated commercial production but has not. Established international firms see little profit in such diagnostic kits since they would be used in poor countries with little prospects for return of investment capital. We attempt to illustrate this issue, using common causes of acute febrile illnesses in the Southeast Asian region. We believe that rapid diagnostic technology could prevent significant delay in starting appropriate therapy, reduce hospital expenses, and even save lives.

  13. Value of serological tests in the diagnosis of viral acute respiratory infections in adults.

    PubMed

    Căruntu, F; Dogaru, D; Stefan, D; Căruntu, V; Angelescu, C; Streinu-Cercel, A; Colţan, G; Petrescu, A L; Tarţă, D; Bârnaure, F

    1986-01-01

    The dynamics of the antibody response to influenza viruses A (H1N1), A (H3N2) and B, to parainfluenza viruses 1, 2, 3, to adenoviruses and respiratory syncytial virus was studied in paired serum samples collected from 110 patients hospitalized with acute respiratory infections (ARI) and in 40 patients suffering from other diseases. Rises in serum antibody titers to 1--5 of the above mentioned antigens were detected in many of the patients of both groups. The fact is most likely due to the presence of some epidemiologically and clinically uncharacteristic viral ARI (influenza included); simultaneous or successive infections with influenza virus and different other viruses were very frequent. A greater efficiency of the etiological diagnosis of viral ARI can be achieved only by the association of epidemiological and clinical criteria with serological data, the visualization of viral antigens and virus isolation.

  14. Surveillance of Acute Respiratory Infections Using Community-Submitted Symptoms and Specimens for Molecular Diagnostic Testing

    PubMed Central

    Goff, Jennifer; Rowe, Aaron; Brownstein, John S.; Chunara, Rumi

    2015-01-01

    Participatory systems for surveillance of acute respiratory infection give real-time information about infections circulating in the community, yet to-date are limited to self-reported syndromic information only and lacking methods of linking symptom reports to infection types. We developed the GoViral platform to evaluate whether a cohort of lay volunteers could, and would find it useful to, contribute self-reported symptoms online and to compare specimen types for self-collected diagnostic information of sufficient quality for respiratory infection surveillance. Volunteers were recruited, given a kit (collection materials and customized instructions), instructed to report their symptoms weekly, and when sick with cold or flu-like symptoms, requested to collect specimens (saliva and nasal swab). We compared specimen types for respiratory virus detection sensitivity (via polymerase-chain-reaction) and ease of collection. Participants were surveyed to determine receptivity to participating when sick, to receiving information on the type of pathogen causing their infection and types circulating near them. Between December 1 2013 and March 1 2014, 295 participants enrolled in the study and received a kit. Of those who reported symptoms, half (71) collected and sent specimens for analysis. Participants submitted kits on average 2.30 days (95 CI: 1.65 to 2.96) after symptoms began. We found good concordance between nasal and saliva specimens for multiple pathogens, with few discrepancies. Individuals report that saliva collection is easiest and report that receiving information about what pathogen they, and those near them, have is valued and can shape public health behaviors. Community-submitted specimens can be used for the detection of acute respiratory infection with individuals showing receptivity for participating and interest in a real-time picture of respiratory pathogens near them. PMID:26075141

  15. Surveillance of Acute Respiratory Infections Using Community-Submitted Symptoms and Specimens for Molecular Diagnostic Testing.

    PubMed

    Goff, Jennifer; Rowe, Aaron; Brownstein, John S; Chunara, Rumi

    2015-05-27

    Participatory systems for surveillance of acute respiratory infection give real-time information about infections circulating in the community, yet to-date are limited to self-reported syndromic information only and lacking methods of linking symptom reports to infection types. We developed the GoViral platform to evaluate whether a cohort of lay volunteers could, and would find it useful to, contribute self-reported symptoms online and to compare specimen types for self-collected diagnostic information of sufficient quality for respiratory infection surveillance. Volunteers were recruited, given a kit (collection materials and customized instructions), instructed to report their symptoms weekly, and when sick with cold or flu-like symptoms, requested to collect specimens (saliva and nasal swab). We compared specimen types for respiratory virus detection sensitivity (via polymerase-chain-reaction) and ease of collection. Participants were surveyed to determine receptivity to participating when sick, to receiving information on the type of pathogen causing their infection and types circulating near them. Between December 1 2013 and March 1 2014, 295 participants enrolled in the study and received a kit. Of those who reported symptoms, half (71) collected and sent specimens for analysis. Participants submitted kits on average 2.30 days (95 CI: 1.65 to 2.96) after symptoms began. We found good concordance between nasal and saliva specimens for multiple pathogens, with few discrepancies. Individuals report that saliva collection is easiest and report that receiving information about what pathogen they, and those near them, have is valued and can shape public health behaviors. Community-submitted specimens can be used for the detection of acute respiratory infection with individuals showing receptivity for participating and interest in a real-time picture of respiratory pathogens near them.

  16. Identification of patients at low risk of dying after acute myocardial infarction, by simple clinical and submaximal exercise test criteria.

    PubMed

    Campbell, S; A'Hern, R; Quigley, P; Vincent, R; Jewitt, D; Chamberlain, D

    1988-09-01

    A consecutive series of 559 hospital survivors of acute myocardial infarction aged less than 66 years were studied; 93 were designated prospectively as low-risk because they were suitable for early submaximal exercise testing and had none of the following clinical or exercise test 'risk factors': (1) angina for at least one month prior to infarction; (2) symptomatic ventricular arrhythmias, or (3) recurrent ischaemic pain, both after the first 24 h of infarction; (4) cardiac failure; (5) cardiomegaly; and (6) an abnormal exercise test (angina, ST-depression or poor blood pressure response). Altogether 301 patients were exercised; their mortality over a median follow-up of 2.4 years was 10.2%, versus 24.6% in the 258 patients not exercised (P = 0.0005). Absence of clinical 'risk factors' alone, in the exercised patients, identified 156 with a mortality of 5.4% versus 15.6% in the 145 with at least one clinical 'risk factor' (P = 0.004). The fully defined low-risk group comprised 93 of the former patients who had neither clinical nor exercise test 'risk factors'. None of these patients died compared with 19 of those with at least one 'risk factor' (mortality = 14.7%; P = 0.002). Their respective rates of non-fatal reinfarction were similar and never exceeded 5% per annum. Therefore, simple clinical and exercise test criteria can positively identify low-risk patients after infarction in whom secondary prevention may be inappropriate.

  17. Acute toxicity of the cationic surfactant C12-benzalkonium in different bioassays: how test design affects bioavailability and effect concentrations.

    PubMed

    Chen, Yi; Geurts, Marc; Sjollema, Sascha B; Kramer, Nynke I; Hermens, Joop L M; Droge, Steven T J

    2014-03-01

    Using an ion-exchange-based solid-phase microextraction (SPME) method, the freely dissolved concentrations of C12-benzalkonium were measured in different toxicity assays, including 1) immobilization of Daphnia magna in the presence or absence of dissolved humic acid; 2) mortality of Lumbriculus variegatus in the presence or absence of a suspension of Organisation for Economic Co-Operation and Development (OECD) sediment; 3) photosystem II inhibition of green algae Chlorella vulgaris; and 4) viability of in vitro rainbow trout gill cell line (RTgill-W1) in the presence or absence of serum proteins. Furthermore, the loss from chemical adsorption to the different test vessels used in these tests was also determined. The C12-benzalkonium sorption isotherms to the different sorbent phases were established as well. Our results show that the freely dissolved concentration is a better indicator of the actual exposure concentration than the nominal or total concentration in most test assays. Daphnia was the most sensitive species to C12-benzalkonium. The acute Daphnia and Lumbriculus tests both showed no enhanced toxicity from possible ingestion of sorbed C12-benzalkonium in comparison with water-only exposure, which is in accordance with the equilibrium partitioning theory. Moreover, the present study demonstrates that commonly used sorbent phases can strongly affect bioavailability and observed effect concentrations for C12-benzalkonium. Even stronger effects of decreased actual exposure concentrations resulting from sorption to test vessels, cells, and sorbent phases can be expected for more hydrophobic cationic surfactants.

  18. Predictive value of D-dimer test for recurrent venous thromboembolism at hospital discharge in patients with acute pulmonary embolism.

    PubMed

    Wang, Yong; Liu, Zhi-Hong; Zhang, Hong-Liang; Luo, Qin; Zhao, Zhi-Hui; Zhao, Qing

    2011-11-01

    D-dimer can be used to exclude acute pulmonary embolism (PE) for its high negative predictive value (NPV). Also, it is a predictor of recurrent venous thromboembolism (VTE) after anticoagulation withdrawal. The aim of the present study was to assess the predictive value of D-dimer for recurrent VTE when tested at hospital discharge. Plasma D-dimer levels were repeatedly measured at hospital discharge in 204 consecutive patients with the first episode of acute pulmonary embolism. Patients were categorized to two groups by D-dimer levels at hospital discharge and followed up at 3, 6, and 12 months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE. D-dimer levels were persistently abnormal in 66 patients (32%). After 31±19 months follow-up, patients with persistently abnormal D-dimer level levels showed a higher rate of of recurrent VTE (14 patients, 21%) compared to those with D-dimer regression (8 patients, 6%) (P = 0.001). At the multivariate analysis, after adjustment for other relevant factors, persistently abnormal D-dimer level levels were an independent predictor of recurrent VTE in all subjects investigated, (hazard ratio, 4.10; 95% CI, 1.61-10.39; P = 0.003), especially in those with unprovoked PE (hazard ratio, 4.61; 95% CI, 1.85-11.49; P = 0.001). The negative predictive value of D-dimer was 94.2 and 92.9% in all subjects or those with unprovoked PE, respectively. Persistently abnormal D-dimer level levels at hospital discharge have a high negative predictive value for recurrence in patients with acute pulmonary embolism, especially in subjects with an unprovoked previous event.

  19. The flap by flap dissection in terminal ballistic applied to less lethal weapons.

    PubMed

    de Freminville, Humbert; Rongieras, Fréderic; Prat, Nicolas; Voiglio, Eric J

    2011-06-01

    Medical examiners often have to solve questions such as firing distance and bullet trajectory for lethal weapons. Knowledge in the field of terminal ballistics has increased during the last 30 years and layer by layer dissection reveals superficial wounds that can be linked with the permanent cavity. At the end of the 1990s, terminal ballistics also focused on less lethal weapons and their wounds. Here, 2 different less lethal weapons with single bullets were tested on nonembalmed and undressed cadavers (N = 26) at different ranges and speeds. We have developed a technique for dissection which we call flap by flap dissection that reveals the advantage of the bullet-skin-bone entity, the absence of wounds linking its components and range of less lethal weapons.

  20. Types, Risk Factors, Clinical symptoms and Diagnostic Tests of Acute Adult Meningitis in Northern Iran During 2006-2012

    PubMed Central

    Bagheri-Nesami, Masoumeh; Babamahmoodi, Farhang

    2015-01-01

    Background Acute bacterial meningitis is a medical emergency condition that requires prompt diagnosis and treatment and otherwise associated with serious morbidity and mortality. Aim The aim of this study was to assess types, risk factors, clinical symptoms and diagnostic tests of meningitis in hospitalized patients of Mazandaran University of medical sciences hospitals during 2006-2012. Matherials and Methods This is a retrospective descriptive study. Following approval of the ethics committee of Mazandaran University of Medical Sciences, records of adult patients diagnosed with acute meningitis from 2006 to 2012 were extracted from Mazandaran Provincial Health Center and patients attending hospitals affiliated to Mazandaran University of Medical Sciences. Statistical Analysis Data were analyzed with SPSS-16 using descriptive statistics (frequency, mean, standard deviation, and median). Results In this study, of the 137 patients with meningitis, 73 (53.9%) were viral, 61 (46%) bacterial, 1 (0.7%) fungal, and 2 (1.4%) unknown. The majority of risk factors in patients were head trauma, upper respiratory infection, and drug addiction. The most common clinical signs were headache, fever, nausea and vomiting, and stiff neck. Conclusion In this study, the incidence of meningitis was much lower than any other country. It could be due to geographic variation or incomplete recording of patient's data. It is recommended to perform a longitudinal study during the coming years on patients with meningitis. PMID:26155497

  1. Comparative proteomic profiling and possible toxicological mechanism of acute injury induced by carbon ion radiation in pubertal mice testes

    NASA Astrophysics Data System (ADS)

    Zhang, Hong

    2016-07-01

    We investigated potential mechanisms of acute injury in pubertal mice testes after exposure to carbon ion radiation (CIR). Serum testosterone was measured following whole-body irradiation with a 2Gy carbon ion beam. Comparative proteomic profiling and Western blotting were applied to identify potential biomarkers and measure protein expression, and terminal dUTP nick end-labeling (TUNEL) was performed to detect apoptotic cells. Immunohistochemistry and immunofluorescence were used to investigate protein localization. Serum testosterone was lowest at 24h after CIR, and 10 differentially expressed proteins were identified at this time point that included eIF4E, an important regulator of initiation that combines with mTOR and 4EBP1 to control protein synthesis via the mTOR signalling pathway during proliferation and apoptosis. Protein expression and localization studies confirmed their association with acute injury following exposure to CIR. These three proteins may be useful molecular markers for detecting abnormal spermatogenesis following exposure to environmental and cosmic radiation

  2. Comparative proteomic profiling and possible toxicological mechanism of acute injury induced by carbon ion radiation in pubertal mice testes.

    PubMed

    Li, Hongyan; Zhang, Hong; Di, Cuixia; Xie, Yi; Zhou, Xin; Yan, Jiawei; Zhao, Qiuyue

    2015-12-01

    We investigated potential mechanisms of acute injury in pubertal mice testes after exposure to carbon ion radiation (CIR). Serum testosterone was measured following whole-body irradiation with a 2Gy carbon ion beam. Comparative proteomic profiling and Western blotting were applied to identify potential biomarkers and measure protein expression, and terminal dUTP nick end-labeling (TUNEL) was performed to detect apoptotic cells. Immunohistochemistry and immunofluorescence were used to investigate protein localization. Serum testosterone was lowest at 24h after CIR, and 10 differentially expressed proteins were identified at this time point that included eIF4E, an important regulator of initiation that combines with mTOR and 4EBP1 to control protein synthesis via the mTOR signaling pathway during proliferation and apoptosis. Protein expression and localization studies confirmed their association with acute injury following exposure to CIR. These three proteins may be useful molecular markers for detecting abnormal spermatogenesis following exposure to environmental and therapeutic radiation.

  3. Laboratory Measures of Postural Control During the Star Excursion Balance Test After Acute First-Time Lateral Ankle Sprain

    PubMed Central

    Doherty, Cailbhe; Bleakley, Chris M.; Hertel, Jay; Caulfield, Brian; Ryan, John; Delahunt, Eamonn

    2015-01-01

    Context No researchers, to our knowledge, have investigated the immediate postinjury-movement strategies associated with acute first-time lateral ankle sprain (LAS) as quantified by center of pressure (COP) and kinematic analyses during performance of the Star Excursion Balance Test (SEBT). Objective To analyze the kinematic and COP patterns of a group with acute first-time LAS and a noninjured control group during performance of the SEBT. Design Case-control study. Setting University biomechanics laboratory. Patients or Other Participants A total of 81 participants with acute first-time LAS (53 men, 28 women; age = 23.22 ± 4.93 years, height = 1.73 ± 0.09 m, mass = 75.72 ± 13.86 kg) and 19 noninjured controls (15 men, 4 women; age = 22.53 ± 1.68 years, height = 1.74 ± 0.08 m, mass = 71.55 ± 11.31 kg). Intervention Participants performed the anterior (ANT), posterolateral (PL), and posteromedial (PM) reach directions of the SEBT. Main Outcome Measure(s) We assessed 3-dimensional kinematics of the lower extremity joints and associated fractal dimension (FD) of the COP path during performance of the SEBT. Results The LAS group had decreased normalized reach distances in the ANT, PL, and PM directions when compared with the control group on their injured (ANT: 58.16% ± 6.86% versus 64.86% ± 5.99%; PL: 85.64% ± 10.62% versus 101.14% ± 8.39%; PM: 94.89% ± 9.26% versus 107.29 ± 6.02%) and noninjured (ANT: 60.98% ± 6.74% versus 64.76% ± 5.02%; PL: 88.95% ± 11.45% versus 102.36% ± 8.53%; PM: 97.13% ± 8.76% versus 106.62% ± 5.78%) limbs (P < .01). This observation was associated with altered temporal sagittal-plane kinematic profiles throughout each reach attempt and at the point of maximum reach (P < .05). This result was associated with a reduced FD of the COP path for each reach direction on the injured limb only (P < .05). Conclusions Acute first-time LAS was associated with bilateral deficits in postural control, as evidenced by the bilateral

  4. Comparison of ethanol toxicity to Daphnia magna and Ceriodaphnia dubia tested at two different temperatures: static acute toxicity test results

    SciTech Connect

    Takahashi, I.T.; Cowgill, U.M.; Murphy, P.G.

    1987-08-01

    Ethanol is a commonly used solvent in toxicity testing, yet there are few studies in the literature devoted to its toxicity to zooplankton. The purpose of this study was to compare the response of Daphnia magna Straus 1820 and Ceriodaphnia dubia J. Richard 1894 to ethanol. Two temperatures were selected because most toxicity data involving D. magna has been carried out at 20/sup 0/C while all discussions concerning C. dubia appear to relate to temperatures oscillating around 25/sup 0/C. Thus, the response of these two organisms to ethanol was examined at 20/sup 0/C and at 24/sup 0/C.r

  5. An Acute Bout of Self-Myofascial Release in the Form of Foam Rolling Improves Performance Testing

    PubMed Central

    PEACOCK, COREY A.; KREIN, DARREN D.; SILVER, TOBIN A.; SANDERS, GABRIEL J.; VON CARLOWITZ, KYLE-PATRICK A.

    2014-01-01

    Recent developments in the strength and conditioning field have shown the incorporation of foam rolling self-myofascial release in adjunct with a dynamic warm-up. This is thought to improve overall training performance; however, minimal research exists supporting this theory. Therefore, determining if an acute bout of foam rolling self-myofascial release in addition to a dynamic warm-up could influence performance is of importance. In order to do so, eleven athletically trained male subjects participated in a two condition, counterbalanced, crossover within-subjects study comparing two particular warm-up routines. The two warm-up routines compared were a total-body dynamic warm-up (DYN) and a total-body dynamic warm-up in adjunct with a self-myofascial release, total-body foam rolling session (SMR). Following each warm-up condition, subjects performed tests of flexibility, power, agility, strength, and speed. Paired samples T-tests were utilized to determine if there were any significant differences in test results between conditions (DYN vs. SMR). The data indicated that SMR was effective at improving power, agility, strength, and speed when compared to DYN (P ≤ 0.024). A warm-up routine consisting of both a dynamic warm-up and a self-myofascial release, total-body foam rolling session resulted in overall improvements in athletic performance testing. PMID:27182404

  6. A review on advantages of implementing luminescence inhibition test (Vibrio fischeri) for acute toxicity prediction of chemicals.

    PubMed

    Parvez, Shahid; Venkataraman, Chandra; Mukherji, Suparna

    2006-02-01

    Evaluation of biological effects using a rapid, sensitive and cost effective method can indicate specific information on toxicity/ecotoxicity. Since assays based on animals, plants and algae are expensive, time consuming and require large sample volume, recent studies have emphasized the benefits of rapid, reproducible and cost effective bacterial assays for toxicity screening and assessment. This review focuses on a bacterial assay, i.e., Vibrio fischeri bioluminescence inhibition assay, which is often chosen as the first test in a test battery based on speed and cost consideration. The test protocol is simple and was originally applied for aqueous phase samples or extracts. The versatility of the assay has increased with subsequent modification, i.e., the kinetic assay for turbid and colored samples and the solid phase test for analyzing sediment toxicity. Researchers have reported the Vibrio fischeri bioluminescence assay as the most sensitive across a wide range of chemicals compared to other bacterial assays such as nitrification inhibition, respirometry, ATP luminescence and enzyme inhibition. This assay shows good correlations with other standard acute toxicity assays and is reported to detect toxicity across a wide spectrum of toxicants.

  7. An Acute Bout of Self-Myofascial Release in the Form of Foam Rolling Improves Performance Testing.

    PubMed

    Peacock, Corey A; Krein, Darren D; Silver, Tobin A; Sanders, Gabriel J; VON Carlowitz, Kyle-Patrick A

    Recent developments in the strength and conditioning field have shown the incorporation of foam rolling self-myofascial release in adjunct with a dynamic warm-up. This is thought to improve overall training performance; however, minimal research exists supporting this theory. Therefore, determining if an acute bout of foam rolling self-myofascial release in addition to a dynamic warm-up could influence performance is of importance. In order to do so, eleven athletically trained male subjects participated in a two condition, counterbalanced, crossover within-subjects study comparing two particular warm-up routines. The two warm-up routines compared were a total-body dynamic warm-up (DYN) and a total-body dynamic warm-up in adjunct with a self-myofascial release, total-body foam rolling session (SMR). Following each warm-up condition, subjects performed tests of flexibility, power, agility, strength, and speed. Paired samples T-tests were utilized to determine if there were any significant differences in test results between conditions (DYN vs. SMR). The data indicated that SMR was effective at improving power, agility, strength, and speed when compared to DYN (P ≤ 0.024). A warm-up routine consisting of both a dynamic warm-up and a self-myofascial release, total-body foam rolling session resulted in overall improvements in athletic performance testing.

  8. Testing an application of a biotic ligand model to predict acute toxicity of metal mixtures to rainbow trout.

    PubMed

    Iwasaki, Yuichi; Kamo, Masashi; Naito, Wataru

    2015-04-01

    The authors tested the applicability of a previously developed biotic ligand model (BLM) to predict acute toxicity of single metals and metal mixtures (cadmium, lead, and zinc) to rainbow trout fry (Oncorhynchus mykiss) from a single available dataset. The BLM used in the present study hypothesizes that metals inhibit an essential cation (calcium) and organisms die as a result of its deficiency, leading to an assumption that the proportion of metal-binding ligand (f) is responsible for the toxic effects of metals on the survival of rainbow trout. The f value is a function of free-ion concentrations of metals computed by a chemical speciation model, and the function has affinity constants as model parameters. First, the survival effects of single metals were statistically modeled separately (i.e., f-survival relationship) by using the generalized linear mixed model with binomial distribution. The modeled responses of survival rates to f overlapped reasonably irrespective of metals tested, supporting the theoretical prediction from the BLM that f-survival relationships are comparable regardless of metal species. The authors thus developed the generalized linear mixed model based on all data pooled across the single-metal tests. The best-fitted model well predicted the survival responses observed in mixture tests (r = 0.97), providing support for the applicability of the BLM to predict effects of metal mixtures.

  9. Guidelines on selection of laboratory tests for monitoring the acute phase response. International Committee for Standardization in Haematology (expert panel on blood rheology).

    PubMed Central

    1988-01-01

    These guidelines refer to laboratory tests for monitoring changes in acute phase proteins in patients with an inflammatory response to tissue damage. Quantitative measurements of acute phase proteins are a valuable indicator of the presence, extent, and response of inflammation to treatment. When short term (less than 24 hours) changes in the inflammatory response are expected, quantitative assay of C reactive protein is the test of choice. The hyperproteinaemia that develops in response to a longer term (more than 24 hours) inflammatory response is complex and may vary from one disease to another. A test that is sensitive to the combined effect of several plasma proteins is therefore indicated, and appropriate tests include the erythrocyte sedimentation rate and plasma viscosity--the latter having several advantages. Tests for monitoring short term and long term changes in acute phase proteins are complementary and should be used for different clinical purposes; no one test is ideal for all clinical situations. A quality control programme is an essential component of laboratory tests for monitoring the acute phase response. PMID:2463272

  10. Developing and testing a patient information booklet for thrombolysis used in acute stroke.

    PubMed

    Knapp, Peter; Wanklyn, Peter; Raynor, D K; Waxman, Robin

    2010-12-01

    Objective  Thrombolysis decreases the chance of post-stroke dependence, although its use carries significant risk, notably of intra-cerebral haemorrhage. Patients (and families) face an important risk/benefit decision before consenting. We drafted a patient information booklet for this purpose, and applied performance-based readability testing with the aim that the most important information in the booklet could be found and understood. Methods  The booklet was developed with reference to best practice in information writing and design. We User-Tested its performance on 56 people without prior experience of stroke. After reading the booklet they were asked to find and explain 15 pieces of information. The booklet was revised according to its performance and re-tested, until each item was found and understood by at least 80% of participants. Key findings  The four-page information booklet contained approximately 900 words, organised into six sections. A risk-palette graphic showed the chance of positive and negative outcomes. The booklet was tested on four participant cohorts and revised, including more bold text, re-wording, changing the title and changing the graphic to a coloured bar chart. Testing the final version on the fourth cohort of 20 people showed that each of the 15 tested items of information met the target of at least 80% participants being able to find and understand it. Conclusions  The use of information design and User Testing produced a booklet that is understandable by people with no prior experience of stroke. User Testing is an inexpensive and quick method to ensure that information intended for patients is usable.

  11. Improving the Quality of Diagnostic Studies Evaluating Point of Care Tests for Acute HIV Infections: Problems and Recommendations.

    PubMed

    Smallwood, Megan; Pant Pai, Nitika

    2017-03-04

    The diagnosis of acute human immunodeficiency virus (HIV) infection (AHI) plays a unique role in preventing the spread of HIV and ending the epidemic. Acutely infected individuals are thought to contribute substantially to forward transmissions of HIV; however, diagnosing AHI in resource-limited settings has proven to be a challenge. While fourth generation antigen-antibody combination assays have been successful in high-resource settings, rapid point of care (POC) versions of these assays have yet to demonstrate high sensitivity to detect AHI. Newer RNA/DNA based POC technologies are being validated, but the challenge to understand the additional value of these devices depends on the quality of study evaluations, in particular choice of study designs and case mix of included populations. In this commentary, we aimed to review the quality of studies evaluating a new fourth generation rapid test for detecting AHI, to identify general methodological limitations and biases in diagnostic accuracy studies, and to recommend strategies for avoiding them in future evaluations. The new studies that were evaluated continued to report the same weaknesses and biases that were seen in previous evaluations of fourth generation rapid tests. We recommend that investigators design future studies carefully, keeping in mind how diagnostic performance may be influenced by prevalence, population, patient case mixes, and reference standards. Care must be taken to avoid biases specific to diagnostic accuracy studies (spectrum, verification, incorporation and reference standard biases). To improve on quality, reporting checklists and guidelines such as Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Standards for Reporting Diagnostic accuracy studies (STARD) should be reviewed prior to conducting studies.

  12. Improving the Quality of Diagnostic Studies Evaluating Point of Care Tests for Acute HIV Infections: Problems and Recommendations

    PubMed Central

    Smallwood, Megan; Pant Pai, Nitika

    2017-01-01

    The diagnosis of acute human immunodeficiency virus (HIV) infection (AHI) plays a unique role in preventing the spread of HIV and ending the epidemic. Acutely infected individuals are thought to contribute substantially to forward transmissions of HIV; however, diagnosing AHI in resource-limited settings has proven to be a challenge. While fourth generation antigen-antibody combination assays have been successful in high-resource settings, rapid point of care (POC) versions of these assays have yet to demonstrate high sensitivity to detect AHI. Newer RNA/DNA based POC technologies are being validated, but the challenge to understand the additional value of these devices depends on the quality of study evaluations, in particular choice of study designs and case mix of included populations. In this commentary, we aimed to review the quality of studies evaluating a new fourth generation rapid test for detecting AHI, to identify general methodological limitations and biases in diagnostic accuracy studies, and to recommend strategies for avoiding them in future evaluations. The new studies that were evaluated continued to report the same weaknesses and biases that were seen in previous evaluations of fourth generation rapid tests. We recommend that investigators design future studies carefully, keeping in mind how diagnostic performance may be influenced by prevalence, population, patient case mixes, and reference standards. Care must be taken to avoid biases specific to diagnostic accuracy studies (spectrum, verification, incorporation and reference standard biases). To improve on quality, reporting checklists and guidelines such as Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Standards for Reporting Diagnostic accuracy studies (STARD) should be reviewed prior to conducting studies. PMID:28273857

  13. Sarcocystis species lethal for domestic pigeons.

    PubMed

    Olias, Philipp; Gruber, Achim D; Kohls, Andrea; Hafez, Hafez M; Heydorn, Alfred Otto; Mehlhorn, Heinz; Lierz, Michael

    2010-03-01

    A large number of Sarcocystis spp. infect birds as intermediate hosts, but pigeons are rarely affected. We identified a novel Sarcocystis sp. that causes lethal neurologic disease in domestic pigeons in Germany. Experimental infections indicated transmission by northern goshawks, and sequence analyses indicated transnational distribution. Worldwide spread is possible.

  14. Deadly Lessons: Understanding Lethal School Violence.

    ERIC Educational Resources Information Center

    Moore, Mark H., Ed.; Petrie, Carol V., Ed.; Braga, Anthony A., Ed.; McLaughlin, Brenda L., Ed.

    This collection of papers is the outcome of the National Academies' effort to glean information from six different case studies of student-perpetrated school shootings. Part 1, "Case Studies of Lethal School Violence," includes: "The Copycat Factor: Mental Illness, Guns, and the Shooting Incident at Heritage High School, Rockdale…

  15. The evolution of lethal intergroup violence.

    PubMed

    Kelly, Raymond C

    2005-10-25

    Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry.

  16. Medical Conditions and Nearly Lethal Suicide Attempts.

    ERIC Educational Resources Information Center

    Ikeda, Robin M.; Kresnow, Marcie-jo; Mercy, James A.; Powell, Kenneth E.; Simon, Thomas R.; Potter, Lloyd B.; Durant, Tonji M.; Swahn, Monica H.

