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Sample records for acute lethal effects

  1. 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

  2. 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.

  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. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  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. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Lethal effects of short-wavelength visible light on insects.

    PubMed

    Hori, Masatoshi; Shibuya, Kazuki; Sato, Mitsunari; Saito, Yoshino

    2014-12-09

    We investigated the lethal effects of visible light on insects by using light-emitting diodes (LEDs). The toxic effects of ultraviolet (UV) light, particularly shortwave (i.e., UVB and UVC) light, on organisms are well known. However, the effects of irradiation with visible light remain unclear, although shorter wavelengths are known to be more lethal. Irradiation with visible light is not thought to cause mortality in complex animals including insects. Here, however, we found that irradiation with short-wavelength visible (blue) light killed eggs, larvae, pupae, and adults of Drosophila melanogaster. Blue light was also lethal to mosquitoes and flour beetles, but the effective wavelength at which mortality occurred differed among the insect species. Our findings suggest that highly toxic wavelengths of visible light are species-specific in insects, and that shorter wavelengths are not always more toxic. For some animals, such as insects, blue light is more harmful than UV light.

  4. Lethal effects of short-wavelength visible light on insects

    NASA Astrophysics Data System (ADS)

    Hori, Masatoshi; Shibuya, Kazuki; Sato, Mitsunari; Saito, Yoshino

    2014-12-01

    We investigated the lethal effects of visible light on insects by using light-emitting diodes (LEDs). The toxic effects of ultraviolet (UV) light, particularly shortwave (i.e., UVB and UVC) light, on organisms are well known. However, the effects of irradiation with visible light remain unclear, although shorter wavelengths are known to be more lethal. Irradiation with visible light is not thought to cause mortality in complex animals including insects. Here, however, we found that irradiation with short-wavelength visible (blue) light killed eggs, larvae, pupae, and adults of Drosophila melanogaster. Blue light was also lethal to mosquitoes and flour beetles, but the effective wavelength at which mortality occurred differed among the insect species. Our findings suggest that highly toxic wavelengths of visible light are species-specific in insects, and that shorter wavelengths are not always more toxic. For some animals, such as insects, blue light is more harmful than UV light.

  5. The effects of anthrax lethal toxin on host barrier function.

    PubMed

    Xie, Tao; Auth, Roger D; Frucht, David M

    2011-06-01

    The pathological actions of anthrax toxin require the activities of its edema factor (EF) and lethal factor (LF) enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA). LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs), but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT) leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects.

  6. 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.

  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. Histopathological effects of anthrax lethal factor on rat liver.

    PubMed

    Altunkaynak, Berrin Zuhal; Ozbek, Elvan

    2015-01-01

    Bacillus anthracis, the causative agent of anthrax, has become an increasingly important scientific topic due to its potential role in bioterrorism. The lethal toxin (LT) of B. anthracis consists of lethal factor (LF) and a protective antigen (PA). This study investigated whether only lethal factor was efficient as a hepatotoxin in the absence of the PA. To achieve this aim, LF (100 µg/kg body weight, dissolved in sterile distilled water) or distilled water vehicle were intraperitoneally injected once into adult rats. At 24 h post-injection, the hosts were euthanized and their livers removed and tissue samples examined under light and electron microscopes. As a result of LF application, hepatic injury - including cytoplasmic and nuclear damage in hepatocytes, sinusoidal dilatation, and hepatocellular lysis - became apparent. Further, light microscopic analyses of liver sections from the LF-injected rats revealed ballooning degeneration and cytoplasmic loss within hepatocytes, as well as peri-sinusoidal inflammation. Additionally, an increase in the numbers of Kupffer cells was evident. Common vascular injuries were also found in the liver samples; these injuries caused hypoxia and pathological changes. In addition, some cytoplasmic and nuclear changes were detected within the liver ultrastructure. The results of these studies allow one to suggest that LF could be an effective toxicant alone and that PA might act in situ to modify the effect of this agent (or the reverse situation wherein LF modifies effects of PA) such that lethality results.

  9. Developing Non-Lethal Weapons: The Human Effects Characterization Process

    DTIC Science & Technology

    2015-06-01

    Review Board ( HERB ). The board provides Non-Lethal Weapons Program Managers and Milestone Decision Authorities with: • An assessment of the...quality and completeness of human effects information • Potential human effects risks • Recommendations to mitigate these risks The HERB consists of...and U.S. Coast Guard. The DoD Instruction states that “… the HERB review ensures human effects of NLWs are evaluated consistently.” In addition to

  10. 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

  11. 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.

  12. Effectiveness of lethal, directed wolf-depredation control in Minnesota

    USGS Publications Warehouse

    Harper, E.K.; Paul, W.J.; Mech, L.D.; Weisberg, S.

    2008-01-01

    Wolf (Canis lupus) depredations on livestock in Minnesota, USA, are an economic problem for many livestock producers, and depredating wolves are lethally controlled. We sought to determine the effectiveness of lethal control through the analysis of data from 923 government-verified wolf depredations from 1979 to 1998. We analyzed the data by 1) assessing the correlations between the number of wolves killed in response to depredations with number of depredations the following year at state and local levels, and 2) the time to the next depredation. No analysis indicated that trapping wolves substantially reduced the following year's depredations at state or local levels. However, more specific analyses indicated that in certain situations, killing wolves was more effective than no action (i.e., not trapping). For example, trapping and killing adult males decreased the re-depredation risk. At sheep farms, killing wolves was generally effective. Attempting to trap, regardless of the results, seemed more effective at reducing depredations than not trapping, suggesting that mere human activity near depredation sites might deter future depredations.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  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 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

  1. Pathogenesis, Lethality, and Immunizing Effect of Experimental Cutaneous Cryptococcosis

    PubMed Central

    Dykstra, Mark A.; Friedman, Lorraine

    1978-01-01

    Mice were subcutaneously inoculated with small numbers of virulent Cryptococcus neoformans and divided into groups. Numbers of viable yeasts at the site were estimated at weekly intervals for 5 weeks on the basis of cultures of minced tissue excised from sacrificed animals. Organisms multiplied at the site for at least 4 weeks and were still detectable after the 5th week, although in reduced numbers. Agglutinins appeared within a week, but these antibodies were not detectable during the 2nd through the 5th week. Cryptococcal polysaccharide began to appear in the sera at 3 weeks, persisting through the duration of 5 weeks. All animals appeared healthy, but a few sickened after many months and died of systemic cryptococcosis. All of these events were observed in many separate experiments. The immunizing capacity of a cutaneous lesion was tested by challenging some of the above animals with viable C. neoformans after various intervals of time, either subcutaneously at a site distant from that of the vaccination or intravenously. Although we were unable to demonstrate reduced multiplication of yeasts in the brains, lungs, and spleens of intravenously challenged animals, it was possible to show that multiplication was inhibited at the site of subcutaneous challenge. It was noted also that vaccinated animals lived longer after lethal intravenous challenge than did nonvaccinated animals. The latter protection was observed, however, only when challenge followed vaccination by 3 weeks or longer, and it was effective only against a relatively low challenge dose. Mice were protected against a higher dose if they had previously received killed cryptococci, alternating subcutaneous and intraperitoneal inoculations, one of which contained a microbial adjuvant. No protection was observed in animals that were subcutaneously vaccinated with inert materials such as chitin, latex spheres, or even cryptococcal cell walls themselves. PMID:352944

  2. 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.

  3. Passive Immunization against Cachectin/Tumor Necrosis Factor Protects Mice from Lethal Effect of Endotoxin

    NASA Astrophysics Data System (ADS)

    Beutler, B.; Milsark, I. W.; Cerami, A. C.

    1985-08-01

    A highly specific polyclonal rabbit antiserum directed against murine cachectin/tumor necrosis factor (TNF) was prepared. When BALB/c mice were passively immunized with the antiserum or with purified immune globulin, they were protected against the lethal effect of the endotoxin lipopolysaccharide produced by Escherichia coli. The prophylactic effect was dose-dependent and was most effective when the antiserum was administered prior to the injection of the endotoxin. Antiserum to cachectin/TNF did not mitigate the febrile response of endotoxin-treated animals, and very high doses of endotoxin could overcome the protective effect. The median lethal dose of endotoxin in mice pretreated with 50 microliters of the specific antiserum was approximately 2.5 times greater the median lethal dose for controls given nonimmune serum. The data suggest that cachectin/TNF is one of the principal mediators of the lethal effect of endotoxin.

  4. 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'.

  5. 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

  6. Cellular and Systemic Effects of Anthrax Lethal Toxin and Edema Toxin

    PubMed Central

    Moayeri, Mahtab; Leppla, Stephen H.

    2009-01-01

    Anthrax lethal toxin (LT) and edema toxin (ET) are the major virulence factors of anthrax and can replicate the lethality and symptoms associated with the disease. This review provides an overview of our current understanding of anthrax toxin effects in animal models and the cytotoxicity (necrosis and apoptosis) induced by LT in different cells. A brief reexamination of early historic findings on toxin in vivo effects in the context of our current knowledge is also presented. PMID:19638283

  7. Influence of hypoxia and hyperoxia on the cardiovascular and lethal effects of ethanol.

    PubMed

    Strubelt, O; Younes, M

    1999-03-01

    The mutual potentiation of the hepatotoxic effects of ethanol and hypoxia raised the question of whether such an interaction also occurs in the cardiovascular system. Therefore, anaesthetized rats were infused intravenously with ethanol (25 mg/kg x min.) over 90 min. to reach blood ethanol concentrations between 2.2 and 2.6 g/l and were ventilated artificially either with room air, 10% O2/90% N2 or 100% O2. Under normoxic conditions, ethanol produced a slow decrease of mean arterial blood pressure from 130 to 100 mmHg due to the decline in cardiac output and stroke volume (-20%) while heart rate and peripheral resistance remained unchanged. Hypoxia (arterial oxygen tension 35-38 mmHg) without ethanol produced immediate hypotension (-60 mmHg) without decreasing the cardiac output, i.e. by reducing peripheral resistance. In combination with ethanol, hypoxia produced an even stronger hypotension (-90 mmHg) due to reduction in both cardiac output and peripheral resistance. On the other hand, respiration with 100% O2 (arterial oxygen tension about 500 mmHg) elevated peripheral resistance, attenuated ethanol-induced cardiodepression and prevented ethanol-induced hypotension. The lethal doses of ethanol evaluated by infusing 75 mg/kg x min. ethanol until death amounted to 4.1 g/kg with 10% O2, to 5.5 g/kg with 20% O2 (room air) and to 6.9 g/kg with 100% O2. Thus decrease in vascular contractility induced by hypoxia combined with ethanol-induced cardiodepression may result in lethal cardiovascular failure. Hyperoxia, on the other hand, counteracts ethanol-induced cardiodepression and its acute toxicity by raising the vascular contractility.

  8. 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.

  9. 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

  10. Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations.

    PubMed

    Sardanyés, Josep; Simó, Carles; Martínez, Regina; Solé, Ricard V; Elena, Santiago F

    2014-04-09

    The distribution of mutational fitness effects (DMFE) is crucial to the evolutionary fate of quasispecies. In this article we analyze the effect of the DMFE on the dynamics of a large quasispecies by means of a phenotypic version of the classic Eigen's model that incorporates beneficial, neutral, deleterious, and lethal mutations. By parameterizing the model with available experimental data on the DMFE of Vesicular stomatitis virus (VSV) and Tobacco etch virus (TEV), we found that increasing mutation does not totally push the entire viral quasispecies towards deleterious or lethal regions of the phenotypic sequence space. The probability of finding regions in the parameter space of the general model that results in a quasispecies only composed by lethal phenotypes is extremely small at equilibrium and in transient times. The implications of our findings can be extended to other scenarios, such as lethal mutagenesis or genomically unstable cancer, where increased mutagenesis has been suggested as a potential therapy.

  11. Variability in mutational fitness effects prevents full lethal transitions in large quasispecies populations

    NASA Astrophysics Data System (ADS)

    Sardanyés, Josep; Simó, Carles; Martínez, Regina; Solé, Ricard V.; Elena, Santiago F.

    2014-04-01

    The distribution of mutational fitness effects (DMFE) is crucial to the evolutionary fate of quasispecies. In this article we analyze the effect of the DMFE on the dynamics of a large quasispecies by means of a phenotypic version of the classic Eigen's model that incorporates beneficial, neutral, deleterious, and lethal mutations. By parameterizing the model with available experimental data on the DMFE of Vesicular stomatitis virus (VSV) and Tobacco etch virus (TEV), we found that increasing mutation does not totally push the entire viral quasispecies towards deleterious or lethal regions of the phenotypic sequence space. The probability of finding regions in the parameter space of the general model that results in a quasispecies only composed by lethal phenotypes is extremely small at equilibrium and in transient times. The implications of our findings can be extended to other scenarios, such as lethal mutagenesis or genomically unstable cancer, where increased mutagenesis has been suggested as a potential therapy.

  12. 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.

  13. Lethal Effects of Helianthemum lippii (L.) on Acanthamoeba castellanii Cysts in Vitro

    PubMed Central

    Badria, F.A.; Hetta, M.H.; Sarhan, Rania M.; Ezz El-Din, M.H.

    2014-01-01

    Acanthamoeba spp. commonly cause Acanthamoeba keratitis which is typically associated with the wear of contact lenses. Therefore, finding an economic, efficient, and safe therapy of natural origin is of outmost importance. This study examined the in vitro lethal potential of ethyl acetate and methanol extracts of Helianthemum lippii (L.) (sun roses) against Acanthamoeba castellanii cysts isolated from patients with amoebic keratitis. Both extracts proved to be potent as regard to their lethal effects on A. castellanii cysts with comparable results to chlorhexidine. The ethyl acetate was more promising with cumulative lethality. It showed a highly significant lethal percentage along the duration of treatment. The analysis of the more potent ethyl acetate extract revealed the presence of 2.96 mg/100 g of total phenolics, 0.289 mg/100 ml of total flavonoids and 37 mg/100 mg of total tannins which highlighted their phytomedicinal role. PMID:25031463

  14. Clinical Effects and Lethal and Forensic Aspects of Propofol*

    PubMed Central

    Levy, Richard J.

    2010-01-01

    Propofol is a potent intravenous anesthetic agent that rapidly induces sedation and unconsciousness. The potential for propofol dependency, recreational use and abuse has only recently been recognized and several cases of accidental overdose and suicide have emerged. In addition, the first documented case of murder using propofol was reported a few months ago and a high profile case of suspected homicide with propofol is currently under investigation. A number of analytical methods have been employed to detect and quantify propofol concentrations in biological specimens. The reported propofol related deaths and post-mortem blood and tissue levels are reviewed. Importantly, limitations of propofol detection are discussed and future considerations are presented. Because propofol has the potential for diversion with lethal consequences, the forensic scientist must have a basic understanding of its clinical indications and uses, pharmacologic properties, and detection methods. In addition, medical institutions should develop systems to prevent and detect diversion of this potential drug of abuse. PMID:20950316

  15. Effects of sulpiride and SCH 23390 on methamphetamine-induced changes in body temperature and lethality.

    PubMed

    Bronstein, D M; Hong, J S

    1995-08-01

    Data from human and animal studies suggest that hyperpyrexia contributes to both the neurotoxic and the lethal effects of stimulant drugs such as methamphetamine (METH). Because many of the effects of METH involve the release of dopamine from CNS neurons, we examined the effects of D1 and D2 dopamine receptor antagonists on METH-induced lethality and determined whether these effects correlated with changes in body temperature. In the first set of experiments, we found that the D2 antagonist sulpiride (SUL; 20, 40 or 80 mg/kg) potentiated the lethality caused by a single injection of METH (10 mg/kg). Pretreatment with the D1 antagonist SCH 23390 (SCH; 0.5 mg/kg) reduced the lethality induced by METH alone or by SUL/METH. Other D2 or 5-hydroxytryptamine antagonists prevented, rather than potentiated, METH-induced lethality. In a second set of experiments, rectal temperatures were recorded in METH-injected animals pretreated with SCH or SUL. METH caused a significant increase (i.e., above vehicle-injected levels) in body temperature at 2.5 hr after injection. The effects of SCH or SUL pretreatment on METH-induced changes in body temperature suggest that the lethality-potentiating and -protective effects of SUL and SCH, respectively, were not due to altered thermoregulatory responses. These data support the idea that D1 receptor activation is an important event in the lethality caused by METH and that SUL may potentiate D1 receptor activation by augmenting METH-induced DA release.

  16. 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.

  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. 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.

  20. 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.

  1. 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

  2. Effect of syngeneic marrow injection upon recovery in sub- and near-lethally irradiated mice

    SciTech Connect

    Boggs, S.S.; Boggs, D.R.; Patrene, K.D.

    1989-06-01

    Mice were given sub-lethal (200-600 cGy) or near-lethal (800 cGy) whole body irradiation and the effect of injecting syngeneic marrow on subsequent hematopoietic recovery was studied. Marrow cell injection enhanced erythropoietic recovery after sub-lethal irradiation as reflected in hematocrit values and rate of appearance of /sup 59/Fe-labeled red cells in blood. However, this enhanced erythropoiesis was only seen in the spleen, and /sup 59/Fe uptake in marrow was reduced. When the irradiation dose was kept constant and the marrow dose increased from 10(5) to 10(6) to 10(7) cells, there was a somewhat erratic increase in spleen /sup 59/Fe and a decrease in marrow /sup 59/Fe uptake. When marrow cell number was kept constant and the dose of irradiation was increased from 200 to 400 to 600 to 800 cGy, there was an exponential increase in spleen /sup 59/Fe uptake but the marrow /sup 59/Fe uptake changed from depressed after lower doses to increased after 800 cGy. Cell injection after sub-lethal irradiation did not increase or decrease granulocytopoiesis. Injection of irradiated marrow cells also reduced marrow erythropoiesis and this was evident after both sub- and near-lethal irradiation. However, injection of irradiated cells did not increase splenic erythropoiesis. Following splenectomy, the depressed marrow erythropoiesis attending injection of viable cells was virtually eliminated but no increase was seen. These data suggest that the injection of autologous or syngeneic marrow may not be effective as a means of accelerating hematopoietic recovery after irradiation unless near-lethal or lethal dose have been received.

  3. Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.

    PubMed

    Wright, Linnzi K M; Lee, Robyn B; Vincelli, Nicole M; Whalley, Christopher E; Lumley, Lucille A

    2016-01-22

    Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX.

  4. 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.

  5. 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

  6. The toxic and lethal effects of the trehalase inhibitor trehazolin in locusts are caused by hypoglycaemia.

    PubMed

    Wegener, Gerhard; Tschiedel, Volker; Schlöder, Paul; Ando, Osamu

    2003-04-01

    The main blood sugar of locusts is trehalose, which is hydrolysed to two glucose units by trehalase. Homogenates of locust flight muscles are rich in trehalase activity, which is bound to membranes. A minor fraction of trehalase is in an overt form while the remainder is latent, i.e. active only after impairing membrane integrity. Trehazolin, an antibiotic pseudosaccharide, inhibits locust flight muscle trehalase with apparent K(i)- and EC(50) values of 10(-8) mol l(-1) and 10(-7) mol l(-1), respectively. Trehazolin is insecticidal: 50 micro g injected into locusts completely and selectively blocked the overt form of muscle trehalase (with little effect on latent activity) and killed 50% of the insects within 24 h. Here, it is demonstrated for the first time that trehazolin causes dramatic hypoglycaemia. Injection of 10 micro g trehazolin caused glucose levels to fall by over 90% in 24 h, from 2.8 mmol l(-1) to 0.23 mmol l(-1), while trehalose increased from 61 mmol l(-1) to 111 mmol l(-1). Feeding glucose to the locusts fully neutralized the effects of a potentially lethal dose of trehazolin. This indicates that hypertrehalosaemia is not acutely toxic, whereas lack of glucose causes organ failure (presumably of the nervous system), and that sufficient haemolymph glucose can only be generated from trehalose by trehalase. The results also suggest that overt flight muscle trehalase is located in the plasma membrane with the active site accessible to the haemolymph. Trehalase inhibitors are valuable tools for studying the molecular physiology of trehalase function and sugar metabolism in insects.

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

    DTIC Science & Technology

    1988-01-01

    Etiocholanolones in Diabetes (db), viable yellow (AY), and normal mice. Endocrinologia 117:2279-2283. Coleman DL, Leiter EH, Applezweig N (1984b...Therapeutic effects of dchydroepiandrosterone metab- olites in diabetes mutant mice (C57BL/KsJ dbldb). Endocrinologia 115:238-248. Coleman DL, Leiter EA

  8. PARP1 inhibitor olaparib (Lynparza) exerts synthetic lethal effect against ligase 4-deficient melanomas

    PubMed Central

    Czyż, Małgorzata; Toma, Monika; Gajos-Michniewicz, Anna; Majchrzak, Kinga; Hoser, Grazyna; Szemraj, Janusz; Nieborowska-Skorska, Margaret; Cheng, Phil; Gritsyuk, Daniel; Levesque, Mitchell; Dummer, Reinhard; Sliwinski, Tomasz; Skorski, Tomasz

    2016-01-01

    Cancer including melanoma may be “addicted” to double strand break (DSB) repair and targeting this process could sensitize them to the lethal effect of DNA damage. PARP1 exerts an important impact on DSB repair as it binds to both single- and double- strand breaks. PARP1 inhibitors might be highly effective drugs triggering synthetic lethality in patients whose tumors have germline or somatic defects in DNA repair genes. We hypothesized that PARP1-dependent synthetic lethality could be induced in melanoma cells displaying downregulation of DSB repair genes. We observed that PARP1 inhibitor olaparib sensitized melanomas with reduced expression of DNA ligase 4 (LIG4) to an alkylatimg agent dacarbazine (DTIC) treatment in vitro, while normal melanocytes remained intact. PARP1 inhibition caused accumulation of DSBs, which was associated with apoptosis in LIG4 deficient melanoma cells. Our hypothesis that olaparib is synthetic lethal with LIG4 deficiency in melanoma cells was supported by selective anti-tumor effects of olaparib used either alone or in combination with dacarbazine (DTIC) in LIG4 deficient, but not LIG4 proficient cells. In addition, olaparib combined with DTIC inhibited the growth of LIG4 deficient human melanoma xenografts. This work for the first time demonstrates the effectiveness of a combination of PARP1 inhibitor olaparib and alkylating agent DTIC for treating LIG4 deficient melanomas. In addition, analysis of the TCGA and transcriptome microarray databases revealed numerous individual melanoma samples potentially displaying specific defects in DSB repair pathways, which may predispose them to synthetic lethality triggered by PARP1 inhibitor combined with a cytotoxic drug. PMID:27705909

  9. 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.