    2002-01-01

    This population-based, case-control study examined physical illness as a risk factor for suicidal behavior. Case patients were more likely than controls to report having any serious medical conditions. Results suggest that young men with medical conditions are at increased risk for nearly lethal suicide attempts. (Contains 33 references and 3…

  17. Acute Oxidative Effect and Muscle Damage after a Maximum 4 Min Test in High Performance Athletes.

    PubMed

    Ferreira, Heros Ribeiro; Ferreira, Pamela Gill; Loures, João Paulo; Fernandes Filho, José; Fernandes, Luiz Cláudio; Buck, Hudson Sousa; Montor, Wagner Ricardo

    2016-01-01

    The purpose of this investigation was to determine lipid peroxidation markers, physiological stress and muscle damage in elite kayakers in response to a maximum 4-min kayak ergometer test (KE test), and possible correlations with individual 1000m kayaking performances. The sample consisted of twenty-three adult male and nine adult female elite kayakers, with more than three years' experience in international events, who voluntarily took part in this study. The subjects performed a 10-min warm-up, followed by a 2-min passive interval, before starting the test itself, which consisted of a maximum 4-min work paddling on an ergometer; right after the end of the test, an 8 ml blood sample was collected for analysis. 72 hours after the test, all athletes took part in an official race, when then it was possible to check their performance in the on site K1 1000m test (P1000m). The results showed that all lipoproteins and hematological parameters tested presented a significant difference (p≤0.05) after exercise for both genders. In addition, parameters related to muscle damage such as lactate dehydrogenase (LDH) and creatine kinase (CK) presented significant differences after stress. Uric acid presented an inverse correlation with the performance (r = -0.76), while CK presented a positive correlation (r = 0.46) with it. Based on these results, it was possible to verify muscle damage and the level of oxidative stress caused by indoor training with specific ergometers for speed kayaking, highlighting the importance of analyzing and getting to know the physiological responses to this type of training, in order to provide information to coaches and optimize athletic performance.

  18. Acute Oxidative Effect and Muscle Damage after a Maximum 4 Min Test in High Performance Athletes

    PubMed Central

    Fernandes Filho, José; Fernandes, Luiz Cláudio

    2016-01-01

    The purpose of this investigation was to determine lipid peroxidation markers, physiological stress and muscle damage in elite kayakers in response to a maximum 4-min kayak ergometer test (KE test), and possible correlations with individual 1000m kayaking performances. The sample consisted of twenty-three adult male and nine adult female elite kayakers, with more than three years’ experience in international events, who voluntarily took part in this study. The subjects performed a 10-min warm-up, followed by a 2-min passive interval, before starting the test itself, which consisted of a maximum 4-min work paddling on an ergometer; right after the end of the test, an 8 ml blood sample was collected for analysis. 72 hours after the test, all athletes took part in an official race, when then it was possible to check their performance in the on site K1 1000m test (P1000m). The results showed that all lipoproteins and hematological parameters tested presented a significant difference (p≤0.05) after exercise for both genders. In addition, parameters related to muscle damage such as lactate dehydrogenase (LDH) and creatine kinase (CK) presented significant differences after stress. Uric acid presented an inverse correlation with the performance (r = -0.76), while CK presented a positive correlation (r = 0.46) with it. Based on these results, it was possible to verify muscle damage and the level of oxidative stress caused by indoor training with specific ergometers for speed kayaking, highlighting the importance of analyzing and getting to know the physiological responses to this type of training, in order to provide information to coaches and optimize athletic performance. PMID:27111088

  19. Assessing executive abilities following acute stroke with the trail making test and digit span.

    PubMed

    Tamez, Elaine; Myerson, Joel; Morris, Lucy; White, Desirée A; Baum, Carolyn; Connor, Lisa Tabor

    2011-01-01

    The Trail Making Test and Digit Span are neuropsychological tests widely used to assess executive abilities following stroke. The Trails B and Digits Backward conditions of these tests are thought to be more sensitive to executive impairment related to frontal lobe dysfunction than the Trails A and Digits Forward conditions. Trails B and Digits Backward are also thought to be more sensitive to brain damage in general. Data from the Stroke and Lesion Registry maintained by the Washington University Cognitive Rehabilitation Research Group were analyzed to compare the effects of frontal versus nonfrontal strokes and to assess the effects of stroke severity. Results showed that the performance of patients with frontal and nonfrontal strokes was comparable in each condition of both the Trail Making Test and Digit Span, providing no support for the widely held belief that Trails B and Digits Backward are more sensitive to frontal lobe damage. Further, Trails A was as strongly correlated with stroke severity as Trails B, whereas Digits Backward was more strongly correlated with stroke severity than Digits Forward. Overall, the Trail Making Test and Digit Span are sensitive to brain damage but do not differentiate between patients with frontal versus nonfrontal stroke.

  20. Acute restraint stress produces behavioral despair in weanling rats in the forced swim test.

    PubMed

    Bernal-Morales, Blandina; Contreras, Carlos M; Cueto-Escobedo, Jonathan

    2009-10-01

    Stressful experiences in the rat during early life increase the vulnerability to later signs of behavioral despair in adulthood, reflected in increased immobility in the forced swim test (FST). However, the possible immediate effects of stress in weanling rats have only been partially described. The present study tested whether a single session of mild restraint stress modifies immobility in the FST in 21-day-old Wistar rats. After evaluating any possible changes in locomotion using the open field test (OFT), the latency and total duration of immobility were assessed in a single FST session. Regardless of gender, mild restraint stress significantly reduced crossings in the OFT, shortened the latency to the first period of immobility, and increased immobility in the FST compared with a control group devoid of stress. We conclude that a single mild physical stress session, as early as postnatal day 21, produces signs of behavioral despair.

  1. In vitro chemosensitivity testing of leukemic cells: prediction of response to chemotherapy in patients with acute non-lymphocytic leukemia.

    PubMed

    Santini, V; Bernabei, P A; Silvestro, L; Dal Pozzo, O; Bezzini, R; Viano, I; Gattei, V; Saccardi, R; Ferrini, P R

    1989-01-01

    The in vitro chemosensitivity to daunorubicin and cytosine arabinoside of blast cells derived from 35 patients affected by acute non-lymphocytic leukemia was assessed by a semiautomated tetrazolium-based colorimetric assay, by the use of p-iodonitrotetrazolium violet. The results of the in vitro testing were then compared a posteriori to clinical outcome of patients, who followed a schedule of therapy which always included the drugs tested in vitro. Three dosages of drugs were employed to allow the determination of a dose-response curve, which was obtained for all the patients. The data collected in INT assay correlated with the clinical sensitivity of patients, evaluated in terms of achievement of complete remission. For the dosage of ARA-C 500 ng/ml it was possible to establish a significant cutoff between responders and non-responders to therapy, while an acceptable distribution of sensitivity/resistance prediction was found for DNR 500 ng/ml and 5 micrograms/ml. Present results, together with rapid and easy execution of the test, encourage the use of INT assay in screening leukemic patients' sensitivity to antiblastic drugs before treatment or, in case of resistance to classical chemotherapy, in detecting individual sensitivity to alternative drugs.

  2. Incorporating Acute HIV Screening into Routine HIV Testing at Sexually Transmitted Infection Clinics, and HIV Testing and Counseling Centers in Lilongwe, Malawi

    PubMed Central

    Pettifor, Audrey E.; Phiri, Sam; Kamanga, Gift; Hoffman, Irving F.; Hosseinipour, Mina C.; Rosenberg, Nora E.; Nsona, Dominic; Pasquale, Dana; Tegha, Gerald; Powers, Kimberly A.; Phiri, Mcleod; Tembo, Bisweck; Chege, Wairimu; Miller, William C.

    2016-01-01

    Background and Objectives: Integrating acute HIV-infection (AHI) testing into clinical settings is critical to prevent transmission, and realize potential treatment-as-prevention benefits. We evaluated acceptability of AHI testing and compared AHI prevalence at sexually transmitted infection (STI) clinics and HIV testing and counseling (HTC) clinics in Lilongwe, Malawi. Methods: We conducted HIV RNA testing for HIV-seronegative patients visiting STI and HTC clinics. AHI was defined as positive RNA and negative/discordant rapid antibody tests. We evaluated demographic, behavioral, and transmission-risk differences between STI and HTC patients and assessed performance of a risk-score for targeted screening. Results: Nearly two-thirds (62.8%, 9280/14,755) of eligible patients consented to AHI testing. We identified 59 persons with AHI (prevalence = 0.64%)–a 0.9% case-identification increase. Prevalence was higher at STI [1.03% (44/4255)] than at HTC clinics [0.3% (15/5025), P < 0.01], accounting for 2.3% of new diagnoses vs 0.3% at HTC clinic. Median viral load (VL) was 758,050 copies per milliliter; 25% (15/59) had VL ≥10,000,000 copies per milliliter. Median VL was higher at STI (1,000,000 copies/mL) compared with HTC (153,125 copies/mL, P = 0.2). Among persons with AHI, those tested at STI clinics were more likely to report genital sores compared with those tested at HTC clinics (54.6% vs 6.7%, P < 0.01). The risk score algorithm performed well in identifying persons with AHI at HTC clinics (sensitivity = 73%, specificity = 89%). Conclusions: The majority of patients consented to AHI testing. AHI prevalence was substantially higher in STI clinics than HTC clinics. Remarkably high VLs and concomitant genital scores demonstrate the potential for transmission. Universal AHI screening at STI clinics, and targeted screening at HTC centers, should be considered. PMID:26428231

  3. D-dimer testing and acute venous thromboembolism. A shortcut to accurate diagnosis?

    PubMed

    Becker, D M; Philbrick, J T; Bachhuber, T L; Humphries, J E

    1996-05-13

    D-dimer fragments can be measured easily in plasma and whole blood, and the presence or absence of D-dimer could be useful in the diagnostic evaluation of venous thromboembolism. We systematically reviewed the English literature for articles that compared D-dimer results with those of other tests for deep venous thrombosis or pulmonary embolism. Twenty-nine studies were selected for detailed review, and we noted wide variability in assay performance, heterogeneity among subjects, and failure to define absence or presence of venous thromboembolism by a comprehensive criterion standard for diagnosis. These methodologic problems limit the generalizability of the published estimates of D-dimer accuracy for deep venous thrombosis or pulmonary embolism, and the clinical utility of this potentially important test remains unproved.

  4. A test of the effects of acute sleep deprivation on general and specific self-reported anxiety and depressive symptoms: an experimental extension.

    PubMed

    Babson, Kimberly A; Trainor, Casey D; Feldner, Matthew T; Blumenthal, Heidemarie

    2010-09-01

    Evidence indicates acute sleep deprivation affects negative mood states. The present study experimentally tested the effects of acute sleep deprivation on self-reported symptoms of state anxiety and depression as well as general distress among 88 physically and psychologically healthy adults. As hypothesized, the effects of acute sleep deprivation increased state anxiety and depression, as well as general distress, relative to a normal night of sleep control condition. Based on the tripartite model of anxiety and depression, these findings replicate and extend prior research by suggesting sleep deprivation among individuals without current Axis I disorders increases both state symptoms of anxiety and depression specifically, and general distress more broadly. Extending this work to clinical samples and prospectively testing mechanisms underlying these effects are important future directions in this area of research.

  5. ANAM4 TBI reaction time-based tests have prognostic utility for acute concussion.

    PubMed

    Norris, Jacob N; Carr, Walter; Herzig, Thomas; Labrie, D Walter; Sams, Richard

    2013-07-01

    The Concussion Restoration Care Center has used the Automated Neuropsychological Assessment Metrics version 4 Traumatic Brain Injury (ANAM4 TBI) battery in clinical assessment of concussion. The study's aim is to evaluate the prognostic utility of the ANAM4 TBI. In 165 concussed active duty personnel (all ultimately returned to duty) seen and tested on the ANAM4 TBI on days 3 and 5 (median times) from their injury, Spearman's ρ statistics showed that all performance subtests (at day 5) were associated with fewer days return-to-duty (RTD) time, whereas concussion history or age did not. Kruskal-Wallis statistics showed that ANAM4 TBI, loss of consciousness, and post-traumatic amnesia were associated with increased RTD time; ANAM4 TBI reaction time-based subtests, collectively, showed the largest effect sizes. A survival analysis using a Kaplan-Meier plot showed that the lowest 25% on the reaction time-based subtests had a median RTD time of 19 days, whereas those in the upper 25% had a median RTD time of approximately 7 days. Results indicate that until validated neurocognitive testing is introduced, the ANAM4 TBI battery, especially reaction time-based tests, has prognostic utility.

  6. Lethality and synthetic lethality in the genome-wide metabolic network of Escherichia coli.

    PubMed

    Ghim, Cheol-Min; Goh, Kwang-Il; Kahng, Byungnam

    2005-12-21

    Recent genomic analyses on the cellular metabolic network show that reaction flux across enzymes are diverse and exhibit power-law behavior in its distribution. While intuition might suggest that the reactions with larger fluxes are more likely to be lethal under the blockade of its catalysing gene products or gene knockouts, we find, by in silico flux analysis, that the lethality rarely has correlations with the flux level owing to the widespread backup pathways innate in the genome-wide metabolism of Escherichia coli. Lethal reactions, of which the deletion generates cascading failure of following reactions up to the biomass reaction, are identified in terms of the Boolean network scheme as well as the flux balance analysis. The avalanche size of a reaction, defined as the number of subsequently blocked reactions after its removal, turns out to be a useful measure of lethality. As a means to elucidate phenotypic robustness to a single deletion, we investigate synthetic lethality in reaction level, where simultaneous deletion of a pair of nonlethal reactions leads to the failure of the biomass reaction. Synthetic lethals identified via flux balance and Boolean scheme are consistently shown to act in parallel pathways, working in such a way that the backup machinery is compromised.

  7. The Acute Toxicity Test of Methanolic Extract of Hyptis pectinata Poit on Liver Balb/c Mice

    NASA Astrophysics Data System (ADS)

    Suzery, M.; Cahyono, B.; Astuti, P.

    2017-02-01

    Plants from Lamiaceae family has almost entirely reported having physiological activities. One of them is Hyptis pectinata Poit plant. Research on the toxicity of Hyptis pectinata needs to be done to protect people from the possibility of its harmful effects. This study aim to know the acute toxicity effects of Hyptis pectinata extract (HPE) on liver of Balb/c mice. This research was a laboratory experimental study using the post test only controlled group design. Balb/c mice were randomly divided into 4 groups. K (control group), P1, P2 and P3 (treatment groups; given HPE 200mg/kgBW, 1000 mg/kgBW, and 5000 mg/kgBW, respectively). The extract was orally given with gastric tube on the first day and the mice were terminated at the 8th day then the livers were observed. The Kruskal-Wallis test for macroscopic morphological and volume of the liver showed there were no significant difference with p=0.406 and p=0.054. The highest liver histopathological score was in P3 group. The Kruskal-Wallis test showed significantly difference (p=0.000). Continued with Mann-Withney test that showed a significant difference in K-P1 (p=0.009), K-P2 (p=0.009), K-P3 (p=0.009), P1-P2 (p=0.028), and P1-P3 (p=0.009). In conclusion, the HPE is safe to use which has no complication with liver of mice.

  8. Acute and chronic toxicity testing of TPH-contaminated soils with the earthworm, Eisenia foetida

    SciTech Connect

    Stewart, A.J.; Wicker, L.F.; Nazerias, M.S.

    1995-12-31

    Responses of Eisenia foetida to petroleum-contaminated soils are being assessed using a 21-day test described previously. The authors prepared dilutions of two soils, referred to as A and B, using their reference-soil counterparts, collected from near the contaminated sites. The total petroleum hydrocarbon (TPH) content of each soil was measured by latroscan before the dilutions were prepared. References for the A and B soils contained 167 and 1,869 ppm of TPH, respectively. Thus, neither reference soil was pristine. Dilutions of the A soil tested with E. foetida contained from 179 to 305 ppm TPH; dilutions of the B soil contained from 1,875 to 1,950 ppm TPH. E foetida survival was 100% in both dilution series. Mean growth of Eisenia in dilutions of the A soil ranged from 48 to 74 mg dry-weight growth per pair of worms; these values were lower than those in any dilution of the B soil series. Lipid levels of worms in higher concentrations of the A and B soils were similar to one another and to published values, suggesting little inhibition of feeding in either dilution series. Earthworm reproduction was zero in the A series, but moderately high in the B series. Thus, the A soil apparently contained materials other than TPH that inhibited earthworm growth and reproduction. This study shows that (1) TPH at concentrations as high as 1,800 ppm may not always be inhibitor to earthworm growth or reproduction and (2) that earthworm survival, as a test endpoint, is much less sensitive than either growth or reproduction.

  9. Effects of chronic and acute stress on rat behaviour in the forced-swim test.

    PubMed

    Suvrathan, Aparna; Tomar, Anupratap; Chattarji, Sumantra

    2010-11-01

    Stress and depression may share common neural plasticity mechanisms. Importantly, the development and reversal of stress-induced plasticity requires time. These temporal aspects, however, are not captured fully in the forced-swim test (FST), a behavioural model for testing antidepressant efficacy, used originally in naïve animals. The present study probed whether and how a rodent model of stress affects behaviour in the FST over time. We found that the intensity and duration of stress are critical in the development of depressive symptoms in male Wistar rats (n = 37) as tested in the FST. Chronic immobilization stress (2 h/day for 10 days) elicited a range of responses, from low to high values of immobility in the FST on day 1, and subsequent immobility on day 2 was inversely related to individual day 1 values. As a whole, chronically stressed rats did not exhibit any significant change in immobility either on day 1 or day 2 compared to control rats. However, climbing behaviour was reduced uniformly from day 1 to day 2, despite the differences in immobility. In contrast, a separate group of rats (n = 30) subjected to the same chronic stressor displayed a significant reduction in open-arm exploration in the elevated plus maze, indicative of a robust increase in anxiety-like behaviour. Furthermore, when the 10-day chronic stress paradigm was reduced to a single 2-h episode of immobilization stress, it triggered a uniform day 1 to day 2 increase in immobility, which was not persistent 10 days later. These results highlight a need for closer examination of the ways in which stress-induced modulation of behaviour in the FST may be used and interpreted in future studies aimed at exploring connections between stress and depression.

  10. Paper-based point-of-care testing for cost-effective diagnosis of acute flavivirus infections.

    PubMed

    Bedin, Frederic; Boulet, Laurent; Voilin, Elodie; Theillet, Gerald; Rubens, Agnes; Rozand, Christine

    2017-03-11

    Flavivirus infections are a serious healthcare concern in tropical and subtropical countries. Although well-established laboratory tests can provide early diagnosis of acute dengue or Zika infections, access to these tests is limited in developing countries, presenting an urgent need to develop simple, rapid, and robust diagnostic tools. Microfluidic Paper-based Analytical Devices (μPAD), are typically rapid, cost-effective, user-friendly, and they can be used as diagnostic tools for the diagnosis of these infections at Point of Care settings. Early and prompt diagnosis is crucial to improve patient management and reduce the risk of complications. In the present study, we developed and evaluated a wax-printed paper-based device for the detection of the dengue and Zika non-structural NS1 viral protein in blood and plasma. Experiments have been carried out to increase specificity, while maintaining the required sensitivity. As a consequence, the quality of the raw materials and the washing steps were proved to be crucial. The μPAD was able to detect specifically in 6-8 min 10 ng/mL of protein in various sample types. A prototype for the differential detection of dengue and/or Zika NS1 protein was developed. The reading of the results was simplified by using a dedicated application on a smartphone.

  11. Acute radiation risk models

    NASA Astrophysics Data System (ADS)

    Smirnova, Olga

    Biologically motivated mathematical models, which describe the dynamics of the major hematopoietic lineages (the thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems) in acutely/chronically irradiated humans are developed. These models are implemented as systems of nonlinear differential equations, which variables and constant parameters have clear biological meaning. It is shown that the developed models are capable of reproducing clinical data on the dynamics of these systems in humans exposed to acute radiation in the result of incidents and accidents, as well as in humans exposed to low-level chronic radiation. Moreover, the averaged value of the "lethal" dose rates of chronic irradiation evaluated within models of these four major hematopoietic lineages coincides with the real minimal dose rate of lethal chronic irradiation. The demonstrated ability of the models of the human thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems to predict the dynamical response of these systems to acute/chronic irradiation in wide ranges of doses and dose rates implies that these mathematical models form an universal tool for the investigation and prediction of the dynamics of the major human hematopoietic lineages for a vast pattern of irradiation scenarios. In particular, these models could be applied for the radiation risk assessment for health of astronauts exposed to space radiation during long-term space missions, such as voyages to Mars or Lunar colonies, as well as for health of people exposed to acute/chronic irradiation due to environmental radiological events.

  12. Lethal and Sublethal Toxicity Comparison of BFRs to Three Marine Planktonic Copepods: Effects on Survival, Metabolism and Ingestion

    PubMed Central

    Gong, Wenjing; Zhu, Liyan; Hao, Ya

    2016-01-01

    The estuarine planktonic copepods have a wide geographical distribution and commendable tolerance to various kinds of contaminants. The primary aim of the present study was to contrast the impacts of model POPs (TBBPA and HBCD) on three common estuarine planktonic copepods (Oithona similis, Acartia pacifica and Pseudodiaptomus inopinus) and establish a protocol for the assessment of acute toxicity of marine organic pollutants. We first quantified the 96h-LC50 (0.566, 0.04 and 0.257 mg/L of TBBPA to the three subjects above respectively and 0.314 mg/L of HBCD to P. inopinus; all reported concentrations are nominal values). In the sub-lethal toxicity tests, it was turned out that the effects of copepods exposed to TBBPA could product different influences on the energy ingestion and metabolism. Different type of pollutions, meanwhile, could also bring varying degree effect on the target copepods. In general, the indicators (the rate of oxygen consumption, ammonia excretion, food ingestion and filtration) in higher concentration groups showed marked significant difference compared with controls as well a dose-effect relationship. The study also extended the research on the joint toxicity of TBBPA and HBCD based on the survival rate of P.inopinus. Whether 1:1 concentration or 1:1 toxic level, the research showed synergy effect relative to single exposure conditions. The result indicated that current single ecological testing used for environmental protection activities may underestimate the risk for copepods. It was also demonstrated that short-term sub-lethal experiment could be a standard to evaluate the sensitivity of copepods to POPs. PMID:26824601

  13. A composite neurobehavioral test to evaluate acute functional deficits after cerebellar haemorrhage in rats.

    PubMed

    McBride, Devin W; Nowrangi, Derek; Kaur, Harpreet; Wu, Guangyong; Huang, Lei; Lekic, Tim; Tang, Jiping; Zhang, John H

    2017-01-01

    Cerebellar haemorrhage accounts for 5-10% of all intracerebral haemorrhages and leads to severe, long-lasting functional deficits. Currently, there is limited research on this stroke subtype, which may be due to the lack of a suitable composite neuroscoring system specific for cerebellar injury in rodents. The purpose of this study is to develop a comprehensive composite neuroscore test for cerebellar injury using a rat model of cerebellar haemorrhage. Sixty male Sprague-Dawley rats were subjected to either sham surgery or cerebellar haemorrhage. Twenty-four hours post-injury, neurological behaviour was evaluated using 17 cost-effective and easy-to-perform tests, and a composite neuroscore was developed. The composite neuroscore was then used to assess functional recovery over seven days after cerebellar haemorrhage. Differences in the composite neuroscore deficits for the mild and moderate cerebellar haemorrhage models were observed for up to five days post-ictus. Until now, a composite neuroscore for cerebellar injury was not available for rodent studies. Herein, using mild and moderate cerebellar haemorrhage rat models a composite neuroscore for cerebellar injury was developed and used to assess functional deficits after cerebellar haemorrhage. This composite neuroscore may also be useful for other cerebellar injury models.

  14. Lethal and sub-lethal effects on the Asian common toad Duttaphrynus melanostictus from exposure to hexavalent chromium.

    PubMed

    Fernando, Vindhya A K; Weerasena, Jagathpriya; Lakraj, G Pemantha; Perera, Inoka C; Dangalle, Chandima D; Handunnetti, Shiroma; Premawansa, Sunil; Wijesinghe, Mayuri R

    2016-08-01

    Chromium discharged in industrial effluents frequently occurs as an environmental pollutant, but the lethal and sub-lethal effects the heavy metal might cause in animals exposed to it have been insufficiently investigated. Selecting the amphibian Duttaphrynus melanostictus, we carried out laboratory tests to investigate the effects of short and long term exposure to hexavalent chromium (Cr(VI)) in both tadpoles and adult toads. The concentrations used were 0.002, 0.02, 0.2, 1.0 and 2.0mg/L, the first three corresponding to field levels. In vitro exposures were also carried out using toad erythrocytes and Cr(VI) concentrations of 0.0015, 0.003, 0.015, 0.03, 0.15mg/L. Mortality, growth retardation, developmental delays and structural aberrations were noted in the metal-treated tadpoles, with increasing incidence corresponding to increase in Cr(VI) level and duration of exposure. Many of the sub-lethal effects were evident with long term exposure to environmentally relevant levels of the toxicant. Changes in selected blood parameters and erythrocyte morphometry were also detected in Cr(VI) exposed toads, indicating anaemic and leucopenic conditions. In the genotoxicity study, DNA damage indicated by comet assay and increased micronuclei frequency, occurred at the low Cr(VI) concentrations tested. The multiple deleterious effects of exposure to chromium signal the need for monitoring and controlling the discharge of chromium to the environment. The dose-dependency and genotoxic effects observed in this widely distributed Asian toad indicates its suitability for monitoring heavy metal pollution in aquatic systems.

  15. Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species - SETAC Abstract

    EPA Science Inventory

    We developed a toxicity database for unionid mussels to examine the extent of intra- and inter-laboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the two life stages; and the variation in sensitiv...

  16. Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species

    EPA Science Inventory

    The authors developed a toxicity database for unionid mussels to examine the extent of intra- and interlaboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the 2 life stages; and the variation in se...

  17. Lethal arthrogryposis with anterior horn cell disease.

    PubMed

    Vuopala, K; Ignatius, J; Herva, R

    1995-01-01

    Fifteen infants (11 families) with lethal arthrogryposis and anterior horn motor neuron loss are described. The clinical presentation was the fetal akinesia deformation sequence (FADS) with multiple contractures and facial anomalies. At autopsy neurogenic muscular atrophy was present in all infants. The spinal cord showed a paucity of anterior horn motor neurons in the 12 infants studied. Both male and female infants were affected. Nine cases were sporadic, whereas in two families there were three affected cases. Consanguinity between the parents was reported in one family with one affected child. This and the recurrence of the condition speak for autosomal recessive inheritance. Detailed neuropathological examination and documentation of the clinical features are needed for a better delineation of and genetic counseling for perinatally lethal arthrogryposis.

  18. Henipaviruses-unanswered questions of lethal zoonoses.

    PubMed

    Field, Hume; Kung, Nina

    2011-12-01

    The highly lethal Hendra and Nipah viruses have been described for little more than a decade, yet within that time have been aetiologically associated with major livestock and human health impacts, albeit on a limited scale. Do these emerging pathogens pose a broader threat, or are they inconsequential 'viral chatter'. Given their lethality, and the evident multi-generational human-to-human transmission associated with Nipah virus in Bangladesh, it seems prudent to apply the precautionary principle. While much is known of their clinical, pathogenic and epidemiologic features in livestock species and humans, a number of fundamental questions regarding the relationship between the viruses, their natural fruit-bat host and the environment remain unanswered. In this paper, we pose and probe these questions in context, and offer perspectives based primarily on our experience with Hendra virus in Australia, augmented with Nipah virus parallels.

  19. PARP inhibitors: Synthetic lethality in the clinic.

    PubMed

    Lord, Christopher J; Ashworth, Alan

    2017-03-17

    PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitive to PARPi because they have a specific type of DNA repair defect. PARPi also show promising activity in more common cancers that share this repair defect. However, as with other targeted therapies, resistance to PARPi arises in advanced disease. In addition, determining the optimal use of PARPi within drug combination approaches has been challenging. Nevertheless, the preclinical discovery of PARPi synthetic lethality and the route to clinical approval provide interesting lessons for the development of other therapies. Here, we discuss current knowledge of PARP inhibitors and potential ways to maximize their clinical effectiveness.

  20. Lethality and entropy of protein interaction networks.

    PubMed

    Manke, Thomas; Demetrius, Lloyd; Vingron, Martin

    2005-01-01

    We characterize protein interaction networks in terms of network entropy. This approach suggests a ranking principle, which strongly correlates with elements of functional importance, such as lethal proteins. Our combined analysis of protein interaction networks and functional profiles in single cellular yeast and multi-cellular worm shows that proteins with large contribution to network entropy are preferentially lethal. While entropy is inherently a dynamical concept, the present analysis incorporates only structural information. Our result therefore highlights the importance of topological features, which appear as correlates of an underlying dynamical property, and which in turn determine functional traits. We argue that network entropy is a natural extension of previously studied observables, such as pathway multiplicity and centrality. It is also applicable to networks in which the processes can be quantified and therefore serves as a link to study questions of structural and dynamical robustness in a unified way.

  1. Ethylene Oxide: Acute Four-Hour and One-Hour Inhalation Toxicity Testing in Rats

    PubMed Central

    Snellings, William M.; Nachreiner, Donald J.; Pottenger, Lynn H.

    2011-01-01

    Ethylene oxide was tested on groups of rats for either 4-hour or 1-hour inhalation exposure, followed by 14 days of observation. Groups of five Sprague-Dawley rats/sex were exposed, and clinical signs and mortality were recorded. Clinical signs noted included irregular breathing, absence of certain reflexes, and tremors. Rats that died had moderate to severe pulmonary congestion. The calculated LC50 values, reported as ppm by volume (with 95% confidence limits), were as follows. 4-hour LC50 values were 1972 (1887 to 2061) ppm for males; 1537 (1391 to 1698) ppm for females; 1741 (1655 to 1831) ppm for the combined sexes. The 1-hour LC50 values were 5748 (5276 to 6262) ppm for males; 4439 (4034 to 4884) ppm for females; 5029 (4634 to 5459) ppm for the combined sexes. PMID:21785591

  2. Models for pulmonary lethality and morbidity after irradiation from internal and external sources

    SciTech Connect

    Scott, B.R.; Filipy, R.E.; Hahn, E.F.

    1989-05-01

    This report provides a hazard-function model for estimating the risk of death from radiation pneumonitis and/or pulmonary fibrosis following a light-water nuclear power accident. A similar model is also provided for estimating the prevalence of respiratory functional morbidity among those that survive death from acute effects. Hazard-function models for lethality and for morbidity were constructed using the cumulative hazard estimator H, which is related to the risk estimator R through the equation R = 1-exp(-H). The estimator H can be calculated using information provided in the report. The method of calculation depends on the exposure scenario. In general, the total normalized dose X for lethality or for morbidity is calculated. For lethality, X = 1 corresponds to a median lethal dose (LD/sub 50/); for morbidity, X = 1 corresponds to a median effective dose (ED/sub 50/). H is related to X by the equation H = 1n(2)X/sup V/, where V depends on the type of radiation (or radiations) involved. Contributions to X can arise from each of two main modes of exposure: (1) brief exposure of the lung, at a relatively high dose rate, to mainly external gammas, followed by (2) chronic internal alpha, and/or beta, and/or gamma irradiation of the lung. Equations are provided for calculating the contributions to X from both modes of exposure. 73 refs., 16 figs., 2 tabs.

  3. Acute effect of different stretching methods on Illinois agility test in soccer players.

    PubMed

    Amiri-Khorasani, Mohammadtaghi; Sahebozamani, Mansour; Tabrizi, Kourosh G; Yusof, Ashril B

    2010-10-01

    The purpose of this study was to examine the effects of static, dynamic, and the combination of static and dynamic stretching within a pre-exercise warm-up on the Illinois agility test (IAT) in soccer players. Nineteen professional soccer players (age = 22.5 ± 2.5 years, height = 1.79 ± 0.003 m, body mass = 74.8 ± 10.9 kg) were tested for agility performance using the IAT after different warm-up protocols consisting of static, dynamic, combined stretching, and no stretching. The players were subgrouped into less and more experienced players (5.12 ± 0.83 and 8.18 ± 1.16 years, respectively). There were significant decreases in agility time after no stretching, among no stretching vs. static stretching; after dynamic stretching, among static vs. dynamic stretching; and after dynamic stretching, among dynamic vs. combined stretching during warm-ups for the agility: mean ± SD data were 14.18 ± 0.66 seconds (no stretch), 14.90 ± 0.38 seconds (static), 13.95 ± 0.32 seconds (dynamic), and 14.50 ± 0.35 seconds (combined). There was significant difference between less and more experienced players after no stretching and dynamic stretching. There was significant decrease in agility time following dynamic stretching vs. static stretching in both less and more experienced players. Static stretching does not appear to be detrimental to agility performance when combined with dynamic warm-up for professional soccer players. However, dynamic stretching during the warm-up was most effective as preparation for agility performance. The data from this study suggest that more experienced players demonstrate better agility skills due to years of training and playing soccer.

  4. Lethality and Autonomous Systems: The Roboticist Demographic

    DTIC Science & Technology

    2008-01-01

    humanoid (22%), and other (23%); 9) Media Influence: only 18% said that media had a strong or very strong influence on their attitude to robots ...and whether certain emotions would be appropriate in a military robot . The Wars question was worded as follows: To what extent do you think ...Lethality and Autonomous Systems: The Roboticist Demographic Lilia V. Moshkina and Ronald C. Arkin Mobile Robot Laboratory, College of

  5. Treatment of acute experimental toxoplasmosis with investigational poloxamers.

    PubMed Central

    Krahenbuhl, J L; Fukutomi, Y; Gu, L

    1993-01-01

    Because of the limited chemotherapeutic approaches available to treat reactivated latent Toxoplasma gondii infection manifested as toxoplasmic encephalitis in AIDS patients, investigation of novel chemotherapeutic agents is warranted. Several poloxamers (nonionic block copolymers composed of a central hydrophobic chain of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene) were tested for their abilities to alter the course of acute infection with a highly virulent T. gondii in mice. The effect varied markedly with the length of the constituent chains of the copolymers. The most effective preparations were highly effective when administered after infection and afforded remarkable protection against 10 to 1,000 100% lethal doses of T. gondii. Protection was dose dependent, and multiple treatments were more effective than single treatment. These preliminary findings warrant additional studies to determine whether this novel form of antitoxoplasma chemotherapy may prove promising in the treatment or prevention of acute toxoplasmic encephalitis in humans. PMID:8285605

  6. Acute toxicity bioassays of mercuric chloride and malathion on air-breathing fish Channa punctatus (Bloch).

    PubMed

    Pandey, Sanjay; Kumar, Ravindra; Sharma, Shilpi; Nagpure, N S; Srivastava, Satish K; Verma, M S

    2005-05-01

    Acute toxicity tests (96 h) were conducted in flow-through systems to determine the lethal toxicity of a heavy metal compound, mercuric chloride, and an organophosphorus pesticide, malathion, to air-breathing teleost fish, Channa punctatus (Bloch) and to study their behavior. The 96-h LC50 values were determined, as well as safe levels. The results indicate that mercuric chloride is more toxic than malathion to the fish species under study. Dose- and dose-time-dependent increases in mortality rate were also observed in response to both test chemicals.

  7. Antidepressant-like activity of sildenafil following acute and subchronic treatment in the forced swim test in mice: effects of restraint stress and monoamine depletion.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Pieróg, Mateusz; Szuster-Ciesielska, Agnieszka; Wyska, Elżbieta; Wlaź, Piotr

    2016-10-01

    Sildenafil is a highly effective oral agent for the treatment of erectile dysfunction of multiple etiologies. Although in clinical practice sildenafil is often used in depressed patients, its influence on the pathophysiology of depression remains unclear. The aim of the present study was to evaluate the antidepressant-like activity following acute and subchronic treatment with sildenafil in naïve mice as well as in mice with reserpine- and restraint stress-induced depressive-like behavior. Since corticosterone is released in response to acute stress, we also aimed to assess the influence of sildenafil on serum corticosterone level in non-stressed and stressed animals. The antidepressant activity of sildenafil was assessed in the forced swim test. Corticosterone serum level was determined by using ELISA method, while brain and serum sildenafil level via HPLC method. Sildenafil administered acutely exerted an antidepressant-like effect. Subchronic (14 days) administration of sildenafil resulted only in a weak antidepressant-like effect when evaluated 24 h after the last dose. Acute but not subchronic sildenafil administration reversed the reserpine- and stress-induced immobility in the forced swim test. The lack of effects of sildenafil after subchronic treatment could have been related to its complete elimination from the brain within 24 h from the last injection. Interestingly, acute administration of sildenafil produced a marked increase in serum corticosterone level in both non-stressed and stressed animals. Sildenafil exerts differential effects in the forced swim test after acute and subchronic administration. Further studies on the antidepressant activity of sildenafil are required.

  8. Complement component 5 promotes lethal thrombosis

    PubMed Central

    Mizuno, Tomohiro; Yoshioka, Kengo; Mizuno, Masashi; Shimizu, Mie; Nagano, Fumihiko; Okuda, Tomoyuki; Tsuboi, Naotake; Maruyama, Shoichi; Nagamatsu, Tadashi; Imai, Masaki

    2017-01-01

    Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis. PMID:28205538

  9. Lethal interpersonal violence in the Middle Pleistocene.

    PubMed

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

  10. Lethal Interpersonal Violence in the Middle Pleistocene

    PubMed Central

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M.; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin. PMID:26018668

  11. Stress-Related Signaling Pathways in Lethal and Non-Lethal Prostate Cancer

    PubMed Central

    Valdimarsdóttir, Unnur; Fang, Fang; Gerke, Travis; Tyekucheva, Svitlana; Fiorentino, Michelangelo; Lambe, Mats; Sesso, Howard D.; Sweeney, Christopher J.; Wilson, Kathryn M.; Giovannucci, Edward L.; Loda, Massimo

    2015-01-01

    Purpose Recent data suggest that neuroendocrine signaling may influence progression in some cancers. We aimed to determine whether genes within the five major stress-related signaling pathways are differentially expressed in tumor tissue when comparing prostate cancer patients with lethal and non-lethal disease. Experimental Design We measured mRNA expression of 51 selected genes involved in predetermined stress-related signaling pathways (adrenergic, glucocorticoid, dopaminergic, serotoninergic, and muscarinic systems) in tumor tissue and normal prostate tissue collected from prostate cancer patients in the Physicians’ Health Study (n=150; n=82 with normal) and the Health Professionals Follow-Up Study (n=254; n=120 with normal). We assessed differences in pathway expression in relation to prostate cancer lethality as the primary outcome, and to biomarkers as secondary outcomes. Results Differential mRNA expression of genes within the adrenergic (p=0.001), glucocorticoid (p<0.0001), serotoninergic (p=0.0019), and muscarinic (p=0.0045) pathways in tumor tissue was associated with the risk of lethality. The adrenergic pathway was also statistically significant (p=0.001) when comparing against differential expression of genes not involved in the pathways. In adjacent normal prostate tissue, none of the pathways was clearly differentially expressed between lethal and non-lethal prostate cancer. The glucocorticoid and adrenergic pathways were associated with cell proliferation, while the glucocorticoid pathway was additionally associated with angiogenesis and perineural invasion. Conclusions Our study suggests that stress-related signaling pathways, particularly the adrenergic and glucocorticoid, may be dysregulated in the tumors of men whose prostate cancer proves to be lethal, and motivates further investigation of these pathways in functional studies. PMID:26490316

  12. Lethal Dietary Toxicities of Environmental Contaminants and Pesticides to Coturnix

    USGS Publications Warehouse

    Hill, E.F.; Camardese, M.B.

    1986-01-01

    Five-day subacute dietary toxicity tests of 193 potential environmental contaminants, pesticides, organic solvents, and various adjuvants are presented for young coturnix (Japanese quail, Coturnix japonica Temminck and Schlegel). The report provides the most comprehensive data base available for avian subacute dietary toxicity tests and is primarily intended for use in ranking toxicities by a standard method that has a reasonable degree of environmental relevance. Findings are presented in two parts: Part I is a critique of selected drugs that includes discussion of subacute toxicity in relation to chemical class and structure, pesticide formulation, and age of animals; Part II is a summary of toxicologic findings for each test substance and provides a statistically basis for comparing toxicities. Data presented include the median lethal concentration (LC50), slope of the probit regression curve (dose-response curve), response chronology, and food consumption. We observed that: 1) fewer than 15% of the compounds were classed 'very' or 'highly' toxic (i.e, LC50 < 200 ppm) and all of these were either chlorinated hydrocarbons, organophosphates, or organometallics; 2) subacute toxicity may vary widely among structurally similar chemicals and between different formulations of the same chemical; therefore, conclusions about lethal hazard must be made cautiously until the actual formulation of inset has been tested: 3) inclusion of a general standard in each battery of tests is useful for detection of atypical trials and monitoring population changes but should not be used indiscriminantly for adjusting LC50's for intertest differences unless the chemicals of concern and the standard elicit their toxicities through the same action; 4) although other species have been tested effectively under the subacute protocol, coturnix were ideal for the stated purpose of this research because they are inexpensive, well-adapted to the laboratory environment, and yield good intertest

  13. Proposal of quality indicators for cardiac rehabilitation after acute coronary syndrome in Japan: a modified Delphi method and practice test

    PubMed Central

    Ohtera, Shosuke; Kanazawa, Natsuko; Ozasa, Neiko; Ueshima, Kenji; Nakayama, Takeo

    2017-01-01

    Objectives Cardiac rehabilitation is underused and its quality in practice is unclear. A quality indicator is a measurable element of clinical practice performance. This study aimed to propose a set of quality indicators for cardiac rehabilitation following an acute coronary event in the Japanese population and conduct a small-size practice test to confirm feasibility and applicability of the indicators in real-world clinical practice. Design and setting This study used a modified Delphi technique (the RAND/UCLA appropriateness method), a consensus method which involves an evidence review, a face-to-face multidisciplinary panel meeting and repeated anonymous rating. Evidence to be reviewed included clinical practice guidelines available in English or Japanese and existing quality indicators. Performance of each indicator was assessed retrospectively using medical records at a university hospital in Japan. Participants 10 professionals in cardiac rehabilitation for the consensus panel. Results In the literature review, 23 clinical practice guidelines and 16 existing indicators were identified to generate potential indicators. Through the consensus-building process, a total of 30 indicators were assessed and finally 13 indicators were accepted. The practice test (n=39) revealed that 74% of patients underwent cardiac rehabilitation. Median performance of process measures was 93% (IQR 46–100%). ‘Communication with the doctor who referred the patient to cardiac rehabilitation’ and ‘continuous participation in cardiac rehabilitation’ had low performance (32% and 38%, respectively). Conclusions A modified Delphi technique identified a comprehensive set of quality indicators for cardiac rehabilitation. The single-site, small-size practice test confirmed that most of the proposed indicators were measurable in real-world clinical practice. However, some clinical processes which are not covered by national health insurance in Japan had low performance. Further

  14. A simultaneous multiple species acute toxicity test comparing relative sensitivities of six aquatic organisms to HgCl{sub 2}

    SciTech Connect

    McCrary, J.E.; Heagler, M.G.

    1995-12-31

    In the last few years there has been concern in the scientific community about observed declines in some amphibian species. These population declines could be reflecting a global phenomenon due to a general class sensitivity or may be part of a natural cycle. The suggestion of an overall greater sensitivity of amphibians is not supported. Studies show that amphibians, as a class, are neither more or less susceptible than fish to environmental conditions. Mercury has been found to be one of the most toxic of the heavy metals introduced into amphibian breeding waters. Six aquatic species were simultaneously exposed in a comparative acute toxicity test with mercury chloride: three amphibians, Rana catesbeiana (bullfrog), R. clamitans (green frog), and R. sphenocephala (southern leopard frog, formally classified as R. utricularia); two fish, Gambusia affinis (mosquitofish) and Notemigonus crysoleucas (golden shiner); one aquatic aligochaete, Lumbriculus variegatus (aquatic earthworm). The five test concentrations used were 1.4, 3.9, 12.0, 110.0, and 487.0 {micro}g Hg/L respectively. Ten organisms per species were randomly placed into the six test tanks (control and five concentrations), each species in a separate chamber. The resultant LC50-96hr values produced the following rank order: R. sphenocephala, 6.59 {micro}g Hg/L; R. clamitans, 14.7 {micro}g Hg/L; N. crysoleucas, 16.75 {micro}g Hg/L; L. variegatus, 43.72,ug Hg/L; G. affinis, 52.62 {micro}g Hg/L; R. catesbeiana, 63.36 {micro}g Hg/L. No general organism class sensitivity trend, for amphibians, was developed from this data, contrary to the implicit suggestions of some researchers.

  15. A test of the catecholamines hypothesis for an acute exercise-cognition interaction.

    PubMed

    McMorris, T; Collard, K; Corbett, J; Dicks, M; Swain, J P

    2008-03-01

    The purpose of the study was to examine the usage of norepinephrine (NE) and dopamine (DA) in the brain when exercising while simultaneously undertaking cognitive tests. Plasma concentrations of the NE metabolite 3-methoxy 4-hydroxyphenylglycol (MHPG) and the DA metabolite homovanillic acid (HVA) showed a linear increase from rest to exercising at 40% and 80% maximum power output (W.max) while simultaneously undertaking cognitive tasks (random number generation (RNG) and response time). Delta plasma concentrations of MHPG and HVA at each exercise intensity while undertaking cognitive tasks and while exercising without cognitive tasks did not differ. Taking blood samples at 0, 1, 3, and 5 min following cessation of exercise did not affect results. Regression correlations showed that delta MHPG and HVA plasma concentrations at the 1 and 3 min sampling times were strong predictors of delta RNG, response time and movement time. Reaction time at 80% W.max significantly increased, while movement time at 80% W.max significantly decreased. It was concluded that these results provide no support for a direct effect of increased catecholamines concentrations on cognitive performance during exercise. The regression data suggest that there is some relationship between exercise, catecholamines concentrations and cognition.

  16. [Detection of the rotavirus group antigen by a screening test using the ELISA-IC kit in subjects with acute gastroenteritis, at the pediatric services of Moldavia].

    PubMed

    Avram, G; Zavate, O; Combiescu, A A; Perşu, A; Ivan, A; Constantiniu, S; Pancu, V; Popovici, S; Boghean, T; Nicola, P

    1987-01-01

    The rotaviral antigen was detected by a screening test using the ELISA-IC kit in 17.6% out of 415 children with acute gastroenteritis. The highest frequency (28.9%) was found in children hospitalized in pediatric services with a diagnosis of diarrhoeic disease associated to acute respiratory infection. The rotavirus infection incidence was about three times higher during the cold season than during summer (30.4% versus 10.5%). The 6-11 month age group was the most severely affected.

  17. Fish embryo toxicity test: identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds.

    PubMed

    Klüver, Nils; König, Maria; Ortmann, Julia; Massei, Riccardo; Paschke, Albrecht; Kühne, Ralph; Scholz, Stefan

    2015-06-02

    The fish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, but concerns have been raised for its predictivity given that a few compounds have been shown to exhibit a weak acute toxicity in the fish embryo. In order to better define the applicability domain and improve the predictive capacity of the fish embryo test, we performed a systematic analysis of existing fish embryo and acute fish toxicity data. A correlation analysis of a total of 153 compounds identified 28 compounds with a weaker or no toxicity in the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of action. We selected a subset of eight compounds with weaker or no embryo toxicity (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide, endosulfan, and esfenvalerate) to study toxicokinetics and a neurotoxic mode of action as potential reasons for the deviating fish embryo toxicity. Published fish embryo LC50 values were confirmed by experimental analysis of zebrafish embryo LC50 according to OECD guideline 236. Except for diquat dibromide, internal concentration analysis did not indicate a potential relation of the low sensitivity of fish embryos to a limited uptake of the compounds. Analysis of locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf embryos (exposed for 96 h) indicated a specific effect on behavior (embryonic movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic compounds were close to the acute fish toxicity LC50. Our data provided the first evidence that the applicability domain of the fish embryo test (LC50s determination) may exclude neurotoxic compounds. However, neurotoxic compounds could be identified by changes in embryonic locomotion. Although a quantitative prediction of acute fish toxicity LC50 using behavioral assays in fish embryos may not yet be possible, the identification of neurotoxicity could trigger the conduction of a conventional fish

  18. Dominant lethal mutations of topoisomerase II inhibitors etoposide and merbarone in male mice: a mechanistic study.

    PubMed

    Attia, Sabry M

    2012-05-01

    Two topoisomerase II inhibitors, etoposide and merbarone, were tested for the induction of dominant lethal mutations in male mice. Etoposide was administered at a dosage of 30 or 60 mg/kg. Merbarone was administered at a dosage of 40 or 80 mg/kg. These males were mated at weekly intervals to virgin females for 6 weeks. In the present experiments, regardless of the agent, spermatids appeared to be the most sensitive germ-cell stage to dominant lethal induction. Etoposide and merbarone clearly induced dominant lethal mutations in the early spermatid stage only with the highest tested doses. The mutagenic effects were also directly correlated with reactive oxygen species accumulation as an obvious increase in 2',7'-dichlorofluorescein fluorescence level was noted in the sperm of animals treated with higher doses of etoposide and merbarone. Treatment of male mice with N-acetylcysteine significantly protected mice from etoposide- and merbarone-induced dominant lethality. Moreover, N-acetylcysteine treatment had no antagonizing effect on etoposide- and merbarone-induced topoisomerase II inhibition. Overall, this study provides for the first time that etoposide and merbarone induce dominant lethal mutations in the early spermatid stage through a mechanism that involves increases in oxidative stress. The demonstrated mutagenicity profile of etoposide and merbarone may support further development of effective chemotherapy with less mutagenicity.

  19. Acute vasoreactivity test results in severe pulmonary hypertension patients with chronic obstructive pulmonary disease: our experience with 29 cases

    PubMed Central

    Asker, Selvi; Asker, Muntecep

    2015-01-01

    Aim The aim of the current study is to evaluate acute vasoreactivity test (AVT) results in severe pulmonary hypertension patients with chronic obstructive pulmonary disease and to compare the demographical, clinical, and laboratory variables in positive and negative cases. Methods This retrospective, clinical study was performed on 29 cases in the departments of cardiology and chest diseases of our tertiary care center. AVT was positive in 12 (41.4%) cases and negative in 17 (58.6%) cases. Demographical variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. Results The mean age was 62.3±7.8 years for AVT negative group, while it was 64.8±7.3 years in AVT positive group (P=0.38). Except for the changes in systolic, diastolic, and mean pulmonary arterial pressures before and after iloprost administration, there were no statistically significant differences regarding any of the parameters under investigation in both groups. Conclusion Despite the high rate of positivity for AVT in severe pulmonary hypertension patients with chronic obstructive pulmonary disease, none of the variables under investigation displayed a noteworthy difference between AVT negative and positive groups. Identification of factors likely to influence AVT results is important for establishment of appropriate treatment protocols especially for AVT negative cases. PMID:26064044

  20. Injury Risk Assessment of Non-Lethal Projectile Head Impacts

    PubMed Central

    Oukara, Amar; Nsiampa, Nestor; Robbe, Cyril; Papy, Alexandre

    2014-01-01

    Kinetic energy non-lethal projectiles are used to impart sufficient effect onto a person in order to deter uncivil or hazardous behavior with a low probability of permanent injury. Since their first use, real cases indicate that the injuries inflicted by such projectiles may be irreversible and sometimes lead to death, especially for the head impacts. Given the high velocities and the low masses involved in such impacts, the assessment approaches proposed in automotive crash tests and sports may not be appropriate. Therefore, there is a need of a specific approach to assess the lethality of these projectiles. In this framework, some recent research data referred in this article as “force wall approach” suggest the use of three lesional thresholds (unconsciousness, meningeal damages and bone damages) that depend on the intracranial pressure. Three corresponding critical impact forces are determined for a reference projectile. Based on the principle that equal rigid wall maximal impact forces will produce equal damage on the head, these limits can be determined for any other projectile. In order to validate the consistence of this innovative method, it is necessary to compare the results with other existing assessment methods. This paper proposes a comparison between the “force wall approach” and two different head models. The first one is a numerical model (Strasbourg University Finite Element Head Model-SUFEHM) from Strasbourg University; the second one is a mechanical surrogate (Ballistics Load Sensing Headform-BLSH) from Biokinetics. PMID:25400712

  1. Injury risk assessment of non-lethal projectile head impacts.

    PubMed

    Oukara, Amar; Nsiampa, Nestor; Robbe, Cyril; Papy, Alexandre

    2014-01-01

    Kinetic energy non-lethal projectiles are used to impart sufficient effect onto a person in order to deter uncivil or hazardous behavior with a low probability of permanent injury. Since their first use, real cases indicate that the injuries inflicted by such projectiles may be irreversible and sometimes lead to death, especially for the head impacts. Given the high velocities and the low masses involved in such impacts, the assessment approaches proposed in automotive crash tests and sports may not be appropriate. Therefore, there is a need of a specific approach to assess the lethality of these projectiles. In this framework, some recent research data referred in this article as "force wall approach" suggest the use of three lesional thresholds (unconsciousness, meningeal damages and bone damages) that depend on the intracranial pressure. Three corresponding critical impact forces are determined for a reference projectile. Based on the principle that equal rigid wall maximal impact forces will produce equal damage on the head, these limits can be determined for any other projectile. In order to validate the consistence of this innovative method, it is necessary to compare the results with other existing assessment methods. This paper proposes a comparison between the "force wall approach" and two different head models. The first one is a numerical model (Strasbourg University Finite Element Head Model-SUFEHM) from Strasbourg University; the second one is a mechanical surrogate (Ballistics Load Sensing Headform-BLSH) from Biokinetics.

  2. 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

  3. Pathophysiology of acute pancreatitis.

    PubMed

    Bhatia, Madhav; Wong, Fei Ling; Cao, Yang; Lau, Hon Yen; Huang, Jiali; Puneet, Padmam; Chevali, Lakshmi

    2005-01-01

    Acute pancreatitis is a common clinical condition. It is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction. If this inflammatory reaction is marked, it leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and the resultant MODS. At the same time, recent research has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In this review, we will discuss about our current understanding of the pathophysiology of acute pancreatitis.

  4. Conditional embryonic lethality to improve the sterile insect technique in Ceratitis capitata (Diptera: Tephritidae)

    PubMed Central

    Schetelig, Marc F; Caceres, Carlos; Zacharopoulou, Antigone; Franz, Gerald; Wimmer, Ernst A

    2009-01-01

    Background The sterile insect technique (SIT) is an environment-friendly method used in area-wide pest management of the Mediterranean fruit fly Ceratitis capitata (Wiedemann; Diptera: Tephritidae). Ionizing radiation used to generate reproductive sterility in the mass-reared populations before release leads to reduction of competitiveness. Results Here, we present a first alternative reproductive sterility system for medfly based on transgenic embryonic lethality. This system is dependent on newly isolated medfly promoter/enhancer elements of cellularization-specifically-expressed genes. These elements act differently in expression strength and their ability to drive lethal effector gene activation. Moreover, position effects strongly influence the efficiency of the system. Out of 60 combinations of driver and effector construct integrations, several lines resulted in larval and pupal lethality with one line showing complete embryonic lethality. This line was highly competitive to wildtype medfly in laboratory and field cage tests. Conclusion The high competitiveness of the transgenic lines and the achieved 100% embryonic lethality causing reproductive sterility without the need of irradiation can improve the efficacy of operational medfly SIT programs. PMID:19173707

  5. A comparative genomic approach for identifying synthetic lethal interactions in human cancer.

    PubMed

    Deshpande, Raamesh; Asiedu, Michael K; Klebig, Mitchell; Sutor, Shari; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff; Shin, Seung Ho; Yoshida, Minoru; Costanzo, Michael; Boone, Charles; Wigle, Dennis A; Myers, Chad L

    2013-10-15

    Synthetic lethal interactions enable a novel approach for discovering specific genetic vulnerabilities in cancer cells that can be exploited for the development of therapeutics. Despite successes in model organisms such as yeast, discovering synthetic lethal interactions on a large scale in human cells remains a significant challenge. We describe a comparative genomic strategy for identifying cancer-relevant synthetic lethal interactions whereby candidate interactions are prioritized on the basis of genetic interaction data available in yeast, followed by targeted testing of candidate interactions in human cell lines. As a proof of principle, we describe two novel synthetic lethal interactions in human cells discovered by this approach, one between the tumor suppressor gene SMARCB1 and PSMA4, and another between alveolar soft-part sarcoma-associated ASPSCR1 and PSMC2. These results suggest therapeutic targets for cancers harboring mutations in SMARCB1 or ASPSCR1 and highlight the potential of a targeted, cross-species strategy for identifying synthetic lethal interactions relevant to human cancer.

  6. Acute test results

    EPA Pesticide Factsheets

    Data used for publicationThis dataset is associated with the following publication:Struewing, K., P. Weaver, J. Lazorchak , B. Johnson , D. Funk, and D. Buckwalter. Part 2: Sensitivity comparisons of the insect Centroptilum triangulifer to Ceriodaphnia dubia and Daphnia magna using standard reference toxicants; NaCl, KCl and CuSO4. CHEMOSPHERE. Elsevier Science Ltd, New York, NY, USA, 11(139): 597-603, (2015).

  7. Improving on army field gauze for lethal vascular injuries: a progress report

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Uncontrolled hemorrhage is the leading cause of death on the battlefield and second leading cause of death in civilian trauma. Recent animal testing using a lethal arterial injury model compared a variety of woven and non woven products with granular products, and found only one product (WoundStat)...

  8. Variation of lead-induced lethality in estradiol-treated mice

    SciTech Connect

    Hogan, G.R.

    1982-03-01

    Studies were undertaken to test the female sex hormone ..beta..-estradiol for its ability to modify lethality in young adult female and male mice exposed to lead acetate. Mice were injected with ..beta..-estradiol on day -1 and 0, and immediately after the second injection lead acetate was administered at four subgroup dosages ranging from 75 to 600 mg/kg body weight. Control mice were injected with only lead acetate. On day 4, 6, and 8 after Pb, the median lethal dosages (LD/sub 50/s) were calculated from the observed mortality ratios by a method for moving averages. LD/sub 50/ values were considerably lower for the Pb- and ..beta..-estradiol-injected groups than for the controls. Data from these experiments indicate that the ..beta..-estradiol treatments render both female and male mice more vulnerable to the lethal effects of lead acetate.

  9. 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.

  10. Activated mouse eosinophils protect against lethal respiratory virus infection.

    PubMed

    Percopo, Caroline M; Dyer, Kimberly D; Ochkur, Sergei I; Luo, Janice L; Fischer, Elizabeth R; Lee, James J; Lee, Nancy A; Domachowske, Joseph B; Rosenberg, Helene F

    2014-01-30

    Eosinophils are recruited to the airways as a prominent feature of the asthmatic inflammatory response where they are broadly perceived as promoting pathophysiology. Respiratory virus infections exacerbate established asthma; however, the role of eosinophils and the nature of their interactions with respiratory viruses remain uncertain. To explore these questions, we established acute infection with the rodent pneumovirus, pneumonia virus of mice (PVM), in 3 distinct mouse models of Th2 cytokine-driven asthmatic inflammation. We found that eosinophils recruited to the airways of otherwise naïve mice in response to Aspergillus fumigatus, but not ovalbumin sensitization and challenge, are activated by and degranulate specifically in response to PVM infection. Furthermore, we demonstrate that activated eosinophils from both Aspergillus antigen and cytokine-driven asthma models are profoundly antiviral and promote survival in response to an otherwise lethal PVM infection. Thus, although activated eosinophils within a Th2-polarized inflammatory response may have pathophysiologic features, they are also efficient and effective mediators of antiviral host defense.