  10. Lethal effect of microwaves on spores of Bacillus spp.

    PubMed

    Wang, Jinn-Chyi; Hu, Shu-Hui; Lin, Chin-Yang

    2003-04-01

    Strains representing four types of common heat-resistant spores of Bacillus spp., B. cereus CCRC 14655, B. coagulans CCRC10606, B. licheniformis CCRC14693, and B. subtilis CCRC14199, were heated with microwaves at different power levels and under different conditions in salt solutions, starch solutions, and containers. The results of this study showed that B. licheniformis spores had the highest microwave tolerance at a power level of 100% for different incubation times. B. coagulans spores showed the lowest microwave tolerance in salt solutions with water activity values of 0.6, 0.7, 0.8, and 0.9, and B. licheniformis spores were the most resistant in the tested salt solutions at different incubation times. An analysis of the effect of the viscosity of the medium revealed that the bacteria had the lowest microwave resistance in a medium containing <0.8% starch in solution. The microwave resistance levels of the test microorganisms were the lower in glass containers than in polypropylene containers and aluminum foil-enclosed pouches. Of the four species of bacilli, B. licheniformis had the highest microwave tolerance (P < 0.05) under all conditions.

  11. 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

  12. Lethal and sublethal effects of a methomyl-based insecticide in Hoplobatrachus rugulosus

    PubMed Central

    Trachantong, Waret; Saenphet, Supap; Saenphet, Kanokporn; Chaiyapo, Monruedee

    2016-01-01

    The aim of this study was to investigate the lethal and sublethal toxicity of a methomyl-based insecticide in Hoplobatrachus rugulosus, as methomyl-based insecticides are applied in massive amounts and agrochemicals have effects on the decline in amphibian populations. To evaluate the toxic effects of methomyl from agricultural application, a methomyl-based insecticide containing 40% methomyl was selected. The median lethal concentration of 96 hours of methomyl exposure was 8.69 ppm for H. rugulosus tadpoles. The lethal concentration also produced severe histological damage in the livers and kidneys of the exposed tadpoles. The sublethal concentration used for methomyl was 144 ppb during the metamorphosis period. It was found that the sublethal concentration of the methomyl compound could decrease growth, metamorphosis time, and size, disturb biochemical parameters, and produce histological damage. In livers, methomyl effects increased oxidative stress and dramatically decreased the glycogen level of the treated froglets. Mononuclear infiltration, blood congestion, amorphous substances, and hepatocytes vacuolization were observed throughout liver tissue. The methomyl-based insecticide also increased oxidative stress and decreased nitric oxide levels in the kidneys of the exposed froglets. Renal tissue damage including blood congestion, amorphous substances, and Bowman’s capsule spaces reduction were found in the methomyl exposure group. The methomyl compound also produced vacuoles in various stages of oocytes, but no histological damage was found in testicular tissue. Our results indicated strong toxic effects of the methomyl-based insecticide on H. rugulosus, a broadly tolerant anuran. PMID:28190921

  13. Lethal and sublethal effects of a methomyl-based insecticide in Hoplobatrachus rugulosus.

    PubMed

    Trachantong, Waret; Saenphet, Supap; Saenphet, Kanokporn; Chaiyapo, Monruedee

    2017-01-01

    The aim of this study was to investigate the lethal and sublethal toxicity of a methomyl-based insecticide in Hoplobatrachus rugulosus, as methomyl-based insecticides are applied in massive amounts and agrochemicals have effects on the decline in amphibian populations. To evaluate the toxic effects of methomyl from agricultural application, a methomyl-based insecticide containing 40% methomyl was selected. The median lethal concentration of 96 hours of methomyl exposure was 8.69 ppm for H. rugulosus tadpoles. The lethal concentration also produced severe histological damage in the livers and kidneys of the exposed tadpoles. The sublethal concentration used for methomyl was 144 ppb during the metamorphosis period. It was found that the sublethal concentration of the methomyl compound could decrease growth, metamorphosis time, and size, disturb biochemical parameters, and produce histological damage. In livers, methomyl effects increased oxidative stress and dramatically decreased the glycogen level of the treated froglets. Mononuclear infiltration, blood congestion, amorphous substances, and hepatocytes vacuolization were observed throughout liver tissue. The methomyl-based insecticide also increased oxidative stress and decreased nitric oxide levels in the kidneys of the exposed froglets. Renal tissue damage including blood congestion, amorphous substances, and Bowman's capsule spaces reduction were found in the methomyl exposure group. The methomyl compound also produced vacuoles in various stages of oocytes, but no histological damage was found in testicular tissue. Our results indicated strong toxic effects of the methomyl-based insecticide on H. rugulosus, a broadly tolerant anuran.

  14. Antimutagenic effect of black tea extract using 'rodent dominant lethal mutation assay'.

    PubMed

    Shukla, Y; Taneja, P

    2001-11-30

    The antimutagenic effect of black tea extract has been evaluated with the 'Dominant Lethal Assay' in Swiss albino mice using benzo[a]pyrene [BaP] as a mutagen. BaP was given through the intraperitoneal (i.p.) route at a single dose of 100 mg/kg b.w. to male mice once only. The animals were given 1, 2 and 4% aqueous solution of black tea as sole source of drinking solution prior to BaP. The pregnant females were analyzed for living implants, pre- and post-implantation losses. The results revealed that during mating weeks, BaP caused a reduction in implants and an increase in pre- and post-implantation losses. The protective effect of tea solution on BaP-induced mutagenicity was observed. The number of living implants increased and dead implants decreased significantly in the animals kept on 2 and 4% tea solution. The increase in dominant lethal mutation rate by BaP was inhibited by black tea extract. Four percent tea solution alone did not produce dominant lethality, and reveals that it is non-toxic/non-mutagenic to sperm. Hence the study suggests that tea has a protective effect against BaP-induced genetic damage to germ cells in Swiss albino mice.

  15. 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

  16. Lethal and mutagenic effects of ion beams and γ-rays in Aspergillus oryzae.

    PubMed

    Toyoshima, Yoshiyuki; Takahashi, Akemi; Tanaka, Hisaki; Watanabe, Jun; Mogi, Yoshinobu; Yamazaki, Tatsuo; Hamada, Ryoko; Iwashita, Kazuhiro; Satoh, Katsuya; Narumi, Issay

    2012-12-01

    Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was (12)C(5+) ion beams with an LET of 121keV/μm. The (12)C(5+) ion beams had a 3.6-times higher lethal effect than low-LET (0.2keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. (12)C(6+) ion beams with an LET of 86keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to (12)C(6+) ion beams increased with an increase in dose and reached 3.47×10(-3) at 700Gy. In the dose range from 0 to 700Gy, (12)C(5+) ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67×10(-3)) at 400Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between (12)C(5+) ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2bp was generally low, deletions >20bp were characteristic for (12)C(5+) ion beams. γ-rays had a tendency to generate mutants carrying a multitude of mutations in the same locus. Both forms of radiation also induced genome-wide large-scale mutations including chromosome rearrangements and large deletions. These results provide new basic insights into the mutation breeding of A. oryzae using ionizing radiation.

  17. Effect of non-homogenous thermal stress during sub-lethal photodynamic antimicrobial chemotherapy

    NASA Astrophysics Data System (ADS)

    Gadura, N.; Kokkinos, D.; Dehipawala, S.; Cheung, E.; Sullivan, R.; Subramaniam, R.; Schneider, P.; Tremberger, G., Jr.; Holden, T.; Lieberman, D.; Cheung, T.

    2012-03-01

    Pathogens could be inactivated via a light source coupled with a photosensitizing agent in photodynamic antimicrobial chemotherapy (PACT). This project studied the effect of non-homogenous substrate on cell colony. The non-homogeneity could be controlled by iron oxide nano-particles doping in porous glassy substrates such that each cell would experience tens of hot spots when illuminated with additional light source. The substrate non-homogeneity was characterized by Atomic Force Microscopy, Transmission Electron Microscopy and Extended X-Ray Absorption Fine Structure at Brookhaven Synchrotron Light Source. Microscopy images of cell motion were used to study the motility. Laboratory cell colonies on non-homogenous substrates exhibit reduced motility similar to those observed with sub-lethal PCAT treatment. Such motility reduction on non-homogenous substrate is interpreted as the presence of thermal stress. The studied pathogens included E. coli and Pseudomonas aeruginosa. Non-pathogenic microbes Bacillus subtilis was also studied for comparison. The results show that sub-lethal PACT could be effective with additional non-homogenous thermal stress. The use of non-uniform illumination on a homogeneous substrate to create thermal stress in sub-micron length scale is discussed via light correlation in propagation through random medium. Extension to sub-lethal PACT application complemented with thermal stress would be an appropriate application.

  18. Colchicine protects mice from the lethal effect of an agonistic anti-Fas antibody

    PubMed Central

    Feng, Guoping; Kaplowitz, Neil

    2000-01-01

    The aim of this study was to determine whether colchicine, which has been reported to protect against various hepatotoxic insults, influences the susceptibility of mice to the agonistic anti-Fas antibody, Jo2. All mice that were pretreated with colchicine (2 mg/kg) survived the lethal challenge of intraperitoneal administration of 10 μg of Jo2, whereas all control mice pretreated with γ-lumicolchicine succumbed to the challenge. Twelve micrograms of Jo2 killed less than half of colchicine-pretreated mice and its lethal effects were delayed relative to control mice, which all died within 8 hours. Other microtubule-disrupting agents such as Taxol, vinblastine, and nocodazole also improved the survival of mice treated with the lethal dose of Jo2. Histologic examination showed that colchicine protected against Jo2-induced fulminant liver injury, and TUNEL assay demonstrated that colchicine protected against massive apoptosis of hepatocytes. Hepatocytes isolated from colchicine-pretreated mice exhibited decreased susceptibility to Jo2-induced apoptosis. In addition, colchicine pretreatment reduced surface expression of Fas and decreased Jo2- and TNF-α–induced apoptosis of cultured hepatocytes in the presence of actinomycin D, but did not affect the susceptibility of cultured sinusoidal endothelial cells to Jo2-induced apoptosis. Remarkably, Fas and TNF receptor-1 mRNA and intracellular protein levels increased after colchicine treatment, indicating that colchicine protects against death ligand–induced apoptosis in the liver by decreasing death-receptor targeting to the cell surface. PMID:10675359

  19. In vivo toxic and lethal cardiovascular effects of a synthetic polymeric 1,3-dodecylpyridinium salt in rodents

    SciTech Connect

    Grandic, Marjana; Sepcic, Kristina; Turk, Tom; Juntes, Polona; Frangez, Robert

    2011-08-15

    APS12-2 is one in a series of synthetic analogs of the polymeric alkylpyridinium salts isolated from the marine sponge Reniera sarai. As it is a potential candidate for treating non small cell lung cancer (NSCLC), we have studied its possible toxic and lethal effects in vivo. The median lethal dose (LD{sub 50}) of APS12-2 in mice was determined to be 11.5 mg/kg. Electrocardiograms, arterial blood pressure and respiratory activity were recorded under general anesthesia in untreated, pharmacologically vagotomized and artificially ventilated rats injected with APS12-2. In one group, the in vivo effects of APS12-2 were studied on nerve-evoked muscle contraction. Administration of APS12-2 at a dose of 8 mg/kg caused a progressive reduction of arterial blood pressure to a mid-circulatory value, accompanied by bradycardia, myocardial ischemia, ventricular extrasystoles, and second degree atrio-ventricular block. Similar electrocardiogram and arterial blood pressure changes caused by APS12-2 (8 mg/kg) were observed in animals pretreated with atropine and in artificially ventilated animals, indicating that hypoxia and cholinergic effects do not play a crucial role in the toxicity of APS12-2. Application of APS12-2 at sublethal doses (4 and 5.5 mg/kg) caused a decrease of arterial blood pressure, followed by an increase slightly above control values. We found that APS12-2 causes lysis of rat erythrocytes in vitro, therefore it is reasonable to expect the same effect in vivo. Indeed, hyperkalemia was observed in the blood of experimental animals. Hyperkalemia probably plays an important role in APS12-2 cardiotoxicity since no evident changes in histopathology of the heart were found. However, acute lesions were observed in the pulmonary vessels of rats after application of 8 mg/kg APS12-2. Predominant effects were dilation of interalveolar blood vessels and lysis of aggregated erythrocytes within their lumina. - Highlights: > LD{sub 50} estimated in mice (11.5 mg/kg) revealed

  20. 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

  1. Simulation study of the lethality effect of high-power laser with supersonic air flow

    NASA Astrophysics Data System (ADS)

    Peng, Xin; Zhao, Guomin; Chen, Minsun

    2016-10-01

    The lethality effect of high power laser on target is simulated with CFD method under different conditions of supersonic air flow on the surface of the target. Materials used in the experiments are 2cm aluminum plate. With the Mach number changing from 1 to 5, the lethality effects of the high power laser can be obtained from the simulations under these conditions of supersonic air flow. The flow-structure-laser coupling impact on the failure time of the target is discussed based on the simulation. Results show that with the increase of mach number, the effect on the aluminum plate is increase first and then decrease by the pressure. Because that it is obvious that the maximum area of pressure is away from the center of deformation region when the mach number is bigger than 5 . At the same time, when mach number is increase, the aerodynamic heating play more important role than the convective heat transfer on the temperature field of aluminum plate. there are two impacts from the supersonic flow. Firstly , the flow can produce the pressure on the surface of the aluminum plate. Secondly, the flow can produce aerodynamic heat on the aluminum plate.

  2. Ethylhexylglycerin Impairs Membrane Integrity and Enhances the Lethal Effect of Phenoxyethanol

    PubMed Central

    Langsrud, Solveig; Steinhauer, Katrin; Lüthje, Sonja; Weber, Klaus; Goroncy-Bermes, Peter; Holck, Askild L.

    2016-01-01

    Preservatives are added to cosmetics to protect the consumers from infections and prevent product spoilage. The concentration of preservatives should be kept as low as possible and this can be achieved by adding potentiating agents. The aim of the study was to investigate the mechanisms behind potentiation of the bactericidal effect of a commonly used preservative, 2-phenoxyethanol (PE), by the potentiating agent ethylhexylglycerin (EHG). Sub-lethal concentrations of EHG (0.075%) and PE (0.675%) in combination led to rapid killing of E. coli (> 5 log reduction of cfu after 30 min), leakage of cellular constituents, disruption of the energy metabolism, morphological deformities of cells and condensation of DNA. Used alone, EHG disrupted the membrane integrity even at low concentrations. In conclusion, sub-lethal concentrations of EHG potentiate the effect of PE through damage of the cell membrane integrity. Thus, adding EHG to PE in a 1:9 ratio has a similar effect on membrane damage and bacterial viability as doubling the concentration of PE. This study provides insight about the mechanism of action of a strong potentiating agent, EHG, which is commonly used in cosmetics together with PE. PMID:27783695

  3. 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.

  4. Non-lethal effects of an invasive species in the marine environment: the importance of early life-history stages.

    PubMed

    Rius, Marc; Turon, Xavier; Marshall, Dustin J

    2009-04-01

    Studies examining the effects of invasive species have focussed traditionally on the direct/lethal effects of the invasive on the native community but there is a growing recognition that invasive species may also have non-lethal effects. In terrestrial systems, non-lethal effects of invasive species can disrupt early life-history phases (such as fertilisation, dispersal and subsequent establishment) of native species, but in the marine environment most studies focus on adult rather than early life-history stages. Here, we examine the potential for an introduced sessile marine invertebrate (Styela plicata) to exert both lethal and non-lethal effects on a native species (Microcosmus squamiger) across multiple early life-history stages. We determined whether sperm from the invasive species interfered with the fertilisation of eggs from the native species and found no effect. However, we did find strong effects of the invasive species on the post-fertilisation performance of the native species. The invasive species inhibited the settlement of native larvae and, in the field, the presence of the invasive species was associated with a ten-fold increase in the post-settlement mortality of the native species, as well as an initial reduction of growth in the native. Our results suggest that larvae of the native species avoid settling near the invasive species due to reduced post-settlement survival in its presence. Overall, we found that invasive species can have complex and pervasive effects (both lethal and non-lethal) across the early life-history stages of the native species, which are likely to result in its displacement and to facilitate further invasion.

  5. 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.

  6. Using photopigment biomarkers to quantify sub-lethal effects of petroleum pollution on natural phytoplankton assemblages

    SciTech Connect

    Swistak, J.; Pinckney, J.; Piehler, M.; Paerl, H.

    1995-12-31

    Although much work has been undertaken to determine the toxicity of petroleum pollutants to phytoplankton, most studies have used pure cultures to monitor growth of selected phytoplankton species. Fewer have considered the net effect on entire microalgal communities. Using high performance liquid chromatography (HPLC) to characterize diagnostic microalgal pigments, the authors were able to simultaneously assess sub-lethal pollutant effects on entire communities as well as on individual phytoplankton functional groups. Incubations of natural water samples with diesel fuel, an important contributor to coastal petroleum pollution, revealed significant changes in photopigments and relative abundance of taxonomic groups at sub-lethal concentrations. Differential rates of change of indicator pigment concentrations suggest a range of sensitivity among phytoplankton groups. In preliminary experiments, cyanobacteria exhibited the greatest overall tolerance to the diesel fuel concentrations tested, while cryptomonads displayed the most sensitivity. The authors are currently evaluating the responses of seasonal phytoplankton populations from 3 sites exposed to varied levels of petroleum pollution. HPLC will be used to characterize phytoplankton populations and to determine if the most abundant groups are also the most tolerant of diesel fuel. Preliminary experiments indicate that diesel fuel pollution may modify the structure and function of phytoplankton communities and subsequently alter the trophodynamics of impacted systems.

  7. On quantifying nonthermal effects on the lethality of pressure-assisted heat preservation processes.

    PubMed

    Peleg, Micha; Corradini, Maria G; Normand, Mark D

    2012-01-01

    Direct experimental identification and quantification of the pressure contribution to a pressure-assisted sterilization process efficacy is difficult. However, dynamic kinetic models of thermal inactivation can be used to assess the lethality of a purely thermal process having the same temperature profile. Thus, a pressure-assisted process' temperature record can be used to generate a corresponding purely thermal survival curve with parameters determined in conventional heating experiments. Comparison of the actual final survival ratio with that calculated for the purely thermal process would reveal whether the hydrostatic pressure had synergistic or antagonistic effect on bacterial spores survival. The effect would be manifested in the number of log cycles subtracted or added to the survival ratio, and in the length of time at the holding temperature needed to produce the final survival ratio of the combined process. A set of combined treatments would reveal how the temperature and pressure profiles affect the pressure's influence on the process' lethality to either vegetative cells or spores. The need to withdraw samples during the thermal and combined processes would be avoided if the thermal survival parameters could be calculated by the "three endpoints method," which does not require the entire survival curve determination. Currently however, this method is limited to thermal inactivation patterns characterized by up to 3 survival parameters, the Weibull-Log logistic (WeLL) model, for example.

  8. Effects of Glyphosate-Based Herbicide Sub-Lethal Concentrations on Fish Feeding Behavior.

    PubMed

    Giaquinto, Percilia Cardoso; de Sá, Marina Borges; Sugihara, Vanessa Seiko; Gonçalves, Bruno Bastos; Delício, Helton Carlos; Barki, Assaf

    2017-04-01

    Glyphosate-based herbicides are widely used in agricultural systems. Although the target organism are particularly plant organisms, there are numerous studies showing adverse effects in aquatic animals, such as inhibition of acetyl cholinesterase, effects on kidney, liver, and gill and stressors effects. This study analyzed the effects of commercial formulation of glyphosate on feeding behavior in Pacu (Piaractus mesopotamicus). Fish were exposed to three glyphosate concentrations (0.2, 0.6, and 1.8 ppm) for 15 days. At concentrations of 0.2 and 0.6 ppm, food intake decreased on day 13 and then returned to normal on day 15. At the highest glyphosate-based herbicide concentration, 1.8 ppm, food consumption decreased dramatically and did not recover on day 15. This study showed that glyphosate-based herbicide at sub-lethal concentrations can affect feed intake in pacu and consequently inhibits its growth.

  9. Lethal and Pre-Lethal Effects of a Fungal Biopesticide Contribute to Substantial and Rapid Control of Malaria Vectors

    PubMed Central

    Blanford, Simon; Shi, Wangpeng; Christian, Riann; Marden, James H.; Koekemoer, Lizette L.; Brooke, Basil D.; Coetzee, Maureen; Read, Andrew F.; Thomas, Matthew B.