  11. Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability

    PubMed Central

    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. PMID:28081568

  12. Boussignac CPAP system for brain death confirmation with apneic test in case of acute lung injury/adult respiratory distress syndrome – series of cases

    PubMed Central

    Wieczorek, Andrzej; Gaszynski, Tomasz

    2015-01-01

    Introduction There are some patients with severe respiratory disturbances like adult respiratory distress syndrome (ARDS) and suspicion of brain death, for whom typical performance of the apneic test is difficult to complete because of quick desaturation and rapid deterioration without effective ventilation. To avoid failure of brain death confirmation and possible loss of organ donation another approach to apneic test is needed. We present two cases of patients with clinical symptoms of brain death, with lung pathology (acute lung injury, ARDS, lung embolism and lung infection), in whom apneic tests for recognizing brain death were difficult to perform. During typical performance of apneic test involving the use of oxygen catheter for apneic oxygenation we observed severe desaturation with growing hypotension and hemodynamic destabilization. But with the use of Boussignac CPAP system all necessary tests were successfully completed, confirming the patient’s brain death, which gave us the opportunity to perform procedures for organ donation. The main reason of apneic test difficulties was severe gas exchange disturbances secondary to ARDS. Thus lack of positive end expiratory pressure during classical performance of apneic test leads to quick desaturation and rapid hemodynamic deterioration, limiting the observation period below dedicated at least 10-minute interval. Conclusion The Boussignac CPAP system may be an effective tool for performing transparent apneic test in case of serious respiratory disturbances, especially in the form of acute lung injury or ARDS. PMID:26124664

  13. Issues surrounding lethal injection as a means of capital punishment.

    PubMed

    Romanelli, Frank; Whisman, Tyler; Fink, Joseph L

    2008-12-01

    Lethal injection as a method of state-sanctioned capital punishment was initially proposed in the United States in 1977 and used for the first time in 1982. Most lethal injection protocols use a sequential drug combination of sodium thiopental, pancuronium bromide, and potassium chloride. Lethal injection was originally introduced as a more humane form of execution compared with existing mechanical methods such as electrocution, toxic gassing, hanging, or firing squad. Lethal injection has not, however, been without controversy. Several states are considering whether lethal injection meets constitutional scrutiny forbidding cruel and unusual punishment. Recently in the case of Ralph Baze and Thomas C. Bowling, Petitioners, v John D. Rees, Commissioner, Kentucky Department of Corrections et al, the United States Supreme Court upheld the constitutionality of the lethal injection protocol as carried out in the Commonwealth of Kentucky. Most of the debate has surrounded the dosing and procedures used in lethal injection and whether the drug combinations and measures for administering the drugs truly produce a timely, pain-free, and fail-safe death. Many have also raised issues regarding the "medicalization" of execution and the ethics of health care professionals' participation in any part of the lethal injection process. As a result of all these issues, the future of lethal injection as a means of execution in the United States is under significant scrutiny. Outcomes of ongoing legislative and judicial reviews might result in cessation of lethal injection in totality or in alterations involving specific drug combinations or administration procedures.

  14. Bacillus anthracis lethal toxin reduces human alveolar epithelial barrier function.

    PubMed

    Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin; Metcalf, Jordan Patrick

    2012-12-01

    The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness.

  15. Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function

    PubMed Central

    Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A.; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M.; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin

    2012-01-01

    The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness. PMID:23027535

  16. IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality.

    PubMed

    Zhang, Hong; Neuhöfer, Patrick; Song, Liang; Rabe, Björn; Lesina, Marina; Kurkowski, Magdalena U; Treiber, Matthias; Wartmann, Thomas; Regnér, Sara; Thorlacius, Henrik; Saur, Dieter; Weirich, Gregor; Yoshimura, Akihiko; Halangk, Walter; Mizgerd, Joseph P; Schmid, Roland M; Rose-John, Stefan; Algül, Hana

    2013-03-01

    Acute lung injury (ALI) is an inflammatory disease with a high mortality rate. Although typically seen in individuals with sepsis, ALI is also a major complication in severe acute pancreatitis (SAP). The pathophysiology of SAP-associated ALI is poorly understood, but elevated serum levels of IL-6 is a reliable marker for disease severity. Here, we used a mouse model of acute pancreatitis-associated (AP-associated) ALI to determine the role of IL-6 in ALI lethality. Il6-deficient mice had a lower death rate compared with wild-type mice with AP, while mice injected with IL-6 were more likely to develop lethal ALI. We found that inflammation-associated NF-κB induced myeloid cell secretion of IL-6, and the effects of secreted IL-6 were mediated by complexation with soluble IL-6 receptor, a process known as trans-signaling. IL-6 trans-signaling stimulated phosphorylation of STAT3 and production of the neutrophil attractant CXCL1 in pancreatic acinar cells. Examination of human samples revealed expression of IL-6 in combination with soluble IL-6 receptor was a reliable predictor of ALI in SAP. These results demonstrate that IL-6 trans-signaling is an essential mediator of ALI in SAP across species and suggest that therapeutic inhibition of IL-6 may prevent SAP-associated ALI.

  17. IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality

    PubMed Central

    Zhang, Hong; Neuhöfer, Patrick; Song, Liang; Rabe, Björn; Lesina, Marina; Kurkowski, Magdalena U.; Treiber, Matthias; Wartmann, Thomas; Regnér, Sara; Thorlacius, Henrik; Saur, Dieter; Weirich, Gregor; Yoshimura, Akihiko; Halangk, Walter; Mizgerd, Joseph P.; Schmid, Roland M.; Rose-John, Stefan; Algül, Hana

    2013-01-01

    Acute lung injury (ALI) is an inflammatory disease with a high mortality rate. Although typically seen in individuals with sepsis, ALI is also a major complication in severe acute pancreatitis (SAP). The pathophysiology of SAP-associated ALI is poorly understood, but elevated serum levels of IL-6 is a reliable marker for disease severity. Here, we used a mouse model of acute pancreatitis–associated (AP-associated) ALI to determine the role of IL-6 in ALI lethality. Il6-deficient mice had a lower death rate compared with wild-type mice with AP, while mice injected with IL-6 were more likely to develop lethal ALI. We found that inflammation-associated NF-κB induced myeloid cell secretion of IL-6, and the effects of secreted IL-6 were mediated by complexation with soluble IL-6 receptor, a process known as trans-signaling. IL-6 trans-signaling stimulated phosphorylation of STAT3 and production of the neutrophil attractant CXCL1 in pancreatic acinar cells. Examination of human samples revealed expression of IL-6 in combination with soluble IL-6 receptor was a reliable predictor of ALI in SAP. These results demonstrate that IL-6 trans-signaling is an essential mediator of ALI in SAP across species and suggest that therapeutic inhibition of IL-6 may prevent SAP-associated ALI. PMID:23426178

  18. The Decline of the Military Ethos and Profession of Arms: An Argument Against Autonomous Lethal Engagements

    DTIC Science & Technology

    2011-02-16

    Ethos and Profession of Arms: An Argument Against Autonomous Lethal Engagements 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Experimental Test Pilot, Colonel Contratto was involved in numerous B-52 and B-1 test programs . After his assignment in the 419 Flight Test Squadron where...of Science degree in Military Operational Art and Science in 2004. He then moved to the Airborne Laser Program Office at Kirtland Air Force Base

  19. Plantar Temperature Response to Walking in Diabetes with and without Acute Charcot: The Charcot Activity Response Test

    PubMed Central

    Najafi, Bijan; Wrobel, James S.; Grewal, Gurtej; Menzies, Robert A.; Talal, Talal K.; Zirie, Mahmoud; Armstrong, David G.

    2012-01-01

    Objective. Asymmetric plantar temperature differences secondary to inflammation is a hallmark for the diagnosis and treatment response of Charcot foot syndrome. However, little attention has been given to temperature response to activity. We examined dynamic changes in plantar temperature (PT) as a function of graduated walking activity to quantify thermal responses during the first 200 steps. Methods. Fifteen individuals with Acute Charcot neuroarthropathy (CN) and 17 non-CN participants with type 2 diabetes and peripheral neuropathy were recruited. All participants walked for two predefined paths of 50 and 150 steps. A thermal image was acquired at baseline after acclimatization and immediately after each walking trial. The PT response as a function of number of steps was examined using a validated wearable sensor technology. The hot spot temperature was identified by the 95th percentile of measured temperature at each anatomical region (hind/mid/forefoot). Results. During initial activity, the PT was reduced in all participants, but the temperature drop for the nonaffected foot was 1.9 times greater than the affected side in CN group (P = 0.04). Interestingly, the PT in CN was sharply increased after 50 steps for both feet, while no difference was observed in non-CN between 50 and 200 steps. Conclusions. The variability in thermal response to the graduated walking activity between Charcot and non-Charcot feet warrants future investigation to provide further insight into the correlation between thermal response and ulcer/Charcot development. This stress test may be helpful to differentiate CN and its response to treatment earlier in its course. PMID:22900177

  20. Technetium Tc 99m dimercaptosuccinic acid renal scintigraphy in children with acute pyelonephritis: correlation with other imaging tests.

    PubMed

    Mohkam, Masoumeh; Maham, Saiid; Rahmani, Afrand; Naghi, Ilana; Otokesh, Babak; Raiiati, Hamid; Mohseni, Nima; Shamshiri, Ahmad Reza; Sharifian, Mostafa; Dalirani, Reza; Ghazi, Ruhollah; Ahoopai, Majid

    2010-10-01

    INTRODUCTION. Urinary tract infection is the most common serious bacterial infection in children. The aim of this study was to compare the value of different laboratory and imaging techniques in detecting renal involvement in acute pyelonephritis. MATERIALS AND METHODS. In a cross-sectional study of patients 1 month to 14 years of age diagnosed with urinary tract infection were examined with systemic inflammatory markers, renal ultrasonography, voiding cystourethrography (VCUG), and technetium Tc 99m dimercaptosuccinic acid ((99m)Tc-DMSA) renal scintigraphy. A total of 1467 pediatric patients were eligible for treatment of pyelonephritis. Evaluations included a complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), urinalysis, urine culture, and measurement of serum blood urea nitrogen and creatinine levels. RESULTS. The results of (99m)Tc-DMSA scans were normal in 20.2%, mild decreased cortical uptake in 45.0%, moderate decreased cortical uptake in 12.3%, severe decreased cortical uptake in 12.0%, and decreased cortical function plus irregularity or scar formation in 10.5%. Voiding cystourethrography showed vesicoureteral reflux in 25.9%. The sensitivity of (99m)Tc-DMSA for prediction of vesicoureteral reflux was 84.1% with a negative predictive value of 80.6%. Significant differences were found in the level of blood leukocyte count (P = .03), urine leukocyte count (P = .003), ESR (P = .008), and age (P = .04) between patients with normal and abnormal (99m)Tc-DMSA scan results. CONCLUSIONS. We found that in patient with clinical signs of pyelonephritis, (99m)Tc-DMSA renal scintigraphy can detect pyelonephritis more accurately than the other inflammatory and imaging tests.

  1. Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts.

    PubMed

    Szymanska, Barbara; Wilczynska-Kalak, Urszula; Kang, Min H; Liem, Natalia L M; Carol, Hernan; Boehm, Ingrid; Groepper, Daniel; Reynolds, C Patrick; Stewart, Clinton F; Lock, Richard B

    2012-01-01

    Current regimens for induction therapy of pediatric acute lymphoblastic leukemia (ALL), or for re-induction post relapse, use a combination of vincristine (VCR), a glucocorticoid, and L-asparaginase (ASP) with or without an anthracycline. With cure rates now approximately 80%, robust pre-clinical models are necessary to prioritize active new drugs for clinical trials in relapsed/refractory patients, and the ability of these models to predict synergy/antagonism with established therapy is an essential attribute. In this study, we report optimization of an induction-type regimen by combining VCR, dexamethasone (DEX) and ASP (VXL) against ALL xenograft models established from patient biopsies in immune-deficient mice. We demonstrate that the VXL combination was synergistic in vitro against leukemia cell lines as well as in vivo against ALL xenografts. In vivo, VXL treatment caused delays in progression of individual xenografts ranging from 22 to >146 days. The median progression delay of xenografts derived from long-term surviving patients was 2-fold greater than that of xenografts derived from patients who died of their disease. Pharmacokinetic analysis revealed that systemic DEX exposure in mice increased 2-fold when administered in combination with VCR and ASP, consistent with clinical findings, which may contribute to the observed synergy between the 3 drugs. Finally, as proof-of-principle we tested the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo platform to prioritize new drugs for clinical trials in children with relapsed/refractory ALL.

  2. Antibiotic treatment of acute uncomplicated cystitis based on rapid urine test and local epidemiology: lessons from a primary care series

    PubMed Central

    2014-01-01

    Background Acute uncomplicated cystitis (AUC) is an ideal target of optimization for antibiotic therapy in primary care. Because surveillance networks on urinary tract infections (UTI) mix complicated and uncomplicated UTI, reliable epidemiological data on AUC lack. Whether the antibiotic choice should be guided by a rapid urine test (RUT) for leukocytes and nitrites has not been extensively studied in daily practice. The aim of this primary care study was to investigate local epidemiology and RUT-daily use to determine the optimal strategy. Methods General practitioners included 18–65 years women with symptoms of AUC, performed a RUT and sent urines for analysis at a central laboratory. Different treatment strategies were simulated based on RUT and resistance results. Results Among 347 enrolled patients, 78% had a positive urine culture. Escherichia coli predominated (71%) with high rates of susceptibility to nitrofurantoin (100%), fosfomycin (99%), ofloxacin (97%), and even pivmecillinam (87%) and trimethoprim-sulfamethoxazole (87%). Modelization showed that the systematic use of RUT would reduce by 10% the number of patients treated. Fosfomycin for patients with positive RUT offered a 90% overall bacterial coverage, compared to 98% for nitrofurantoin. 95% for ofloxacin, 86% for trimethoprim-sulfamethoxazole and 78% for pivmecillinam. Conclusion Local epidemiology surveillance data not biased by complicated UTI demonstrates that the worldwide increase in antibiotic resistance has not affected AUC yet. Fosfomycin first line in all patients with positive RUT seems the best treatment strategy for AUC, combining good bacterial coverage with expected low toxicity and limited effect on fecal flora. Trial registration The current study was registered at clinicaltrials.gov (NCT00958295) PMID:24612927

  3. OUP: lethal gene drive selects inbreeding

    PubMed Central

    Bull, James J.

    2017-01-01

    The use of ‘selfish’ gene drive systems to suppress or even extinguish populations has been proposed on theoretical grounds for almost half a century. Creating these genes has recently become possible with CRISPR technology. One seemingly feasible approach, originally proposed by Burt, is to create a homing endonuclease gene (HEG) that inserts into an essential gene, enabling heterozygote viability but causing homozygote lethality. With 100% segregation distortion in gametes, such genes can cause profound population suppression if resistance does not evolve. Here, population genetic models are used to consider the evolution of inbreeding (specifically selfing) as a possible response to a recessively lethal HEG with complete segregation distortion. Numerical analyses indicate a rich set of outcomes, but selfing often evolves in response to the HEG, with a corresponding partial restoration of mean fitness. Whether selfing does indeed evolve and its effect in restoring fitness depends heavily on the magnitude of inbreeding depression. Overall, these results point toward an underappreciated evolutionary response to block the harmful effects of a selfish gene. They raise the possibility that extreme population suppression may be resisted by mechanisms that are independent of the molecular basis of gene drive. At the same time, the evolution of inbreeding is not assured even if the genetic basis for inbreeding is present. As the models here strictly apply to hermaphrodites (plants), an important next step is to consider inbreeding in populations with separate sexes. PMID:28013241

  4. A lethal combination for cancer cells: synthetic lethality screenings for drug discovery.

    PubMed

    Ferrari, Elisa; Lucca, Chiara; Foiani, Marco

    2010-11-01

    In recent years, cancer drug discovery has faced the challenging task of integrating the huge amount of information coming from the genomic studies with the need of developing highly selective target-based strategies within the context of tumour cells that experience massive genome instability. The combination between genetic and genomic technologies has been extremely useful and has contributed to efficiently transfer certain approaches typical of basic science to drug discover projects. An example comes from the synthetic lethal approaches, very powerful procedures that employ the rational used by geneticists working on model organisms. Applying the synthetic lethality (SL) screenings to anticancer therapy allows exploiting the typical features of tumour cells, such as genome instability, without changing them, as opposed to the conventional anticancer strategies that aim at counteracting the oncogenic signalling pathways. Recent and very encouraging clinical studies clearly show that certain promising anticancer compounds work through a synthetic lethal mechanism by targeting pathways that are specifically essential for the viability of cancer cells but not of normal cells. Herein we describe the rationale of the synthetic lethality approaches and the potential applications for anticancer therapy.

  5. Suicide Intent and Accurate Expectations of Lethality: Predictors of Medical Lethality of Suicide Attempts

    ERIC Educational Resources Information Center

    Brown, Gregory K.; Henriques, Gregg R.; Sosdjan, Daniella; Beck, Aaron T.

    2004-01-01

    The degree of intent to commit suicide and the severity of self-injury were examined in individuals (N = 180) who had recently attempted suicide. Although a minimal association was found between the degree of suicide intent and the degree of lethality of the attempt, the accuracy of expectations about the likelihood of dying was found to moderate…

  6. Potential lethal and non-lethal effects of predators on dispersal of spider mites.

    PubMed

    Otsuki, Hatsune; Yano, Shuichi

    2014-11-01

    Predators can affect prey dispersal lethally by direct consumption or non-lethally by making prey hesitate to disperse. These lethal and non-lethal effects are detectable only in systems where prey can disperse between multiple patches. However, most studies have drawn their conclusions concerning the ability of predatory mites to suppress spider mites based on observations of their interactions on a single patch or on heavily infested host plants where spider mites could hardly disperse toward intact patches. In these systems, specialist predatory mites that penetrate protective webs produced by spider mites quickly suppress the spider mites, whereas generalist predators that cannot penetrate the webs were ineffective. By using a connected patch system, we revealed that a generalist ant, Pristomyrmex punctatus Mayr (Hymenoptera: Formicidae), effectively prevented dispersal of spider mites, Tetranychus kanzawai Kishida (Acari: Tetranychidae), by directly consuming dispersing individuals. We also revealed that a generalist predatory mite, Euseius sojaensis Ehara (Acari: Phytoseiidae), prevented between-patch dispersal of T. kanzawai by making them hesitate to disperse. In contrast, a specialist phytoseiid predatory mite, Neoseiulus womersleyi Schicha, allowed spider mites to escape an initial patch, increasing the number of colonized patches within the system. Our results suggest that ants and generalist predatory mites can effectively suppress Tetranychus species under some conditions, and should receive more attention as agents for conservation biological control in agroecosystems.

  7. Gonadosomatic mosaicism for lethal mutations in Drosophila lethal mutations disturbing larval development

    SciTech Connect

    Ivanov, A.I.; Sakharova, N.Yu.

    1988-11-01

    Phenogenetic analysis of autonomous lethal mutations obtained by the method of gonadosomatic mosaicism which manifested during larval stages, established that the nuclei of hypodermal cells, salivary glands suprapharyngeal ganglion, pharynx, esophagus, gizzard, and hindgut are the derivatives of the same nucleus (from the first two nuclei of cleavage) as the nuclei of the cells of the imaginal-somatic tissues.

  8. Acute Vestibulopathy

    PubMed Central

    Cha, Yoon-Hee

    2011-01-01

    The presentation of acute vertigo may represent both a common benign disorder or a life threatening but rare one. Familiarity with the common peripheral vestibular disorders will allow the clinician to rapidly “rule-in” a benign disorder and recognize when further testing is required. Key features of vertigo required to make an accurate diagnosis are duration, chronicity, associated symptoms, and triggers. Bedside tests that are critical to the diagnosis of acute vertigo include the Dix-Hallpike maneuver and canalith repositioning manuever, occlusive ophthalmoscopy, and the head impulse test. The goal of this review is to provide the clinician with the clinical and pathophysiologic background of the most common disorders that present with vertigo to develop a logical differential diagnosis and management plan. PMID:23983835

  9. A case of acute generalized exanthematous pustulosis due to amoxicillin-clavulanate with multiple positivity to beta-lactam patch testing.

    PubMed

    Bomarrito, L; Zisa, G; Delrosso, G; Farinelli, P; Galimberti, M

    2013-09-01

    We present a case of acute generalized exanthematous pustolosis (AGEP) induced by amoxicillin-clavulanate. Clinical diagnosis was confirmed by symptoms presentation and  histological features (Euroscar score point compatible with definite diagnosis). Patch testing performer six months later confirmed sensitization to the culprit drug and showed positivity also to other beta-lactam antibiotics (penicillin G and cephalexin). We believe that a T cell delayed response to betalactams common ring could be involved.

  10. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats

    PubMed Central

    Li, Jianzhong; Xu, Jing; Xu, Weiheng; Qi, Yang; Lu, Yiming; Qiu, Lei; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2015-01-01

    Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage. PMID:26274957

  11. Drug target validation: Lethal infection blocked by inducible peptide

    NASA Astrophysics Data System (ADS)

    Tao, Jianshi; Wendler, Philip; Connelly, Gene; Lim, Audrey; Zhang, Jiansu; King, Megan; Li, Tongchuan; Silverman, Jared A.; Schimmel, Paul R.; Tally, Francis P.

    2000-01-01

    Genome projects are generating large numbers of potential new targets for drug discovery. One challenge is target validation, proving the usefulness of a specific target in an animal model. In this paper, we demonstrate a new approach to validation and assay development. We selected in vitro specific peptide binders to a potential pathogen target. By inducing the expression of a selected peptide in pathogen cells causing a lethal infection in mice, the animals were rescued. Thus, by combining in vitro selection methods for peptide binders with inducible expression in animals, the target's validity was rigorously tested and demonstrated. This approach to validation can be generalized and has the potential to become a valuable tool in the drug discovery process.

  12. Interclonal variation in the acute and delayed toxicity of cadmium to the European prosobranch gastropod Potamopyrgus antipodarum (Gray).

    PubMed

    Jensen, A; Forbes, V E

    2001-02-01

    The lethal responses of three European clones--A, B, and C-of the prosobranch snail Potamopyrgus antipodarum to acute cadmium exposure were examined by the use of a conventional LC50 test and a delayed toxicity test. The questions addressed were: (1) Are there differences in susceptibility (LC50 values and uniformity of response) among the three European clones of P. antipodarum? (2) Are the patterns of differences in susceptibility among clones observed in the LC50 test also observed for the delayed toxicity test? (3) Is there concordance in the ranking of susceptibility among clones under acute cadmium exposure and under chronic cadmium exposure? The results showed that the widths of the tolerance distribution differed among clones. Clones A and B had a steeper slope than clone C (for clone A the difference was marginally significant), which indicates that individuals from clones A and B showed a more uniform response to acute lethal cadmium stress than individuals from clone C. On the basis of the measured differences in LC50 values, clone A individuals showed the highest tolerance to acute cadmium (LC50 value: 1.92 mg Cd L(-1)) followed by clone B (LC50 value: 1.29 mg Cd L(-1)) and clone C (LC50 value: 0.56 mg Cd L(-1)). Clone C was significantly less tolerant than clones A and B. The delayed toxicity test showed a similar pattern to the LC50 test with regard to tolerance differences among clones; however, mortality continued following transfer to clean water, indicating that cadmium was lethal at much lower concentrations than indicated by the conventional LC50 test. Results of the LC50 test and the delayed toxicity test in the present study were in general agreement with results from chronic cadmium exposure experiments (Jensen et al. [2000] Ecol Appl [submitted]), i.e., the least susceptible clone A in the acute cadmium exposure test was also the least susceptible clone in the chronic cadmium exposure test. Based on the dramatic differences between the LC50

  13. [Triggering of acute coronary syndromes. Pathophysiologic relationships].

    PubMed

    González Pliego, José Angel

    2006-01-01

    In this review, the relationship of external triggers with the development of acute coronary syndromes is described. Based on current evidence, the pathophysiological mechanisms that probably result in the rupture of vulnerable coronary plaques are revised and preventive measures to stop the functional and lethal consequences of its occurrence are proposed.

  14. Ants defend aphids against lethal disease.

    PubMed

    Nielsen, Charlotte; Agrawal, Anurag A; Hajek, Ann E

    2010-04-23

    Social insects defend their own colonies and some species also protect their mutualist partners. In mutualisms with aphids, ants typically feed on honeydew produced by aphids and, in turn guard and shelter aphid colonies from insect natural enemies. Here we report that Formica podzolica ants tending milkweed aphids, Aphis asclepiadis, protect aphid colonies from lethal fungal infections caused by an obligate aphid pathogen, Pandora neoaphidis. In field experiments, bodies of fungal-killed aphids were quickly removed from ant-tended aphid colonies. Ant workers were also able to detect infective conidia on the cuticle of living aphids and responded by either removing or grooming these aphids. Our results extend the long-standing view of ants as mutualists and protectors of aphids by demonstrating focused sanitizing and quarantining behaviour that may lead to reduced disease transmission in aphid colonies.

  15. Lethal Synergism between Influenza and Streptococcus pneumoniae

    PubMed Central

    Rudd, Jennifer M; Ashar, Harshini K; Chow, Vincent TK; Teluguakula, Narasaraju

    2016-01-01

    The devastating synergism of bacterial pneumonia with influenza viral infections left its mark on the world over the last century. Although the details of pathogenesis remain unclear, the synergism is related to a variety of factors including pulmonary epithelial barrier damage which exposes receptors that influence bacterial adherence and the triggering of an exaggerated innate immune response and cytokine storm, which further acts to worsen the injury. Several therapeutics and combination therapies of antibiotics, anti-inflammatories including corticosteroids and toll-like receptor modifiers, and anti-virals are being discussed. This mini review summarizes recent developments in unearthing the pathogenesis of the lethal synergism of pneumococcal co-infection following influenza, as well as addresses potential therapeutic options and combinations of therapies currently being evaluated. PMID:27981251

  16. Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia

    PubMed Central

    Knaus, Hanna A.; Kanakry, Christopher G.; Luznik, Leo; Gojo, Ivana

    2016-01-01

    Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body’s own immune system to fight leukemic cells. PMID:25981611

  17. Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia.

    PubMed

    Knaus, Hanna A; Kanakry, Christopher G; Luznik, Leo; Gojo, Ivana

    2017-01-01

    Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body's own immune system to fight leukemic cells.

  18. Case series of 226 γ-hydroxybutyrate-associated deaths: lethal toxicity and trauma.

    PubMed

    Zvosec, Deborah L; Smith, Stephen W; Porrata, Trinka; Strobl, A Quinn; Dyer, Jo Ellen

    2011-03-01

    γ-Hydroxybutyrate (GHB) and its prodrugs are drugs of abuse that were also sold as "dietary supplements." Users present to emergency departments with overdose, impaired driving, withdrawal, and associated trauma. We compiled a series of GHB-associated deaths to elucidate lethal risks, GHB concentrations, cointoxicants, products, uses, and medical interventions. Death records were reviewed for toxicology, autopsy findings, and history. Inclusion cutoffs were as follows: 5/10 mg/L of GHB (antemortem blood/urine) and 50/20/7 mg/L of GHB (postmortem blood/urine/vitreous). Of 226 deaths included, 213 had cardiorespiratory arrest and 13 had fatal accidents. Seventy-eight deaths (35%) had no cointoxicants. Sixteen deaths involved "supplements" and 1 involved pharmaceutical GHB (Xyrem, Jazz Pharmaceuticals, Palo Alto, CA). Postmortem blood GHB was 18 to 4400 mg/L (median, 347 mg/L) in deaths negative for cointoxicants. Cardiorespiratory arrest occurred prehospital in 100% of 184 cases with available history. Of 72 cases with antemortem adverse effects reported, medical assistance was delayed or absent in 66; of these, acute GHB ingestion was known in 51, including 40 left to "sleep off" adverse effects. Thirty others were left "sleeping" and found dead. γ-Hydroxybutyrate is lethal even without cointoxicants, directly and through fatal accidents. Medical interventions were frequently delayed or absent despite known GHB ingestion, and witnessed adverse events and cardiorespiratory arrest occurred prehospital. Education is needed about the lethality of GHB and the necessity for prompt medical intervention.

  19. Toxicology of cupric salts in honeybees. I. Hormesis effects of organic derivatives on lethality parameters.

    PubMed

    Bounias, M; Navone-Nectoux, M; Popeskovic, D S

    1995-07-01

    Feeding bees with organic cupric salts provides long-term control of the parasite Varroa jacobsoni. A set of new algebraic parameters (M. Bounias C.R. Acad. Sci. 310(3), 65-70, 1990) completely describing the population lethality function has been calculated following chronic administration of cupric gluconate, aspartate, and isoleucinate, with or without dietary pollen. Mortality curves allowed the calculation of LT50 (time for 50% lethality) as well as Hill coefficients (h) of the curves and the LD50 as a function of time. The tangent at the inflexion point of the sigmoidal time/mortality curves (delta i) gave the maximum mortality acceleration as an additional parameter. No toxicity (i.e., no decrease of TL50 vs doses and no LD50 values) was found for cupric gluconate and isoleucinate with pollen, whereas increases in LT50 and decreases in delta indicated hormesis effects. Doses decreasing by half-time LT50, h, or delta were used as objective lethality indexes for comparisons of toxicity in the other cases. Routine acute toxicity at high dosage was also compared with phosalone and lindane effects 24 hr after treatment.

  20. Lethal and behavioural impacts of diesel and fuel oil on the Antarctic amphipod Paramoera walkeri.

    PubMed

    Brown, Kathryn E; King, Catherine K; Harrison, Peter L

    2017-03-03

    Toxicity testing with Antarctic species is required for risk assessment of fuel spills in Antarctic coastal waters. The lethal and sub-lethal (movement behaviour) sensitivity of adults and juveniles of the Antarctic amphipod Paramoera walkeri to the water accommodated fractions (WAF) of three fuels were estimated in extended duration tests at -1°C to 21 d. Response of P. walkeri for lethal hydrocarbon concentrations was slow, with 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 three 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; however, at 21 d juveniles were more than twice as sensitive as adults to SAB (LC50 = 153 µg/L and 377 µg/L respectively). Significant effects on movement behaviour were evident at earlier time points and lower concentrations than was mortality in all three fuel WAFs, and juveniles were highly sensitive to sub-lethal effects of MGO. These first estimates of Antarctic amphipod sensitivity to diesel and fuel oils in seawater contribute to development of ecologically relevant water quality guidelines for management of hydrocarbon contamination in the region. This article is protected by copyright. All rights reserved.