    2011-01-01

    Rapidly emerging insecticide resistance is creating an urgent need for new active ingredients to control the adult mosquitoes that vector malaria. Biopesticides based on the spores of entomopathogenic fungi have shown considerable promise by causing very substantial mortality within 7–14 days of exposure. This mortality will generate excellent malaria control if there is a high likelihood that mosquitoes contact fungi early in their adult lives. However, where contact rates are lower, as might result from poor pesticide coverage, some mosquitoes will contact fungi one or more feeding cycles after they acquire malaria, and so risk transmitting malaria before the fungus kills them. Critics have argued that ‘slow acting’ fungal biopesticides are, therefore, incapable of delivering malaria control in real-world contexts. Here, utilizing standard WHO laboratory protocols, we demonstrate effective action of a biopesticide much faster than previously reported. Specifically, we show that transient exposure to clay tiles sprayed with a candidate biopesticide comprising spores of a natural isolate of Beauveria bassiana, could reduce malaria transmission potential to zero within a feeding cycle. The effect resulted from a combination of high mortality and rapid fungal-induced reduction in feeding and flight capacity. Additionally, multiple insecticide-resistant lines from three key African malaria vector species were completely susceptible to fungus. Thus, fungal biopesticides can block transmission on a par with chemical insecticides, and can achieve this where chemical insecticides have little impact. These results support broadening the current vector control paradigm beyond fast-acting chemical toxins. PMID:21897846

  10. The (non)effects of lethal population control on the diet of Australian dingoes.

    PubMed

    Allen, Benjamin L; Leung, Luke K-P

    2014-01-01

    Top-predators contribute to ecosystem resilience, yet individuals or populations are often subject to lethal control to protect livestock, managed game or humans from predation. Such management actions sometimes attract concern that lethal control might affect top-predator function in ways ultimately detrimental to biodiversity conservation. The primary function of a predator is predation, which is often investigated by assessing their diet. We therefore use data on prey remains found in 4,298 Australian dingo scats systematically collected from three arid sites over a four year period to experimentally assess the effects of repeated broad-scale poison-baiting programs on dingo diet. Indices of dingo dietary diversity and similarity were either identical or near-identical in baited and adjacent unbaited treatment areas in each case, demonstrating no control-induced change to dingo diets. Associated studies on dingoes' movement behaviour and interactions with sympatric mesopredators were similarly unaffected by poison-baiting. These results indicate that mid-sized top-predators with flexible and generalist diets (such as dingoes) may be resilient to ongoing and moderate levels of population control without substantial alteration of their diets and other related aspects of their ecological function.

  11. The (Non)Effects of Lethal Population Control on the Diet of Australian Dingoes

    PubMed Central

    Allen, Benjamin L.; Leung, Luke K.-P.

    2014-01-01

    Top-predators contribute to ecosystem resilience, yet individuals or populations are often subject to lethal control to protect livestock, managed game or humans from predation. Such management actions sometimes attract concern that lethal control might affect top-predator function in ways ultimately detrimental to biodiversity conservation. The primary function of a predator is predation, which is often investigated by assessing their diet. We therefore use data on prey remains found in 4,298 Australian dingo scats systematically collected from three arid sites over a four year period to experimentally assess the effects of repeated broad-scale poison-baiting programs on dingo diet. Indices of dingo dietary diversity and similarity were either identical or near-identical in baited and adjacent unbaited treatment areas in each case, demonstrating no control-induced change to dingo diets. Associated studies on dingoes' movement behaviour and interactions with sympatric mesopredators were similarly unaffected by poison-baiting. These results indicate that mid-sized top-predators with flexible and generalist diets (such as dingoes) may be resilient to ongoing and moderate levels of population control without substantial alteration of their diets and other related aspects of their ecological function. PMID:25243466

  12. Effects of whole-body VX vapor exposure on lethality in rats.

    PubMed

    Benton, B J; McGuire, J M; Sommerville, D R; Dabisch, P A; Jakubowski, E M; Matson, K L; Mioduszewski, R J; Thomson, S A; Crouse, C L

    2006-12-01

    Male and female rats were whole-body exposed to VX vapor in a 1000-L single-pass exposure chamber. Estimated exposure dosages producing lethal (LCT50) effects in 50% of exposed male and female rats were established for 10, 60, and 240 min exposure durations. A potency comparison with GB and GF shows that VX becomes increasingly more potent than these G agents with increasing exposure duration. VX is approximately 4-30 times more potent than GB and 5-15 times more potent than GF. Gender differences in the estimated median dosages were not significant at the 10, 60, and 240 min exposure durations. An empirical toxic load model was developed and the toxic load exponent for lethality (n) in the equation Cn x T = k was determined to be n = 0.92. The VX-G regeneration assay was successfully used as a biomarker for the presence of VX in the blood plasma and RBC fractions of the blood 24 h postexposure.

  13. Effect of two viscosity models on lethality estimation in sterilization of liquid canned foods.

    PubMed

    Calderón-Alvarado, M P; Alvarado-Orozco, J M; Herrera-Hernández, E C; Martínez-González, G M; Miranda-López, R; Jiménez-Islas, H

    2016-09-01

    A numerical study on 2D natural convection in cylindrical cavities during the sterilization of liquid foods was performed. The mathematical model was established on momentum and energy balances and predicts both the heating dynamics of the slowest heating zone (SHZ) and the lethal rate achieved in homogeneous liquid canned foods. Two sophistication levels were proposed in viscosity modelling: 1) considering average viscosity and 2) using an Arrhenius-type model to include the effect of temperature on viscosity. The remaining thermodynamic properties were kept constant. The governing equations were spatially discretized via orthogonal collocation (OC) with mesh size of 25 × 25. Computational simulations were performed using proximate and thermodynamic data for carrot-orange soup, broccoli-cheddar soup, tomato puree, and cream-style corn. Flow patterns, isothermals, heating dynamics of the SHZ, and the sterilization rate achieved for the cases studied were compared for both viscosity models. The dynamics of coldest point and the lethal rate F0 in all food fluids studied were approximately equal in both cases, although the second sophistication level is closer to physical behavior. The model accuracy was compared favorably with reported sterilization time for cream-style corn packed at 303 × 406 can size, predicting 66 min versus an experimental time of 68 min at retort temperature of 121.1 ℃.

  14. Effects of ganglion blocking agents on nicotine extensor convulsions and lethality in mice

    PubMed Central

    Aceto, M. D.; Bentley, H. C.; Dembinski, J. R.

    1969-01-01

    1. The ganglion blocking agents, chlorisondamine, pentamethonium, mecamylamine, decamethonium and hexamethonium all block nicotine extensor convulsions when administered intraventricularly in mice. Tetraethylammonium was inactive. 2. For the intraventricular route, there is a relationship between ganglionic blocking potency and blocking of nicotine extensor convulsions. Indirect evidence suggests that the site(s) of action of nicotine extensor convulsions and lethality is central in origin and associated with brain areas near the ventricles. 3. When ganglion blocking agents are given orally, subcutaneously or intravenously varying degrees of protection can be observed probably depending on factors such as whether or not the drugs cross the blood-brain barrier, absorption, etc., and the effectiveness in protecting mice from nicotine is not related to ganglionic blocking potency. 4. Atropine and morphine given intraventricularly or subcutaneously did not protect mice from the LD95 of nicotine. Chlorpromazine gave very erratic results and phenobarbitone was effective subcutaneously and to a lesser extent intraventricularly. PMID:4390479

  15. Sub-lethal effects of Vip3A toxin on survival, development and fecundity of Heliothis virescens and Plutella xylostella.

    PubMed

    Gulzar, Asim; Wright, Denis J

    2015-11-01

    The assessment of sub-lethal effects is important to interpret the overall insecticide efficacy in controlling insect pest populations. In addition to the lethal effect, sub-lethal effects may also occur in exposed insects. Vegetative insecticidal proteins (Vips) have shown a broad spectrum of insecticidal activity against many insect pest species. In this study the sub-lethal effects of the Bacillus thuringiensis vegetative insecticidal toxin Vip3A on the development and reproduction of Heliothis virescens F. and Plutella xylostella L. were evaluated in the laboratory. The results indicated that the sub-lethal concentration of Vip3A increased the duration of the larval and pupal stages as compared with the control treatment for both species. The percent pupation and percent adult emergence were significantly lower for Vip3A-treated insects. The proportion of pairs that produced eggs and the longevity of adults were not significantly different between treatments. H. virescens and P. xylostella treated with Vip3A showed an 11 and 17 % decrease in their intrinsic rate of increase (rm) respectively compared with untreated insects. The results from this study will be helpful to develop the strategy to incorporate Vip 3A containing crops in an integrated pest management programme.

  16. Intrinsic resistance to the lethal effects of x-irradiation in insect and arachnid cells

    PubMed Central

    Koval, Thomas M.

    1983-01-01

    Twelve cell lines representing 10 genera of three orders (Diptera, Lepidoptera, and Orthoptera) of the class Insecta and one cell line (Acarina) from the class Arachnida were examined to discern their sensitivity to the lethal effects of x-irradiation. Radiosensitivity was measured by a combination of colony formation and population growth curve techniques. Each of these arthropod cell lines is significantly more radioresistant than mammalian cells, though the degree of resistance varies greatly with order. Dipteran cells are 3 to 9 times and lepidopteran cells 52 to 104 times more radioresistant than mammalian cells. Orthopteran and acarine cells are intermediate in radiosensitivity between dipteran and lepidopteran cells. These cells, especially the lepidopteran, should be valuable in determining the molecular nature of repair mechanisms that result in resistance to ionizing radiation. PMID:16593348

  17. Lethal effect of the serotonin-xylocaineR association in ganglion-blocked rats.

    PubMed

    Valle, L B; Oliveira-Filho, R M; Armonia, P L; Saraceni, G; Nassif, M; De Lucia, R

    1976-12-01

    In rats anestetized with urethane and under ganglionic blockade by hexamethonium (20 mg/kg, i.v.), the i.v. injection of serotonin (60 mug/kg) determined apnea, ECG alterations and a brief hypotensive response which is similar to that as elicited when 5-HT is given to intact rats. During the hypertension which follows that initial response, apnea is still present along with more severe ECG changes. After that, blood pressure falls into a prolonged hypotension, which is invariably accompanied by death. Neither norepinephrine, nor respiratory analeptics (CoramineR, RemeflinF) were able to prevent the fatal outcome. Only artificial respiration was found to be useful in some instances. It was concluded that the association serotonin plus lidocaine becomes lethal when given to ganglion-blocked rate, and this toxic effect can be ascribed mainly to the respiratory depressor activity of the drugs.

  18. Effects of Training with Lethal Chemicals on Job Proficiency and Job Confidence.

    ERIC Educational Resources Information Center

    Smith, Paula; And Others

    A study was designed to determine if soldiers trained to use chemical agents are more proficient in performing their jobs in an environment where lethal chemical agents are used and more confident of their ability to survive. A treatment group, composed of 150 soldiers, knew that their training would involve lethal agents in the Chemical…

  19. Constitutive MEK1 activation rescues anthrax lethal toxin-induced vascular effects in vivo.

    PubMed

    Bolcome, Robert E; Chan, Joanne

    2010-12-01

    Anthrax lethal toxin (LT) increases vascular leakage in a number of mammalian models and in human anthrax disease. Using a zebrafish model, we determined that vascular delivery of LT increased permeability, which was phenocopied by treatment with a selective chemical inhibitor of MEK1 and MEK2 (also known as mitogen-activated protein kinase [MAPK] kinase, MEK, or MKK). Here we investigate further the role of MEK1/phospho-ERK (pERK) in the action of LT. Overexpression of wild-type zebrafish MEK1 at high levels did not induce detrimental effects. However, a constitutively activated version, MEK1(S219D,S223D) (MEK1DD), induced early defects in embryonic development that correlated with increased ERK/MAPK phosphorylation. To bypass these early developmental defects and to provide a genetic tool for examining the action of lethal factor (LF), we generated inducible transgenic zebrafish lines expressing either wild-type or activated MEK1 under the control of a heat shock promoter. Remarkably, induction of MEK1DD transgene expression prior to LT delivery prevented vascular damage, while the wild-type MEK1 line did not. In the presence of both LT and MEK1DD transgene expression, cardiovascular development and function proceeded normally in most embryos. The resistance to microsphere leakage in transgenic animals demonstrated a protective role against LT-induced vascular permeability. A consistent increase in ERK phosphorylation among LT-resistant MEK1DD transgenic animals provided additional confirmation of transgene activation. These findings provide a novel genetic approach to examine mechanism of action of LT in vivo through one of its known targets. This approach may be generally applied to investigate additional pathogen-host interactions and to provide mechanistic insights into host signaling pathways affected by pathogen entry.

  20. Effects of sub-lethal doses of glyphosate on honeybee navigation.

    PubMed

    Sol Balbuena, María; Tison, Léa; Hahn, Marie-Luise; Greggers, Uwe; Menzel, Randolf; Farina, Walter M

    2015-07-10

    Glyphosate (GLY) is a herbicide that is widely used in agriculture for weed control. Although reports about the impact of GLY in snails, crustaceans and amphibians exist, few studies have investigated its sub-lethal effects in non-target organisms such as the honeybee Apis mellifera, the main pollen vector in commercial crops. Here, we tested whether exposure to three sub-lethal concentrations of GLY (2.5, 5 and 10 mg/L corresponding to 0.125, 0.250 and 0.500 µg/animal) affects the homeward flight path of honeybees in an open field. We performed an experiment in which forager honeybees were trained to an artificial feeder, and then captured, fed with sugar solution containing GLY traces and released from a novel site (the release site, RS) either once or twice. Their homeward trajectories were tracked using harmonic radar technology. We found that honeybees that had been fed with solution containing 10 mg/L GLY spent more time performing homeward flights than control bees or bees treated with lower GLY concentrations. They also performed more indirect homing flights. Moreover, the proportion of direct homeward flights performed after a second release at the RS increased in control bees but not in treated bees. These results suggest that, in honeybees, exposure to GLY doses commonly found in agricultural settings impairs the cognitive capacities needed to retrieve and integrate spatial information for a successful return to the hive. Therefore, honeybee navigation is affected by ingesting traces of the most widely used herbicide worldwide, with potential long-term negative consequences for colony foraging success.

  1. Lethal and sublethal effects of azadirachtin on the bumblebee Bombus terrestris (Hymenoptera: Apidae).

    PubMed

    Barbosa, Wagner Faria; De Meyer, Laurens; Guedes, Raul Narciso C; Smagghe, Guy

    2015-01-01

    Azadirachtin is a biorational insecticide commonly reported as selective to a range of beneficial insects. Nonetheless, only few studies have been carried out with pollinators, usually emphasizing the honeybee Apis mellifera and neglecting other important pollinator species such as the bumblebee Bombus terrestris. Here, lethal and sublethal effects of azadirachtin were studied on B. terrestris via oral exposure in the laboratory to bring out the potential risks of the compound to this important pollinator. The compound was tested at different concentrations above and below the maximum concentration that is used in the field (32 mg L(-1)). As most important results, azadirachtin repelled bumblebee workers in a concentration-dependent manner. The median repellence concentration (RC50) was estimated as 504 mg L(-1). Microcolonies chronically exposed to azadirachtin via treated sugar water during 11 weeks in the laboratory exhibited a high mortality ranging from 32 to 100 % with a range of concentrations between 3.2 and 320 mg L(-1). Moreover, no reproduction was scored when concentrations were higher than 3.2 mg L(-1). At 3.2 mg L(-1), azadirachtin significantly inhibited the egg-laying and, consequently, the production of drones during 6 weeks. Ovarian length decreased with the increase of the azadirachtin concentration. When azadirachtin was tested under an experimental setup in the laboratory where bumblebees need to forage for food, the sublethal effects were stronger as the numbers of drones were reduced already with a concentration of 0.64 mg L(-1). Besides, a negative correlation was found between the body mass of male offspring and azadirachtin concentration. In conclusion, our results as performed in the laboratory demonstrated that azadirachtin can affect B. terrestris with a range of sublethal effects. Taking into account that sublethal effects are as important as lethal effects for the development and survival of the colonies of B. terrestris

  2. Lethal control of an apex predator has unintended cascading effects on forest mammal assemblages.

    PubMed

    Colman, N J; Gordon, C E; Crowther, M S; Letnic, M

    2014-05-07

    Disruption to species-interaction networks caused by irruptions of herbivores and mesopredators following extirpation of apex predators is a global driver of ecosystem reorganization and biodiversity loss. Most studies of apex predators' ecological roles focus on effects arising from their interactions with herbivores or mesopredators in isolation, but rarely consider how the effects of herbivores and mesopredators interact. Here, we provide evidence that multiple cascade pathways induced by lethal control of an apex predator, the dingo, drive unintended shifts in forest ecosystem structure. We compared mammal assemblages and understorey structure at seven sites in southern Australia. Each site comprised an area where dingoes were poisoned and an area without control. The effects of dingo control on mammals scaled with body size. Activity of herbivorous macropods, arboreal mammals and a mesopredator, the red fox, were greater, but understorey vegetation sparser and abundances of small mammals lower, where dingoes were controlled. Structural equation modelling suggested that both predation by foxes and depletion of understorey vegetation by macropods were related to small mammal decline at poisoned sites. Our study suggests that apex predators' suppressive effects on herbivores and mesopredators occur simultaneously and should be considered in tandem in order to appreciate the extent of apex predators' indirect effects.

  3. Contribution of ammonium ions to the lethality and antimetamorphic effects of ammonium perchlorate.

    PubMed

    Goleman, Wanda L; Carr, James A

    2006-04-01

    Ammonium perchlorate (AP) is a widespread military waste product in the United States and is a potent thyroid function disruptor in all vertebrates tested thus far. To determine the relative contribution of ammonium ions to the toxicity of AP, we exposed embryonic and larval Xenopus laevis to various concentrations of sodium perchlorate (SP) or ammonium chloride (AC). Ammonium perchlorate was significantly more lethal than SP; 5-d LC50s were 83 and 2,780 mg/L, respectively. To determine whether ammonium ions contribute to the antithyroid effects of AP, we exposed embryonic and larval X. laevis to two sublethal, environmentally relevant concentrations of AP or identical concentrations of AC or SP. At the smaller concentration, only AP delayed metamorphosis and reduced hindlimb growth. Sodium perchlorate and AP, but not AC, prevented metamorphosis and reduced hindlimb growth at the greater concentration. Although AP was slightly more effective in reducing outward manifestations of thyroid disruption, both perchlorate salts, unlike AC, caused profound histopathologic changes in the thyroid. Exposure to the higher concentration of either perchlorate salt produced a feminizing effect, resulting in a skewed sex ratio. We conclude that ammonium ions contribute significantly to the toxicity of AP but not to the direct antithyroid effects of perchlorate.

  4. 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

  5. Effects of inhibitors of radiation-induced potentially lethal damage repair on chemotherapy in murine tumors

    SciTech Connect

    Nakatsugawa, S.; Sugahara, T.

    1982-09-01

    Enhancement of various antitumor drugs effects by inhibitors of radiation-induced potentially lethal damage (PLD) repair was studied in three murine tumors (EMT-6, RIF-1 and SQ-1). In EMT-6 tumors, PLD repair inhibitors, 3'-deoxyguanosine (3'dG) and 7904 (a derivative of 3'-deoxyadenosine) showed a marked enhancement of tumor growth inhibition by anticancerous drugs (FT-207 (a derivative of 5-FU), bleomycin, Ara-C, ACNU). However, the effects of mitomycin-C and vincristine were not potentiated by the inhibitors. In SQ-1 carcinomas, another repair inhibitor, ara-A (1-..beta..-D-arabinofuranosyladenine) (32 mg/kg) potentiated the effect of ACNU. In RIF-1 sarcomas, in which a low PLD repair function has been reported after ionizing radiation exposure, the potentiation was not so marked as in EMT-6 or SQ-1 tumors. Thus, as a possibility, the potentiation by inhibitors of radiation-induced PLD repair might be a result of the inhibition of chemical-induced PLD repair. The study of this field may contribute to the improvement of cancer treatment not only by radiotherapy but also by chemotherapy.

  6. Protective effect of Cl-amidine against CLP-induced lethal septic shock in mice

    PubMed Central

    Zhao, Ting; Pan, Baihong; Alam, Hasan B.; Liu, Baoling; Bronson, Roderick T.; Deng, Qiufang; Wu, Erxi; Li, Yongqing

    2016-01-01

    Production of innate and adaptive immune cells from hematopoietic stem cells, and maturation of T lymphocytes are effective immune responses to fight severe microbial infection. In sepsis, this emergency myelopoiesis is damaged, leading to failure of bacterial clearance, and excessive stress-induced steroids cause immature T-lymphocyte apoptosis in thymus. We recently found that Cl-amidine, a peptidylarginine deiminase (PAD) inhibitor, improves survival in a mouse model of cecal ligation and puncture (CLP)-induced septic shock. In the present study we investigated how Cl-amidine promotes survival, focusing on protective effects of Cl-amidine on immune response. We confirmed survival-improving effect of Cl-amidine and are the first to explore the role of Cl-amidine in immune response. CLP caused bone marrow (BM) and thymus atrophy, decreased innate immune cells in BM. CLP increased levels of cytokines (IL-1β, IL-6, and TNF-α) and bacteria load in blood/liver. In primary splenocyte culture, lipopolysaccharide increased TNF-α production. In contrast, Cl-amidine attenuated these CLP and lipopolysaccharide-induced alterations. Moreover, Cl-amidine increased circulating monocytes. Collectively, our results demonstrate Cl-amidine plays protective roles by significantly decreasing BM and thymus atrophy, restoring innate immune cells in BM, increasing blood monocytes and blood/liver bacteria clearance, and attenuating pro-inflammatory cytokine production in a murine model of lethal sepsis. PMID:27819302

  7. Sub-lethal effects of titanium dioxide nanoparticles on the physiology and reproduction of zebrafish.

    PubMed

    Ramsden, C S; Henry, T B; Handy, R D

    2013-01-15

    There are limited data on the sub-lethal physiological effects of titanium dioxide nanoparticles (TiO(2) NPs) in adult fishes, and the consequences of TiO(2) NP exposure on reproductive success are also unclear. This study aimed to examine the sub-lethal effects of a 14-d aqueous TiO(2) (TiO(2) NP, 0.1 or 1.0 mg l(-1); TiO(2) bulk, 1.0 mg l(-1)) exposure on the physiology and reproductive health of zebrafish. After the 14-d exposure, fish were examined for haematology, whole body electrolyte and trace metal profiles, biochemistry, and histopathology. Then, during a 21-d post exposure recovery period, effects of the TiO(2) exposure on reproductive success were evaluated. Whole body Ti concentrations increased significantly in fish exposed to both the 1.0 mg l(-1) TiO(2) NP and bulk TiO(2) compared to controls, but concentrations returned to control levels by the end of the recovery period. No change in erythrocyte counts were observed, but there was a two-fold decline in leukocyte counts in all TiO(2) treatment groups relative to time-matched controls. Whole body electrolyte and trace metal profiles were not affected by exposure to TiO(2), and there were no changes in Na(+)K(+)-ATPase activity in brain, gill or liver tissues. Total glutathione (GSH) levels in brain, gill and liver tissues were higher in fish exposed to TiO(2) NP (both 0.1 and 1.0 mg l(-1)) compared to bulk TiO(2) and control fish. Histological examination of gill, liver, brain and gonad tissues showed little evidence of treatment-related morphological change. At the end of the 14-d exposure adult zebrafish were able to reproduce; however, the cumulative number of viable embryos produced was lower in fish exposed to 1.0 mg l(-1) TiO(2) (both NP and bulk) by the end of the 21-d recovery period. Overall, this study showed limited toxicity of bulk or nano scale TiO(2) during the exposure; however reproduction was affected in both bulk and NP 1.0 mg l(-1) groups.