  1. 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 kidneyacute term) and the experimental periods (in sublethal term). In the acute and sublethal experiments, comet assay parameters such as the tail intensity (i.e. DNA percentage), tail extent moment and olive tail

  2. The lethal injection quandary: how medicine has dismantled the death penalty.

    PubMed

    Denno, Deborah W

    2007-10-01

    On February 20, 2006, Michael Morales was hours away from execution in California when two anesthesiologists declined to participate in his lethal injection procedure, thereby halting all state executions. The events brought to the surface the long-running schism between law and medicine, raising the question of whether any beneficial connection between the professions ever existed in the execution context. History shows it seldom did. Decades of botched executions prove it. This Article examines how states ended up with such constitutionally vulnerable lethal injection procedures, suggesting that physician participation in executions, though looked upon with disdain, is more prevalent--and perhaps more necessary--than many would like to believe. The Article also reports the results of this author's unique nationwide study of lethal injection protocols and medical participation. The study demonstrates that states have continued to produce grossly inadequate protocols that severely restrict sufficient understanding of how executions are performed and heighten the likelihood of unconstitutionality. The analysis emphasizes in particular the utter lack of medical or scientific testing of lethal injection despite the early and continuous involvement of doctors but ongoing detachment of medical societies. Lastly, the Article discusses the legal developments that led up to the current rush of lethal injection lawsuits as well as the strong and rapid reverberations that followed, particularly with respect to medical involvement. This Article concludes with two recommendations. First, much like what occurred in this country when the first state switched to electrocution, there should be a nationwide study of proper lethal injection protocols. An independent commission consisting of a diverse group of qualified individuals, including medical personnel, should conduct a thorough assessment of lethal injection, especially the extent of physician participation. Second, this

  3. An exome sequencing strategy to diagnose lethal autosomal recessive disorders.

    PubMed

    Ellard, Sian; Kivuva, Emma; Turnpenny, Peter; Stals, Karen; Johnson, Matthew; Xie, Weijia; Caswell, Richard; Lango Allen, Hana

    2015-03-01

    Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0-4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies.

  4. An exome sequencing strategy to diagnose lethal autosomal recessive disorders

    PubMed Central

    Ellard, Sian; Kivuva, Emma; Turnpenny, Peter; Stals, Karen; Johnson, Matthew; Xie, Weijia; Caswell, Richard; Lango Allen, Hana

    2015-01-01

    Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0–4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies. PMID:24961629

  5. Lethal and sublethal effects of thiamethoxam on the whitefly predator Serangium japonicum (Coleoptera: Coccinellidae) through different exposure routes.

    PubMed

    Yao, Feng-Luan; Zheng, Yu; Zhao, Jian-Wei; Desneux, Nicolas; He, Yu-Xian; Weng, Qi-Yong

    2015-06-01

    Given expectations for a booming usage of thiamethoxam and increasing availability of the promising biological agent Serangium japonicum for the control of Bemisia tabaci in China, an evaluation of their compatibility is crucial for integrated pest management (IPM). This study examined the lethal and sublethal effects of thiamethoxam on S. japonicum through three exposure routes. An acute toxicity bioassay showed that LC50 values of thiamethoxam for S. japonicum through residue contact, egg-dip, and systemic treatment were 6.65, 4.37, and 2.43 mg AI L(-1), respectively. The prey consumption of S. japonicum given different densities of B. tabaci eggs under control, discontinuous, egg-dip and systemic exposure scenarios showed a good fit to a Type II functional response. Predation of S. japonicum was most affected under systemic exposure, followed by egg-dip, and discontinuous, which was only slightly affected. In all cases tested, however, predators recovered their predation capacity rapidly, either after 24h of exposure or 24h after the end of exposure. Thiamethoxam was highly toxic to S. japonicum regardless of exposure routes. Sublethal effects of thiamethoxam applied systemically or foliar both impaired the biological control of S. japonicum on B. tabaci. Therefore, thiamethoxam should be used with caution in IPM of B. tabaci.

  6. Syn-Lethality: An Integrative Knowledge Base of Synthetic Lethality towards Discovery of Selective Anticancer Therapies

    PubMed Central

    Li, Xue-juan; Mishra, Shital K.; Wu, Min; Zhang, Fan

    2014-01-01

    Synthetic lethality (SL) is a novel strategy for anticancer therapies, whereby mutations of two genes will kill a cell but mutation of a single gene will not. Therefore, a cancer-specific mutation combined with a drug-induced mutation, if they have SL interactions, will selectively kill cancer cells. While numerous SL interactions have been identified in yeast, only a few have been known in human. There is a pressing need to systematically discover and understand SL interactions specific to human cancer. In this paper, we present Syn-Lethality, the first integrative knowledge base of SL that is dedicated to human cancer. It integrates experimentally discovered and verified human SL gene pairs into a network, associated with annotations of gene function, pathway, and molecular mechanisms. It also includes yeast SL genes from high-throughput screenings which are mapped to orthologous human genes. Such an integrative knowledge base, organized as a relational database with user interface for searching and network visualization, will greatly expedite the discovery of novel anticancer drug targets based on synthetic lethality interactions. The database can be downloaded as a stand-alone Java application. PMID:24864230

  7. Chronic Exposure of Corals to Fine Sediments: Lethal and Sub-Lethal Impacts

    PubMed Central

    Flores, Florita; Hoogenboom, Mia O.; Smith, Luke D.; Cooper, Timothy F.; Abrego, David; Negri, Andrew P.

    2012-01-01

    Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS) for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata) more than the upright branching species (Acropora millepora). The lowest sediment treatments that caused full colony mortality were 30 mg l−1 TSS (25 mg cm−2 day−1) for M. aequituberculata and 100 mg l−1 TSS (83 mg cm−2 day−1) for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue. PMID:22662225

  8. The Influence of Geographic Mobility on Nearly Lethal Suicide Attempts.

    ERIC Educational Resources Information Center

    Potter, Lloyd B.; Kresnow, Marcie-jo; Powell, Kenneth E.; Simon, Thomas R.; Mercy, James A.; Lee, Roberta K.; Frankowski, Ralph F.; Swann, Alan C.; Bayer, Timothy; O'Carroll, Patrick W.

    2002-01-01

    Presents a population-based, case-control study of nearly lethal suicide attempts with 153 cases and 513 controls. Results indicate that moving in the past year is positively associated with a nearly lethal suicide attempt, as are specific characteristics of the move. Findings confirm and extend prior research by demonstrating a relationship…

  9. Impact of the Timing of Morphine Administration on Lipopolysaccharide-Mediated Lethal Endotoxic Shock in Mice.

    PubMed

    Fukada, Tomoko; Kato, Hidehito; Ozaki, Makoto; Yagi, Junji

    2016-05-01

    Sepsis is a serious condition related to systemic inflammation, organ dysfunction, and organ failure. It is a subset of the cytokine storm caused by dysregulation of cytokine production. Morphine influences the severity of infection in vivo and in vitro because it regulates cytokine production. We investigated the immunological function of morphine using a mouse model of septic shock. We treated mice with α-galactosylceramide (2 μg/mouse) to induce lethal endotoxic shock following a challenge with lipopolysaccharide (LPS, 1.5 μg/mouse). This model represents acute lung injury and respiratory failure, and reflects the clinical features of severe septic shock. We evaluated the effect of the timing of morphine (0.8 mg/mouse) administration on the survival rate, cytokine production in vivo, and histological changes of mice with LPS-mediated lethal endotoxic shock. Morphine treatment before LPS challenge suppressed lethal endotoxic shock. In contrast, when we administered after LPS, morphine exacerbated lethal endotoxic shock; hematoxylin and eosin staining revealed a marked increase in the accumulation of infiltrates comprising polymorphonuclear leukocytes and mononuclear cells in the lung; and Elastica van Gieson staining revealed the destruction of alveoli. The plasma levels of tumor necrosis factor-α, interferon-γ, monocyte-chemotactic protein-1, and interleukin-12 in the group treated with morphine after LPS challenge were higher than those treated with morphine before LPS challenge. In conclusion, one of the factors that determine whether morphine exacerbates or inhibits infection is the timing of its administration. Morphine treatment before shock improved the survival rate, and morphine treatment after shock decreased the rate of survival.

  10. Lethal Mutagenesis of HIV with Mutagenic Nucleoside Analogs

    NASA Astrophysics Data System (ADS)

    Loeb, Lawrence A.; Essigmann, John M.; Kazazi, Farhad; Zhang, Jue; Rose, Karl D.; Mullins, James I.

    1999-02-01

    The human immunodeficiency virus (HIV) replicates its genome and mutates at exceptionally high rates. As a result, the virus is able to evade immunological and chemical antiviral agents. We tested the hypothesis that a further increase in the mutation rate by promutagenic nucleoside analogs would abolish viral replication. We evaluated deoxynucleoside analogs for lack of toxicity to human cells, incorporation by HIV reverse transcriptase, resistance to repair when incorporated into the DNA strand of an RNA\\cdot DNA hybrid, and mispairing at high frequency. Among the candidates tested, 5-hydroxydeoxycytidine (5-OH-dC) fulfilled these criteria. In seven of nine experiments, the presence of this analog resulted in the loss of viral replicative potential after 9-24 sequential passages of HIV in human CEM cells. In contrast, loss of viral replication was not observed in 28 control cultures passaged in the absence of the nucleoside analog, nor with other analogs tested. Sequence analysis of a portion of the HIV reverse transcriptase gene demonstrated a disproportionate increase in G -> A substitutions, mutations predicted to result from misincorporation of 5-OH-dC into the cDNA during reverse transcription. Thus, "lethal mutagenesis" driven by the class of deoxynucleoside analogs represented by 5-OH-dC could provide a new approach to treating HIV infections and, potentially, other viral infections.

  11. Comparison of an Ampelisca abdita growth rate test with other standard amphipod sediment toxicity tests

    SciTech Connect

    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. 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.

  12. Antidotes to anthrax lethal factor intoxication. Part 1: Discovery of potent lethal factor inhibitors with in vivo efficacy.

    PubMed

    Jiao, Guan-Sheng; Kim, Seongjin; Moayeri, Mahtab; Cregar-Hernandez, Lynne; McKasson, Linda; Margosiak, Stephen A; Leppla, Stephen H; Johnson, Alan T

    2010-11-15

    Sub-nanomolar small molecule inhibitors of anthrax lethal factor have been identified using SAR and Merck L915 (4) as a model compound. One of these compounds (16) provided 100% protection in a rat lethal toxin model of anthrax disease.

  13. TLR4 antagonist FP7 inhibits LPS-induced cytokine production and glycolytic reprogramming in dendritic cells, and protects mice from lethal influenza infection

    PubMed Central

    Perrin-Cocon, Laure; Aublin-Gex, Anne; Sestito, Stefania E.; Shirey, Kari Ann; Patel, Mira C.; André, Patrice; Blanco, Jorge C.; Vogel, Stefanie N.; Peri, Francesco; Lotteau, Vincent

    2017-01-01

    Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection. Thus, therapeutic control of the TLR4 signalling pathway is of major interest. Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice. Our results indicate that FP7 antagonized the secretion of proinflammatory cytokines (IL-6, IL-8, and MIP-1β) by monocytes and DCs (IC50 < 1 μM) and prevented DC maturation upon TLR4 activation by ultrapure lipopolysaccharide (LPS). FP7 selectively blocked TLR4 stimulation, but not TLR1/2, TLR2/6, or TLR3 activation. TLR4 stimulation of human DCs resulted in increased glycolytic activity that was also antagonized by FP7. FP7 protected mice from influenza virus-induced lethality and reduced both proinflammatory cytokine gene expression in the lungs and acute lung injury (ALI). Therefore, FP7 can antagonize TLR4 activation in vitro and protect mice from severe influenza infection, most likely by reducing TLR4-dependent cytokine storm mediated by damage-associated molecular patterns (DAMPs) like HMGB1. PMID:28106157

  14. Tetracycline-suppressible female lethality and sterility in the Mexican fruit fly, Anastrepha ludens.

    PubMed

    Schetelig, M F; Targovska, A; Meza, J S; Bourtzis, K; Handler, A M

    2016-08-01

    The sterile insect technique (SIT) involves the mass release of sterile males to suppress insect pest populations. SIT has been improved for larval pests by the development of strains for female-specific tetracycline-suppressible (Tet-off) embryonic lethal systems for male-only populations. Here we describe the extension of this approach to the Mexican fruit fly, Anastrepha ludens, using a Tet-off driver construct with the Tet-transactivator (tTA) under embryo-specific Anastrepha suspensa serendipity α (As-sry-α) promoter regulation. In the absence of tetracycline, tTA acts upon a Tet-response element linked to the pro-apoptotic cell death gene lethal effector, head involuation defective (hid), from A. ludens (Alhid(Ala2) ) that contains a sex-specific intron splicing cassette, resulting in female-specific expression of the lethal effector. Parental adults double-homozygous for the driver/effector vectors were expected to yield male-only progeny when reared on Tet-free diet, but a complete lack of oviposited eggs resulted for each of the three strains tested. Ovary dissection revealed nonvitellogenic oocytes in all strains that was reversible by feeding females tetracycline for 5 days after eclosion, resulting in male-only adults in one strain. Presumably the sry-α promoter exhibits prezygotic maternal expression as well as zygotic embryonic expression in A. ludens, resulting in a Tet-off sterility effect in addition to female-specific lethality.

  15. Lethal body burdens of polar narcotics: Chlorophenols

    SciTech Connect

    Wezel, A.P. van; Punte, S.S.; Opperhuizen, A.

    1995-09-01

    The goal of the present study was to measure in fathead minnow (Pimephales promelas) the lethal body burden (LBB) of three chlorophenols that are known as polar narcotic chemicals. The LBBs of the chlorophenols were compared to LBBs of nonpolar narcotic chemicals to consider if the two classes of narcotic chemicals differ on a body burden level. The LBB of the most acidic chlorophenol was measured at two different levels of pH exposure to determine the influence of the degree of ionization on the magnitude of the LBB. Both n-octanol/water partition coefficients and n-hexane/water partition coefficients of the chlorophenols were determined at different pH levels to consider the influence of ionization on the partition coefficient and to determine the importance of a polar group in the organic phase on the partitioning behavior. Partitioning to n-octanol and n-hexane was used as input in a model to simulate the equilibrium partitioning between hydrophobic and nonhydrophobic and target and nontarget compartments in the fish.

  16. Inhibitors of the Metalloproteinase Anthrax Lethal Factor

    PubMed Central

    Goldberg, Allison B.; Turk, Benjamin E.

    2016-01-01

    Bacillus anthracis, a rod shaped, spore forming, gram positive bacteria, is the etiological agent of anthrax. B. anthracis virulence is partly attributable to two secreted bipartite protein toxins, which act inside host cells to disrupt signaling pathways important for host defense against infection. These toxins may also directly contribute to mortality in late stage infection. The zinc-dependent metalloproteinase anthrax lethal factor (LF) is a critical component of one of these protein toxins and a prime target for inhibitor development to produce anthrax therapeutics. Here, we describe recent efforts to identify specific and potent LF inhibitors. Derivatization of peptide substrate analogs bearing zinc-binding groups has produced potent and specific LF inhibitors, and X-ray crystallography of LF-inhibitor complexes has provided insight into features required for high affinity binding. Novel inhibitor scaffolds have been identified through several approaches, including fragment-based drug discovery, virtual screening, and high-throughput screening of diverse compound libraries. Lastly, efforts to discover LF inhibitors have led to the development of new screening strategies, such as the use of full-length proteins as substrates, that may prove useful for other proteases as well. Overall, these efforts have led to a collection of chemically and mechanistically diverse molecules capable of inhibiting LF activity in vitro and in cells, as well as in animal models of anthrax infection. PMID:27072692

  17. Lethal Mutagenesis Failure May Augment Viral Adaptation

    PubMed Central

    Paff, Matthew L.; Stolte, Steven P.; Bull, James J.

    2014-01-01

    Lethal mutagenesis, the attempt to extinguish a population by elevating its mutation rate, has been endorsed in the virology literature as a promising approach for treating viral infections. In support of the concept, in vitro studies have forced viral extinction with high doses of mutagenic drugs. However, the one known mutagenic drug used on patients commonly fails to cure infections, and in vitro studies typically find a wide range of mutagenic conditions permissive for viral growth. A key question becomes how subsequent evolution is affected if the viral population is mutated but avoids extinction—Is viral adaptation augmented rather than suppressed? Here we consider the evolution of highly mutated populations surviving mutagenesis, using the DNA phage T7. In assays using inhibitory hosts, whenever resistance mutants were observed, the mutagenized populations exhibited higher frequencies, but some inhibitors blocked plaque formation by even the mutagenized stock. Second, outgrowth of previously mutagenized populations led to rapid and potentially complete fitness recovery but polymorphism was slow to decay, and mutations exhibited inconsistent patterns of change. Third, the combination of population bottlenecks with mutagenesis did cause fitness declines, revealing a vulnerability that was not apparent from mutagenesis of large populations. The results show that a population surviving high mutagenesis may exhibit enhanced adaptation in some environments and experience little negative fitness consequences in many others. PMID:24092771

  18. Tumor clone dynamics in lethal prostate cancer.

    PubMed

    Carreira, Suzanne; Romanel, Alessandro; Goodall, Jane; Grist, Emily; Ferraldeschi, Roberta; Miranda, Susana; Prandi, Davide; Lorente, David; Frenel, Jean-Sebastien; Pezaro, Carmel; Omlin, Aurelius; Rodrigues, Daniel Nava; Flohr, Penelope; Tunariu, Nina; S de Bono, Johann; Demichelis, Francesca; Attard, Gerhardt

    2014-09-17

    It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers.

  19. Lethal methemoglobinemia and automobile exhaust inhalation.

    PubMed

    Vevelstad, Merete; Morild, Inge

    2009-05-30

    Inhalation of automobile exhaust gas often leads to death by CO intoxication. In some cases the measured carbon monoxide hemoglobin saturation level (COHb) is considerably below what is considered to be lethal. The death in such cases has been attributed to a combination of a high CO2 and a low O2 tension. In a recent case the deceased was found dead in a car equipped with a catalytic converter, with a hose leading exhaust from the engine to the interior of the car. Analysis revealed a moderately elevated COHb and a high methemoglobin saturation level (MetHb) in peripheral blood. No ethanol, narcotics or drugs were detected. Reports mentioning MetHb or methemoglobinemia in post-mortem cases are surprisingly scarce, and very few have related exhaust gas deaths to methemoglobinemia. High-degree methemoglobinemia causes serious tissue hypoxia leading to unconsciousness, arrhythmia and death. The existing literature in this field and the knowledge that exhaust fumes contain nitrogen oxide gases (NOx) that by inhalation and absorption can result in severe methemoglobinemia, led us to postulate that this death could possibly be attributed to a combination of methemoglobinemia and a moderately high COHb concentration.

  20. Tumor clone dynamics in lethal prostate cancer

    PubMed Central

    Carreira, Suzanne; Romanel, Alessandro; Goodall, Jane; Grist, Emily; Ferraldeschi, Roberta; Miranda, Susana; Prandi, Davide; Lorente, David; Frenel, Jean-Sebastien; Pezaro, Carmel; Omlin, Aurelius; Rodrigues, Daniel Nava; Flohr, Penelope; Tunariu, Nina; de Bono, Johann S.; Demichelis, Francesca; Attard, Gerhardt

    2015-01-01

    It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers. PMID:25232177

  1. Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever

    PubMed Central

    Golden, Joseph W.; Maes, Piet; Kwilas, Steven A.; Ballantyne, John

    2016-01-01

    ABSTRACT Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaviruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaviruses. In the present study, we produced arenavirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junín virus (JUNV), Machupo virus (MACV), and Guanarito virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT50), exceeded 5,000 against homologous viruses. Antisera against each targeted virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (∼30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenavirus immunotherapeutic. IMPORTANCE Arenaviruses are an important family of emerging viruses. In infected humans, convalescent-phase plasma containing neutralizing antibodies can

  2. Key tissue targets responsible for anthrax-toxin-induced lethality.

    PubMed

    Liu, Shihui; Zhang, Yi; Moayeri, Mahtab; Liu, Jie; Crown, Devorah; Fattah, Rasem J; Wein, Alexander N; Yu, Zu-Xi; Finkel, Toren; Leppla, Stephen H

    2013-09-05

    Bacillus anthracis, the causative agent of anthrax disease, is lethal owing to the actions of two exotoxins: anthrax lethal toxin (LT) and oedema toxin (ET). The key tissue targets responsible for the lethal effects of these toxins are unknown. Here we generated cell-type-specific anthrax toxin receptor capillary morphogenesis protein-2 (CMG2)-null mice and cell-type-specific CMG2-expressing mice and challenged them with the toxins. Our results show that lethality induced by LT and ET occurs through damage to distinct cell types; whereas targeting cardiomyocytes and vascular smooth muscle cells is required for LT-induced mortality, ET-induced lethality occurs mainly through its action in hepatocytes. Notably, and in contradiction to what has been previously postulated, targeting of endothelial cells by either toxin does not seem to contribute significantly to lethality. Our findings demonstrate that B. anthracis has evolved to use LT and ET to induce host lethality by coordinately damaging two distinct vital systems.

  3. 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 LC50s 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.

  4. Sticky foam as a less-than-lethal technology

    NASA Astrophysics Data System (ADS)

    Scott, Steven H.

    1997-01-01

    Sandia National Laboratories (SNL) in 1994 completed a project funded by the National Institute of Justice (NIJ) to determine the applicability of sticky foam for correctional applications. Sticky foam is an extremely tacky, tenacious material used to block, entangle, and impair individuals. The NIJ project developed a gun capable of firing multiple shots of sticky foam, tested the gun and sticky foam effectiveness on SNL volunteers acting out prison and law enforcement scenarios, and had the gun and sticky foam evaluated by correctional representatives. Based on the NIJ project work, SNL supported the Marine Corps Mission, Operation United Shield, with sticky foam guns and supporting equipment to assist in the withdrawal of UN Peacekeepers from Somalia. Prior to the loan of the waste disposal, use limitations, use protocol and precautions, emergency facial clean-up, skin clean-up, gun filling, targeting and firing, and gun cleaning. The Marine Corps successfully used the sticky foam guns as part of that operation. This paper describes these recent developments of sticky foam for non-lethal uses and some of the lessons learned from scenario and application testing.

  5. Sticky foam as a less-than-lethal technology

    SciTech Connect

    Scott, S.H.

    1996-12-31

    Sandia National Labs (SNL) in 1994 completed a project funded by the National Institute of Justice (NIJ) to determine the applicability of sticky foam for correctional applications. Sticky foam is an extremely tacky, tenacious material used to block, entangle, and impair individuals. The NIJ project developed a gun capable of firing multiple shots of sticky foam, tested the gun and sticky foam effectiveness on SNL volunteers acting out prison and law enforcement scenarios, and had the gun and sticky foam evaluated by correctional representatives. Based on the NIJ project work, SNL supported the Marine Corps Mission, Operation United Shield, with sticky foam guns and supporting equipment to assist in the withdrawal of UN Peacekeepers from Somalia. Prior to the loan of the equipment, the Marines were given training in sticky foam characterization, toxicology, safety issues, cleanup and waste disposal, use limitations, use protocol and precautions, emergency facial clean-up, skin cleanup, gun filling, targeting and firing, and gun cleaning. The Marine Corps successfully used the sticky foam guns as part of that operation. This paper describes these recent developments of sticky foam for non-lethal uses and some of the lessons learned from scenario and application testing.

  6. The danger assessment: validation of a lethality risk assessment instrument for intimate partner femicide.

    PubMed

    Campbell, Jacquelyn C; Webster, Daniel W; Glass, Nancy

    2009-04-01

    The Danger Assessment (DA) is an instrument designed to assess the likelihood of lethality or near lethality occurring in a case of intimate partner violence. This article describes the development, psychometric validation, and suggestions for use of the DA. An 11-city study of intimate partner femicide used multivariate analysis to test the predictive validity of the risk factors on the DA from intimate partner femicide cases (N = 310) compared with 324 abused women in the same cities (controls). The results were used to revise the DA (four items added; one "double-barreled" item divided into two), and the calculated weights (adjusted odds ratios) used to develop a scoring algorithm with levels of risk. These levels of risk were then tested with an independent sample of attempted femicides (N = 194) with a final outcome of .90 of the cases included in the area under the receiver operating characteristic (ROC) curve.

  7. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  8. 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

  9. Behavioral effects of low, acute doses of morphine in nontolerant groups of rats in an open-field test.

    PubMed

    Schiørring, E; Hecht, A

    1979-06-28

    Groups of eight rats were treated with low, acute doses of morphine (2, 3.5, and 5 mg/kg body weight) or a corresponding volume of isotonic NaCl solution. The formation of groups, certain other features of social interaction, plus some individual items were recorded. Morphine induced an increase in the frequency of group formations without disruption of grooming and rearing patterns. The total picture of morphine-induced behavior changes at the dose levels used might be characterized as a polyactivation (or a varied stimulation); different from the selective stimulation reported for d-amphetamine.

  10. [Neuroimmunocorrection therapy for the prophylaxis of infectious complications in acute stroke patients].

    PubMed

    Kul'chikov, A E; Makarenko, A N

    2008-01-01

    Neuroimmunocorrection therapy with cerebrolysin has been used for the prophylaxis of clinical pneumonia development in the early stage of acute stroke in a group of 140 patients with heavy clinical course of acute ischemic stroke (AIS). All patients in the test and control groups received the basal anti-AIS therapy and antibacterial drugs (IV-generation cephalosporins) in case of pneumonia development. The efficacy of cerebrolysin administration was evaluated both on the clinical scale (NIH-NINDS, CPIS, SIRS immonograms) and using laboratory indices. It is established that the proposed neuroimmunocorrection therapy with cerebrolysin decreases the frequency of the clinical pneumonia development. A relationship between the pneumonia onset rate and the focus localization in limbico-diencephalic part of the brain is established. The use of cerebrolysin decreases lethality, normalizes the impaired immunity indices, accelerates the restoration of violated neural functions, suppresses pneumonia development, restores the level of albumin, and normalizes the laboratory indices of inflammatory syndrome.

  11. mRNA Expression Signature of Gleason Grade Predicts Lethal Prostate Cancer

    PubMed Central

    Penney, Kathryn L.; Sinnott, Jennifer A.; Fall, Katja; Pawitan, Yudi; Hoshida, Yujin; Kraft, Peter; Stark, Jennifer R.; Fiorentino, Michelangelo; Perner, Sven; Finn, Stephen; Calza, Stefano; Flavin, Richard; Freedman, Matthew L.; Setlur, Sunita; Sesso, Howard D.; Andersson, Swen-Olof; Martin, Neil; Kantoff, Philip W.; Johansson, Jan-Erik; Adami, Hans-Olov; Rubin, Mark A.; Loda, Massimo; Golub, Todd R.; Andrén, Ove; Stampfer, Meir J.; Mucci, Lorelei A.

    2011-01-01

    Purpose Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis. Patients and Methods Using the complementary DNA–mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases. Results We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006). Conclusion Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment. PMID:21537050

  12. Prospective study on the overuse of blood test-guided antibiotics on patients with acute diarrhea in primary hospitals of China

    PubMed Central

    Liu, Xinghui; Tong, Xueke; Jin, Liyin; Ha, Minghao; Cao, Feng; Xu, Fengxia; Chi, Yongbin; Zhang, Denghai; Xu, Limin

    2017-01-01

    Background Overuse with antibiotics in the treatment of infectious diseases has become a central focus of public health over the years. The aim of this study was to provide an up-to-date evaluation of the blood test-guided antibiotic use on patients with acute diarrhea in primary hospitals of China. Materials and methods A cross-sectional survey was conducted on 330 patients with acute diarrhea in Shanghai, People’s Republic of China, from March 2013 to February 2016. These patients were treated with or without antibiotics based on the results of their blood tests, including examinations of C-reactive protein (CRP), white blood cells (WBC), and the percentage of neutrophils (Neu%). The infection types, which included bacterial, viral, and combination diarrhea, were determined by microbiological culture methods. Antibiotics used in non-bacterial diarrhea patients were considered misused and overused. Results There were significant overall differences in the clinical characteristics and blood tests between patients with diarrhea with a bacterial infection and patients with other types of infections. The patients were divided into four grading groups (0–3) according to the number of the positive results from three blood testes (CRP, WBC, and Neu%). The misuse rates of antibiotics in each group (0–3) were 81.3%, 71.1%, 72.4%, and 64.9%, respectively. Conclusion In this prospective study, the current diagnostic criteria (CRP, WBC, and Neu%) based on blood tests are not reliable in diagnosing bacterial diarrhea or guiding antibiotics use. To limit antibiotic overuse, a rapid and accurate differentiation of bacterial diarrhea from other types of diarrhea is pivotal. PMID:28352160

  13. Synthetic Lethality in Breast Cancer Cells: Genes Required for Tumor Survival

    DTIC Science & Technology

    2004-07-01

    that the goals of this grant and that of the Innovator award are distinct. The innovator award is to develop high-throughput procedures to create a...revised report The original goal of this application was to develop strategies to permit synthetic lethal screens to be carried out in mammalian cells. In...parallel, one needed to develop systems in which such interactions could be effectively tested. When this application was initially submitted four

  14. 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.

  15. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice.

    PubMed

    Channappanavar, Rudragouda; Fehr, Anthony R; Vijay, Rahul; Mack, Matthias; Zhao, Jincun; Meyerholz, David K; Perlman, Stanley

    2016-02-10

    Highly pathogenic human respiratory coronaviruses cause acute lethal disease characterized by exuberant inflammatory responses and lung damage. However, the factors leading to lung pathology are not well understood. Using mice infected with SARS (severe acute respiratory syndrome)-CoV, we show that robust virus replication accompanied by delayed type I interferon (IFN-I) signaling orchestrates inflammatory responses and lung immunopathology with diminished survival. IFN-I remains detectable until after virus titers peak, but early IFN-I administration ameliorates immunopathology. This delayed IFN-I signaling promotes the accumulation of pathogenic inflammatory monocyte-macrophages (IMMs), resulting in elevated lung cytokine/chemokine levels, vascular leakage, and impaired virus-specific T cell responses. Genetic ablation of the IFN-αβ receptor (IFNAR) or IMM depletion protects mice from lethal infection, without affecting viral load. These results demonstrate that IFN-I and IMM promote lethal SARS-CoV infection and identify IFN-I and IMMs as potential therapeutic targets in patients infected with pathogenic coronavirus and perhaps other respiratory viruses.

  16. Evaluation of the SD BIOLINE Dengue Duo rapid test in the course of acute and convalescent dengue infections in a Mexican endemic region.

    PubMed

    Sánchez-Vargas, Luis A; Sánchez-Marce, Elvis E; Vivanco-Cid, Héctor

    2014-04-01

    In this study, we evaluated the performance of a rapid test, the SD BIOLINE Dengue Duo (SD BDD) kit, with a panel of serum samples from 310 Mexican patients with diagnosis of dengue infection previously confirmed by reference enzyme-linked immunosorbent assay tests. Eighty-seven negative samples from other febrile illnesses were included as controls. The SD BDD showed an overall sensitivity of 90.65% and specificity of 89.66%. No statistically significant differences were found in the sensitivity of the SD BDD kit compared between primary or secondary infections (87.05% versus 93.57%, respectively, P = 0.0761) and dengue fever or dengue hemorrhagic fever cases (90.77% versus 89.74%, respectively, P = 0.7716). However, a higher sensitivity in the acute phase of dengue infection was found compared with the convalescent phase (93.03% versus 81.82%, respectively, P = 0.0089). These results indicate that the SD BDD kit is a useful tool to diagnose dengue infections, both in primary or secondary infections and mainly during the acute phase.

  17. Comparative Evaluation of Norovirus Infection in Children with Acute Gastroenteritis by Rapid Immunochromatographic Test, RT-PCR and Real-time RT-PCR.

    PubMed

    Kumthip, Kattareeya; Khamrin, Pattara; Saikruang, Wilaiporn; Supadej, Kanittapon; Ushijima, Hiroshi; Maneekarn, Niwat

    2017-03-02

    Immunochromatographic (IC) test for norovirus detection is a rapid and simple detection method. This study evaluated the sensitivity and specificity of a recent version of R-Biopharm RIDA®QUICK Norovirus IC assay for norovirus detection in fecal specimens from children hospitalized with acute gastroenteritis. Fecal specimens were tested by IC kit in comparison with gold standard reverse transcription polymerase chain reaction (RT-PCR) and real-time RT-PCR. The IC kit showed high sensitivity and specificity comparable with PCR-based methods. None of false positive and false negative was found and the assay did not cross-react with other gastroenteritis viruses. The IC assay could detect genogroup I.5 (GI.5) and a wide range of genotypes in the GII noroviruses including GII.3, GII.4, GII.6, GII.7, GII.14, GII.15, GII.21, and also newly emerging GII.17 norovirus. In conclusion, this norovirus IC kit could be an alternative choice for rapid screening or a quick diagnostic tool for norovirus detection in fecal specimens of acute gastroenteritis patients.

  18. Somatic Mosaicism for a Lethal TRPV4 Mutation Results in Non-Lethal Metatropic Dysplasia

    PubMed Central

    Weinstein, Michael M.; Kang, Taekyu; Lachman, Ralph S.; Bamshad, Michael; Nickerson, Deborah A.; Krakow, Deborah; Cohn, Daniel H.

    2016-01-01

    Dominant mutations in TRPV4, which encodes the Transient Receptor Potential Cation Channel Subfamily V Member 4 calcium channel, result in a series of musculoskeletal disorders that include a set of peripheral neuropathies and a broad phenotypic spectrum of skeletal dysplasias. The skeletal pheno-types range from brachyolmia, in which there is scoliosis with mild short stature, through perinatal lethal metatropic dysplasia. We describe a case with phenotypic findings consistent with metatropic dysplasia, but in whom no TRPV4 mutation was detected by Sanger sequence analysis. Exome sequence analysis identified a known lethal metatropic dysplasia mutation, TRPV4L618P, which was present at lower frequency than would be expected for a heterozygous change. The affected individual was shown to be a somatic mosaic for the mutation, providing an explanation for the milder than expected phenotype. The data illustrate that high-throughput sequencing of genomic DNA can facilitate detection of mosaicism with higher sensitivity than Sanger sequence analysis and identify a new genetic mechanism for metatropic dysplasia. PMID:27530454

  19. Evaluation of greater petrosal nerve function in patients with acute peripheral facial paralysis: comparison of soft palate electrogustometry and Schirmer's tear test.

    PubMed

    Kawamoto, Hidetoshi; Ikeda, Minoru

    2002-01-01

    We tested sensory and secretomotor function of the greater petrosal nerve (GPN) by means of electrogustometry (EGM) of the soft palate and Schirmer's tear test in 115 patients (59 males, 56 females) with acute peripheral facial paralysis. Facial paralysis was caused by Bell's palsy in 78 cases, Ramsay Hunt syndrome in 27 cases and zoster sine herpetic lesions in 10. All patients had dysfunction of the stapedial nerve. An electrogustometer was used to test taste (GPN sensory function), and elevation of the threshold by > 6 dB on the affected side was considered abnormal. Schirmer's test was used to evaluate lacrimal (GPN secretomotor) function, which was considered abnormal when tear secretion on the affected side was < 50% of secretion on the non-affected side. Of the 78 patients with Bell's palsy, 28.2% had altered taste on the soft palate (sensory dysfunction) and 10.3% had lacrimal dysfunction, indicating that EGM of the soft palate is more sensitive than Schirmer's test for identifying dysfunction of the GPN in patients with facial paralysis due to Bell's palsy. Of the total of 115 patients, 32 (28%) had taste dysfunction and 9 (28.1%) of these 32 patients also had lacrimal dysfunction. This finding indicates that facial paralysis has different effects on the sensory and secretory nerve fibers of the GPN. The results of Schirmer's test were more closely related to the severity of, and prognosis for, facial paralysis than the results of EGM.

  20. Implementation of routine HIV testing in an acute care hospital in Rhode Island: a nurse-initiated opt-out pilot project.

    PubMed

    Costello, Joanne F; Sliney, Anne; MacLeod, Cindy; Carpentier, Michelle; Garofalo, Rebecca; Flanigan, Timothy

    2013-01-01

    The Centers for Disease Control and Prevention (CDC) expanded HIV screening of adults ages 13-64 years in 2006 from risk based to routine. Early detection and treatment improve patient outcomes and prevent disease transmission. This article describes a pilot program in which nurses in an adult inpatient unit at an acute care hospital offer HIV testing to all patients ages 18-64 upon admission through standing orders. The pilot, Standing Orders for Routine Testing (SORT), is a response to changes in state law and regulations in the majority of states including Rhode Island, which have occurred following the CDC policy change. The SORT pilot involves collaboration with interdisciplinary partners and education of unit nurses.

  1. Anthrax lethal factor inhibitors as potential countermeasure of the infection.

    PubMed

    Kumar, B V S Suneel; Malik, Siddharth; Grandhi, Pradeep; Dayam, Raveendra; Sarma, J A R P

    2014-01-01

    Anthrax Lethal Factor (LF) is a zinc-dependent metalloprotease, one of the virulence factor of anthrax infection. Three forms of the anthrax infection have been identified: cutaneous (through skin), gastrointestinal (through alimentary tract), and pulmonary (by inhalation of spores). Anthrax toxin is composed of protective antigen (PA), lethal factor (LF), and edema factor (EF). Protective antigen mediates the entry of Lethal Factor/Edema Factor into the cytosol of host cells. Lethal factor (LF) inactivates mitogen-activated protein kinase kinase inducing cell death, and EF is an adenylyl cyclase impairing host defenses. In the past few years, extensive studies are undertaken to design inhibitors targeting LF. The current review focuses on the small molecule inhibitors targeting LF activity and its structure activity relationships (SAR).

  2. 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.

  3. Acute oral toxicities of wildland fire control chemicals to birds.

    PubMed

    Vyas, Nimish B; Spann, James W; Hill, Elwood F

    2009-03-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24h 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 2000mg 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.

  4. Perinatal-lethal Gaucher disease presenting as hydrops fetalis

    PubMed Central

    BenHamida, Emira; Ayadi, Imene; Ouertani, Ines; Chammem, Maroua; Bezzine, Ahlem; BenTmime, Riadh; Attia, Leila; Mrad, Ridha; Marrakchi, Zahra

    2015-01-01

    Perinatal-lethal Gaucher disease is very rare and is considered a variant of type 2 Gaucher disease that occurs in the neonatal period. The most distinct features of perinatal-lethal Gaucher disease are non-immune hydrops fetalis. Less common signs of the disease are hepatosplenomegaly, ichthyosis and arthrogryposis. We report a case of Gaucher's disease (type 2) diagnosed in a newborn who presented with Hydrops Fetalis. PMID:26327947

  5. Conflict Without Casualties: Non-Lethal Weapons in Irregular Warfare

    DTIC Science & Technology

    2007-09-01

    Recognizing this, in 2006 the British Royal Marines reached out to the international community and, along with U.S. Marines, established a non-lethal...obstruction. But as the scenario intensified, they moved into the city alleys for a more authentic feel. British Royal Marine Capt. Rhys Hopkins stated...89 United States Federal News Service, “ Royal Marines Teach Non-Lethal Crowd Control for 2007

  6. Field Evaluation of Lethal Ovitrap against Dengue Vectors

    DTIC Science & Technology

    2005-04-01

    AD Award Number: DAMD17-02-1-0217 TITLE: Field Evaluation of Lethal Ovitrap against Dengue Vectors PRINCIPAL INVESTIGATOR: Dr. Lane Foil CONTRACTING...2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Field Evaluation of Lethal Ovitrap against Dengue Vectors 5b. GRANT NUMBER DAMD17-02-1-0217 5c. PROGRAM...to effectively sample dengue mosquito vector populations, particularly Aedes aegypti for over a decade. Modifying a standard ovitrap by incorporating

  7. Bleomycin: female-specific dominant lethal effects in mice.

    PubMed

    Sudman, P D; Rutledge, J C; Bishop, J B; Generoso, W M

    1992-12-01

    Limited comparative data in mice indicate that chemical mutagens that induce dominant lethal mutations in males are not necessarily effective in females, but those which are effective in females are generally equally or more effective in males. Recently, however, a few chemicals have been identified that are female-specific with respect to induction of dominant lethal mutations. The antitumor antibiotic adriamycin is among them. Another antitumor antibiotic, bleomycin was examined for its ability to induce dominant lethal mutations in the reproductive cells of male and female mice. No dominant lethal or cytotoxic effects were observed in males treated with bleomycin, even at a maximum tolerated dose. In females, on the other hand, a dose nearly 1/4 of that used in males induced not only a high level of dominant lethal mutations but also killed oocytes in certain stages of follicular development. The effectiveness of bleomycin in inducing dominant lethal mutations in mouse oocytes makes it a valuable tool for investigating whether gonadal transport, inherent differences in the configuration of chromatin in the germ cells of the two sexes or other factors are responsible for the differential susceptibility to bleomycin, which implies potential gender-specific genetic risk in cancer chemotherapy.

  8. Mechanism by which caffeine potentiates lethality of nitrogen mustard.

    PubMed Central

    Lau, C C; Pardee, A B

    1982-01-01

    Caffeine is synergistic with many DNA-damaging agents in increasing lethality to mammalian cells. The mechanism is not well understood. Our results show that caffeine potentiates the lethality of the nitrogen mustard 2-chloro-N-(2-chloroethyl)-N-methylethanamine (HN2) by inducing damaged cells to undergo mitosis before properly repairing lesions in their DNA. Treatment with low doses of HN2 (0.5 microM for 1 hr) caused little lethality in baby hamster kidney cells (90% survival). These cells were arrested in G2 shortly after treatment with HN2 as shown by flow microfluorimetry and autoradiography. After an arrest of 6 hr, HN2-treated cells began to move into mitosis and from then on behaved like normal cells. Repair synthesis was shown to continue during the G2 arrest by using synchronized cells pulse labeled with [3H]thymidine after HN2 treatment and autoradiography. Caffeine (2mM) increased the lethality of HN2 by 5- to 10-fold. It prevented the G2 arrest. Caffeine did not prevent these HN2-treated cells from entering or completing S phase but rather allowed them to divide without finishing the repair processes and as a consequence caused nuclear fragmentation after mitosis. Caffeine-induced nuclear fragmentation and enhanced lethality were proportional, as shown with dose--response curves and time dependence. In addition, both lethality and nuclear fragmentation were abolished by low doses of cycloheximide, an inhibitor of protein synthesis. Images PMID:6953438

  9. Evolution of the Drosophila Feminizing Switch Gene Sex-lethal

    PubMed Central

    Cline, Thomas W.; Dorsett, Maia; Sun, Sha; Harrison, Melissa M.; Dines, Jessica; Sefton, Louise; Megna, Lisa

    2010-01-01

    In Drosophila melanogaster, the gene Sex-lethal (Sxl) controls all aspects of female development. Since melanogaster males lacking Sxl appear wild type, Sxl would seem to be functionally female specific. Nevertheless, in insects as diverse as honeybees and houseflies, Sxl seems not to determine sex or to be functionally female specific. Here we describe three lines of work that address the questions of how, when, and even whether the ancestor of melanogaster Sxl ever shed its non-female-specific functions. First, to test the hypothesis that the birth of Sxl's closest paralog allowed Sxl to lose essential ancestral non-female-specific functions, we determined the CG3056 null phenotype. That phenotype failed to support this hypothesis. Second, to define when Sxl might have lost ancestral non-female-specific functions, we isolated and characterized Sxl mutations in D. virilis, a species distant from melanogaster and notable for the large amount of Sxl protein expression in males. We found no change in Sxl regulation or functioning in the 40+ MY since these two species diverged. Finally, we discovered conserved non-sex-specific Sxl mRNAs containing a previously unknown, potentially translation-initiating exon, and we identified a conserved open reading frame starting in Sxl male-specific exon 3. We conclude that Drosophila Sxl may appear functionally female specific not because it lost non-female-specific functions, but because those functions are nonessential in the laboratory. The potential evolutionary relevance of these nonessential functions is discussed. PMID:20837995

  10. Sub-lethal ammonia toxicity in largemouth bass.

    PubMed

    Suski, C D; Kieffer, J D; Killen, S S; Tufts, B L

    2007-03-01

    Guidelines for ammonia toxicity in fish are often determined using static exposure tests with immature fish over a 96-h period. These results may not be relevant to aquaculture, hauling or angling tournament scenarios where mature fish can be exposed to ammonia for shorter durations, often following additional stressors such as handling. The current study sought to quantify (1) the impact of ambient ammonia on the ability of largemouth bass to recover from exercise, (2) the behavioural response of largemouth bass to elevated ambient ammonia and (3) the concentration of ammonia that can accumulate in a live-release vessel at an angling tournament. After approximately 3 h, total ammonia (T(amm)) concentrations in a live-release vessel at an angling tournament were almost 200 muM. Exposure of fish to 1000 microM T(amm) (a value approximately 80% below the criteria maximum concentration for largemouth bass) caused significant reductions in ventilation rates, and increases in erratic swimming and irregular ventilation. Exposure to 100 microM T(amm) impaired the ability of largemouth bass to recover from exercise relative to fish recovering in fresh water. Therefore, sub-lethal ambient ammonia concentrations cause physiological disturbances that can impair the recovery of largemouth bass from exercise.

  11. Toxicity of white phosphorus to waterfowl: acute exposure in mallards

    USGS Publications Warehouse

    Sparling, D.W.; Gustafson, M.; Klein, P.; Karouna-Renier, N.

    1997-01-01

    As part of an effort to understand extensive, white phosphorus (P4)-induced waterfowl mortality at Eagle River Flats, Fort Richardson, Alaska, we conducted a number of acute toxicity tests using penned mallards (Anas platyrhynchos) in 1993 and 1994. The 24-hr median lethal dose (LD50) for P4 dissolved in oil was 6.46 mg/kg in adult males and 6.96 mg/kg in adult females. Although the median lethal doses were not statistically different, the female dose-response curve had a statistically shallower slope than that of males. The LD50 for the ecologically more relevant pelletized form of P4 in adult males was 4.05 mg/kg. In mallards, one mechanism of P4 toxicity caused rapid (3 to 10 hr) mortality and had signs consistent with anoxia. A second, slower acting mechanism resulted in hepatic and renal pathology including extensive fat deposition in the liver and cellular necrosis. White phosphorus accumulated in adipose tissues, but only for a few days.

  12. Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species

    USGS Publications Warehouse

    Raimondo, Sandy; Lilavois, Crystal R.; Lee, Larisa; Augspurger, Tom; Wang, Ning; Ingersoll, Christopher G.; Bauer, Candice R.; Hammer, Edward J.; Barron, Mace G.

    2016-01-01

    We developed a toxicity database for unionid mussels to examine the extent of intra- and inter-laboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the two life stages; and the variation in sensitivity among commonly tested mussels (Lampsilis siliquoidea, Utterbackia imbecillis, Villosa iris), commonly tested cladocerans (Daphnia magna, Ceriodaphnia dubia) and fish (Oncorhynchus mykiss, Pimephales promelas, Lepomis macrochirus). The results of these analyses indicate intra-laboratory variability for median effect concentrations (EC50) averaged about 2 fold for both life stages, while inter-laboratory variability averaged 3.6 fold for juvenile mussels and 6.3 fold for glochidia. The EC50s for juveniles and glochidia were within a factor of 2 of each other for 50% of paired records across chemicals, with juveniles more sensitive than glochidia by more than 2 fold for 33% of the comparisons made between life stages. There was a high concurrence of the sensitivity of commonly tested L. siliquoidea, U. imbecillis, and V. iris to that of other mussels. However, this concurrence decreases as the taxonomic distance of the commonly tested cladocerans and fish to mussels increases. The compiled mussel database and determination of data variability will advance risk assessments by including more robust species sensitivity distributions, interspecies correlation estimates, and availability of taxon-specific empirically derived application factors for risk assessment.

  13. Qualitative study of primary care clinicians’ views on point-of-care testing for C-reactive protein for acute respiratory tract infections in family medicine

    PubMed Central

    Hardy, Victoria; Thompson, Matthew; Keppel, Gina A; Alto, William; Dirac, M Ashworth; Neher, Jon; Sanford, Christopher; Hornecker, Jaime; Cole, Allison

    2017-01-01

    Objective To explore clinicians views of the barriers and facilitators to use of C-reactive protein (CRP) point-of-care tests (POCT) in US family medicine clinics for the management of acute respiratory tract infections (ARTIs) in adults. Setting Five family medicine clinics across two US states. Participants 30 clinicians including 18 physicians, 9 physician residents, 2 physician assistants and 1 nurse practitioner, took part in the study. Design A qualitative study using a grounded theory approach to thematically analyse focus group interviews. Results These clinicians had limited access to diagnostic tests for patients with ARTI, and very little knowledge of CRP POCT. Three major themes were identified and included the potential clinical role of CRP POCT, concerns related to implementing CRP POCT and evidence needed prior to wider adoption in family medicine. Clinicians believed CRP POCT could support decision-making for some presentations of ARTIs and patient populations when used in conjunction with clinical criteria. Clinicians had concerns about possible overuse and inaccuracy of CRP POCT which they believed might increase antibiotic prescribing rates. Other concerns identified included integration of the test with clinic workflows and cost-effectiveness. Conclusions Clinicians stand at the forefront of antibiotic stewardship efforts, but have few diagnostic tests to help them confidently manage ARTIs. CRP POCT may facilitate some aspects of clinical practice. Incorporating CRP POCT with clinical guidelines may strengthen utility of this test, when there is diagnostic uncertainty. PMID:28122829

  14. The role of an acute pasireotide suppression test in predicting response to treatment in patients with Cushing's disease: findings from a pilot study.

    PubMed

    Trementino, L; Zilio, M; Marcelli, G; Michetti, G; Barbot, M; Ceccato, F; Boscaro, M; Scaroni, C; Arnaldi, G

    2015-09-01

    Pasireotide is a multireceptor-targeted somatostatin analog effective in the treatment of Cushing's disease (CD). We evaluate the value of an acute pasireotide suppression test (PST) in predicting response to medium/long-term treatment in CD. Nineteen patients with active CD were prospectively investigated at two referral centers from May 2013 to August 2014. Follow-up data (median 6 months; range 1-9 months) were available for sixteen patients. All patients received at 09:00 h a single subcutaneous (sc) injection of 600 μg pasireotide. Serum cortisol and plasma ACTH were assessed before, and every 2 h for 8 h after, drug administration. Late-night salivary cortisol (LNSC) was assessed before and after pasireotide administration. After acute PST, all patients were continued on pasireotide 600 μg sc twice a day. During PST, cortisol and ACTH levels quickly decreased in all patients except one with a mean percentage fall, respectively, of 48.9 ± 24.3 and 48.1 ± 25.4 % compared to baseline. LNSC decreased in about 82 % of patients (14/17) achieving a normalization in five of them. Pasireotide treatment was associated with a normalization of 24-h urinary-free cortisol at last follow-up in about 68 % of patients. A fall >27 % of LNSC during PST calculated by ROC curve was the best parameter in predicting a positive response to treatment with pasireotide (sensitivity 91 %; specificity 100 %; positive predictive value 100 %; negative predictive value 75 %). Acute PST may be useful to identify CD patients who will benefit from pasireotide treatment. A LNSC fall >27 % as well as a LNSC normalization during PST is associated with a probability of 100 % of achieving a favorable response to pasireotide treatment in the medium/long term.

  15. Prophylactic and therapeutic intranasal administration with an immunomodulator, Hiltonol(®) (Poly IC:LC), in a lethal SARS-CoV-infected BALB/c mouse model.

    PubMed

    Kumaki, Yohichi; Salazar, Andres M; Wandersee, Miles K; Barnard, Dale L

    2017-03-01

    Hiltonol(®), (Poly IC:LC), a potent immunomodulator, is a synthetic, double-stranded polyriboinosinic-polyribocytidylic acid (poly IC) stabilized with Poly-L-lysine and carboxymethyl cellulose (LC). Hiltonol(®) was tested for efficacy in a lethal SARS-CoV-infected BALB/c mouse model. Hiltonol(®) at 5, 1, 0.5 or 0.25 mg/kg/day by intranasal (i.n.) route resulted in significant survival benefit when administered at selected times 24 h prior to challenge with a lethal dose of mouse-adapted severe acute respiratory syndrome coronavirus (SARS-CoV). The infected BALB/c mice receiving the Hiltonol(®) treatments were also significantly effective in protecting mice against weight loss due to infection (p < 0.001). Groups of 20 mice were dosed with Hiltonol(®) at 2.5 or 0.75 mg/kg by intranasal instillation 7, 14, and 21 days before virus exposure and a second dose was given 24 h later, prophylactic Hiltonol(®) treatments (2.5 mg/kg/day) were completely protective in preventing death, and in causing significant reduction in lung hemorrhage scores, lung weights and lung virus titers. Hiltonol(®) was also effective as a therapeutic when give up to 8 h post virus exposure; 100% of the-infected mice were protected against death when Hiltonol(®) was administered at 5 mg/kg/day 8 h after infection. Our data suggest that Hiltonol(®) treatment of SARS-CoV infection in mice leads to substantial prophylactic and therapeutic effects and could be used for treatment of other virus disease such as those caused by MERS-CoV a related coronavirus. These properties might be therapeutically advantageous if Hiltonol(®) is considered for possible clinical use.

  16. Misregulation of Sex-Lethal and Disruption of Male-Specific Lethal Complex Localization in Drosophila Species Hybrids

    PubMed Central

    Pal Bhadra, Manika; Bhadra, Utpal; Birchler, James A.

    2006-01-01

    A major model system for the study of evolutionary divergence between closely related species has been the unisexual lethality resulting from reciprocal crosses of Drosophila melanogaster and D. simulans. Sex-lethal (Sxl), a critical gene for sex determination, is misregulated in these hybrids. In hybrid males from D. melanogaster mothers, there is an abnormal expression of Sxl and a failure of localization of the male-specific lethal (MSL) complex to the X chromosome, which causes changes in gene expression. Introduction of a Sxl mutation into this hybrid genotype will allow expression of the MSL complex but there is no sequestration to the X chromosome. Lethal hybrid rescue (Lhr), which allows hybrid males from this cross to survive, corrects the SXL and MSL defects. The reciprocal cross of D. simulans mothers by D. melanogaster males exhibits underexpression of Sxl in embryos. PMID:16951071

  17. Strongyloidiasis: a case with acute pancreatitis and a literature review.

    PubMed

    Makker, Jasbir; Balar, Bhavna; Niazi, Masooma; Daniel, Myrta

    2015-03-21

    Strongyloides stercoralis, a soil transmitted helminth infection, affects millions with varying prevalence worldwide. A large number of affected hosts are asymptomatic. Symptoms pertaining to pulmonary and gastrointestinal involvement may be present. Manifestations of involvement beyond lung and intestine can be seen with dissemination of infection and lethal hyperinfection. Immunosuppression secondary to use of steroids or other immunosuppressants and coexistence of human T-lymphotropic virus type-1 are the known risk factors for dissemination and hyperinfection. Diagnostic modalities comprise stool examination, serology and molecular testing. Stool tests are inexpensive but are limited by low sensitivity, whereas serologic and molecular tests are more precise but at the expense of higher cost. Treatment with Ivermectin or Albendazole as an alternative is safe and efficacious. We present a rare case of acute pancreatitis secondary to Strongyloides. High index of suspicion in patients specifically from endemic countries of origin and lack of other common etiologies of acute pancreatitis may help in early diagnosis and prompt treatment of this potentially fatal infection.

  18. Strongyloidiasis: A case with acute pancreatitis and a literature review

    PubMed Central

    Makker, Jasbir; Balar, Bhavna; Niazi, Masooma; Daniel, Myrta

    2015-01-01

    Strongyloides stercoralis, a soil transmitted helminth infection, affects millions with varying prevalence worldwide. A large number of affected hosts are asymptomatic. Symptoms pertaining to pulmonary and gastrointestinal involvement may be present. Manifestations of involvement beyond lung and intestine can be seen with dissemination of infection and lethal hyperinfection. Immunosuppression secondary to use of steroids or other immunosuppressants and coexistence of human T-lymphotropic virus type-1 are the known risk factors for dissemination and hyperinfection. Diagnostic modalities comprise stool examination, serology and molecular testing. Stool tests are inexpensive but are limited by low sensitivity, whereas serologic and molecular tests are more precise but at the expense of higher cost. Treatment with Ivermectin or Albendazole as an alternative is safe and efficacious. We present a rare case of acute pancreatitis secondary to Strongyloides. High index of suspicion in patients specifically from endemic countries of origin and lack of other common etiologies of acute pancreatitis may help in early diagnosis and prompt treatment of this potentially fatal infection. PMID:25805946

  19. Acute toxicity impacts of Euphorbia hirta L extract on behavior, organs body weight index and histopathology of organs of the mice and Artemia salina

    PubMed Central

    Rajeh, Mohammad Abu Basma; Kwan, Yuet Ping; Zakaria, Zuraini; Latha, Lachimanan Yoga; Jothy, Subramanion L.; Sasidharan, Sreenivasan

    2012-01-01

    Background: The methanol extract of Euphorbia hirta L (Euphorbiaceae), which is used in traditional medicines, was tested for in vivo toxicity. Materials and Methods: In vivo brine shrimp lethality assay and oral acute toxicity study at single high dose of 5000 mg/kg and observation for 14 days in mice were used to study the toxic effect of E. hirta. Results: Brine shrimp lethality assay was used to calculate the median lethal concentration (LC50) of E. hirta (for leaves, stems, flowers and roots) methanolic extracts at concentrations from 100 to 0.07 mg/ml. The LC50 values of 1.589, 1.420, 0.206 and 0.0827 mg/ml were obtained for stems, leaves, flowers and roots, respectively. Potassium dichromate (the positive control) had LC50 value of 0.00758 mg/ml. The acute oral toxicity study of the leaf extract resulted in one third mortality and mild behavioral changes among the treated mice. No significant statistical differences found between body weight, relative (%) and absolute (g) organ weights of treated and untreated groups (P> 0.05). Gross and microscopic examination of the vital organ tissues revealed no differences between control and treated mice. All the tissues appeared normal. Conclusions: E. hirta leaves methanol extract has exhibited mild toxic effects in mice. PMID:22923956

  20. Immobilizing and lethal effects of spider venoms on the cockroach and the common mealbeetle.

    PubMed

    Friedel, T; Nentwig, W

    1989-01-01

    Immobilizing and lethal effects of the venoms obtained from six spider species (Brachypelma albopilosum, Atrax robustus, Cupiennius salei, Selenops mexicanus, Tegenaria atrica, Argiope bruennichi) were tested on Blatta orientalis (cockroach) and Tenebrio molitor (common mealbeetle). The immobilizing effects were quantified by measuring insect locomotor activity in circle arenas observed over 72 hr after venom injection. Both insect species showed cramps, quivering and jerking of the limbs as well as flaccid paralysis after venom injection. Through relative toxicity of the venoms tested is the same in T. molitor and B. orientalis, T. molitor is absolutely less sensitive to spider venoms. The effects on locomotor activity show time characteristics specific for each venom. A dependence of the venom paralyzing effects on insect locomotor activity, low intensity of the initial excitatory phase of the venom effects and partial recovery of the insects was found with A. bruennichi and T. atrica venom. The maximal venom yields of A. bruennichi and S. mexicanus are not lethal to B. orientalis, indicating that the mere immobilizing effects of spider venoms are far more crucial to prey capture than their lethal effects. The contribution of a variety of differently acting neurotoxic components in spider venoms to the observed venom effects on insects and the significance of the venoms in spider nutrition, hunting behaviour and ecology are discussed.

  1. Peripheral immunization blocks lethal actions of vesicular stomatitis virus within the brain.

    PubMed

    Ozduman, Koray; Wollmann, Guido; Ahmadi, Sebastian A; van den Pol, Anthony N

    2009-11-01

    Vesicular stomatitis virus (VSV) is the prototype virus for 75 or more negative-strand RNA viruses in the rhabdovirus family. Some of these viruses, including VSV, can cause neurological impairment or death upon brain infection. VSV has shown promise in the prevention and treatment of disease as a vaccine vector and an oncolytic virus, but infection of the brain remains a concern. Three VSV variants, the wild-type-related VSV-G/GFP and two attenuated viruses, VSV-CT1 and VSV-CT9-M51, were compared for neuroinvasiveness and neuromorbidity. In nonimmunized mice, direct VSV-G/GFP injection into the brain invariably resulted in lethal encephalitis; in contrast, partial survival was seen after direct injection of the attenuated VSV strains. In addition, both attenuated VSV strains showed significantly reduced neuroinvasiveness after intranasal inoculation of young postnatal day 16 mice. Of the three tested variants, VSV-CT9-M51 generated the lowest degree of neuropathology. Despite its attenuated state, peripheral inoculations of VSV-CT9-M51 targeted and killed human glioblastoma implanted into the mouse brain. Importantly, we show here that intranasal or intramuscular immunization prevents the lethal effects of subsequent VSV-G/GFP, VSV-CT1, and VSV-CT9-M51 injections into the brain. These results indicate that attenuated recombinant viruses show reduced neurovirulence and that peripheral immunization blocks the lethal actions of all VSVs tested.