  8. 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

  9. 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.

  10. [Acute and long-term effects of ecstasy].

    PubMed

    Salzmann, Julie; Marie-Claire, Cynthia; Noble, Florence

    2004-10-23

    Side effects in the short term Recreational use of Ecstasy (3,4-methylenedioxymethamphetamine or MDMA), a synthetic drug, has considerably increased over the last decade. Since its appearance it is associated with the rave culture, but its use has spread to other social settings. The drug produces euphoria and empathy, but can lead to side effects, notably acute, potentially lethal, toxicity (malignant hyperthermia and/or hepatitis). Neurotoxicity in the long-term Moreover, MDMA has been shown to induce long-term deleterious effects and provoke neurotoxic affecting the serotoninergic system. However, the psychopathological consequences of such neurotoxicity are still controversial, particularly since many ecstasy consumers are multi-drug users. A complex pharmacological profile The mechanism of action of MDMA involves various neurobiological systems (serotonin, dopamine, noradrenalin), that may all interact.

  11. Functional diversity of non-lethal effects, chemical camouflage, and variation in fish avoidance in colonizing beetles.

    PubMed

    Resetarits, William J; Pintar, Matthew R

    2016-12-01

    Predators play an extremely important role in natural communities. In freshwater systems, fish can dominate sorting both at the colonization and post-colonization stage. Specifically, for many colonizing species, fish can have non-lethal, direct effects that exceed the lethal direct effects of predation. Functionally diverse fish species with a range of predatory capabilities have previously been observed to elicit functionally equivalent responses on oviposition in tree frogs. We tested this hypothesis of functional equivalence of non-lethal effects for four predatory fish species, using naturally colonizing populations of aquatic beetles. Among taxa other than mosquitoes, and with the exception of the chemically camouflaged pirate perch, Aphredoderus sayanus, we provide the first evidence of variation in colonization or oviposition responses to different fish species. Focusing on total abundance, Fundulus chrysotus, a gape-limited, surface-feeding fish, elicited unique responses among colonizing Hydrophilidae, with the exception of the smallest and most abundant taxa, Paracymus, while Dytiscidae responded similarly to all avoided fish. Neither family responded to A. sayanus. Analysis of species richness and multivariate characterization of the beetle assemblages for the four fish species and controls revealed additional variation among the three avoided species and confirmed that chemical camouflage in A. sayanus results in assemblages essentially identical to fishless controls. The origin of this variation in beetle responses to different fish is unknown, but may involve variation in cue sensitivity, different behavioral algorithms, or differential responses to species-specific fish cues. The identity of fish species occupying aquatic habitats is crucial to understanding community structure, as varying strengths of lethal and non-lethal effects, as well as their interaction, create complex landscapes of predator effects and challenge the notion of functional

  12. ENHANCED LETHAL EFFECTS OF X-RAYS ON BACILLUS COLI IN THE PRESENCE OF INORGANIC SALTS

    PubMed Central

    Claus, Walter D.

    1933-01-01

    1. When B. coli are irradiated by x-rays in a series of salt solutions of tenth molar concentration, the synergistic effect does not become appreciable until heavy salts are used. 2. When Pb(NO3)2 or KBr solutions are used in increasing concentrations, the synergistic effect is not appreciable until large concentrations or absorption coefficients are reached, whereupon the effect increases sharply. Thus the number of effective hits per bacterium per minute, α, is a function of the absorption coefficient, µ. 3. The sharp increase in α does not occur at the same concentration, or same µ, for Pb(NO3)2 and for KBr. Thus α is a function of the nature of the salt, or possibly of the penetration of the salt into the cell, some measure of which may be obtained from the initial toxicity of the solution. 4. For a given solution, α increases as the wave length λ of the x-rays decreases, although µ decreases by the same process as the cube of λ. Thus α is a function of λ to some power greater than the cube. 5. A possible mechanism whereby the synergistic effect takes place is discussed briefly, as is the possibility that the heterogeneity of the x-rays accounts for all or part of the increased bactericidal effect of the rays in the presence of heavy metal salts. 6. Results indicate that within the range investigated, short wave lengths of x-rays, in conjunction with sensitizers, are the more efficacious in producing lethal effects. PMID:19870133

  13. Acute neurobehavioural effects of toluene.

    PubMed Central

    Echeverria, D; Fine, L; Langolf, G; Schork, A; Sampaio, C

    1989-01-01

    An acute inhalation chamber study of 42 college students was performed to investigate the relation between exposure to 0, 75, and 150 ppm of toluene and changes in central nervous system function and symptoms. Paid subjects were exposed for seven hours over three days. Verbal and visual short term memory (Sternberg, digit span, Benton, pattern memory); perception (pattern recognition); psychomotor skill (simple reaction time, continuous performance, digit symbol, hand-eye coordination, finger tapping, and critical tracking); manual dexterity (one hole); mood (profile of mood scales (POMS]; fatigue (fatigue checklist); and verbal ability were evaluated at 0800, 1200, and 1600 hours. Voluntary symptoms and observations of sleep were collected daily. An analysis of variance and test for trend was performed on the difference and score for each concentration reflecting an eight hour workday where each subject was their own control. A 3 x 3 Latin square study design evaluated toluene effects simultaneously, controlling for learning across the three days and the solvent order. Intersubject variation in solvent uptake was monitored in breath and urine. A 5-10% decrement in performance was considered significant if it was consistent with a linear trend at p less than 0.05. Adverse performance at 150 ppm toluene was found at 6.0% for digit span, 12.1% for pattern recognition (latency), 5.0% for pattern memory (number correct), 6.5% for one hole, and 3.0% for critical tracking. The number of headaches and eye irritation also increased in a dose response manner. The greatest effect was found for an increasing number of observations of sleep. Overall, no clear pattern of neurobehavioural effects was found consistent with the type 1 central nervous system as classified by the World Health Organisation. Subtle acute effects, however, were found just below and above the ACGIH TLV of 100 ppm toluene, supporting the position that the guideline be lowered since the biological

  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. Knowledge of Psychiatric Nurses About the Potentially Lethal Side-Effects of Clozapine.

    PubMed

    De Hert, Marc; De Beugher, Annelien; Sweers, Kim; Wampers, Martien; Correll, Christoph U; Cohen, Dan

    2016-02-01

    Clozapine is an antipsychotic with superior efficacy in treatment refractory patients, and has unique anti-suicidal properties and a low propensity to cause extrapyramidal side-effects. Despite these advantages, clozapine utilization is low. This can in part be explained by a number of potentially lethal side effects of clozapine. Next to psychiatrists nurses play a crucial role in the long-term management of patients with schizophrenia. It is therefore important that nurses know, inform and monitor patients about the specific side-effects of clozapine. A recent study of psychiatrists published in 2011 has shown that there was a gap in the knowledge about side-effects of clozapine. The knowledge about side-effects of clozapine in nurses has never been studied. This cross-sectional study evaluated the knowledge base regarding the safety of clozapine, and its potential mediators, of psychiatric nurses in 3 psychiatric hospitals in Belgium with a specifically developed questionnaire based on the literature and expert opinion (3 clozapine experts). A total of 85 nurses completed the questionnaire. The mean total score was 6.1 of a potential maximum score of 18. Only 3 of the 18 multiple choice knowledge questions were answered correctly by more than 50% of nurses. Only 24.9% of participants passed the test (>50% correct answers). Nurses working on psychosis units were more likely to pass the test (xx.y% vs yy.z%, p=0.0124). There was a trend that nurses with a lower nursing diploma were more likely to fail the test (p=0.0561). Our study clearly identifies a large gap in the basic knowledge of psychiatric nurses about clozapine and its side-effects. Knowledge could be increased by more emphasis on the topic in nurse's training curricula as well as targeted onsite training. Only 23.5% of participants indicate that there was sufficient information in their basic nursing training.

  16. Lethal and estrogenic effects of 4-nonylphenol in the cockle Cerastoderma glaucum.

    PubMed

    Marin, Maria Gabriella; Rigato, Stefano; Ricciardi, Francesco; Matozzo, Valerio

    2008-01-01

    The lethal and sublethal effects of the xenoestrogen 4-nonylphenol (NP) were evaluated in the cockle Cerastoderma glaucum. In a 96-h lethality test, bivalves were exposed to 0, 0+ acetone, 0.19, 0.38, 0.75, 1.5 and 3.0 mg NP/l. The 96-h LC(50) value was 0.3mg NP/l. No mortality was observed at 0.1 mg NP/l. The potential estrogenicity of NP was studied in both sexually undifferentiated (resting phase) and differentiated (pre-spawning phase) cockles, exposed for 7 and 14 days to 0, 0+ acetone, 0.0125, 0.025, 0.05, and 0.1 mg NP/l. Vitellogenin (Vg)-like protein levels were determined in both haemolymph and digestive gland by the alkali-labile phosphate (ALP) assay. In the resting phase, exposure for 7 days to 0.1 mg NP/l resulted in significant increases in ALP in both haemolymph and digestive gland, compared with controls. A significant increase was also observed in digestive gland of animals exposed to 0.0125 mg NP/l-exposed animals. After 14 days of exposure, haemolymph ALP levels were significantly increased in exposed animals at all NP concentrations tested, whereas no difference was recorded in digestive gland. In the pre-spawning phase, exposure for 7 days to NP significantly increased ALP levels in haemolymph from males exposed at all NP concentrations tested, whereas no significant variations were found in haemolymph from females. NP (0.05 and 0.1 mg/l) was also shown to increase ALP concentrations significantly in digestive gland of males, but not in those of females. Likewise, after 14 days' exposure, ALP levels significantly increased in haemolymph from males only at 0.1 mg NP/l. Conversely, NP caused significant increases in ALP levels in digestive gland from both males (at all NP concentrations tested) and females (at 0.025 and 0.1 mg NP/l). These results demonstrate that NP induces Vg synthesis in C. glaucum. Interestingly, males were more responsive to NP than females.

  17. Lethal and sublethal effects of marine sediment extracts on fish cells and chromosomes

    NASA Astrophysics Data System (ADS)

    Landolt, Marsha L.; Kocan, Richard M.

    1984-03-01

    The cost of conducting conventional chronic bioassays with every potentially toxic compound found in marine ecosystems is prohibitive; therefore short-term toxicity tests which can be used for rapid screening were developed. The tests employ cultured fish cells to measure lethal, sublethal or genotoxic effects of pure compounds and complex mixtures. The sensitivity of these tests has been proven under laboratory conditions; the following study used two of these tests, the anaphase aberration test and a cytotoxicity assay, under field conditions. Sediment was collected from 97 stations within Puget Sound, Washington. Serial washings of the sediment in methanol and dichloromethane yielded an organic extract which was dried, dissolved in DMSO and incubated as a series of dilutions with rainbow trout gonad (RTG-2) cells. The toxic effects of the extract were measured by examining the rate of cell proliferation and the percentage of damaged anaphase figures. Anaphase figures were considered to be abnormal if they exhibited non-disjunctions, chromosome fragments, or chromosome bridges. A second cell line (bluegill fry, BF-2) was also tested for cell proliferation and was included because, unlike the RTG-2 cell line, it contains little or no mixed function oxygenase activity. Of 97 stations tested, 35 showed no genotoxic activity, 42 showed high genotoxic activity (P≤.01) and the remainder were intermediate. Among the toxic sites were several deep water stations adjacent to municipal sewage outfalls and four urban waterways contaminated by industrial and municipal effluents. Extracts from areas that showed genotoxic effects also inhibited cell proliferation and were cytotoxic to RTG-2 cells. Few effects were noted in the MFO deficient BF-2 cells. Short term in vitro tests provide aquatic toxicologists with a versatile and cost effective tool for screening complex environments. Through these tests one can identify compounds or geographic regions that exhibit high

  18. The effect of sexual harassment on lethal mutation rate in female Drosophila melanogaster.

    PubMed

    Maklakov, Alexei A; Immler, Simone; Løvlie, Hanne; Flis, Ilona; Friberg, Urban

    2013-01-07

    The rate by which new mutations are introduced into a population may have far-reaching implications for processes at the population level. Theory assumes that all individuals within a population have the same mutation rate, but this assumption may not be true. Compared with individuals in high condition, those in poor condition may have fewer resources available to invest in DNA repair, resulting in elevated mutation rates. Alternatively, environmentally induced stress can result in increased investment in DNA repair at the expense of reproduction. Here, we directly test whether sexual harassment by males, known to reduce female condition, affects female capacity to alleviate DNA damage in Drosophila melanogaster fruitflies. Female gametes can repair double-strand DNA breaks in sperm, which allows manipulating mutation rate independently from female condition. We show that male harassment strongly not only reduces female fecundity, but also reduces the yield of dominant lethal mutations, supporting the hypothesis that stressed organisms invest relatively more in repair mechanisms. We discuss our results in the light of previous research and suggest that social effects such as density and courtship can play an important and underappreciated role in mediating condition-dependent mutation rate.

  19. 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.

  20. Lethal and Sublethal Effects of Ivermectin on Onthophagus landolti (Coleoptera: Scarabaeidae).

    PubMed

    Pérez-Cogollo, L C; Rodríguez-Vivas, R I; Delfín-González, H; Reyes-Novelo, E; Ojeda-Chi, M M

    2015-12-01

    Previous work has documented toxic effects of ivermectin (IVM) on dung beetles from the Old World, but very little is known about this drug's effect on Neotropical dung beetles. Accordingly, we conducted a bioassay with dung spiked with IVM to assess its lethal and sublethal effects on the Neotropical dung beetle Onthophagus landolti Harold. The experimental design consisted of five treated groups G1, G2, G3, G4, and G5 receiving 0.001, 0.01, 0.1, 1.0, and 10 mg IVM/kg dung fresh weight, respectively, and two control groups (solvent control [CGA] and untreated control [CGU]). Adult survival and fecundity were measured throughout a 10-d period, and subsequent egg development and survival were monitored. Adult survival was only affected for treatment groups G4 and G5 groups (70 and 30%, respectively); groups G1, G2, G3 and both controls exhibited 100% survival. Fecundity was completely suppressed under treatment groups G4 and G5. Group G3 only had 1.7 and 2.1% brood mass production relative to CGA and CGU, respectively. Additionally, for groups G1 and G2 the proportion of adults emerging from brood masses was lower relative to CGA. Furthermore, development time for the second generation in groups G1 and G2 was 12.5% slower relative to control groups. Finally, dung removal by beetles from groups G3, G4, and G5 was significantly lower relative to control groups. In conclusion, toxic effects of IVM on O. landolti are associated mainly with reduced fecundity and lower dung-removal by adult beetles as well as reduced survival and slower development of offspring.

  1. Cis-by-Trans Regulatory Divergence Causes the Asymmetric Lethal Effects of an Ancestral Hybrid Incompatibility Gene

    PubMed Central

    Maheshwari, Shamoni; Barbash, Daniel A.

    2012-01-01

    The Dobzhansky and Muller (D-M) model explains the evolution of hybrid incompatibility (HI) through the interaction between lineage-specific derived alleles at two or more loci. In agreement with the expectation that HI results from functional divergence, many protein-coding genes that contribute to incompatibilities between species show signatures of adaptive evolution, including Lhr, which encodes a heterochromatin protein whose amino acid sequence has diverged extensively between Drosophila melanogaster and D. simulans by natural selection. The lethality of D. melanogaster/D. simulans F1 hybrid sons is rescued by removing D. simulans Lhr, but not D. melanogaster Lhr, suggesting that the lethal effect results from adaptive evolution in the D. simulans lineage. It has been proposed that adaptive protein divergence in Lhr reflects antagonistic coevolution with species-specific heterochromatin sequences and that defects in LHR protein localization cause hybrid lethality. Here we present surprising results that are inconsistent with this coding-sequence-based model. Using Lhr transgenes expressed under native conditions, we find no evidence that LHR localization differs between D. melanogaster and D. simulans, nor do we find evidence that it mislocalizes in their interspecific hybrids. Rather, we demonstrate that Lhr orthologs are differentially expressed in the hybrid background, with the levels of D. simulans Lhr double that of D. melanogaster Lhr. We further show that this asymmetric expression is caused by cis-by-trans regulatory divergence of Lhr. Therefore, the non-equivalent hybrid lethal effects of Lhr orthologs can be explained by asymmetric expression of a molecular function that is shared by both orthologs and thus was presumably inherited from the ancestral allele of Lhr. We present a model whereby hybrid lethality occurs by the interaction between evolutionarily ancestral and derived alleles. PMID:22457639

  2. 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

  3. 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.

  4. Lethal and Sublethal Effects of Insecticides Used on Citrus, on the Ectoparasitoid Tamarixia radiata

    PubMed Central

    Beloti, Vitor Hugo; Alves, Gustavo Rodrigues; Araújo, Diogo Feliciano Dias; Picoli, Mateus Manara; Moral, Rafael de Andrade; Demétrio, Clarice Garcia Borges; Yamamoto, Pedro Takao

    2015-01-01

    Huanglongbing (HLB) is a disease associated with the bacteria “Candidatus Liberibacter spp.” and has been devastating citrus orchards around the world. Its management involves control of the insect vector, the Asian citrus psyllid Diaphorina citri Kuwayama. However, the indiscriminate use of chemicals has caused pest outbreaks and eliminated the natural enemies of the vector, such as the parasitoid Tamarixia radiata (Waterston), the main agent for biological control of D. citri. This study assessed the lethal and sublethal effects of insecticides recommended for integrated production of citrus on the parasitoid T. radiata. When adult parasitoids were exposed to residues of 25 insecticides, 20% of them, i.e., gamma-cyhalothrin, etofenprox, azadirachtin, tebufenozide and pyriproxyfen, were considered as harmless (Class 1), 12% as slightly harmful (Class 2), 12% as moderately harmful (Class 3) and 56% as harmful (Class 4), according to the classification proposed by the IOBC/WPRS. Afterward, 14 insecticides (5 harmless and 9 harmful) were sprayed on the parasitoid pupae. Of the 14 insecticides tested, only the organophosphates dimethoate and chlorpyrifos affected the parasitoid emergence. The effects of insecticides on the parasitism capacity of adults exposed to residues of azadirachtin, etofenprox, gamma-cyhalothrin, pyriproxyfen and tebufenozide (harmless) were also evaluated. Tebufenozide and gamma-cyhalothrin affected the parasitism of the F0 generation, but did not affect the emergence of the F1 and F2 generations. Therefore, for an effective IPM program, selective insecticides or harmful pesticides to adult parasitoids could be used in the field, provided that the adults do not occur naturally and the chemical applications do not coincide with parasitoid releases. PMID:26132327

  5. Lethal and Sublethal Effects of Insecticides Used on Citrus, on the Ectoparasitoid Tamarixia radiata.

    PubMed

    Beloti, Vitor Hugo; Alves, Gustavo Rodrigues; Araújo, Diogo Feliciano Dias; Picoli, Mateus Manara; Moral, Rafael de Andrade; Demétrio, Clarice Garcia Borges; Yamamoto, Pedro Takao

    2015-01-01

    Huanglongbing (HLB) is a disease associated with the bacteria "Candidatus Liberibacter spp." and has been devastating citrus orchards around the world. Its management involves control of the insect vector, the Asian citrus psyllid Diaphorina citri Kuwayama. However, the indiscriminate use of chemicals has caused pest outbreaks and eliminated the natural enemies of the vector, such as the parasitoid Tamarixia radiata (Waterston), the main agent for biological control of D. citri. This study assessed the lethal and sublethal effects of insecticides recommended for integrated production of citrus on the parasitoid T. radiata. When adult parasitoids were exposed to residues of 25 insecticides, 20% of them, i.e., gamma-cyhalothrin, etofenprox, azadirachtin, tebufenozide and pyriproxyfen, were considered as harmless (Class 1), 12% as slightly harmful (Class 2), 12% as moderately harmful (Class 3) and 56% as harmful (Class 4), according to the classification proposed by the IOBC/WPRS. Afterward, 14 insecticides (5 harmless and 9 harmful) were sprayed on the parasitoid pupae. Of the 14 insecticides tested, only the organophosphates dimethoate and chlorpyrifos affected the parasitoid emergence. The effects of insecticides on the parasitism capacity of adults exposed to residues of azadirachtin, etofenprox, gamma-cyhalothrin, pyriproxyfen and tebufenozide (harmless) were also evaluated. Tebufenozide and gamma-cyhalothrin affected the parasitism of the F0 generation, but did not affect the emergence of the F1 and F2 generations. Therefore, for an effective IPM program, selective insecticides or harmful pesticides to adult parasitoids could be used in the field, provided that the adults do not occur naturally and the chemical applications do not coincide with parasitoid releases.