  2. X-ray-induced dominant lethal mutations in mouse oocytes detected by an in vitro assay

    SciTech Connect

    Goldstein, L.S.

    1987-11-01

    Female mice were X-irradiated with 0.5-4.5 Gy 2 h before mating to unirradiated males of the same strain. The dominant lethal frequencies (DLF) were determined by growing the embryos in vitro from the two-cell stage and determining the relative rates of successful embryogenesis to the blastocyst stage and to the trophectoderm outgrowth with proliferated inner cell mass stage. The DLF increased with increasing dose, the two linear aspects having a breakpoint at about 1.5 Gy. The nature of embryo failure was also dose dependent. At doses less than 2.0 Gy embryos failed predominantly after blastocyst formation, but at higher doses the embryos failed both before and after blastocyst formation. Over the dose range tested, the frequency with which lesions leading to dominant lethality were induced (i.e., -ln(1 - DLF)) increased linearly with increasing dose.

  3. Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction

    PubMed Central

    Twerenbold, Raphael; Jaeger, Cedric; Rubini Gimenez, Maria; Wildi, Karin; Reichlin, Tobias; Nestelberger, Thomas; Boeddinghaus, Jasper; Grimm, Karin; Puelacher, Christian; Moehring, Berit; Pretre, Gil; Schaerli, Nicolas; Campodarve, Isabel; Rentsch, Katharina; Steuer, Stephan; Osswald, Stefan; Mueller, Christian

    2016-01-01

    Aims High-sensitivity cardiac troponin (hs-cTn) assays provide higher diagnostic accuracy for acute myocardial infarction (AMI) when compared with conventional assays, but may result in increased use of unnecessary coronary angiographies due to their increased detection of cardiomyocyte injury in conditions other than AMI. Methods and results We evaluated the impact of the clinical introduction of high-sensitivity cardiac troponin T (hs-cTnT) on the use of coronary angiography, stress testing, and time to discharge in 2544 patients presenting with symptoms suggestive of AMI to the emergency department (ED) within a multicentre study either before (1455 patients) or after (1089 patients) hs-cTnT introduction. Acute myocardial infarction was more often the clinical discharge diagnosis after hs-cTnT introduction (10 vs. 14%, P < 0.001), while unstable angina less often the clinical discharge diagnosis (14 vs. 9%, P = 0.007). The rate of coronary angiography was similar before and after the introduction of hs-cTnT (23 vs. 23%, P = 0.092), as was the percentage of coronary angiographies showing no stenosis (11 vs. 7%, P = 0.361). In contrast, the use of stress testing was substantially reduced from 29 to 19% (P < 0.001). In outpatients, median time to discharge from the ED decreased by 79 min (P < 0.001). Mean total costs decreased by 20% in outpatients after the introduction of hs-cTnT (P = 0.002). Conclusion The clinical introduction of hs-cTn does not lead to an increased or inappropriate use of coronary angiography. Introduction of hs-cTn is associated with an improved rule-out process and thereby reduces the need for stress testing and time to discharge. Clinical Trial Registration Information www.clinicaltrials.gov. Identifier, NCT00470587. PMID:27357358

  4. 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.

  5. Poor performance of the determine HIV-1/2 Ag/Ab combo fourth-generation rapid test for detection of acute infections in a National Household Survey in Swaziland.

    PubMed

    Duong, Yen T; Mavengere, Yvonne; Patel, Hetal; Moore, Carole; Manjengwa, Julius; Sibandze, Dumile; Rasberry, Christopher; Mlambo, Charmaine; Li, Zhi; Emel, Lynda; Bock, Naomi; Moore, Jan; Nkambule, Rejoice; Justman, Jessica; Reed, Jason; Bicego, George; Ellenberger, Dennis L; Nkengasong, John N; Parekh, Bharat S

    2014-10-01

    Fourth-generation HIV rapid tests (RTs) claim to detect both p24 antigen (Ag) and HIV antibodies (Ab) for early identification of acute infections, important for targeting prevention and reducing HIV transmission. In a nationally representative household survey in Swaziland, 18,172 adults, age 18 to 49 years, received home-based HIV rapid testing in 2010 and 2011. Of the 18,172 individuals, 5,822 (32.0%) were Ab positive (Ab(+)) by the Determine HIV-1/2 Ab/Ab combo test, and 5,789 (99.4%) of those were confirmed to be reactive in the Uni-Gold test. Determine combo identified 12 individuals as having acute infections (Ag(+)/Ab negative [Ab(-)]); however, none had detectable HIV-1 RNA and 8 of 12 remained HIV negative at their 6-week follow-up visit (4 were lost to follow-up). All RT-nonreactive samples were pooled and tested by nucleic acid amplification testing (NAAT) to identify acute infections. NAAT identified 13 (0.1%) of the 12,338 HIV antibody-negative specimens as HIV RNA positive, with RNA levels ranging from 300 to >10,000,000 copies/ml. However, none of them were Ag(+) by Determine combo. Follow-up testing of 12 of the 13 NAAT-positive individuals at 6 months demonstrated 12 seroconversions (1 individual was lost to follow-up). Therefore, the Determine combo test had a sensitivity of 0% (95% confidence interval, 0 to 28) and positive predictive value of 0% for the detection of acute infections. The ability of the 4th-generation Determine combo to detect antigen was very poor in Swaziland. Thus, the Determine combo test does not add any value to the current testing algorithm; rather, it adds additional costs and complexity to HIV diagnosis. The detection of acute HIV infections may need to rely on other testing strategies.

  6. Lipase Test

    MedlinePlus

    ... known as: LPS Formal name: Lipase Related tests: Amylase , Trypsin , Trypsinogen At a Glance Test Sample The ... lipase is most often used, along with an amylase test , to help diagnose and monitor acute pancreatitis . ...

  7. The role of appropriate diagnostic testing in acute respiratory tract infections: An antibiotic stewardship strategy to minimise diagnostic uncertainty in primary care.

    PubMed

    Brink, Adrian John; Van Wyk, Johan; Moodley, V M; Corcoran, Craig; Ekermans, Pieter; Nutt, Louise; Boyles, Tom; Perovic, Olga; Feldman, Charles; Richards, Guy; Mendelson, Marc

    2016-05-10

    Antibiotic resistance has increased worldwide to the extent that it is now regarded as a global public health crisis. Interventions to reduce excessive antibiotic prescribing to patients can reduce resistance and improve microbiological and clinical outcomes. Therefore, although improving outpatient antibiotic use is crucial, few data are provided on the key interventional components and the effectiveness of antibiotic stewardship in the primary care setting, in South Africa. The reasons driving the excessive prescription of antibiotics in the community are multifactorial but, perhaps most importantly, the overlapping clinical features of viral and bacterial infections dramatically reduce the ability of GPs to distinguish which patients would benefit from an antibiotic or not. As a consequence, the need for tools to reduce diagnostic uncertainty is critical. In this regard, besides clinical algorithms, a consensus of collaborators in European and UK consortia recently provided guidance for the use of C-reactive protein point-of-care testing in outpatients presenting with acute respiratory tract infections (ARTIs) and/or acute cough, if it is not clear after proper clinical assessment whether antibiotics should be prescribed or not. A targeted application of stewardship principles, including diagnostic stewardship as described in this review, to the ambulatory setting has the potential to affect the most common indications for systemic antibiotic use, in that the majority (80%) of antibiotic use occurs in the community, with ARTIs the most common indication.

  8. ACUTE AND CHRONIC INTAKES OF FALLOUT RADIONUCLIDES BY MARSHALLESE FROM NUCLEAR WEAPONS TESTING AT BIKINI AND ENEWETAK AND RELATED INTERNAL RADIATION DOSES

    PubMed Central

    Simon, Steven L.; Bouville, André; Melo, Dunstana; Beck, Harold L.; Weinstock, Robert M.

    2014-01-01

    Annual internal radiation doses resulting from both acute and chronic intakes of all important dose-contributing radionuclides occurring in fallout from nuclear weapons testing at Bikini and Enewetak from 1946 through 1958 have been estimated for the residents living on all atolls and separate reef islands of the Marshall Islands. Internal radiation absorbed doses to the tissues most at risk to cancer induction (red bone marrow, thyroid, stomach, and colon) have been estimated for representative persons of all population communities for all birth years from 1929 through 1968, and for all years of exposure from 1948 through 1970. The acute intake estimates rely on a model using, as its basis, historical urine bioassay data, for members of the Rongelap Island and Ailinginae communities as well as for Rongerik residents. The model also utilizes fallout times of arrival and radionuclide deposition densities estimated for all tests and all atolls. Acute intakes of 63 radionuclides were estimated for the populations of the 20 inhabited atolls and for the communities that were relocated during the testing years for reasons of safety and decontamination. The model used for chronic intake estimates is based on reported whole-body, urine, and blood counting data for residents of Utrik and Rongelap. Dose conversion coefficients relating intake to organ absorbed dose were developed using internationally accepted models but specifically tailored for intakes of particulate fallout by consideration of literature-based evidence to choose the most appropriate alimentary tract absorption fraction (f1) values. Dose estimates were much higher for the thyroid gland than for red marrow, stomach wall, or colon. The highest thyroid doses to adults were about 7,600 mGy for the people exposed on Rongelap; thyroid doses to adults were much lower, by a factor of 100 or more, for the people exposed on the populated atolls of Kwajalein and Majuro. The estimates of radionuclide intake and

  9. Acute and chronic intakes of fallout radionuclides by Marshallese from nuclear weapons testing at Bikini and Enewetak and related internal radiation doses.

    PubMed

    Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold L; Weinstock, Robert M

    2010-08-01

    Annual internal radiation doses resulting from both acute and chronic intakes of all important dose-contributing radionuclides occurring in fallout from nuclear weapons testing at Bikini and Enewetak from 1946 through 1958 have been estimated for the residents living on all atolls and separate reef islands of the Marshall Islands. Internal radiation absorbed doses to the tissues most at risk to cancer induction (red bone marrow, thyroid, stomach, and colon) have been estimated for representative persons of all population communities for all birth years from 1929 through 1968, and for all years of exposure from 1948 through 1970. The acute intake estimates rely on a model using, as its basis, historical urine bioassay data, for members of the Rongelap Island and Ailinginae communities as well as for Rongerik residents. The model also utilizes fallout times of arrival and radionuclide deposition densities estimated for all tests and all atolls. Acute intakes of 63 radionuclides were estimated for the populations of the 20 inhabited atolls and for the communities that were relocated during the testing years for reasons of safety and decontamination. The model used for chronic intake estimates is based on reported whole-body, urine, and blood counting data for residents of Utrik and Rongelap. Dose conversion coefficients relating intake to organ absorbed dose were developed using internationally accepted models but specifically tailored for intakes of particulate fallout by consideration of literature-based evidence to choose the most appropriate alimentary tract absorption fraction (f1) values. Dose estimates were much higher for the thyroid gland than for red marrow, stomach wall, or colon. The highest thyroid doses to adults were about 7,600 mGy for the people exposed on Rongelap; thyroid doses to adults were much lower, by a factor of 100 or more, for the people exposed on the populated atolls of Kwajalein and Majuro. The estimates of radionuclide intake and

  10. A proposal for a test method for assessment of hazard property HP 12 ("Release of an acute toxic gas") in hazardous waste classification - Experience from 49 waste.

    PubMed

    Hennebert, Pierre; Samaali, Ismahen; Molina, Pauline

    2016-12-01

    A stepwise method for assessment of the HP 12 is proposed and tested with 49 waste samples. The hazard property HP 12 is defined as "Release of an acute toxic gas": waste which releases acute toxic gases (Acute Tox. 1, 2 or 3) in contact with water or an acid. When a waste contains a substance assigned to one of the following supplemental hazards EUH029, EUH031 and EUH032, it shall be classified as hazardous by HP 12 according to test methods or guidelines (EC, 2014a, 2014b). When the substances with the cited hazard statement codes react with water or an acid, they can release HCl, Cl2, HF, HCN, PH3, H2S, SO2 (and two other gases very unlikely to be emitted, hydrazoic acid HN3 and selenium oxide SeO2 - a solid with low vapor pressure). Hence, a method is proposed:For a set of 49 waste, water addition did not produce gas. Nearly all the solid waste produced a gas in contact with hydrochloric acid in 5 min in an automated calcimeter with a volume >0.1L of gas per kg of waste. Since a plateau of pressure is reached only for half of the samples in 5 min, 6 h trial with calorimetric bombs or glass flasks were done and confirmed the results. Identification of the gases by portable probes showed that most of the tested samples emit mainly CO2. Toxic gases are emitted by four waste: metallic dust from the aluminum industry (CO), two air pollution control residue of industrial waste incinerator (H2S) and a halogenated solvent (organic volatile(s) compound(s)). HF has not been measured in these trials started before the present definition of HP 12. According to the definition of HP 12, only the H2S emission of substances with hazard statement EUH031 is accounted for. In view of the calcium content of the two air pollution control residue, the presence of calcium sulphide (EUH031) can be assumed. These two waste are therefore classified potentially hazardous for HP 12, from a total of 49 waste. They are also classified as hazardous for other properties (HP 7, 10and14 for one

  11. [Secondary metabolites, lethality and antimicrobial activity of extracts from three corals and three marine mollusks from Sucre, Venezuela].

    PubMed

    Ordaz, Gabriel; D'Armas, Haydelba; Yáñez, Dayanis; Hernández, Juan; Camacho, Angel

    2010-06-01

    The study of biochemical activity of extracts obtained from marine organisms is gaining interest as some have proved to have efficient health or industrial applications. To evaluate lethality and antimicrobial activities, some chemical tests were performed on crude extracts of the octocorals Eunicea sp., Muricea sp. and Pseudopterogorgia acerosa and the mollusks Pteria colymbus, Phyllonotus pomum and Chicoreus brevifrons, collected in Venezuelan waters. The presence of secondary metabolites like alkaloids, unsaturated sterols and pentacyclic triterpenes in all invertebrates, was evidenced. Additionally, sesquiterpenlactones, saponins, tannins, cyanogenic and cardiotonic glycosides were also detected in some octocoral extracts, suggesting that biosynthesis of these metabolites is typical in this group. From the lethality bioassays, all extracts resulted lethal to Artemia salina (LC50<1000 microg/ml) with an increased of lethal activity with exposition time. P. pomum extract showed the highest lethality rate (LC50=46.8 microg/ml). Compared to the octocorals, mollusks extracts displayed more activity and a greater action spectrum against different bacterial strains, whereas octocorals also inhibited some fungi strains growth. Staphylococcus aureus was the most susceptible to the antimicrobial power of the extracts (66.7%), whereas Pseudomonas aeruginosa, Candida albicans and Aspergillus niger were not affected. The antibiosis shown by marine organisms extracts indicates that some of their biosynthesized metabolites are physiologically active, and may have possible cytotoxic potential or as a source of antibiotic components.

  12. Synthetic lethal targeting of DNA double strand break repair deficient cells by human apurinic/apyrimidinic endonuclease (APE1) inhibitors

    PubMed Central

    Sultana, Rebeka; McNeill, Daniel R.; Abbotts, Rachel; Mohammed, Mohammed Z.; Zdzienicka, Małgorzata Z.; Qutob, Haitham; Seedhouse, Claire; Laughton, Charles A.; Fischer, Peter M.; Patel, Poulam M.; Wilson, David M.; Madhusudan, Srinivasan

    2013-01-01

    An apurinic/apyrimidinic (AP) site is an obligatory cytotoxic intermediate in DNA Base Excision Repair (BER) that is processed by human AP endonuclease 1 (APE1). APE1 is essential for BER and an emerging drug target in cancer. We have isolated novel small molecule inhibitors of APE1. In the current study we have investigated the ability of APE1 inhibitors to induce synthetic lethality in a panel of DNA double strand break (DSB) repair deficient and proficient cells; a) Chinese hamster (CH) cells: BRCA2 deficient (V-C8), ATM deficient (V-E5), wild type (V79) and BRCA2 revertant (V-C8(Rev1)). b) Human cancer cells: BRCA1 deficient (MDA-MB-436), BRCA1 proficient (MCF-7), BRCA2 deficient (CAPAN-1 and HeLa SilenciX cells), BRCA2 proficient (PANC1 and control SilenciX cells). We also tested synthetic lethality (SL) in CH ovary cells expressing a dominant–negative form of APE1 (E8 cells) using ATM inhibitors and DNA-PKcs inhibitors (DSB inhibitors). APE1 inhibitors are synthetically lethal in BRCA and ATM deficient cells. APE1 inhibition resulted in accumulation of DNA DSBs and G2/M cell cycle arrest. Synthetic lethality was also demonstrated in CH cells expressing a dominant–negative form of APE1 treated with ATM or DNA-PKcs inhibitors. We conclude that APE1 is a promising synthetic lethality target in cancer. PMID:22377908

  13. 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

  14. A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis.

    PubMed

    Nieves, Wildaliz; Petersen, Hailey; Judy, Barbara M; Blumentritt, Carla A; Russell-Lodrigue, Kasi; Roy, Chad J; Torres, Alfredo G; Morici, Lisa A

    2014-05-01

    The environmental Gram-negative encapsulated bacillus Burkholderia pseudomallei is the causative agent of melioidosis, a disease associated with high morbidity and mortality rates in areas of Southeast Asia and northern Australia in which the disease is endemic. B. pseudomallei is also classified as a tier I select agent due to the high level of lethality of the bacterium and its innate resistance to antibiotics, as well as the lack of an effective vaccine. Gram-negative bacteria, including B. pseudomallei, secrete outer membrane vesicles (OMVs) which are enriched with multiple protein, lipid, and polysaccharide antigens. Previously, we demonstrated that immunization with multivalent B. pseudomallei-derived OMVs protects highly susceptible BALB/c mice against an otherwise lethal aerosol challenge. In this work, we evaluated the protective efficacy of OMV immunization against intraperitoneal challenge with a heterologous strain because systemic infection with phenotypically diverse environmental B. pseudomallei strains poses another hazard and a challenge to vaccine development. We demonstrated that B. pseudomallei OMVs derived from strain 1026b afforded significant protection against septicemic infection with B. pseudomallei strain K96243. OMV immunization induced robust OMV-, lipopolysaccharide-, and capsular polysaccharide-specific serum IgG (IgG1, IgG2a, and IgG3) and IgM antibody responses. OMV-immune serum promoted bacterial killing in vitro, and passive transfer of B. pseudomallei OMV immune sera protected naive mice against a subsequent challenge. These results indicate that OMV immunization provides antibody-mediated protection against acute, rapidly lethal sepsis in mice. B. pseudomallei-derived OMVs may represent an efficacious multivalent vaccine strategy against melioidosis.

  15. Sediment toxicity and lethal body burdens of chlorophenols in an oligochaete worm, Lumbriculus variegatus

    SciTech Connect

    Kukkonen, J.; Halme, A.; Nikkilae, A.

    1995-12-31

    The toxicokinetics, acute toxicity and lethal body burden of 2,4,5-trichlorophenol (TCP) and pentachlorophenol (PCP) in Lumbriculus variegatus were measured in two different clean sediments. The sediments had an organic carbon content of 0.5% and 6.5%. The uptake rate coefficients (k{sub s}) of TCP at low TCP concentration (0.25 {micro}g g{sup {minus}1}) were 0.67 and 0.13 g dry sed. g{sup {minus}1} org. h{sup {minus}1} in low and high organic carbon content sediments, respectively. Organic carbon normalized uptake rate coefficient (k{sub oc}) was 0.0034 gOC g{sup {minus}1} org. h{sup {minus}1} for the low organic content sediment and 0.0085 gOC g{sup {minus}1} org. h{sup {minus}1} for the high organic content sediment showing that the organic carbon content does not explain all of the difference between the sediments. Similar to that, LC{sub 50} (24h) for the TCP was 37.4 and 121.5 {micro}g g{sup {minus}1} dw in low and high organic carbon content sediments, respectively. If organic carbon normalization is done the figures are 7,880 and 1,869 {micro}g g{sup {minus}1} OC. However, the lethal body burden of TCP in Lumbriculus variegatus is between 0.5--0.9 {micro}mol g{sup {minus}1} in both sediments. Similar type of results will be shown for PCP and the use of lethal body burden approach in sediment toxicology will be discussed.

  16. Using a Lethality Index to Assess Susceptibility of Tribolium confusum and Oryzaephilus surinamensis to Insecticides.

    PubMed

    Agrafioti, Paraskevi; Athanassiou, Christos G; Vassilakos, Thomas N; Vlontzos, George; Arthur, Frank H

    2015-01-01

    We evaluated knockdown caused by four insecticides: alpha-cypermethrin, chlorfenapyr, pirimiphos-methyl and fipronil against adults of Tribolium confusum Jacquelin Duval, the confused flour beetle and Oryzaephilus surinamensis (L.), the sawtoothed grain beetle. Bioassays were conducted on concrete and metal surfaces. Adults of the tested species were exposed on both surfaces treated with the above insecticides at two doses (low and high). Knockdown assessment was done after 15, 30 and 60 min of adult exposure in the treated surfaces. Also, after 1, 3, 5, 7 and 14 d of exposure, a lethality index was calculated with an equation resulting to values from 0 to 100, where 100 indicated complete mortality and 0 complete survival. We also developed a lethality index by ranking each adult on each surface from 0 to 4, 0: adults moved normally, 1: adults were knocked down, but were able to walk for short intervals, 2: adults were knocked down and unable to walk, but with visible movement of antennae etc., 3: adults were knocked down, with very minimal movement of the tarsi and the antennae and 4: adults were dead (no movement). Knockdown of adults immediately after exposure (15-60 min) was higher for pirimiphos-methyl followed by alpha-cypermethrin, for both dose rates tested and species, but only on the metal surface. The lethality index was nearly 100 for all insecticides after 5d of exposure for O. surinamensis, while for T. confusum the adult lethality index was considerably lower for alpha-cypermethrin, suggesting that that recovery from knockdown occurred. Chlorfenapyr was the only insecticide that was more effective on concrete than on metal, while the reverse was noted for the other three insecticides. These results show that knockdown has different levels, which can be used as indicators of insect mortality or recovery.

  17. Using a Lethality Index to Assess Susceptibility of Tribolium confusum and Oryzaephilus surinamensis to Insecticides

    PubMed Central

    Vlontzos, George; Arthur, Frank H.

    2015-01-01

    We evaluated knockdown caused by four insecticides: alpha-cypermethrin, chlorfenapyr, pirimiphos-methyl and fipronil against adults of Tribolium confusum Jacquelin Duval, the confused flour beetle and Oryzaephilus surinamensis (L.), the sawtoothed grain beetle. Bioassays were conducted on concrete and metal surfaces. Adults of the tested species were exposed on both surfaces treated with the above insecticides at two doses (low and high). Knockdown assessment was done after 15, 30 and 60 min of adult exposure in the treated surfaces. Also, after 1, 3, 5, 7 and 14 d of exposure, a lethality index was calculated with an equation resulting to values from 0 to 100, where 100 indicated complete mortality and 0 complete survival. We also developed a lethality index by ranking each adult on each surface from 0 to 4, 0: adults moved normally, 1: adults were knocked down, but were able to walk for short intervals, 2: adults were knocked down and unable to walk, but with visible movement of antennae etc., 3: adults were knocked down, with very minimal movement of the tarsi and the antennae and 4: adults were dead (no movement). Knockdown of adults immediately after exposure (15–60 min) was higher for pirimiphos-methyl followed by alpha-cypermethrin, for both dose rates tested and species, but only on the metal surface. The lethality index was nearly 100 for all insecticides after 5d of exposure for O. surinamensis, while for T. confusum the adult lethality index was considerably lower for alpha-cypermethrin, suggesting that that recovery from knockdown occurred. Chlorfenapyr was the only insecticide that was more effective on concrete than on metal, while the reverse was noted for the other three insecticides. These results show that knockdown has different levels, which can be used as indicators of insect mortality or recovery. PMID:26560316

  18. 9 CFR 430.4 - Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Control of Listeria monocytogenes in post-lethality exposed ready-to-eat products. 430.4 Section 430.4 Animals and Animal Products FOOD... L. monocytogenes, its sanitation program must: (A) Provide for testing of food contact surfaces...

  19. New microbioassays based on biomarkers are more sensitive to fluvial water micropollution than standard testing methods.

    PubMed

    Esteban, S; Fernández Rodríguez, J; Díaz López, G; Nuñez, M; Valcárcel, Y; Catalá, M

    2013-07-01

    Recent investigations suggest that, despite lack of lethality in validated bioassays, micropollutants in surface waters could induce sublethal toxicity in sensitive taxa, jeopardizing their biological performance and eventually leading to populations' extinction. A broader array of testing species, the miniaturization of bioassays and the development of reliable biomarkers of damage are sought in order to improve ecological relevance and cost efficiency of environmental monitoring. Our aim is to assess the different sensitivity of validated bioassays and new approaches using biomarkers as sensitive endpoints of toxicity in spores of Polystichum setiferum and Danio rerio embryos. Six water samples were collected in Tagus basin in summer and winter. Samples tested induce no acute toxicity in validated methods (algae growth inhibition and daphnia mobility inhibition). Summer water samples induced acute membrane damage (lipid peroxidation) in Danio rerio embryos and hormetic increases in fern spore mitochondrial activity. One of the samples dramatically reduced mitochondrial activity indicating severe acute sublethal phytotoxicity. All the winter samples induced significant decreases in fern spore mitochondrial activity and membrane damage increases in Danio rerio embryo. Furthermore, three samples induced lethal phytotoxicity in fern spores. We conclude that the new microbioassays show a better sensitivity to fluvial water micropollution and confirm the necessity to test critical life stages such as development and provide cost-efficient methods for environmental monitoring.

  20. Serological Diagnosis of Acute Scrub Typhus in Southern India: Evaluation of InBios Scrub Typhus Detect IgM Rapid Test and Comparison with other Serological Tests

    PubMed Central

    Anitharaj, Velmurugan; Pradeep, Jothimani; Park, Sungman; Kim, Seung-Han; Kim, Young Jin; Kim, Eun-Ye; Kim, Yoon-Won

    2016-01-01

    Introduction Scrub Typhus (ST) is being reported from different parts of India in the recent past. However, the diagnosis and confirmation of ST cases require specific serological and molecular diagnostic tests. Both rapid and conventional ELISA tests need to be properly evaluated. Aim Evaluation of a new ST IgM Immunochromatography (ICT) test kit (InBios Scrub Typhus Detect IgM Rapid Test) and compare it with another rapid kit, conventional ELISA kit and Weil-Felix (WF) test. Materials and Methods This prospective study was carried out in Mahatma Gandhi Medical College and Research Institute, Puducherry, during November 2015 to June 2016. Clinically suspected 220 ST patients were examined by a new kit, InBios Scrub Typhus Detect IgM Rapid Test, taking the conventional InBios Scrub Typhus Detect IgM ELISA as reference. Additional comparison was made with ImmuneMed Scrub Typhus Rapid, and WF test (single OXK titers ≥1:320). Statistical analysis was performed (Chi-square, Spearman’s correlation and Kappa) using IBM SPSS Statistics 17 for Windows (SPSS Inc; Chicago, USA). Results Percentage Sensitivity, Specificity, Positive Predictive and Negative Predictive Values for InBios, ImmuneMed and WF were 99.25, 93.02, 95.68, 98.77; 94.87, 94.19, 96.21, 92.05 and 50.38, 95.51, 94.29, 56.67 respectively. A total of 134 patients were positive in reference standard InBios IgM ELISA. Conclusion This new rapid ST IgM kit validated for the first time in India, showed good sensitivity and specificity. As a Point-of-Care (PoC) test, the kit would be helpful in both urban and remote rural parts of India. PMID:28050364

  1. Interactive effects of catastrophizing and suppression on responses to acute pain: a test of an appraisal x emotion regulation model.

    PubMed

    Gilliam, Wesley; Burns, John W; Quartana, Phillip; Matsuura, Justin; Nappi, Carla; Wolff, Brandy

    2010-06-01

    We examined whether people who tend to catastrophize about pain and who also attempt to regulate negative thoughts and feelings through suppression may represent a distinct subgroup of individuals highly susceptible to pain and distress. Ninety-seven healthy normal participants underwent a 4-min ischemic pain task followed by a 2-min recovery period. Self-reported pain and distress was recorded during the task and every 20 s during recovery. Participants completed the Pain Catastrophizing Scale and the White Bear Suppression Inventory. Repeated measures multiple regression analysis (using General Linear Model procedures) revealed significant 3-way interactions such that participants scoring high on the rumination and/or helplessness subscales of the Pain Catastrophizing Scale and who scored high on the predisposition to suppress unwanted thoughts and feelings reported the greatest pain and distress during recovery. Results suggest that pain catastrophizers who attempt to regulate their substantial pain intensity and distress with maladaptive emotion regulation strategies, such as suppression, may be especially prone to experience prolonged recovery from episodes of acute pain. Thus, emotion regulation factors may represent critical variables needed to understand the full impact of catastrophic appraisals on long-term adjustment to pain.

  2. Recombinant raccoon pox vaccine protects mice against lethal plague

    USGS Publications Warehouse

    Osorio, J.E.; Powell, T.D.; Frank, R.S.; Moss, K.; Haanes, E.J.; Smith, S.R.; Rocke, T.E.; Stinchcomb, D.T.