  6. Predator-hunting success and prey vulnerability: quantifying the spatial scale over which lethal and non-lethal effects of predation occur.

    PubMed

    Cresswell, Will; Lind, Johan; Quinn, John L

    2010-05-01

    1. The shape of the function linking predator-attack success rate with distance to predator-concealing cover, or prey refuge, will affect population dynamics, distribution patterns and community trophic structure. Theory predicts that predator-attack success should decline exponentially with distance from predator-concealing cover, resulting in a threshold distance value above which there is little change in risk. Animals should then completely avoid areas of otherwise suitable habitat below this threshold, except when starvation risk exceeds predation risk. 2. We measured the shape of the function linking attack success with distance from cover in a system of Eurasian Sparrowhawks Accipiter nisus attacking (n = 445) and killing (n = 71) Redshanks Tringa totanus. We then determined if there was a threshold value and whether redshanks avoided areas below this threshold. 3. Sparrowhawk success rate with distance to predator-concealing cover declined exponentially with a threshold value of approximately 30 m. Redshanks used habitat above the threshold according to profitability and only fed below it, on average, in cold weather when starvation risk can be imminently high. Above about 5 degrees C, 26% of available habitat was avoided. 4. Our data support the hypothesis that predators create discrete areas with respect to cover that are avoided by prey. Large areas of suitable habitat may be unused, except in times of high starvation risk, when such areas may provide a foraging reserve, with large implications for population distribution and dynamics. 5. Our results are generated from a system in which predators attack their prey from concealing cover. But in the theoretically identical reverse scenario where the prey animal's distance from protective cover determines predation risk, such non-lethal effects will be equally important, especially in heavily fragmented landscapes.

  7. Effects of metallothionein on zinc metabolism in lethal-milk mutant mice

    SciTech Connect

    Grider, A. Jr.

    1986-01-01

    The lethal-milk mice (C57BL/6J-Im) exhibit various pleiotropic effects, including a congenital otolith defect, production of zinc-deficient milk, and clinical signs of a systemic Zn deficiency by one year of age. The clinical signs include alopecia, dermatitis, and skin lesions. The systemic zinc deficiency may be due to increased levels of metallothionein (MT) in the intestine and/or liver of Im mice. The untreated Im mice contain twice as much intestinal MT as do C57BL/6J-(+/sup im//+ /sup Im/) (B6) controls. This was determined by a sulfhydryl assay, by the /sup 109/Cd-saturation/hemolysate method, and by the /sup 65/Zn-binding assay. Various concentrations of Cd or Zn were added to the drinking water three days before assaying for MT. Compared to B6 mice, the Im mice exhibited more MT in their liver by the /sup 65/Zn-MT binding assay (3-fold) and by the /sup 109/Cd-saturation/hemolysate method (18-fold). The effects of the two zinc treatments did not differ significantly between Im and B6 mice. The retention and excretion of /sup 65/Zn (administered intraperitoneally) were determined over a 14-day period, but the results did not different between the Im and B6 mice. The increased concentrations of MT within the Im mice was not significantly different for the intestine and liver. Based on these data and other studies, the Im mice may exhibit alterations in zinc homeostasis due to some deregulation of MT metabolism, including the inner ear of the fetus, the lactating mammary gland, and the intestine and liver of adults by one year of age.

  8. Prediction of lethal/effective concentration/dose in the presence of multiple auxiliary covariates and components of variance

    USGS Publications Warehouse

    Gutreuter, S.; Boogaard, M.A.

    2007-01-01

    Predictors of the percentile lethal/effective concentration/dose are commonly used measures of efficacy and toxicity. Typically such quantal-response predictors (e.g., the exposure required to kill 50% of some population) are estimated from simple bioassays wherein organisms are exposed to a gradient of several concentrations of a single agent. The toxicity of an agent may be influenced by auxiliary covariates, however, and more complicated experimental designs may introduce multiple variance components. Prediction methods lag examples of those cases. A conventional two-stage approach consists of multiple bivariate predictions of, say, medial lethal concentration followed by regression of those predictions on the auxiliary covariates. We propose a more effective and parsimonious class of generalized nonlinear mixed-effects models for prediction of lethal/effective dose/concentration from auxiliary covariates. We demonstrate examples using data from a study regarding the effects of pH and additions of variable quantities 2???,5???-dichloro-4???- nitrosalicylanilide (niclosamide) on the toxicity of 3-trifluoromethyl-4- nitrophenol to larval sea lamprey (Petromyzon marinus). The new models yielded unbiased predictions and root-mean-squared errors (RMSEs) of prediction for the exposure required to kill 50 and 99.9% of some population that were 29 to 82% smaller, respectively, than those from the conventional two-stage procedure. The model class is flexible and easily implemented using commonly available software. ?? 2007 SETAC.

  9. Lethal effects of heat and use of localized heat treatment for control of bed bug infestations.

    PubMed

    Pereira, Roberto M; Koehler, Philip G; Pfiester, Margie; Walker, Wayne

    2009-06-01

    Bed bugs, Cimex lectularius L., hide in cracks and crevices in furniture and are difficult to control. The bed bug thermal death kinetics were examined to develop a heat treatment method to eliminate bed bug infestations in room contents. High temperatures caused temporary immobilization (knockdown) of bed bugs even with exposures that did not have lethal effects. Exposure of bed bug adults to 39 degrees C for 240 min caused no mortality; however, as temperatures increased from 41 to 49 degrees C, exposure times that caused 100% mortality decreased. The temperature difference to provide a 10-fold change in the mortality was estimated at 4 degrees C, and the estimated activation energy (EA) was between 484 and 488.3 kJ/mol. This demonstrates that bed bugs are not more resistant or susceptible to changes in temperature than other tested insects and that the temperatures needed to kill bed bugs are relatively low. In room treatment tests, heat treatment times varied from 2 to 7 h with complete mortality of exposed bed bugs within the treatment envelope created by surrounding the treated furniture with polystyrene sheathing boards. Containment and circulation of heat around the treated material were crucial factors in an efficient heat treatment for bed bug control. The room floor material greatly affected containment of the heat. The tested method for limited heat treatment of furniture and other room contents required equipment costing less than US$400 and provided opportunity for residual pesticide application around the room with minimal disruption in use of treated room.

  10. A study of the shape of dose-response curves for acute lethality at low response: a megadaphnia study'

    SciTech Connect

    Sebaugh, J.L.; Wilson, J.D.; Tucker, M.W.; Adams, W.J. )

    1991-12-01

    Dose-response curves were developed for the immobilization response in Daphnia magna to four toxicants. The purpose of this work was to study the effect of the form of the model and the number of concentration levels used on the estimates of typical low-dose effective concentrations (1%, 5%, 10%). The generalized four-parameter logistic model was used as the reference. When using 12 concentration levels, one of the logistic family two- or three-parameter models was shown reliably to represent each of these various sets of dose-response data, and to provide adequate estimates of EC01 and EC05, as well as EC10 and EC50. For two of the toxicants, an asymmetric model was required. When reducing the number of concentrations to five, the EC10 and EC50 were well estimated by the probit model, with acceptable results at the EC05 level.

  11. 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.

  12. Antibacterial and brine shrimp lethality effect of marine actinobacterium Streptomyces sp. CAS72 against human pathogenic bacteria

    PubMed Central

    Sivasankar, Palaniappan; Manivasagan, Panchanathan; Vijayanand, Packiyaraj; Sivakumar, Kannan; Sugesh, Shanmugam; Poongodi, Subramaniam; Maharani, Viswanathan; Vijayalakshmi, Shanmugam; Balasubramanian, Thangavel

    2013-01-01

    Objective To investigate the in vitro antibacterial activity against human pathogenic bacteria and brine shrimp lethality bioassay of the marine actinobacterium. Methods Forty six marine actinobacterial strains were isolated from sediment samples of Uppanar estuary, Cuddalore, India. Preliminary screening was done by cross-streak method and the potential strain was identified by morphological, chemotaxonomical and molecular methods. Fermentation was done and the metabolite was obtained by liquid-liquid extraction using ethyl acetate and purified by silica gel (100-200 mesh) column chromatography. The purified metabolite was tested for antibacterial activity, minimal inhibitory concentration and brine shrimp lethality bioassay. Results Among the forty six strains, CAS72 was found effective against human pathogenic bacteria. The strain CAS72 was identified as Streptomyces sp. The purified metabolite exhibited a significant in vitro antibacterial activity. The MIC value was also determined against human pathogenic bacteria and a strong cytotoxic activity in brine shrimp lethality assay was observed and the LC50 value was 23.5 µg/mL. Conclusions The present investigation reveals that the marine actinobacteria are well obtainable in Uppanar estuary environment and it can provide a definite source for novel bioactive metabolites.

  13. Protective effects of imipramine in murine endotoxin-induced acute lung injury.

    PubMed

    Yang, Jin; Qu, Jie-ming; Summah, Hanssa; Zhang, Jin; Zhu, Ying-gang; Jiang, Hong-ni

    2010-07-25

    The tricyclic antidepressant imipramine has recently emerged as a cytoprotective agent, exerting beneficial effects in inflammatory tissue injury. The present study aimed to investigate therapeutic effects of imipramine in murine model of endotoxin-induced acute lung injury. Mice were administrated intraperitoneally with LPS (lipopolysaccharide) from Escherichia coli or vehicle. Imipramine was administrated intraperitoneally 30 min before LPS challenge. Pretreatment of mice with imipramine reduced lethality. Impramine also significantly attenuated lung inflammation, lung edema, MPO (myeloperoxidase) activity, lung tissue pathological changes and nuclear factor-kappaB DNA binding activity. The results of this study suggest that imipramine can exert protective effects in endotoxin-induced acute lung injury by suppressing nuclear factor-kappaB-mediated expression of inflammatory genes. Thus, imipramine could be a potential novel therapeutic agent for the treatment for acute lung injury.

  14. 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

  15. 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.

  16. Effects of diiospropyl-1,3-dithiol-2-ylidene malonate (NKK-105) on acute toxicity of various drugs and heavy metals.

    PubMed

    Kitagawa, H; Saito, H; Sugimoto, T; Yanaura, S; Kitagawa, H; Hosokawa, T; Sakamoto, K

    1982-05-01

    The influence of NKK-105 on the acute toxicity of strychnine nitrate, potassium cyanide, chloral hydrate, atropine, tetrodotoxin, mercuric chloride, cadmium chloride, lead acetate and arsenic trioxide were examined in rats. NKK-105 prolonged the time of death induced by strychnine, potassium cyanide and tetrodotoxin in acute toxicity. Survival time was prolonged in rats treated with the toxic metals by pretreatment with NKK-105. NKK-105 counteracted the lethal effect of strychnine, potassium cyanide, chloral hydrate, mercuric chloride and cadmium chloride. NKK-105 significantly decreased the acute toxicity of these drugs but the inhibitory effect was not observed in the acute toxicity of atropine, tetrodotoxin, lead acetate and arsenic trioxide.

  17. Reflexive retaliation for violent victimization: the effect of social distance on weapon lethality.

    PubMed

    Jacques, Scott; Rennison, Callie Marie

    2013-01-01

    During the course of being victimized, why do people sometimes fight back with their fists; in other cases, with a knife or blunt object; and at other times, with a firearm? One theory is that the weapons involved in self-defense, also known as reflexive retaliation, become less lethal as offenders and victims become more intimate and alike culturally. Using National Crime Victimization Survey data, we test hypotheses derived from this theory and primarily find support. This article concludes by discussing implications for future work.

  18. The influence of the time of antidotal treatment administration on the potency of newly developed oximes to counteract acute toxic effects of tabun in mice.

    PubMed

    Kassa, Jirí

    2005-01-01

    (1) The influence of the time of administration of antidotal treatment consisting of anticholinergic drug (atropine) and newly developed oxime (K027 or K048) on its effectiveness to eliminate tabun-induced lethal toxic effects was studied in mice. (2) The therapeutic efficacy of antidotal treatment of tabun-induced acute poisoning depends on the time of its administration regardless of the choice of the oxime. (3) Our results show that both oximes studied (K027, K048) are able to sufficiently eliminate lethal effects of tabun. Nevertheless, their efficacy significantly decreases when they were administered 5 min after tabun poisoning. (4) The findings support the hypothesis that both newly developed oximes appear to be suitable oximes to counteract acute toxicity of tabun although their ability to eliminate lethal toxic effects of tabun significantly decreases with prolonged time interval between tabun challenge and antidotal treatment administration.

  19. Mutagenesis-Mediated Virus Extinction: Virus-Dependent Effect of Viral Load on Sensitivity to Lethal Defection

    PubMed Central

    Moreno, Héctor; Tejero, Héctor; de la Torre, Juan Carlos; Domingo, Esteban; Martín, Verónica

    2012-01-01

    Background Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI) on progeny production of several RNA viruses under enhanced mutagenesis. Results The effect of the mutagenic base analogue 5-fluorouracil (FU) on the replication of the arenavirus lymphocytic choriomeningitis virus (LCMV) can result either in inhibition of progeny production and virus extinction in infections carried out at low multiplicity of infection (MOI), or in a moderate titer decrease without extinction at high MOI. The effect of the MOI is similar for LCMV and vesicular stomatitis virus (VSV), but minimal or absent for the picornaviruses foot-and-mouth disease virus (FMDV) and encephalomyocarditis virus (EMCV). The increase in mutation frequency and Shannon entropy (mutant spectrum complexity) as a result of virus passage in the presence of FU was more accentuated at low MOI for LCMV and VSV, and at high MOI for FMDV and EMCV. We present an extension of the lethal defection model that agrees with the experimental results. Conclusions (i) Low infecting load favoured the extinction of negative strand viruses, LCMV or VSV, with an increase of mutant spectrum complexity. (ii) This behaviour is not observed in RNA positive strand viruses, FMDV or EMCV. (iii) The accumulation of defector genomes may underlie the MOI-dependent behaviour. (iv) LCMV coinfections are allowed but superinfection is strongly restricted in BHK-21 cells. (v) The dissimilar effects of the MOI on the efficiency of mutagenic-based extinction of different RNA viruses can have implications for the design of antiviral protocols based on lethal mutagenesis, presently under development. PMID:22442668

  20. Lethal and sublethal effects of the sediment-associated PCB Aroclor 1254 on a meiobenthic copepod

    SciTech Connect

    DiPinto, L.M.; Coull, B.C.; Chandler, G.T. . Dept. of Environmental Health Sciences, Marine Science Program, and Belle W. Baruch Inst. for Marine Biology and Coastal Research)

    1993-10-01

    Acute toxicity tests were performed on field-collected copepods (Microarthridion littorale) using the sediment-associated polychlorinated biphenyl (PCB) Aroclor 1254 (i.e., PCB concentrations in bulk sediments in the bound and/or unbound states). Three replicates of 50 adult copepods were exposed to five levels of PCB-contaminated sediments for 96 h and compared to untreated controls and solvent controls. LC50 concentrations were nearly twice as high for females as for males. To determine the effects of the PCB on reproductive output of the copepods, copulating pairs of Microarthridion littorale were allowed to reproduce in concentrations of Aroclor 1254-contaminated sediments below LC50 values. Two experimental trials with 10 and 15 replicates, each with one pair of Microarthridion littorale in copulus, were conducted for 12 d, the normal time needed for females to produce one set of nauplii and carry a second clutch of eggs. In both experiments, a significant decrease in number of nauplii was found with Aroclor contamination. Although NOECs were not determined, high concentrations of the sediment-associated Aroclor NOECs were required to affect mortality significantly, whereas lower levels impaired reproduction.

  1. Relationship between lethal toxicity in oral administration and injection to mice: effect of exposure routes.

    PubMed

    Wang, Yu; Ning, Zhong H; Tai, Hong W; Long, Shuang; Qin, Wei C; Su, Li M; Zhao, Yuan H

    2015-03-01

    The lethal toxicity (LD₅₀) in oral administration, intravenous, intraperitoneal, intramuscular and subcutaneous injections were used to investigate relationships of log 1/LD₅₀ from different exposure routes. Regression analysis showed that log 1/LD₅₀ in oral route was related to the toxicity in injection route. This relationship in lethality between the two routes is apparently due to the same mechanisms of the compounds to the same species. However, the scatter in the correlation curve indicates that exposure route is an important factor that influences the relationship. Some compounds with low intestinal absorption exhibit much less toxicity in oral administration than that in the injection route. A systemic bias of log 1/LD₅₀ between oral and injection routes indicates that tissue distribution of compounds between blood and target site is a very rapid process, leading to log 1/LD₅₀ in injection greater than those in oral administration. Although compounds can be metabolized in the body both from oral and injection routes, first-pass metabolism occurs in oral route but not in injection route. This will result in decrease of toxicity in oral route for most compounds as compared with injection route. In addition, experimental uncertainty, differences in gender, and species can also affect relationships of log1/LD₅₀ between exposure routes.

  2. Effects of lethal and sublethal concentrations of the herbicide, triclopyr butoxyethyl ester, in the diet of zebra finches.

    PubMed

    Holmes, S B; Thompson, D G; Wainio-Keizer, K L; Capell, S S; Staznik, B

    1994-07-01

    Lethal and sublethal effects of dietary triclopyr butoxyethyl ester (TBEE) on zebra finches (Poephila guttata Gould) were determined in laboratory experiments conducted between 8 January and 1 May 1991. The 8-day median lethal dietary concentration, LC50 (95% confidence interval), of TBEE to zebra finches was 1,923 (1,627 to 2,277) mg/kg. In the sublethal effects experiment, when birds were exposed to 500 mg/kg TBEE in the diet for 29 days, food consumption and body weight were significantly depressed (P < 0.05). Similar prolonged exposures to 50 and 150 mg/kg TBEE in the diet had no significant effect on food consumption or body weight (P > 0.05). Perch-hopping activity was depressed relative to controls in the 500 mg/kg group, and elevated in the 150 mg/kg group, but neither of these differences was significantly (P > 0.05). Disappearance of TBEE residues from treated seeds over the 29 day experimental period followed an exponential decay model, with half-lives in the order of 15 to 18 days. On the basis of our observation that TBEE had no significant adverse effects at a concentration greater than the maximum expected environmental concentration, we propose that forestry applications of triclopyr at registered dosage rates pose little risk to wild songbirds.

  3. Lethal and sublethal effects of seven insecticides on three beneficial insects in laboratory assays and field trials.

    PubMed

    Fernandes, Maria E S; Alves, Flávia M; Pereira, Renata C; Aquino, Leonardo A; Fernandes, Flávio L; Zanuncio, José C

    2016-08-01

    Lethal and sublethal effects of insecticides on target and non-target arthropods are a concern of pest management programs. Cycloneda sanguinea, Orius insidiosus and Chauliognathus flavipes are important biological control agents for aphids, whitefly, lepidopterus eggs, thrips and mites. All three test species were subjected to a toxicity study using the insecticides acephate, bifenthrin, chlorantraniliprole, chlorpyrifos, deltamethrin, imidacloprid, and thiamethoxam. Experiments were done in the lab and field. In the laboratory we evaluated the mortality and sublethal effects of the concentration that killed 20% of the population (LC20) on feeding, repellence and reproduction of the species tested. The lethal effects of these insecticides at the recommended doses was evaluated in the field. Concentration-response bioassays indicated chlorantraniliprole had the lowest toxicity, while chlorpyrifos and acephate were the most toxic. Test species exposed to filter paper surfaces treated with pyrethroids, neonicotinoids and organophosphates were repelled. On the other hand, test species were not repelled from surfaces treated with chlorantraniliprole. Chlorantraniliprole therefore seemed to be the least dangerous insecticide for these three beneficial arthropod test species.

  4. Seasonal variations of the effect of temperature on lethal and sublethal toxicities of ammonia for three common freshwater shredders.

    PubMed

    Dehedin, Arnaud; Piscart, Christophe; Marmonier, Pierre

    2013-01-01

    In a context of global change, increases in temperature and in ammonia concentration should strongly affect the crustaceans of wetlands. We experimentally examined, at three different seasons (i.e. winter, spring, and summer), the effect of temperature (12, 18, and 24°C) on the lethal (survival rates) and sublethal (oxygen consumption) toxicity of unionized ammonia (NH(3)) on the amphipods Gammarus pulex and Gammarus roeselii and the isopod Asellus aquaticus. Our results demonstrate (1) a gradient of increasing tolerance and survival from G. roeselii to G. pulex and A. aquaticus, (2) an increasing toxicity of ammonia with temperature, and (3) a strong seasonal variation of the tolerance to ammonia, with a higher tolerance of individuals in winter than in summer. However, the sub-lethal effect of ammonia on the oxygen consumption rate was species dependant and changed according to temperature or season. Global change and resulting variations in crustacean densities will potentially affect the ecosystem functioning (e.g. organic matter recycling).

  5. Protection of mammalian cells by o-phenanthroline from lethal and DNA-damaging effects produced by active oxygen species.

    PubMed

    de Mello Filho, A C; Meneghini, R

    1985-10-30

    Active oxygen species are suspected as being a cause of the cellular damage that occurs at the site of inflammation. Phagocytic cells accumulate at these sites and produce superoxide ion, hydrogen peroxide and hydroxyl radical. The ultimate killing species, the cellular target and the mechanism whereby the lethal injury is produced are unknown. We exposed mouse fibroblasts to xanthine oxidase and acetaldehyde, a system which mimics the membrane of phagocytic cells in terms of production of oxygen species. We observed that the generation of these species produced DNA strand breaks and cellular death. The metal chelator o-phenanthroline completely abolished the former effect, and at the same time it effectively protected the cells from lethal injuries. Because complexing iron o-phenanthroline prevents the formation of hydroxyl radical by the Fendon reaction (Fe(II) + H2O2----Fe(III) + OH- + OH.), it is proposed that most of the cell death and DNA damage are brought about by OH radical, produced from other species by iron-mediated reactions.

  6. Effect of Diazepam on Severity of Acute Pancreatitis: Possible Involvement of Peripheral Benzodiazepine Receptors

    PubMed Central

    Abed, Alireza; Minaiyan, Mohsen; Safaei, Azadeh; Taheri, Diana

    2013-01-01

    Acute pancreatitis is a lethal inflammatory condition of pancreas with high mortality rate. There is a pressing need for research to explore active agents and novel mechanisms involving in the treatment of pancreatitis. Clinical studies have shown after the initial acinar cell injury plasma levels of pro-inflammatory cytokines are elevated in patients with acute pancreatitis and the degree of cytokine elevation correlates with disease severity. Diazepam may decrease interleukin release from macrophages, suppress neutrophil activities, and exhibit anti-inflammatory effects. So it is expected that in vivo pretreatment of acute pancreatitis with different doses of diazepam can attenuate its severity. Thus, we evaluated the effects of diazepam, intraperitoneally (5, 10, and 20 mg/kg i.p.), intracerebroventricularly (ICV 10 μg), and concurrently with flumazenil (1 mg/kg) on cerulein-induced acute pancreatitis in mice. Interestingly, the pretreatment with diazepam (5 mg/kg i.p.) reduced significantly the inflammatory response of acute pancreatitis by ameliorating pancreatic edema, amylase and lipase serum levels, myeloperoxidase activity, pancreatic TNF-alpha, and pathological alteration compared to control group. Diazepam i.c.v. was ineffective, suggesting that central benzodiazepine receptors have no significant role in this property. These results demonstrate that pretreatment with diazepam exhibits anti-inflammatory property in cerulein-induced acute pancreatitis possibly through peripheral benzodiazepine receptors. PMID:23956866

  7. Acute lethal and sublethal effects of neem leaf extract on the neotropical freshwater fish Prochilodus lineatus.

    PubMed

    Winkaler, Elissandra U; Santos, Thiago R M; Machado-Neto, Joaquim G; Martinez, Cláudia B R

    2007-03-01

    The aim of this study was to determine the toxicity of the aqueous extract of neem leaves, a product extensively used in fish-farms as alternative for the control of fish parasites and fish fry predators, for the neotropical fish Prochilodus lineatus. The 24 h LC(50) of neem leaf extract for juveniles P. lineatus was estimated as 4.8 g L(-1); the fish were then exposed for 24 h to 2.5, 5.0 and 7.5 g L(-1) or only clean water (control). Plasma glucose levels were higher in fish exposed to 2.5 g L(-1) and 5.0 g L(-1) neem extract, relative to control, indicating a typical stress response. Neem extract did not interfere with the osmoregulating capacity of the fish, as their plasma sodium, chloride, total protein and osmolarity did not change. The presence of the biopesticide interfered with the antioxidant defense system of P. lineatus, as there was a decrease in liver catalase activity at all neem concentrations and the detoxifying enzyme glutathione-S-transferase was activated in fish exposed to 5.0 g L(-1). Fish exposed to all neem extract concentrations exhibited damaged gill and kidney tissue. These results indicate that although neem extract is less toxic to P. lineatus than other synthetic insecticides used in fish-farming it does cause functional and morphological changes in this fish species.

  8. Mitigation of lethal effects of Karlodinium veneficum and K. armiger on Sparus aurata: changes in haematocrit and plasma osmolality.

    PubMed

    Fernández-Tejedor, Margarita; Soubrier-Pedreño, M Angeles; Furones, M Dolores

    2007-08-13

    Between January and April 2000, several experiments were performed during a Karlodinium spp. proliferation in Alfacs Bay (Ebro delta, NW Mediterranean) to determine the effects of these dinoflagellates on sea bream Sparus aurata cultivated in the area. Moribund fish showed an increase in plasma osmolality together with a decrease in the haematocrit percentage compared to control fish. The efficacy of copper sulphate, hydrogen peroxide, potassium permanganate and formalin against Karlodinium spp. was also tested. None of these treatments had mitigation effects when applied in the presence of fish; on the contrary, lethal effects appeared at lower Karlodinium spp. densities compared to fish control groups. When a lytic agent, such as copper sulphate, was used as a water pre-treatment, in the absence of fish, Karlodinium spp. toxicity was significantly reduced. Protocols for water pre-treatments were studied as a potential tool for combating Karlodinium spp. in fish farms.

  9. Lethal and sublethal effects of essential oils from Eucalyptus camaldulensis and Heracleum persicum against the adults of Callosobruchus maculatus.

    PubMed

    Izakmehri, Khadijeh; Saber, Moosa; Mehrvar, Ali; Hassanpouraghdam, Mohammad Bagher; Vojoudi, Samad

    2013-01-01

    The cowpea weevil, Callosobruchus maculatus F. (Coleoptera: Bruchidae), is an important pest of stored cowpea, Vigna ungiculata (L.) Walpers (Fabales: Fabaceae), with ample distribution in tropical and subtropical regions. Many plant essential oils have a broad-spectrum activity against pest insects, and these oils traditionally have been used in the protection of stored products. In this study, the lethal and sublethal effects of essential oils from Eucalyptus camaldulensis Dehnh. (Myrtales: Myrtaceae) and Heracleum persicum Desf. (Apiales: Apiaceae) were evaluated on the adults of C. maculatus at 26 ± 1° C, 70 ± 5% RH, and a photoperiod of 16:8 L:D. The LC50 values of E. camaldulensis and H. persicum were 56.7 and 219.4 µL/L air after 12 hr and 26.1 and 136.4 µL/L air after 24 hr of exposure, respectively. The LT50 values of E. camaldulensis and H.persicum were 6.3 and 10.9 hr, respectively. The results showed that low lethal concentration (LC20) of essential oils negatively affected the longevity, fecundity, and fertility of female adults. The sex ratio of C. maculatus offspring was not significantly affected by essential oils. Therefore, these essential oils can be suggested for controlling C. maculatus in storage systems. The introduction of essential oils into storage systems could potentially decrease seed losses.

  10. Lethal and Sublethal Effects of Essential Oils from Eucalyptus camaldulensis and Heracleum persicum Against the Adults of Callosobruchus Maculatus

    PubMed Central

    Izakmehri, Khadijeh; Saber, Moosa; Mehrvar, Ali; Hassanpouraghdam, Mohammad Bagher; Vojoudi, Samad

    2013-01-01

    The cowpea weevil, Callosobruchus maculatus F. (Coleoptera: Bruchidae), is an important pest of stored cowpea, Vigna ungiculata (L.) Walpers (Fabales: Fabaceae), with ample distribution in tropical and subtropical regions. Many plant essential oils have a broad-spectrum activity against pest insects, and these oils traditionally have been used in the protection of stored products. In this study, the lethal and sublethal effects of essential oils from Eucalyptus camaldulensis Dehnh. (Myrtales: Myrtaceae) and Heracleum persicum Desf. (Apiales: Apiaceae) were evaluated on the adults of C. maculatus at 26 ± 1° C, 70 ± 5% RH, and a photoperiod of 16:8 L:D. The LC50 values of E. camaldulensis and H. persicum were 56.7 and 219.4 µL/L air after 12 hr and 26.1 and 136.4 µL/L air after 24 hr of exposure, respectively. The LT50 values of E. camaldulensis and H.persicum were 6.3 and 10.9 hr, respectively. The results showed that low lethal concentration (LC20) of essential oils negatively affected the longevity, fecundity, and fertility of female adults. The sex ratio of C. maculatus offspring was not significantly affected by essential oils. Therefore, these essential oils can be suggested for controlling C. maculatus in storage systems. The introduction of essential oils into storage systems could potentially decrease seed losses. PMID:24773362

  11. Population-level effects of fitness costs associated with repressible female-lethal transgene insertions in two pest insects.

    PubMed

    Harvey-Samuel, Tim; Ant, Thomas; Gong, Hongfei; Morrison, Neil I; Alphey, Luke

    2014-05-01

    Genetic control strategies offer great potential for the sustainable and effective control of insect pests. These strategies involve the field release of transgenic insects with the aim of introducing engineered alleles into wild populations, either permanently or transiently. Their efficacy can therefore be reduced if transgene-associated fitness costs reduce the relative performance of released insects. We describe a method of measuring the fitness costs associated with transgenes by analyzing their evolutionary trajectories when placed in competition with wild-type alleles in replicated cage populations. Using this method, we estimated lifetime fitness costs associated with two repressible female-lethal transgenes in the diamondback moth and olive fly as being acceptable for field suppression programs. Furthermore, using these estimates of genotype-level fitness costs, we were able to project longer-term evolutionary trajectories for the transgenes investigated. Results from these projections demonstrate that although transgene-associated fitness costs will ultimately cause these transgenes to become extinct, even when engineered lethality is repressed, they may persist for varying periods of time before doing so. This implies that tetracycline-mediated transgene field persistence in these strains is unlikely and suggests that realistic estimates of transgene-associated fitness costs may be useful in trialing 'uncoupled' gene drive system components in the field.

  12. Population-level effects of fitness costs associated with repressible female-lethal transgene insertions in two pest insects

    PubMed Central

    Harvey-Samuel, Tim; Ant, Thomas; Gong, Hongfei; Morrison, Neil I; Alphey, Luke

    2014-01-01

    Genetic control strategies offer great potential for the sustainable and effective control of insect pests. These strategies involve the field release of transgenic insects with the aim of introducing engineered alleles into wild populations, either permanently or transiently. Their efficacy can therefore be reduced if transgene-associated fitness costs reduce the relative performance of released insects. We describe a method of measuring the fitness costs associated with transgenes by analyzing their evolutionary trajectories when placed in competition with wild-type alleles in replicated cage populations. Using this method, we estimated lifetime fitness costs associated with two repressible female-lethal transgenes in the diamondback moth and olive fly as being acceptable for field suppression programs. Furthermore, using these estimates of genotype-level fitness costs, we were able to project longer-term evolutionary trajectories for the transgenes investigated. Results from these projections demonstrate that although transgene-associated fitness costs will ultimately cause these transgenes to become extinct, even when engineered lethality is repressed, they may persist for varying periods of time before doing so. This implies that tetracycline-mediated transgene field persistence in these strains is unlikely and suggests that realistic estimates of transgene-associated fitness costs may be useful in trialing ‘uncoupled’ gene drive system components in the field. PMID:24944572

  13. 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.

  14. Evaluation of effects of long term exposure on lethal toxicity with mammals.

    PubMed

    Verma, Vibha; Yu, Qiming J; Connell, Des W

    2014-02-01

    The relationship between exposure time (LT50) and lethal exposure concentration (LC50) has been evaluated over relatively long exposure times using a novel parameter, Normal Life Expectancy (NLT), as a long term toxicity point. The model equation, ln(LT50) = aLC50(ν) + b, where a, b and ν are constants, was evaluated by plotting lnLT50 against LC50 using available toxicity data based on inhalation exposure from 7 species of mammals. With each specific toxicant a single consistent relationship was observed for all mammals with ν always <1. Use of NLT as a long term toxicity point provided a valuable limiting point for long exposure times. With organic compounds, the Kow can be used to calculate the model constants a and v where these are unknown. The model can be used to characterise toxicity to specific mammals and then be extended to estimate toxicity at any exposure time with other mammals.

  15. Effects of DDE on experimentally poisoned free-tailed bats (Tadarida brasiliensis): lethal brain concentrations.

    PubMed

    Clark, D R; Kroll, J C

    1977-12-01

    Adult female free-tailed bats (Tadarida brasiliensis) were collected at Bracken Cave, Texas, and shipped to the Patuxent Wildlife Research Center. Treated mealworms (Tenebrio molitor) containing 107 ppm DDE were fed to 17 bats; five other bats were fed untreated mealworms. After 40 days on dosage, during which one dosed bat was killed accidentally, four dosed bats were frozen and the remaining 17 were starved to death. The objective was to elevate brain levels of DDE to lethality and measure these concentrations. After the feeding period, dosed bats weighed less than controls. After starvation, the body condition of dosed bats was poorer than that of controls even though there was no difference in the amounts of carcass fat. During starvation, dosed bats lost weight faster than controls. Also, four dosed bats exhibited the prolonged tremoring that characterizes DDE poisoning. DDE increased in brains of starving bats as fat was metabolized. The estimated mean brain concentration of DDE diagnostic of death was 519 ppm with a range of 458-564 ppm. These values resemble diagnostic levels known for two species of passerine birds, but they exceed published levels for two free-tailed bats from Carlsbad Caverns, New Mexico.

  16. Effects of DDE on experimentally poisoned free-tailed bats (Tadarida brasiliensis): Lethal brain concentrations

    USGS Publications Warehouse

    Clark, D.R.; Kroll, J.C.

    1977-01-01

    Adult female free-tailed bats (Tadarida brasiliensis) were collected at Bracken Cave, Texas, and shipped to the Patuxent Wildlife Research Center. Treated mealworms (Tenebrio molitor) containing 107 ppm DDE were fed to 17 bats; five other bats were fed untreated mealworms. After 40 days on dosage, during which one dosed bat was killed accidentally, four dosed bats were frozen and the remaining 17 were starved to death. The objective was to elevate brain levels of DDE to lethality and measure these concentrations. After the feeding period, dosed bats weighed less than controls. After starvation, the body condition of dosed bats was poorer than that of controls even though there was no difference in the amounts of carcass fat. During starvation, dosed bats lost weight faster than controls. Also, four dosed bats exhibited the prolonged tremoring that characterizes DDE poisoning. DDE increased in brains of starving bats as fat was metabolized. The estimated mean brain concentration of DDE diagnostic of death was 519 ppm with a range of 458-564 ppm. These values resemble diagnostic levels known for two species of passerine birds, but they exceed published levels for two free-tailed bats from Carlsbad Caverns, New Mexico.

  17. Priming dose of phenylhydrazine protects against hemolytic and lethal effects of 2-butoxyethanol

    SciTech Connect

    Palkar, Prajakta S.; Philip, Binu K.; Reddy, Ramesh N.; Mehendale, Harihara M.

    2007-11-15

    Protection against a high dose of a toxicant by prior exposure to another toxicant is called heteroprotection. Our objective was to establish a heteroprotection model in RBCs. Female Sprague Dawley rats treated with an LD90 dose of 2-butoxyethanol (BE, 1500 mg/kg in water, 5 ml/kg po) 14 days after priming with 0.9% NaCl suffered 90% mortality by 15 days, whereas all rats receiving the LD90 dose of BE 14 days after priming with phenylhydrazine (PHZ, 125 mg/kg in 0.9% NaCl, 3 ml/kg po) survived. Hematocrit decreased from normal 45% to 24% by day 3 after PHZ priming and improved thereafter. Increasing the time interval between the priming and LD90 dose to 21 days abolished the heteroprotection. RBCs obtained on days 7 and 14 after PHZ priming unlike those on day 21 were resilient to the hemotoxic metabolite of BE, butoxyacetic acid (BAA). Unaltered hepatic alcohol and aldehyde dehydrogenase activities upon PHZ priming suggested that bioactivation of BE to BAA was unaffected. Lower renal (6 and 12 h) and hepatic (12 h) BAA levels and 3 fold higher excretion of BAA in PHZ-primed rat urine suggested a protective role of toxicokinetics. Higher erythropoietin, reticulocytes, and resiliency of PHZ-primed rat RBCs indicated that newly formed RBCs are resilient to hemolytic BAA. The antioxidant levels in the PHZ-primed rat RBCs did not indicate a protective role in heteroprotection. In conclusion, the resistance of PHZ-primed rats against BE-induced hemotoxicity and lethality is mediated by a combination of altered toxicokinetics, robust erythropoiesis, and resiliency of new RBCs.

  18. Priming dose of phenylhydrazine protects against hemolytic and lethal effects of 2-butoxyethanol.

    PubMed

    Palkar, Prajakta S; Philip, Binu K; Reddy, Ramesh N; Mehendale, Harihara M

    2007-11-15

    Protection against a high dose of a toxicant by prior exposure to another toxicant is called heteroprotection. Our objective was to establish a heteroprotection model in RBCs. Female Sprague Dawley rats treated with an LD90 dose of 2-butoxyethanol (BE, 1500 mg/kg in water, 5 ml/kg po) 14 days after priming with 0.9% NaCl suffered 90% mortality by 15 days, whereas all rats receiving the LD90 dose of BE 14 days after priming with phenylhydrazine (PHZ, 125 mg/kg in 0.9% NaCl, 3 ml/kg po) survived. Hematocrit decreased from normal 45% to 24% by day 3 after PHZ priming and improved thereafter. Increasing the time interval between the priming and LD90 dose to 21 days abolished the heteroprotection. RBCs obtained on days 7 and 14 after PHZ priming unlike those on day 21 were resilient to the hemotoxic metabolite of BE, butoxyacetic acid (BAA). Unaltered hepatic alcohol and aldehyde dehydrogenase activities upon PHZ priming suggested that bioactivation of BE to BAA was unaffected. Lower renal (6 and 12 h) and hepatic (12 h) BAA levels and 3 fold higher excretion of BAA in PHZ-primed rat urine suggested a protective role of toxicokinetics. Higher erythropoietin, reticulocytes, and resiliency of PHZ-primed rat RBCs indicated that newly formed RBCs are resilient to hemolytic BAA. The antioxidant levels in the PHZ-primed rat RBCs did not indicate a protective role in heteroprotection. In conclusion, the resistance of PHZ-primed rats against BE-induced hemotoxicity and lethality is mediated by a combination of altered toxicokinetics, robust erythropoiesis, and resiliency of new RBCs.

  19. Differentiation factor/leukemia inhibitory factor protection against lethal endotoxemia in mice: synergistic effect with interleukin 1 and tumor necrosis factor

    PubMed Central

    1992-01-01

    Differentiation factor (D factor), also called leukemia inhibitory factor (LIF), is a glycoprotein that has been increasingly recognized to possess a wide range of physiological activities. We examined the possibility that the administration of D factor may confer beneficial effects and enhance host resistance against lethal endotoxemia. A single intravenous dose of recombinant human D factor completely protected C57/Bl6 mice from the lethal effect of Escherichia coli endotoxin (lipopolysaccharide [LPS]). The protective effects were dose dependent and observed when administered 2-24 h before LPS. Previous work has shown that interleukin 1 (IL-1) and tumor necrosis factor (TNF) also protect against a subsequent LPS challenge in a dose- dependent manner. When human D factor was combined with sub-protective doses of IL-1 beta or TNF-alpha, there was dramatic synergistic protection against a subsequent lethal LPS challenge. PMID:1552284

  20. Extended hypoxia in the alfalfa leafcutting bee, Megachile rotundata, increases survival but causes sub-lethal effects.

    PubMed

    Abdelrahman, H; Rinehart, J P; Yocum, G D; Greenlee, K J; Helm, B R; Kemp, W P; Schulz, C H; Bowsher, J H

    2014-05-01

    Many insects are tolerant of hypoxic conditions, but survival may come at a cost to long-term health. The alfalfa leaf-cutting bee, Megachile rotundata, develops in brood cells inside natural cavities, and may be exposed to hypoxic conditions for extended periods of time. Whether M. rotundata is tolerant of hypoxia, and whether exposure results in sub-lethal effects, has never been investigated. Overwintering M. rotundata prepupae were exposed to 10%, 13%, 17%, 21% and 24% O2 for 11 months. Once adults emerged, five indicators of quality - emergence weight, body size, feeding activity, flight performance, and adult longevity, - were measured to determine whether adult bees that survived past exposure to hypoxia were competent pollinators. M. rotundata prepupae are tolerant of hypoxic condition and have higher survival rates in hypoxia, than in normoxia. Under hypoxia, adult emergence rates did not decrease over the 11 months of the experiment. In contrast, bees reared in normoxia had decreased emergence rates by 8 months, and were dead by 11 months. M. rotundata prepupae exposed to extended hypoxic conditions had similar emergence weight, head width, and cross-thorax distance compared to bees reared in standard 21% oxygen. Despite no significant morphological differences, hypoxia-exposed bees had lower feeding rates and shorter adult lifespans. Hypoxia may play a role in post-diapause physiology of M. rotundata, with prepupae showing better survival under hypoxic conditions. Extended exposure to hypoxia, while not fatal, causes sub-lethal effects in feeding rates and longevity in the adults, indicating that hypoxia tolerance comes at a cost.

  1. Alcohol Acute Effects in Aircrew

    DTIC Science & Technology

    1990-06-01

    we derive the name "whiskey." In the Elizabethan era the physiological effects were known to Shakespeare , who in Hamlet noted that alcohol provoked...the Elizabethan era the physiological effects were alluded to by Porter in Hamlet , who noted alcohol provoked only "nose-painting, sleep and urine" (8...atlas of wine. London: Mitchell Beazley Pub, 1985. 7. Lord T. The World Guide to Spirits. pp. 6-27, 1979. 8. Shakespeare W. Macbeth. Act II, Scene 3

  2. Critical body residues for lethal and sublethal effects of membrane narcotics in the midge, Chironomus riparius

    SciTech Connect

    Fisher, S.W.; Hwang, H.; Landrum, P.F.