    2003-01-01

    Using a raccoon poxvirus (RCN) expression system, we have developed new recombinant vaccines that can protect mice against lethal plague infection. We tested the effects of a translation enhancer (EMCV-IRES) in combination with a secretory (tPA) signal or secretory (tPA) and membrane anchoring (CHV-gG) signals on in vitro antigen expression of F1 antigen in tissue culture and the induction of antibody responses and protection against Yersinia pestis challenge in mice. The RCN vector successfully expressed the F1 protein of Y. pestis in vitro. In addition, the level of expression was increased by the insertion of the EMCV-IRES and combinations of this and the secretory signal or secretory and anchoring signals. These recombinant viruses generated protective immune responses that resulted in survival of 80% of vaccinated mice upon challenge with Y. pestis. Of the RCN-based vaccines we tested, the RCN-IRES-tPA-YpF1 recombinant construct was the most efficacious. Mice vaccinated with this construct withstood challenge with as many as 1.5 million colony forming units of Y. pestis (7.7??104LD50). Interestingly, vaccination with F1 fused to the anchoring signal (RCN-IRES-tPA-YpF1-gG) elicited significant anti-F1 antibody titers, but failed to protect mice from plague challenge. Our studies demonstrate, in vitro and in vivo, the potential importance of the EMCV-IRES and secretory signals in vaccine design. These molecular tools provide a new approach for improving the efficacy of vaccines. In addition, these novel recombinant vaccines could have human, veterinary, and wildlife applications in the prevention of plague. ?? 2002 Elsevier Science Ltd. All rights reserved.

  3. Induction of dominant lethal mutations by Ascaris trypsin inhibitor in male mice.

    PubMed

    Blaszkowska, Joanna

    2010-01-01

    Trypsin inhibitor (ATI) isolated from Ascaris suum, a gastrointestinal nematode parasite, was tested for the induction of dominant lethal mutations in male mice. Dominant lethal effects of ATI for the main stages of germ cell development were analyzed by mating at specific time points after dosing. Three groups of adult BALB/c males received 50, 100 or 250mg/kg body weight (bw) single intraperitoneal (ip) injection of ATI in sterile phosphate-buffered saline (PBS). The control group received concurrent injection of PBS. After the administration of ATI or PBS, each male was mated with two untreated females. For fractionated examination with regard to successive germ cell stages (spermatozoa, spermatids, spermatocytes, and spermatogonia), every second week two other untreated virgin females were placed with each male for mating. The uteri of the females were inspected on the 15th day of gestation, and preimplantation loss and postimplantation loss determined from dominant lethal parameters. Exposure of mice germ cells to ATI did not impair mating activity of males. Pregnancy rates were reduced ( approximately 5-10%) by treatment of males with higher doses of ATI, but differences between treatment and control groups were not statistically significant (P>0.05). In the females bred to ATI-treated males, significant increase in preimplantation loss was observed at post-injection week 1 (reflecting exposure to spermatozoa) and 3 (reflecting exposure to mid and early spermatids) for higher doses of the inhibitor (P<0.05 or P<0.01). During mating days 15-21 a statistically significant increase in postimplantation loss and dominant lethal effects were observed for all doses of ATI. At higher doses, dominant lethal effects were restricted to spermatozoa (P<0.01). These data suggest that ATI induces dominant lethal mutations at postmeiotic stages of spermatogenesis, but spermatids are the most sensitive cell stage to the effect of ATI. These preliminary findings show that ATI

  4. Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras.

    PubMed

    Wang, Tim; Yu, Haiyan; Hughes, Nicholas W; Liu, Bingxu; Kendirli, Arek; Klein, Klara; Chen, Walter W; Lander, Eric S; Sabatini, David M

    2017-02-23

    The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) cell lines. Sets of genes with correlated patterns of essentiality across the lines reveal new gene relationships, the essential substrates of enzymes, and the molecular functions of uncharacterized proteins. Comparisons of differentially essential genes between Ras-dependent and -independent lines uncover synthetic lethal partners of oncogenic Ras. Screens in both human AML and engineered mouse pro-B cells converge on a surprisingly small number of genes in the Ras processing and MAPK pathways and pinpoint PREX1 as an AML-specific activator of MAPK signaling. Our findings suggest general strategies for defining mammalian gene networks and synthetic lethal interactions by exploiting the natural genetic and epigenetic diversity of human cancer cells.

  5. The toxic mechanism of high lethality of herbicide butachlor in marine flatfish flounder, Paralichthys olivaceus

    NASA Astrophysics Data System (ADS)

    Guo, Huarong; Yin, Licheng; Zhang, Shicui; Feng, Wenrong

    2010-09-01

    The toxic mechanism of herbicide butachlor to induce extremely high lethality in marine flatfish flounder, Paralichthys Olivaceus, was analyzed by histopathological examination, antioxidant enzymes activities and ATP content assay. Histopathological examination of gill, liver and kidney of exposed fishes showed that gill was a target organ of butachlor. The butachlor seriously impaired the respiration of gills by a series of lesions such as edema, lifting and detachment of lamellar epithelium, breakdown of pillar cells, and blood congestion. The dysfunction of gill respiration caused suffocation to the exposed flounder with extremely high acute lethality. Antioxidant enzyme activity assay of the in vitro cultured flounder gill (FG) cells exposed to butachlor indicated that butachlor markedly inhibited the antioxidant enzyme activities of Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Furthermore, along with the decline of antioxidant enzyme activities, ATP content in the exposed FG cells decreased, too. This infers that the oxidative stress induced by butachlor can inhibit the production of cellular ATP. Similar decrease of ATP content was also observed in the exposed flounder gill tissues. Taken together, as in FG cells, butachlor possibly induced a short supply of ATP in pillar cells by inhibiting the antioxidant enzyme activities and then affecting the contractibility of the pillar cells, which in turn resulted in the blood congestion and suffocation of exposed flounder.

  6. Anthrax Lethal Toxin Impairs Innate Immune Functions of Alveolar Macrophages and Facilitates Bacillus anthracis Survival

    DTIC Science & Technology

    2006-06-14

    germinate into vegetative bacteria (10, 23), which are capable of secreting anthrax lethal toxin (LT) and edema toxin . In the lymph nodes, bacteria ...inability of AM to completely eradicate bacteria suggests that intracellularly secreted lethal FIG. 5. Lethal toxin impairs bactericidal activity but...Microbiology. All Rights Reserved. Anthrax Lethal Toxin Impairs Innate Immune Functions of Alveolar Macrophages and Facilitates Bacillus anthracis

  7. Acute effects of guarana (Paullinia cupana Mart.) on mouse behaviour in forced swimming and open field tests.

    PubMed

    Campos, A R; Barros, A I S; Albuquerque, F A A; M Leal, L K A; Rao, V S N

    2005-05-01

    Guarana, a herbal extract from the seeds of Paullinia cupana Mart. has been evaluated in comparison with caffeine on mouse behaviour in forced swimming and open field tests. Guarana (25 and 50 mg/kg, p.o.) and caffeine (10 and 20 mg/kg, p.o.) each significantly reduced the duration of immobility in the forced swimming test suggesting an antidepressant-like effect in mice. At these doses, neither substance affected ambulation in the open field test. However, a high dose of guarana (100 mg/kg) and caffeine (30 mg/kg) significantly enhanced the locomotor activity in the open field test. Caffeine, but not guarana, could effectively block an adenosine agonist, cyclopentyl adenosine (CPA)-induced increase in swimming immobility suggesting that mechanism(s) other than the adenosinergic mechanism are involved in the antidepressant-like activity of guarana.

  8. Prevalence of patients with acute febrile illnesses and positive dengue NS1 tests in a tertiary hospital in Papua New Guinea.

    PubMed

    Asigau, Viola; Lavu, Evelyn K; McBride, William J H; Biloh, Eric; Naroi, Francis; Koana, Egi; Ferguson, John K; Laman, Moses

    2015-01-01

    Because the prevalence of dengue fever in urban settings in Papua New Guinea is unknown, we investigated the presence of dengue using the NS1 antigen test in an outpatient-based prospective observational study at Port Moresby General Hospital. Of 140 patients with acute febrile illnesses, dengue fever was diagnosed in 14.9% (20 of 134; 95% confidence interval [95% CI] = 9.6-22.4). Malaria (2 of 137; 1.5%; 95% CI = 0.3-5.7), chikungunya (3 of 140; 2.1%; 95% CI = 0.6-6.6), and bacterial bloodstream infections (0 of 80; 0%; 95% CI = 0-5.7) were uncommon. Dengue fever should no longer be considered rare in Papua New Guinea.

  9. Dengue NS1 and prM antibodies increase the sensitivity of acute dengue diagnosis test and differentiate from Japanese encephalitis infection.

    PubMed

    Gowri Sankar, S; Balaji, T; Venkatasubramani, K; Thenmozhi, V; Dhananjeyan, K J; Paramasivan, R; Tyagi, B K; John Vennison, S

    2014-05-01

    Accurate and early diagnosis of dengue infection is essential for dengue case management. In outbreak conditions, it is essential to include two different tests to diagnose dengue and the choice depends on the number of days after the onset of illness in which the sample is collected. During the laboratory diagnosis of dengue in late acute and convalescent phase by MAC-ELISA, it is necessary to rule out possible cross reactions of closely related flavivirus, such as Japanese encephalitis virus which is commonly co-circulating. In the present investigation, the usefulness of dengue virus NS1 and prM antibodies in diagnosing and differentiating dengue from Japanese encephalitis infection was assessed using samples collected during out-breaks. It was shown here that, detection of antibodies against dengue NS1 and prM proteins increases the sensitivity of dengue diagnosis until 15days. Moreover, detection of antibodies against both proteins was able to differentiate dengue from Japanese encephalitis infection.

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

    PubMed

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

    2013-10-01

    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.

  11. Heat shock protein 27 expression in human proximal tubule cells exposed to lethal and sublethal concentrations of CdCl2.

    PubMed Central

    Somji, S; Sens, D A; Garrett, S H; Sens, M A; Todd, J H

    1999-01-01

    The expression of hsp 27 mRNA and protein was determined in cultured human proximal tubule (HPT) cells exposed to lethal and sublethal concentrations of Cd2+ under both acute and extended conditions. Initial procedures demonstrated that HPT cells display the classic stress response following physical and chemical stress. Heat stress (42.5 degrees C for 1 hr) caused an increase in both hsp 27 mRNA and protein as well as a shift in the protein to a more phosphorylated state. Results were similar when the cells were subjected to chemical stress (exposure to 100 microM sodium arsenite for 4 hr). Acute exposure to 53 microM CdCl2 for 4 hr also resulted in an increase in hsp 27 mRNA and protein and a shift to the more phosphorylated protein isoform. Extended Cd2+ exposure involved continuous treatment with Cd2+ at both lethal and sublethal levels over a 16-day time course. The results of this treatment showed that chronic exposure to Cd2+ failed to increase either hsp 27 mRNA or protein expression in HPT cells, even at lethal Cd2+ concentrations. In fact, hsp 27 protein levels decreased as compared to controls at both lethal and sub-lethal exposure to Cd2+. These findings imply that hsp 27 expression in human proximal tubule cells may have two distinct modes depending on the nature (acute vs. chronic) of the stress. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:10379001

  12. Enhancement of Hsp70 synthesis protects common carp, Cyprinus carpio L., against lethal ammonia toxicity.

    PubMed

    Sung, Y Y; Roberts, R J; Bossier, P

    2012-08-01

    Exposure to TEX-OE®, a patented extract of the prickly pear cactus (Opuntia ficus indica) containing chaperone-stimulating factor, was shown to protect common carp, Cyprinus carpio L., fingerlings against acute ammonia stress. Survival was enhanced twofold from 50% to 95% after exposure to 5.92 mg L(-1) NH(3) , a level determined in the ammonia challenge bioassay as the 1-h LD50 concentration for this species. Survival of TEX-OE®-pre-exposed fish was enhanced by 20% over non-exposed controls during lethal ammonia challenge (14.21 mg L(-1)  NH(3) ). Increase in the levels of gill and muscle Hsp70 was evident in TEX-OE®-pre-exposed fish but not in the unexposed controls, indicating that application of TEX-OE® accelerated carp endogenous Hsp70 synthesis during ammonia perturbation. Protection against ammonia was correlated with Hsp70 accretion.

  13. Systematic, theoretically-grounded development and feasibility testing of an innovative, preventive web-based game for children exposed to acute trauma

    PubMed Central

    Marsac, Meghan L.; Winston, Flaura K.; Hildenbrand, Aimee K.; Kohser, Kristen L.; March, Sonja; Kenardy, Justin; Kassam-Adams, Nancy

    2015-01-01

    Background Millions of children are affected by acute medical events annually, creating need for resources to promote recovery. While web-based interventions promise wide reach and low cost for users, development can be time- and cost-intensive. A systematic approach to intervention development can help to minimize costs and increase likelihood of effectiveness. Using a systematic approach, our team integrated evidence on the etiology of traumatic stress, an explicit program theory, and a user-centered design process to intervention development. Objective To describe evidence and the program theory model applied to the Coping Coach intervention and present pilot data evaluating intervention feasibility and acceptability. Method Informed by empirical evidence on traumatic stress prevention, an overarching program theory model was articulated to delineate pathways from a) specific intervention content to b) program targets and proximal outcomes to c) key longer-term health outcomes. Systematic user-testing with children ages 8–12 (N = 42) exposed to an acute medical event and their parents was conducted throughout intervention development. Results Functionality challenges in early prototypes necessitated revisions. Child engagement was positive throughout revisions to the Coping Coach intervention. Final pilot-testing demonstrated promising feasibility and high user-engagement and satisfaction. Conclusion Applying a systematic approach to the development of Coping Coach led to the creation of a functional intervention that is accepted by children and parents. Development of new e-health interventions may benefit from a similar approach. Future research should evaluate the efficacy of Coping Coach in achieving targeted outcomes of reduced trauma symptoms and improved health-related quality of life. PMID:25844276

  14. Comparing cognitive and screening tests for neurotoxicity. Effects of acute chlorpyrifos on visual signal detection and a neurobehavioral test battery in rats.

    PubMed

    Bushnell, P J; Moser, V C; Samsam, T E

    2001-01-01

    It is often assumed that cognitive function is more sensitive to neurotoxic chemicals than are the unconditioned behaviors employed in neurobehavioral screens; however, direct comparisons of the sensitivity of these test methods are lacking. The present studies were conducted to compare the effects of the widely used cholinesterase-inhibiting insecticide, chlorpyrifos (O,O'-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothionate, CPF), on a visual signal detection task (SDT) with its effects on a neurobehavioral test battery. Adult male Long-Evans rats were trained to perform the SDT, dosed with CPF, and then assessed with both test instruments. Oral CPF (50 mg/kg) impaired signal detection for 8 days, and subcutaneous CPF (250 mg/kg) did so for 4 weeks. CPF (30 and 50 mg/kg po and 250 mg/kg sc) also lowered activity in the test battery for up to 18 days. Thus, CPF impaired attention and altered behavior in the test battery in the same dose ranges under two very different dosing scenarios.

  15. The Rorschach Suicide Constellation: assessing various degrees of lethality.

    PubMed

    Fowler, J C; Piers, C; Hilsenroth, M J; Holdwick, D J; Padawer, J R

    2001-04-01

    In this article we examine the relation between the Rorschach Comprehensive System's Suicide Constellation (S-CON; Exner, 1993; Exner & Wiley, 1977) and lethality of suicide attempts during the course of patients' hospitalization at the Austen Riggs Center (Stockbridge, MA). Patient records were rated as nonsuicidal (n = 37), parasuicidal (n = 37), or near-lethal (n = 30) based on the presence and lethality of self-destructive acts. Diagnostic efficiency statistics utilizing a cutoff score of 7 or more positive indicators successfully predicted which patients would engage in near-lethal suicidal activity relative to parasuicidal patients (overall correct classification rate [OCC] = .79), nonsuicidal inpatients (OCC = .79), and college students (OCC = .89). Although these predictions were influenced by relatively high base rates in the hospital population (14.5%), base rate estimates were calculated for other hypothetical populations revealing different prediction estimates that should be considered when judging the relative efficacy of the S-CON. Logistic regression analysis revealed that an S-CON score of 7 or more was the sole predictor of near-lethal suicide attempts among 9 psychiatric and demographic variables.

  16. A screen for F1 hybrid male rescue reveals no major-effect hybrid lethality loci in the Drosophila melanogaster autosomal genome.

    PubMed

    Cuykendall, Tawny N; Satyaki, P; Ji, Shuqing; Clay, Derek M; Edelman, Nathaniel B; Kimchy, Alexandra; Li, Ling-Hei; Nuzzo, Erin A; Parekh, Neil; Park, Suna; Barbash, Daniel A

    2014-10-27

    Hybrid sons between Drosophila melanogaster females and D. simulans males die as 3rd instar larvae. Two genes, D. melanogaster Hybrid male rescue (Hmr) on the X chromosome, and D. simulans Lethal hybrid rescue (Lhr) on chromosome II, interact to cause this lethality. Loss-of-function mutations in either gene suppress lethality, but several pieces of evidence suggest that additional factors are required for hybrid lethality. Here we screen the D. melanogaster autosomal genome by using the Bloomington Stock Center Deficiency kit to search for additional regions that can rescue hybrid male lethality. Our screen is designed to identify putative hybrid incompatibility (HI) genes similar to Hmr and Lhr which, when removed, are dominant suppressors of lethality. After screening 89% of the autosomal genome, we found no regions that rescue males to the adult stage. We did, however, identify several regions that rescue up to 13% of males to the pharate adult stage. This weak rescue suggests the presence of multiple minor-effect HI loci, but we were unable to map these loci to high resolution, presumably because weak rescue can be masked by genetic background effects. We attempted to test one candidate, the dosage compensation gene male specific lethal-3 (msl-3), by using RNA interference with short hairpin microRNA constructs targeted specifically against D. simulans msl-3 but failed to achieve knockdown, in part due to off-target effects. We conclude that the D. melanogaster autosomal genome likely does not contain additional major-effect HI loci. We also show that Hmr is insufficient to fully account for the lethality associated with the D. melanogaster X chromosome, suggesting that additional X-linked genes contribute to hybrid lethality.

  17. Antimicrobial, antitumor and brine shrimp lethality assay of Ranunculus arvensis L. extracts.

    PubMed

    Bhatti, Muhammad Zeeshan; Ali, Amjad; Saeed, Asma; Saeed, Ahmad; Malik, Salman Akbar

    2015-05-01

    To investigate the antitumor activity, brine shrimp lethality assay, antibacterial and antifungal activity of Methanol Extract (ME), Water Extract (WE), Acetone Extract (AE), Chloroform Extract (CE), Methanol-Water Extract (MWE), Methanol-Acetone Extract (MAE), Methanol-Chloroform Extract (MCE) of Ranunculus arvensis (L.). Antitumor activity was evaluated with Agrobacterium tumefaciens (At10) induced potato disc assay. Cytotoxicity was evaluated with brine shrimp lethality assay. Antibacterial activity was evaluated with six bacterial strains including Escherichia coli, Enterobacter aerogenes, Bordetella bronchiseptica, Klebsiella pneumoniae, Micrococcus luteus and Streptococcus anginosus and antifungal screening was done against five fungal strains including Aspergillus niger, A. flavus, A. fumigates, Fusarium solani and Mucor species by using disc diffusion method. Best antitumor activity was obtained with ME and WE, having highest IC50 values 20.27 ± 1.62 and 93.01 ± 1.33μg/disc. Brine shrimp lethality assay showed LC50 values of AE, MAE and ME were obtained as 384.66 ± 9.42μg/ml, 724.11 ± 8.01μg/ml and 978.7 ±8.01 μg/ml respectively. WE of R. arvensis revealed weak antimicrobial result against the tested microorganisms. On the other hand, the antifungal activity of the plant extracts was found to be insignificant. These findings demonstrate that extracts of R. arvensis possesses significant antitumor activity. Further extensive study is necessary to assess the therapeutic potential of the plant.

  18. Cost of reproduction in the Queensland fruit fly: Y-model versus lethal protein hypothesis.

    PubMed

    Fanson, Benjamin G; Fanson, Kerry V; Taylor, Phillip W

    2012-12-22

    The trade-off between lifespan and reproduction is commonly explained by differential allocation of limited resources. Recent research has shown that the ratio of protein to carbohydrate (P : C) of a fly's diet mediates the lifespan-reproduction trade-off, with higher P : C diets increasing egg production but decreasing lifespan. To test whether this P : C effect is because of changing allocation strategies (Y-model hypothesis) or detrimental effects of protein ingestion on lifespan (lethal protein hypothesis), we measured lifespan and egg production in Queensland fruit flies varying in reproductive status (mated, virgin and sterilized females, virgin males) that were fed one of 18 diets varying in protein and carbohydrate amounts. The Y-model predicts that for sterilized females and for males, which require little protein for reproduction, there will be no effect of P : C ratio on lifespan; the lethal protein hypothesis predicts that the effect of P : C ratio should be similar in all groups. In support of the lethal protein hypothesis, and counter to the Y-model, the P : C ratio of the ingested diets had similar effects for all groups. We conclude that the trade-off between lifespan and reproduction is mediated by the detrimental side-effects of protein ingestion on lifespan.

  19. Thyroid follicular cell function after non-lethal complement membrane attack.

    PubMed Central

    Weetman, A P; Freeman, M; Morgan, B P

    1990-01-01

    Terminal complement complexes have been identified around thyroid follicles in Graves' disease and Hashimoto's thyroiditis, and the concentrations of such complexes are increased in the sera of these patients, suggesting a role for complement activation and membrane attack complexes (MAC) in autoimmune thyroiditis. This has been investigated further using cultured human and rat thyroid cells. Thyrocytes were resistant to lysis by homologous complement, in contrast to the effects of heterologous (rabbit) complement. The formation of non-lethal amounts of MAC, using reactive lysis or classical pathway activation, significantly reduced cAMP production by these cells in response to thyroid-stimulating hormone (TSH) (P less than 0.01); similar effects were seen with thyroid-stimulating antibodies. Thyroid cells were able to recover rapidly from complement attack after washing and incubation for 30 min. Non-lethal MAC formation also resulted in reactive oxygen metabolite production, detected by luminol-dependent chemiluminescence in three out of five thyroid cell preparations tested. Ionomycin, but not TSH, also stimulated reactive oxygen metabolite production. These results suggest that repeated or continuous sub-lethal complement attack on thyroid cells may exacerbate hypothyroidism in Hashimoto's thyroiditis, or partially counter the effects of thyroid-stimulating antibodies in Graves' disease. Furthermore, the production of reactive oxygen metabolites in these circumstances could increase the intra-thyroidal inflammatory response; oxygen radical scavenging by anti-thyroid drugs (which are concentrated by thyrocytes) may account in part for the amelioration of thyroiditis observed with such treatment. PMID:2170066

  20. Lethal body burdens of chlorophenols and mixtures of chlorophenols in an oligochaete worm, Lumbriculus variegatus

    SciTech Connect

    Kukkonen, J.

    1995-12-31

    The lethal body burdens (LBB) of a few chlorophenol congeners were measured in the oligochaete worm, Lumbriculus variegatus. LBB is defined as the concentration of the compound in the organism on molar basis to cause a death. Groups of 40 organisms were exposed to different chlorophenol concentrations in artificial soft freshwater to achieve differential mortality. Exposure times were either 24 hours or 48 hours. Besides exposures with individual congener, mixtures of chlorophenols were also tested. After each exposure, the surviving organisms were collected and the body burden of chlorophenols were measured by GC with electron capture detection. Only the surviving organisms were analyzed, because dead worms started to decay rather quickly. The analyzed tissue concentrations were actually lower than in surviving organisms. The trichlorophenols and pentachlorophenol have a LBB of 0.4--0.7 {micro}mol/g wet weight. The 2,6-dichlorophenol has a slightly higher LBB of 1.0--1.6 {micro}mol/g wet weight. The LBB of chlorophenol mixtures (two congeners at a time) were of the same, on molar basis, as individual congeners demonstrating fully additive toxicity. The lethal body burdens of 2,4,5-trichlorophenol and pentachlorophenol in Lumbriculus variegatus were the same for these water-only exposures as previously reported for these compounds in two different sediments. The use of lethal body burden approach in sediment toxicology is further discussed.

  1. Engineered Repressible Lethality for Controlling the Pink Bollworm, a Lepidopteran Pest of Cotton

    PubMed Central

    Morrison, Neil I.; Simmons, Gregory S.; Fu, Guoliang; O’Connell, Sinead; Walker, Adam S.; Dafa’alla, Tarig; Walters, Michelle; Claus, John; Tang, Guolei; Jin, Li; Marubbi, Thea; Epton, Matthew J.; Harris, Claire L.; Staten, Robert T.; Miller, Ernest; Miller, Thomas A.; Alphey, Luke

    2012-01-01

    The sterile insect technique (SIT) is an environmentally friendly method of pest control in which insects are mass-produced, irradiated and released to mate with wild counterparts. SIT has been used to control major pest insects including the pink bollworm (Pectinophora gossypiella Saunders), a global pest of cotton. Transgenic technology has the potential to overcome disadvantages associated with the SIT, such as the damaging effects of radiation on released insects. A method called RIDL (Release of Insects carrying a Dominant Lethal) is designed to circumvent the need to irradiate insects before release. Premature death of insects’ progeny can be engineered to provide an equivalent to sterilisation. Moreover, this trait can be suppressed by the provision of a dietary antidote. In the pink bollworm, we generated transformed strains using different DNA constructs, which showed moderate-to-100% engineered mortality. In permissive conditions, this effect was largely suppressed. Survival data on cotton in field cages indicated that field conditions increase the lethal effect. One strain, called OX3402C, showed highly penetrant and highly repressible lethality, and was tested on host plants where its larvae caused minimal damage before death. These results highlight a potentially valuable insecticide-free tool against pink bollworm, and indicate its potential for development in other lepidopteran pests. PMID:23226548

  2. Acute effects of Yo-Yo intermittent recovery test level 1 (Yo-YoIR1) on hemorheological parameters in female volleyball players.

    PubMed

    Kilic-Toprak, Emine; Yapici, Ayşegül; Kilic-Erkek, Ozgen; Koklu, Yusuf; Tekin, Volkan; Alemdaroglu, Utku; Bor-Kucukatay, Melek

    2015-07-16

    In the present study, we investigated possible alterations in red blood cell (RBC) deformability, plasma and whole blood viscosities (WBV) and hematological parameters in response to Yo-Yo intermittent recovery test level 1 (Yo-YoIR1) which is currently used to assess endurance performance, in female volleyball players. Eight volleyball player volunteers from Pamukkale University (mean age19,9 ± 2,2 years; mean body height 177.5 ± 1.99 cm; mean body mass index 21.66 ± 0.64 kg/m2) participated to the study. Blood samples were collected before and immediately after test. Red blood cell (RBC) deformability was determined by ektacytometer, plasma and whole blood viscosities (WBV) by a cone-plate rotational viscometer. Hematological parameters were determined using an electronic hematology analyzer. The Yo-YoIR1 applied, induced acute increments in WBV at native hematocrit (Hct) measured at a shear rate of 150 s-1 and 375 s-1, RBC deformability and WBC count. The results of the current study indicate that, the Yo-Yo IR1 test used to determine physical capacity of the player, by resulting in increments in RBC deformability contributes blood flow and thus, athletic performance of the individual.

  3. [Dominant lethality and translocations in the sex cells of male rats under low-intensity gamma irradiation].

    PubMed

    Baev, I A; Rupova, I M

    1978-11-01

    Adult male rats were given 1300 rad of chronic gamma-irradiation (0.08 rad/min) Dominant lethal rates were found to be high (ranging from 48 to 75%) in irradiated postmeiotic cells and clearly lower (6.8%) in spermatogonia. The chromosome aberration (reciprocal translocation) yields observed with 1300 rad chronic irradiation were comparatively low, averaging 1.6%. Spermatogonia irradiation at low dose rate resulted in a smaller effect as compared to the genetic effects of a single acute exposure.

  4. Evaluation of acute toxicity potential of water hyacinth leaves.

    PubMed

    Wu, Wenbiao; Guo, Xiaoguang; Huang, Mingliang

    2014-06-01

    Although higher protein yield per hectare of water hyacinth than that of soy, high protein content of its leaves and good essential amino acid pattern have been proven, its dietary toxicity for human or animal consumption has not yet been evaluated. Therefore, the acute toxicity of water hyacinth leaves has been evaluated by an animal feeding test. The concentrations of common toxic metals including cadmium, lead, platinum, palladium, tin, mercury, barium, silver, stibium and aluminum in the water hyacinth leaf powder (WHLP) used for the animal feeding test were within their maximum limits in food additives as reported by the World Health Organization. The median lethal dose (LD50) of WHLP was more than 16 g kg(-1) body weight. In the study, after feeding for 7 and 28 days, the body weight of all the mice increased. The results of hematological analysis, clinical biochemical analysis, histopathological evaluation, general dissection or investigations of internal organs, appearance and behavior observations did not indicate any adverse effects from the diet containing WHLP. It is therefore concluded that water hyacinth leaves are not acutely toxic.

  5. Standard operating procedures for conducting acute and chronic aquatic toxicity tests with Eurytemora affinis, a calanoid copepod

    SciTech Connect

    Ziegenfuss, M.C.; Hall, L.W.

    1998-10-01

    Eurytemora affinis, a calanoid copepod, was selected for standard toxicity testing protocol development subsequent to screening 25 resident Chesapeake Bay species including fish, invertebrates, and plants. Eurytemora was selected because of its ecological importance as an essential component in the trophic structure of the estuary, its relative practicability of culturing in the laboratory for year-round availability, and its sensitivity to toxic substances. The standards operating procedures described in this document provide detailed procedures for culturing, holding, and toxicity testing of E. affinis.

  6. Lethal coalitionary aggression and long-term alliance formation among Yanomamö men

    PubMed Central

    Macfarlan, Shane J.; Walker, Robert S.; Flinn, Mark V.; Chagnon, Napoleon A.

    2014-01-01

    Some cross-cultural evidence suggests lethal coalitionary aggression in humans is the product of residence and descent rules that promote fraternal interest groups, i.e., power groups of coresident males bonded by kinship. As such, human lethal coalitions are hypothesized to be homologous to chimpanzee (Pan troglodytes) border patrols. However, humans demonstrate a unique metagroup social structure in which strategic alliances allow individuals to form coalitions transcending local community boundaries. We test predictions derived from