    1995-12-31

    The concept of the critical body residue (CBR) offers a compelling new way to evaluate hazard posed by persistent contaminants such as PCBs. The authors tested the utility of using CBRs for PCBs in an invertebrate species, Chironomus riparius. Acute toxicity (< 10 d) tests were performed with 2nd instar larvae by adding trace amounts of {sup 14}C-labeled PCBs to unlabeled PCBs in amounts sufficient to generate a dose-responsive mortality curve. Because of the limited water solubility of the PCBs tested, it was not possible to produce a toxic tissue concentration via aqueous exposure. This difficulty was overcome by allowing the midges to feed upon contaminated algae (Chlorella vulgaris) which could be loaded with much higher levels of PCBs than would dissolve in water. CBRs for acute toxicity were measured for 3 PCBs; an average CBR of about 1 mmol/kg was determined. If the midge CBRs are lipid normalized, they fall into the range of values that have previously been determined for vertebrates. The authors also evaluated CBRs in midges for a variety of sublethal impairments including development time within a stadium, larval weight and fecundity. A CBR of 1.09 {micro}mol/kg resulted in a significant increase in larval development time and decrease in larval weight for second instar larvae. Tissue residues declined in the third and fourth instars, despite continuing exposure suggesting that the animals developed attenuating mechanisms or that contaminant loss at ecdysis is significant. Despite declining tissue residues throughout the larval instars, fecundity was reduced from 284 eggs/female in controls to 244 eggs/female in animals exposed to the highest sublethal concentration.

  3. Acute Biphasic Effects of Ayahuasca.

    PubMed

    Schenberg, Eduardo Ekman; Alexandre, João Felipe Morel; Filev, Renato; Cravo, Andre Mascioli; Sato, João Ricardo; Muthukumaraswamy, Suresh D; Yonamine, Maurício; Waguespack, Marian; Lomnicka, Izabela; Barker, Steven A; da Silveira, Dartiu Xavier

    2015-01-01

    Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8-13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30-50 and 50-100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca's chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it's potential therapeutic effects is offered.

  4. Acute Biphasic Effects of Ayahuasca

    PubMed Central

    Schenberg, Eduardo Ekman; Alexandre, João Felipe Morel; Filev, Renato; Cravo, Andre Mascioli; Sato, João Ricardo; Muthukumaraswamy, Suresh D.; Yonamine, Maurício; Waguespack, Marian; Lomnicka, Izabela; Barker, Steven A.; da Silveira, Dartiu Xavier

    2015-01-01

    Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8–13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca’s chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it's potential therapeutic effects is offered. PMID:26421727

  5. Acute and Developmental Behavioral Effects of Flame ...

    EPA Pesticide Factsheets

    As polybrominated diphenyl ethers are phased out, numerous compounds are emerging as potential replacement flame retardants for use in consumer and electronic products. Little is known, however, about the neurobehavioral toxicity of these replacements. This study evaluated the neurobehavioral effects of acute or developmental exposure to t-butylphenyl diphenyl phosphate (BPDP), 2-ethylhexyl diphenyl phosphate (EHDP), isodecyl diphenyl phosphate (IDDP), isopropylated phenyl phosphate (IPP), tricresyl phosphate (TMPP; also abbreviated TCP), triphenyl phosphate (TPHP; also abbreviated TPP), tetrabromobisphenol A (TBBPA), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloroisopropyl) phosphate (TDCIPP; also abbreviated TDCPP), tri-o-cresyl phosphate (TOCP), and 2,2-,4,4’-tetrabromodiphenyl ether (BDE-47) in zebrafish (Danio rerio) larvae. Larvae (n≈24 per dose per compound) were exposed to test compounds (0.4 - 120 µM) at sub-teratogenic concentrations either developmentally or acutely, and locomotor activity was assessed at 6 days post fertilization. When given developmentally, all chemicals except BPDP, IDDP and TBBPA produced behavioral effects. When given acutely, all chemicals produced behavioral effects, with TPHP, TBBPA, EHDP, IPP, and BPDP eliciting the most effects at the most concentrations. The results indicate that these replacement flame retardants may have developmental or pharmacological effects on the vertebrate nervous system. This study

  6. Effects of acute caffeine administration on adolescents.

    PubMed

    Temple, Jennifer L; Dewey, Amber M; Briatico, Laura N

    2010-12-01

    Acute caffeine administration has physiological, behavioral, and subjective effects. Despite its widespread use, few studies have described the impact of caffeine consumption in children and adolescents. The purpose of this study was to investigate the effects of acute caffeine administration in adolescents. We measured cardiovascular responses and snack food intake after acute administration of 0 mg, 50 mg, 100 mg, and 200 mg of caffeine. We also compared usual food intake and subjective effects of caffeine between high- and low-caffeine consumers. Finally, we conducted a detailed analysis of caffeine sources and consumption levels. We found main effects of caffeine dose on heart rate (HR) and diastolic blood pressure (DBP), with HR decreasing and DBP increasing with increasing caffeine dose. There were significant interactions among gender, caffeine use, and time on DBP. High caffeine consumers (>50 mg/day) reported using caffeine to stay awake and drinking coffee, tea, soda, and energy drinks more than low consumers (<50 mg/day). Boys were more likely than girls to report using getting a rush, more energy, or improved athletic performance from caffeine. Finally, when we examined energy and macronutrient intake, we found that caffeine consumption was positively associated with laboratory energy intake, specifically from high-sugar, low-fat foods and also positively associated with protein and fat consumption outside of the laboratory. When taken together, these data suggest that acute caffeine administration has a broad range of effects in adolescents and that the magnitude of these effects is moderated by gender and chronic caffeine consumption.

  7. The Effect of Oseltamivir on the Disease Progression of Lethal Influenza A Virus Infection: Plasma Cytokine and miRNA Responses in a Mouse Model

    PubMed Central

    Chockalingam, Ashok K.; Hamed, Salaheldin; Goodwin, David G.; Rosenzweig, Barry A.; Pang, Eric; Boyne II, Michael T.

    2016-01-01

    Lethal influenza A virus infection leads to acute lung injury and possibly lethal complications. There has been a continuous effort to identify the possible predictors of disease severity. Unlike earlier studies, where biomarkers were analyzed on certain time points or days after infection, in this study biomarkers were evaluated over the entire course of infection. Circulating proinflammatory cytokines and/or miRNAs that track with the onset and progression of lethal A/Puerto Rico/8/34 (PR8) influenza A virus infection and their response to oseltamivir treatment were investigated up to 10 days after infection. Changes in plasma cytokines (IL-1β, IL-10, IL-12p70, IL-6, KC, TNF-α, and IFN-γ) and several candidate miRNAs were profiled. Among the cytokines analyzed, IL-6 and KC/GRO cytokines appeared to correlate with peak viral titer. Over the selected 48 miRNAs profiled, certain miRNAs were up- or downregulated in a manner that was dependent on the oseltamivir treatment and disease severity. Our findings suggest that IL-6 and KC/GRO cytokines can be a potential disease severity biomarker and/or marker for the progression/remission of infection. Further studies to explore other cytokines, miRNAs, and lung injury proteins in serum with different subtypes of influenza A viruses with varying disease severity may provide new insight into other unique biomarkers. PMID:27110056

  8. Lethal, sublethal and transgenerational effects of the novel chiral neonicotinoid pesticide cycloxaprid on demographic and behavioral traits of Aphis gossypii (Hemiptera: Aphididae).

    PubMed

    Yuan, Hai-Bin; Li, Jin-Hua; Liu, Yong-Qiang; Cui, Li; Lu, Yan-Hui; Xu, Xiao-Yong; Li, Zhong; Wu, Kong-Ming; Desneux, Nicolas

    2016-05-11

    Aphis gossypii Glover (Hemiptera: Aphididae) is a key pest in cotton crops, notably owing to its increasing resistance to commonly used pesticides. Such resistance prompts for the development of integrated pest management (IPM) programs that include novel pesticides being effective against the aphid. In the present study, we assessed lethal and sublethal effects of cycloxaprid, a novel chiral neonicotinoid pesticide developed in China, on A. gossypii. The lethal concentration at 50% (LC50 ) value of cycloxaprid on A. gossypii was estimated, using the dipping method, at 7.73 mg/L. The impact of a sublethal concentration (LC10 ) and a lethal concentration (LC40 ) of cycloxaprid on A. gossypii population growth and feeding behavior (using electrical penetration graph technique [EPG]), and its transgenerational effect were further assessed. Adult longevity and fecundity significantly decreased after exposure to LC40 or LC10 of cycloxaprid. Cycloxaprid with sublethal concentrations (especially LC40 ) had negative effects on phloem ingestion by A. gossypii. Additionally, the offspring of the adults exposed to LC40 of cycloxaprid had shorter nymphal development duration and adult longevity than the control, and those from LC10 and LC40 treatments had lower adult fecundity and net productive rate. We demonstrated that cycloxaprid is a pesticide showing both lethal and sublethal activities, and transgenerational effects on A. gossypii; it may be useful for implementation in IPM programs against this aphid pest.

  9. Enhancing the Antibiotic Antibacterial Effect by Sub Lethal Tellurite Concentrations: Tellurite and Cefotaxime Act Synergistically in Escherichia coli

    PubMed Central

    Molina-Quiroz, Roberto C.; Muñoz-Villagrán, Claudia M.; de la Torre, Erick; Tantaleán, Juan C.; Vásquez, Claudio C.; Pérez-Donoso, José M.

    2012-01-01

    The emergence of antibiotic-resistant pathogenic bacteria during the last decades has become a public health concern worldwide. Aiming to explore new alternatives to treat antibiotic-resistant bacteria and given that the tellurium oxyanion tellurite is highly toxic for most microorganisms, we evaluated the ability of sub lethal tellurite concentrations to strengthen the effect of several antibiotics. Tellurite, at nM or µM concentrations, increased importantly the toxicity of defined antibacterials. This was observed with both Gram negative and Gram positive bacteria, irrespective of the antibiotic or tellurite tolerance of the particular microorganism. The tellurite-mediated antibiotic-potentiating effect occurs in laboratory and clinical, uropathogenic Escherichia coli, especially with antibiotics disturbing the cell wall (ampicillin, cefotaxime) or protein synthesis (tetracycline, chloramphenicol, gentamicin). In particular, the effect of tellurite on the activity of the clinically-relevant, third-generation cephalosporin (cefotaxime), was evaluated. Cell viability assays showed that tellurite and cefotaxime act synergistically against E. coli. In conclusion, using tellurite like an adjuvant could be of great help to cope with several multi-resistant pathogens. PMID:22536386

  10. Laboratory Evaluation of Two Commercial Abamectin-Based Insecticides Against Anastrepha ludens (Diptera: Tephritidae): Lethal and Sublethal Effects.

    PubMed

    Díaz-Fleischer, Francisco; Pérez-Staples, Diana; Valle-Mora, Javier; Antonio García-Pérez, José

    2016-10-05

    Toxic environmental effects of most insecticides have led to a search for bio-organic insecticides. In this study, we tested the effects of lethal and sublethal exposure to two abamectin-based insecticides (VOLIAM TARGO and LUQ-THOR) on survival, mating, and oviposition of the tephritid Anastrepha ludens (Loew). Different doses of insecticides (0.001-2.00% of the commercial products) were offered mixed with the phagostimulant bait Captor commonly used in spraying and in trapping activities for the control of flies. Both insecticides exhibited 90% killing effectiveness (Abbott index) when offered in doses between 0.02 to 2.00%. The LC50 obtained from the bioassay at 72 h after treatment was 0.003% of commercial product for TARGO and 0.008% for LUQ-THOR. Sublethal exposures to insecticides (0.003%; LC50 for TARGO and LC30 for LUQ-THOR) caused a reduction in oviposition but not in mating parameters, indicating that females were more susceptible than males to reduced doses of insecticide. The mean amount of eggs deposited 5 d after feeding on the insecticide-bait mixtures was reduced up to a third compared with the amount of eggs deposited by untreated females. Both insecticides are promising bio-organic alternatives to malathion in bait control programs against A. ludens.

  11. How Close is too Close? The Effect of a Non-Lethal Electric Shark Deterrent on White Shark Behaviour.

    PubMed

    Kempster, Ryan M; Egeberg, Channing A; Hart, Nathan S; Ryan, Laura; Chapuis, Lucille; Kerr, Caroline C; Schmidt, Carl; Huveneers, Charlie; Gennari, Enrico; Yopak, Kara E; Meeuwig, Jessica J; Collin, Shaun P

    2016-01-01

    Sharks play a vital role in the health of marine ecosystems, but the potential threat that sharks pose to humans is a reminder of our vulnerability when entering the ocean. Personal shark deterrents are being marketed as the solution to mitigate the threat that sharks pose. However, the effectiveness claims of many personal deterrents are based on our knowledge of shark sensory biology rather than robust testing of the devices themselves, as most have not been subjected to independent scientific studies. Therefore, there is a clear need for thorough testing of commercially available shark deterrents to provide the public with recommendations of their effectiveness. Using a modified stereo-camera system, we quantified behavioural interactions between white sharks (Carcharodon carcharias) and a baited target in the presence of a commercially available, personal electric shark deterrent (Shark Shield Freedom7™). The stereo-camera system enabled an accurate assessment of the behavioural responses of C. carcharias when encountering a non-lethal electric field many times stronger than what they would naturally experience. Upon their first observed encounter, all C. carcharias were repelled at a mean (± std. error) proximity of 131 (± 10.3) cm, which corresponded to a mean voltage gradient of 9.7 (± 0.9) V/m. With each subsequent encounter, their proximity decreased by an average of 11.6 cm, which corresponded to an increase in tolerance to the electric field by an average of 2.6 (± 0.5) V/m per encounter. Despite the increase in tolerance, sharks continued to be deterred from interacting for the duration of each trial when in the presence of an active Shark Shield™. Furthermore, the findings provide no support to the theory that electric deterrents attract sharks. The results of this study provide quantitative evidence of the effectiveness of a non-lethal electric shark deterrent, its influence on the behaviour of C. carcharias, and an accurate method for testing

  12. How Close is too Close? The Effect of a Non-Lethal Electric Shark Deterrent on White Shark Behaviour

    PubMed Central

    Hart, Nathan S.; Ryan, Laura; Chapuis, Lucille; Kerr, Caroline C.; Schmidt, Carl; Huveneers, Charlie; Gennari, Enrico; Yopak, Kara E.; Meeuwig, Jessica J.; Collin, Shaun P.

    2016-01-01

    Sharks play a vital role in the health of marine ecosystems, but the potential threat that sharks pose to humans is a reminder of our vulnerability when entering the ocean. Personal shark deterrents are being marketed as the solution to mitigate the threat that sharks pose. However, the effectiveness claims of many personal deterrents are based on our knowledge of shark sensory biology rather than robust testing of the devices themselves, as most have not been subjected to independent scientific studies. Therefore, there is a clear need for thorough testing of commercially available shark deterrents to provide the public with recommendations of their effectiveness. Using a modified stereo-camera system, we quantified behavioural interactions between white sharks (Carcharodon carcharias) and a baited target in the presence of a commercially available, personal electric shark deterrent (Shark Shield Freedom7™). The stereo-camera system enabled an accurate assessment of the behavioural responses of C. carcharias when encountering a non-lethal electric field many times stronger than what they would naturally experience. Upon their first observed encounter, all C. carcharias were repelled at a mean (± std. error) proximity of 131 (± 10.3) cm, which corresponded to a mean voltage gradient of 9.7 (± 0.9) V/m. With each subsequent encounter, their proximity decreased by an average of 11.6 cm, which corresponded to an increase in tolerance to the electric field by an average of 2.6 (± 0.5) V/m per encounter. Despite the increase in tolerance, sharks continued to be deterred from interacting for the duration of each trial when in the presence of an active Shark Shield™. Furthermore, the findings provide no support to the theory that electric deterrents attract sharks. The results of this study provide quantitative evidence of the effectiveness of a non-lethal electric shark deterrent, its influence on the behaviour of C. carcharias, and an accurate method for testing

  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. Transient receptor potential (TRP) channels as a therapeutic target for intervention of respiratory effects and lethality from phosgene.

    PubMed

    Andres, Devon; Keyser, Brian; Benton, Betty; Melber, Ashley; Olivera, Dorian; Holmes, Wesley; Paradiso, Danielle; Anderson, Dana; Ray, Radharaman

    2016-02-26

    Phosgene (CG), a toxic inhalation and industrial hazard, causes bronchoconstriction, vasoconstriction and associated pathological effects that could be life threatening. Ion channels of the transient receptor potential (TRP) family have been identified to act as specific chemosensory molecules in the respiratory tract in the detection, control of adaptive responses and initiation of detrimental signaling cascades upon exposure to various toxic inhalation hazards (TIH); their activation due to TIH exposure may result in broncho- and vasoconstriction. We studied changes in the regulation of intracellular free Ca(2+) concentration ([Ca(2+)]i) in cultures of human bronchial smooth muscle cells (BSMC) and human pulmonary microvascular endothelial cells (HPMEC) exposed to CG (16ppm, 8min), using an air/liquid interface exposure system. CG increased [Ca(2+)]i (p<0.05) in both cell types, The CG-induced [Ca(2+)]i was blocked (p<0.05) by two types of TRP channel blockers, SKF-96365, a general TRP channel blocker, and RR, a general TRPV (vanilloid type) blocker, in both BSMC and HPMEC. These effects correlate with the in vivo efficacies of these compounds to protect against lung injury and 24h lethality from whole body CG inhalation exposure in mice (8-10ppm×20min). Thus the TRP channel mechanism appears to be a potential target for intervention in CG toxicity.

  15. Lethal and sublethal effects of essential oil of Lippia sidoides (Verbenaceae) and monoterpenes on Chagas’ disease vector Rhodnius prolixus

    PubMed Central

    Figueiredo, Marcela B; Gomes, Geovany A; Santangelo, Jayme M; Pontes, Emerson G; Azambuja, Patricia; Garcia, Elói S; de Carvalho, Mário G

    2016-01-01

    The aim of this study was to identify the composition of the essential oil from leaves of Lippia sidoides (EOLS), a typical shrub commonly found in the dry northeast of Brazil, popularly known as “alecrim-pimenta”. Additionally, we investigated the nymphicidal, ovicidal, phagoinhibitory and excretion effects of EOLS, its major constituent thymol and its isomer carvacrol, on fourth instar nymphs and eggs of Rhodnius prolixus, the Chagas’ disease vector. The nymphicidal and ovicidal activity of thymol, carvacrol, and EOLS was assessed by tests using impregnated Petri dishes. The lethal concentration values (LC50) for EOLS, carvacrol, and thymol were 54.48, 32.98, and 9.38 mg/cm2, respectively. The ovicidal test showed that both carvacrol and thymol (50 mg/cm2) inhibited hatching (50% and 23.3%, respectively), while treatments with 10 mg/cm2 or 50 mg/cm2 EOLS did not affect the hatching rate at all (80% and 90%, respectively). We observed an anti-feeding effect in insects fed with blood containing natural products at the higher concentrations (100 µg/mL). Finally, excretion rate was affected by EOLS and carvacrol, but not by thymol. These findings offer novel insights into basic physiological processes that make the tested natural compounds interesting candidates for new types of insecticides. PMID:27878214

  16. Lethal and sublethal effects of essential oil of Lippia sidoides (Verbenaceae) and monoterpenes on Chagas' disease vector Rhodnius prolixus.

    PubMed

    Figueiredo, Marcela B; Gomes, Geovany A; Santangelo, Jayme M; Pontes, Emerson G; Azambuja, Patricia; Garcia, Elói S; Carvalho, Mário G de

    2017-01-01

    The aim of this study was to identify the composition of the essential oil from leaves of Lippia sidoides (EOLS), a typical shrub commonly found in the dry northeast of Brazil, popularly known as "alecrim-pimenta". Additionally, we investigated the nymphicidal, ovicidal, phagoinhibitory and excretion effects of EOLS, its major constituent thymol and its isomer carvacrol, on fourth instar nymphs and eggs of Rhodnius prolixus, the Chagas' disease vector. The nymphicidal and ovicidal activity of thymol, carvacrol, and EOLS was assessed by tests using impregnated Petri dishes. The lethal concentration values (LC50) for EOLS, carvacrol, and thymol were 54.48, 32.98, and 9.38 mg/cm2, respectively. The ovicidal test showed that both carvacrol and thymol (50 mg/cm2) inhibited hatching (50% and 23.3%, respectively), while treatments with 10 mg/cm2 or 50 mg/cm2 EOLS did not affect the hatching rate at all (80% and 90%, respectively). We observed an anti-feeding effect in insects fed with blood containing natural products at the higher concentrations (100 µg/mL). Finally, excretion rate was affected by EOLS and carvacrol, but not by thymol. These findings offer novel insights into basic physiological processes that make the tested natural compounds interesting candidates for new types of insecticides.

  17. Sub-lethal behavioral and physiological effects of the biomedical bleeding process on the American horseshoe crab, Limulus polyphemus

    PubMed Central

    Anderson, Rebecca L.; Watson, Winsor H.; Chabot, Christopher C.

    2014-01-01

    The hemolymph of the American horseshoe crab, Limulus polyphemus, is harvested from over 500,000 animals annually to produce Limulus Amebocyte Lysate, a medically important product used to detect pathogenic bacteria. Declining abundance of spawning Limulus females in heavily harvested regions suggests deleterious effects of this activity and, while mortality rates of the harvest process are known to be 10–30%, sub-lethal behavioral and physiological effects are not known. In this study, we determined the impact of the harvest process on locomotion and hemocyanin levels of 28 female horseshoe crabs. While mortality rates after bleeding (18%) were similar to previous studies, we found significant decreases in the linear and angular velocity of freely moving animals, as well as changes in their activity levels and expression of circatidal behavioral rhythms. Further, we found reductions in hemocyanin levels, which may alter immune function and cuticle integrity. These previously unrecognized behavioral and physiological deficits suggest that the harvest of Limulus Amebocyte Lysate may decrease female fitness, and thus may contribute to the current population decline. PMID:24445440

  18. Mutagenic and lethal effects of near-ultraviolet radiation (290-400 nm) on bacteria and phage.

    PubMed

    Eisenstark, A

    1987-01-01

    Despite decades of study of the effect of near-ultraviolet radiation (NUV) on bacterial cells, insights into mechanisms of deleterious alterations and subsequent recovery are just now emerging. These insights are based on observations that 1) damage by NUV may be caused by a reactive oxygen molecule, since H2O2 may be a photoproduct of NUV; 2) some, but not all, of the effects of NUV and H2O2 are interchangeable; 3) there is an inducible regulon (oxyR) that responds to oxidative stress and is involved in protection against NUV; 4) a number of NUV-sensitive mutants are defective either in the capacity to detoxify reactive oxygen molecules or to repair DNA damage caused by NUV; and 5) recovery from NUV damage may not directly involve induction of the SOS response. Since several distinctly different photoreceptors and targets are involved, it is unknown whether NUV lethality and mutagenesis result from an accumulation of damages or whether there is a particularly critical photoeffect. To fully understand the mechanisms involved, it is important to identify the chromophore(s) of NUV, the mechanism of toxic oxygen species generation, the role of the oxidative defense regulon (oxyR), the specific lesions in the DNA, and the enzymatic events of subsequent repair.

  19. An Enhancing Effect of Gold Nanoparticles on the Lethal Action of 2450 MHz Electromagnetic Radiation in Microwave Oven.

    PubMed

    Mollazadeh-Moghaddam, Kamyar; Moradi, Bardia Varasteh; Dolatabadi-Bazaz, Reza; Shakibae, Mojtaba; Shahverdi, Ahmad Reza

    2011-10-01

    Today, there is an increasing interest in the use of metal nanoparticles in health sciences. Amongst all nanoparticles, the gold nanoparticles have been known to kill the cancer cells under hyperthermic condition by near-infrared frequency electromagnetic waves. On the other hand, although there are different physiochemical methods for disinfection of microbial pollution, however applications of irradiated gold nanoparticles against microorganisms have not yet been investigated. In this study, gold nanoparticles were prepared using D-glucose and characterized (particle size <26 nm). In the next step, the enhancing effect of the non toxic level of gold nanoparticles (50 µg/mL) on the antimicrobial activity of 2450 MHz electromagnetic radiation generated at a microwave oven operated at low power (100 W), was investigated by time-kill course assay against Staphylococcus aureus (S.aureus) ATCC 29737. The results showed that application of gold nanoparticles can enhance the lethal effect of low power microwave in a very short exposure time (5 s).

  20. 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.

  1. Lethal and sublethal effects of cadmium on marine organisms--a critical discussion about "safety levels".

    PubMed

    Sperling, K R

    1983-12-01

    The applicability of terms such as "safety level" and "safety factor" for the purpose of risk assessment in the frame of the marine dumping conventions is discussed. In view of a series of experiments on sublethal effects of cadmium on marine organisms it is stated that the dose-response relationships cover a range of 10(4), and that there is no indication that the lowest level found so far is actually just above a no-effect threshold.

  2. Lethal and sublethal effects of cadmium on marine organisms: a critical discussion about ''safety levels''

    SciTech Connect

    Sperling, K.R.

    1983-12-01

    The applicability of terms such as ''safety level'' and ''safety factor'' for the purpose of risk assessment in the frame of the marine dumping conventions is discussed. In view of a series of experiments on sublethal effects of cadmium on marine organisms it is stated that the dose-response relationships cover a range of 10(4), and that there is no indication that the lowest level found so far is actually just above a no-effect threshold.

  3. Electric shocks are ineffective in treatment of lethal effects of rattlesnake envenomation in mice.

    PubMed

    Johnson, E K; Kardong, K V; Mackessy, S P

    1987-01-01

    Electrical shocks, even crudely delivered from 'stun guns' and gasoline engine spark plugs, have been reported to be effective in the treatment of snake bite. We thus applied similar electric shocks to mice artificially injected with reconstituted rattlesnake venom at various LD50 multiples. Those envenomated mice treated with electric shock survived no better than the controls. We thus found no evidence that electric shocks crudely administered had any life saving effect in mice.

  4. The vitamin B12 analog cobinamide is an effective hydrogen sulfide antidote in a lethal rabbit model

    PubMed Central

    BRENNER, M.; BENAVIDES, S.; MAHON, S. B.; LEE, J.; YOON, D.; MUKAI, D.; VISEROI, M.; CHAN, A.; JIANG, J.; NARULA, N.; AZER, S. M.; ALEXANDER, C.; BOSS, G. R.

    2014-01-01

    Background and purpose Hydrogen sulfide (H2S) is a highly toxic gas for which no effective antidotes exist. It acts, at least in part, by binding to cytochrome c oxidase, causing cellular asphyxiation and anoxia. We investigated the effects of three different ligand forms of cobinamide, a vitamin B12 analog, to reverse sulfide (NaHS) toxicity. Methods New Zealand white rabbits received a continuous intravenous (IV) infusion of NaHS (3 mg/min) until expiration or a maximum 270 mg dose. Animals received six different treatments, administered at the time when they developed signs of severe toxicity: Group 1—saline (placebo group, N = 9); Group 2—IV hydroxocobalamin (N = 7); Group 3—IV aquohydroxocobinamide (N = 6); Group 4—IV sulfitocobinamide (N = 6); Group 5—intramuscular (IM) sulfitocobinamide (N = 6); and Group 6—IM dinitrocobinamide (N = 8). Blood was sampled intermittently, and systemic blood pressure and deoxygenated and oxygenated hemoglobin were measured continuously in peripheral muscle and over the brain region; the latter were measured by diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS). Results Compared with the saline controls, all cobinamide derivatives significantly increased survival time and the amount of NaHS that was tolerated. Aquohydroxocobinamide was most effective (261.5 ± 2.4 mg NaHS tolerated vs. 93.8 ± 6.2 mg in controls, p < 0.0001). Dinitrocobinamide was more effective than sulfitocobinamide. Hydroxocobalamin was not significantly more effective than the saline control. Conclusions Cobinamide is an effective agent for inhibiting lethal sulfide exposure in this rabbit model. Further studies are needed to determine the optimal dose and form of cobinamide and route of administration. PMID:24716792

  5. Lethal and Sublethal Effects of Cantharidin on Development and Reproduction of Plutella xylostella (Lepidoptera: Plutellidae).

    PubMed

    Huang, Zhengyu; Wang, Yao; Zhang, Yalin

    2015-06-01

    The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), is a major pest of cruciferous vegetables throughout the world. Cantharidin, a natural toxin isolated from beetles in the families Meloidae and Oedemeridae, has been reported to be toxic to some pests, including the diamondback moth. However, the effects of cantharidin, especially its sublethal effects on development and reproduction of diamondback moth, are less known. In this study, we investigated the sublethal effects of cantharidin at LC2 (0.41 mg liter(-1)), LC10 (1.33 mg liter(-1)), LC25 (3.38 mg liter(-1)), and LC50 (9.53 mg liter(-1)) on development and reproduction parameters of two consecutive diamondback moth generations. The results indicated that cantharidin reduced population growth by decreasing its pupation rate, pupal weight, and adult emergence, and by delaying its development. Furthermore, the duration of the female preoviposition period increased, while the oviposition and postoviposition periods, fecundity, and survival rates of the offspring decreased. The peaks of age-specific fecundity in LC10, LC25, and LC50 treatment groups lagged behind the control group. The mean values of the net reproductive rate (R0), intrinsic rate of increase (r), and finite rate of increase (λ) were significantly lower than those of the control, and the mean generation time (T) was prolonged. The present study demonstrates that cantharidin exhibits significant adverse effects on the population dynamics of diamondback moth, leading to fitness disadvantages.

  6. Lethal and sublethal effects of four essential oils on the egg parasitoids Trissolcus basalis.

    PubMed

    Werdin González, Jorge Omar; Laumann, Raúl Alberto; da Silveira, Samantha; Moraes, Maria Carolina Blassioli; Borges, Miguel; Ferrero, Adriana Alicia

    2013-07-01

    The essential oils from leaves of Schinus molle var. areira, Aloysia citriodora, Origanum vulgare and Thymus vulgaris have showed potential as phytoinsecticides against the green stink bug, Nezara viridula. In this work were evaluated their toxicological and behavioral effects on the parasitoid Trissolcus basalis, a biological control agent of this pest insect. Essential oils were obtained via hydrodestillation from fresh leaves. Insecticide activity in T. basalis females was evaluated in direct contact and fumigation bioassays. Behavioral effects were evaluated in olfactometer bioassays. To evaluate the residual toxicity, females of the parasitoids were exposed to oil residues; in these insects, the sublethal effects were evaluated (potential parasitism and survivorship of immature stages). The essential oils from O. vulgare and T. vulgaris proved to be highly selective when used as fumigant and did not change parasitoid behavior. After one week, the residues of these oils were harmless and did not show sublethal effects against T. basalis. According with these results, essential oils have potential applications for the integrated management of N. viridula.

  7. Effect of Drugs on the Lethality in Mice of the Venoms and Neurotoxins from Sundry Snakes

    DTIC Science & Technology

    1990-07-10

    maximal when the drugs were administered immediately after the irjection of venom or toxin. Nifedipine. piracetam , reserpine, and vesamicol analog 72...California, Santa Barbara, CA, U.S.A. Chloroquine, chlorpromazine, 5 dexamethasone, diltiazem, piracetam , primaquine, and quinacrine were dissolved in...nifedipine had no overt effect on 20 mice observed for 24 hr. , , I I I I I i ii i l I ! ! ! !0 Piracerwn Piracetam failed to protect mice from the

  8. Lethal and sublethal effects of the chitin synthesis inhibitor chlorfluazuron on Bradysia odoriphaga Yang and Zhang (Diptera: Sciaridae).

    PubMed

    Zhang, Peng; Zhao, Yun-He; Wang, Qiu-Hong; Mu, Wei; Liu, Feng

    2017-03-01

    Bradysia odoriphaga Yang and Zhang is the primary insect pest that affects Chinese chive in northern China. Nevertheless, very few studies have been conducted on the use of chitin synthesis inhibitors (CSIs) for the control of B. odoriphaga. Here, lethal and sublethal effects of the CSI chlorfluazuron on B. odoriphaga were studied to explore the use for integrated pest management (IPM) of B. odoriphaga. A contact and ingestion toxicity bioassay showed that chlorfluazuron was more active against B. odoriphaga than three other CSIs, with a 72h LC50 of 0.1593mg/L. Treatment with the LC50 dose of chlorfluazuron decreased both the intrinsic and finite rates of increase of B. odoriphaga, in addition to reproduction rate, survival rate, and fecundity, and the mean generation time, total preovipositional period and larval development duration were shortened, compared with those of the control and LC10 groups. The mean generation time, total preovipositional period and larval development duration were all also markedly decreased by treatment with chlorfluazuron at the LC10. Furthermore, chlorfluazuron inhibited the feeding of the final instar larvae for a short period. Glutathione S-transferase and microsomal mixed function oxidase activities increased after exposure to the chemical. These results showed that chlorfluazuron at the sublethal LC50 treatment inhibited B. odoriphaga population growth, whereas the danger of causing rapid population growth by using a lower sublethal concentration was demonstrated with the sublethal LC10 treatment. Therefore, chlorfluazuron should be used with caution in an IPM program for B. odoriphaga.

  9. Breakthrough of ultraviolet light from various brands of fluorescent lamps: lethal effects on DNA repair-defective bacteria.

    PubMed

    Hartman, P E; Biggley, W H

    1996-01-01

    In a comparative study of 17 pairs of 15 W fluorescent lamps intended for use in homes and purchased in local stores, we detect over 10-fold differences in UVB + UVC emissions between various lamps. This breakthrough of ultraviolet (UV) light is in part correlated with ability of lamps to kill DNA repair-defective recA-uvrB- Salmonella. Relative proficiency of lamps in eliciting photoreactivation of UV-induced DNA lesions also plays a prominent role in the relative rates of bacterial inactivation by emissions from different lamps. Lamps made in Chile, such as Philips brand lamps and one type of General Electric lamp, produce far less UVB + UVC and fail to kill recA-uvrB- bacteria. In contrast, all tested lamps manufactured in the USA, Hungary, and Japan exhibit readily observed deleterious biological effects. When an E. coli recA-uvrB-phr- (photolyase-negative) triple mutant is used for assay, lethal radiations are detected from all lamps, and single-hit exponential inactivation rates rather closely correlate to amount of directly measured UVB + UVC output of each pair of lamps. Although all lamps tested may meet international and United States standards for radiation safety, optimal practices in lamp manufacture are clearly capable of decreasing human exposure to indoor UV light.

  10. Breakthrough of ultraviolet light from various brands of fluorescent lamps: Lethal effects on DNA repair-defective bacteria

    SciTech Connect

    Hartman, P.E.; Biggley, W.H.

    1996-12-31

    In a comparative study of 17 pairs of 15 W fluorescent lamps intended for use in homes and purchased in local stores, we detect over 10-fold differences in UVB + UVC emissions between various lamps. This breakthrough of ultraviolet (UV) light is in part correlated with ability of lamps to kill DNA repair-defective recA{sup {minus}}uvrB{sup {minus}} Salmonella. Relative proficiency of lamps in eliciting photoreactivation of UV-induced DNA lesions also plays a prominent role in the relative rates of bacterial inactivation by emissions from different lamps. Lamps made in Chile, such as Phillips brand lamps and one type of General Electric lamp, produce far less UVB + UVC and fail to kill recA{sup {minus}} uvrB{sup {minus}} bacteria. In contrast, all tested lamps manufactured in the USA, Hungary, and Japan exhibit readily observed deleterious biological effects. When an E. coli recA{sup {minus}} uvrB{sup {minus}} phr{sup {minus}} (photolyase-negative) triple mutant is used for assay, lethal radiations are detected from all lamps, and single-hit exponential inactivation rates rather closely correlate to amount of directly measured UVB + UVC output of each pair of lamps. Although all lamps tested may meet international and Unite States standards for radiation safely, optimal practices in lamp manufacture are clearly capable of decreasing human exposure to indoor UV light. 38 refs., 3 figs., 1 tab.

  11. Lethal and sublethal effects of three insecticides on two developmental stages of Xenopus laevis and comparison with other amphibians.

    PubMed

    Yu, Shuangying; Wages, Mike R; Cai, Qingsong; Maul, Jonathan D; Cobb, George P

    2013-09-01

    It has been suggested that Xenopus laevis is less sensitive than other amphibians to some chemicals, and therefore, that the Frog Embryo Teratogenesis Assay-Xenopus (FETAX) may have limited use in risk assessments for other amphibians. However, comparisons are based mostly on results of FETAX, which emphasizes embryos. Larval X. laevis may be more sensitive to chemicals than embryos and may serve as a better life stage in risk assessments. The present study was conducted to determine the lethal and sublethal effects of 3 insecticides (malathion, endosulfan, and α-cypermethrin) on X. laevis embryos and larvae and to compare toxicity of X. laevis with that of other amphibians. All 3 insecticides have different modes of action, and they caused mortality, malformations, and growth inhibition in both developmental stages. Compared with embryos, larvae were more sensitive to endosulfan and α-cypermethrin but not to malathion. Xenopus laevis larvae had low sensitivity to endosulfan, median sensitivity to malathion, and high sensitivity to α-cypermethrin/cypermethrin relative to other larval amphibians. Our results suggest that X. laevis larvae may generate more protective toxicity estimates in risk assessments than embryos. Xenopus laevis may have limited use in evaluating risk of organochlorine insecticides to other amphibians but may provide useful toxicity thresholds for pyrethroid and perhaps organophosphorus insecticides.

  12. Effect of exposure routes on the relationships of lethal toxicity to rats from oral, intravenous, intraperitoneal and intramuscular routes.

    PubMed

    Ning, Zhong H; Long, Shuang; Zhou, Yuan Y; Peng, Zi Y; Sun, Yi N; Chen, Si W; Su, Li M; Zhao, Yuan H

    2015-11-01

    The lethal toxicity values (log 1/LD(50)) of 527 aliphatic and aromatic compounds in oral, intravenous, intramuscular and intraperitoneal routes were used to investigate the relationships of log 1/LD(50) from different exposure routes. Regression analysis shows that the log 1/LD(50) values are well correlated between intravenous and intraperitoneal or intramuscular injections. However, the correlations between oral and intravenous or intraperitoneal routes are relatively poor. Comparison of the average residuals indicates that intravenous injection is the most sensitive exposure route and oral administration is the least sensitive exposure route. This is attributed to the difference in kinetic process of toxicity testing. The toxic effect of a chemical can be similar or significantly different between exposure routes, depending on the absorption rates of chemicals into blood. Inclusion of hydrophobic parameter and fractions of ionic forms can improve the correlations between intravenous and intraperitoneal or oral routes, but not between intraperitoneal and oral routes. This is due to the differences of absorption rate in different exposure environments from different routes. Several factors, such as experimental uncertainty, metabolism and toxic kinetics, can affect the correlations between intravenous and intraperitoneal or oral routes.

  13. Temperature and salinity effects on cadmium toxicity on lethal and sublethal responses of Amphibalanus amphitrite nauplii.

    PubMed

    Piazza, Veronica; Gambardella, Chiara; Canepa, Sara; Costa, Elisa; Faimali, Marco; Garaventa, Francesca

    2016-01-01

    The official protocol of an ecotoxicological assay employing larvae of the crustacean Amphibalanus amphitrite as a model organism has recently been published by the Italian regulatory authority UNICHIM. Such assay is now one of the applicable tests for water quality assessment under Italian law. While specific temperature and salinity values are recommended by ecotoxicology bioassay protocols for test set up, little information is available on response changes in case of parameter variations. In particular, information is totally lacking for this innovative model organism. Under the standard test protocol, 20°C and 37‰ temperature and salinity, respectively, are required to be set in A. amphitrite bioassay. In order to evaluate the environmental relevance of the test, laboratory experiments simulating the effect on larval responses due to variations of temperature and salinity expected in field collected samples were carried out. The effect of temperature and salinity changes on different end-points, involving increasing sensitivity levels, has been investigated, with and without the presence of cadmium nitrate, Cd(NO3)2, as a reference toxicant, to determine the possible interactions between pollutants and environmental parameters fluctuations. Three end-points - mortality, immobilization, and swimming speed alteration - were measured in order to evaluate the impact of a wide range of temperature (5, 10, 15, 20, 25, 30, 35, 40°C) and salinity values (10, 20, 30, 37, 40, 50, 60, 70‰) on response variation after 24 and 48h of exposure. For each parameter, a Non-Effect Range (NER) - namely the limit values within which no effect related to environmental parameter changes is observed - has been defined. For both parameters, NER resulted to be wider for the less sensitive end-points - such as mortality and immobilization - and for shorter exposure time (24h). Later, the same end-points have been evaluated by exposing the same organisms to a reference toxic

  14. Lethality Effects of a High-Power Solid-State Laser

    SciTech Connect

    Boley, C; Fochs, S; Rubenchik, A

    2007-03-07

    We study the material interactions of a 25-kW solid-state laser, in experiments characterized by relatively large spot size sizes ({approx}3 cm) and the presence of airflow. The targets are 1-cm slabs of iron or aluminum. In the experiments with iron, we show that combustion plays an important role in heating the material. In the experiments with aluminum, there is a narrow range of intensities within which the material interactions vary from no melting at all to complete melt-through. A paint layer serves to increase the absorption. We explain these effects and incorporate them into a comprehensive computational model.

  15. Lethality Effects of a High-Power Solid-State Laser

    SciTech Connect

    Boley, C D; Fochs, S N; Rubenchik, A M

    2007-08-24

    We study the material interactions of a 25-kW solid-state laser, in experiments characterized by relatively large spot sizes ({approx}3 cm) and the presence of airflow. The targets are iron or aluminum slabs, of thickness 1 cm. In the experiments with iron, we show that combustion plays an important role in heating the material. In the experiments with aluminum, there is a narrow range of intensities within which the material interactions vary from no melting at all to complete melt-through. A layer of paint serves to increase the absorption. We explain these effects and incorporate them into a comprehensive computational model.

  16. Effects of clothianidin on aquatic communities: Evaluating the impacts of lethal and sublethal exposure to neonicotinoids.

    PubMed

    Miles, Jesse C; Hua, Jessica; Sepulveda, Maria S; Krupke, Christian H; Hoverman, Jason T

    2017-01-01

    The widespread usage of neonicotinoid insecticides has sparked concern over their effects on non-target organisms. While research has largely focused on terrestrial systems, the low soil binding and high water solubility of neonicotinoids, paired with their extensive use on the landscape, puts aquatic environments at high risk for contamination via runoff events. We assessed the potential threat of these compounds to wetland communities using a combination of field surveys and experimental exposures including concentrations that are representative of what invertebrates experience in the field. In laboratory toxicity experiments, LC50 values ranged from 0.002 ppm to 1.2 ppm for aquatic invertebrates exposed to clothianidin. However, freshwater snails and amphibian larvae showed high tolerance to the chemical with no mortality observed at the highest dissolvable concentration of the insecticide. We also observed behavioral effects of clothianidin. Water bugs, Belostoma flumineum, displayed a dose-dependent reduction in feeding rate following exposure to clothianidin. Similarly, crayfish, Orconectes propinquus, exhibited reduced responsiveness to stimulus with increasing clothianidin concentration. Using a semi-natural mesocosm experiment, we manipulated clothianidin concentration (0.6, 5, and 352 ppb) and the presence of predatory invertebrates to explore community-level effects. We observed high invertebrate predator mortality with increases in clothianidin concentration. With increased predator mortality, prey survival increased by 50% at the highest clothianidin concentration. Thus, clothianidin contamination can result in a top-down trophic cascade in a community dominated by invertebrate predators. In our Indiana field study, we detected clothianidin (max = 176 ppb), imidacloprid (max = 141 ppb), and acetamiprid (max = 7 ppb) in soil samples. In water samples, we detected clothianidin (max = 0.67 ppb), imidacloprid (max = 0.18 ppb), and thiamethoxam (max = 2

  17. Effects of clothianidin on aquatic communities: Evaluating the impacts of lethal and sublethal exposure to neonicotinoids

    PubMed Central

    Miles, Jesse C.; Hua, Jessica; Sepulveda, Maria S.; Krupke, Christian H.

    2017-01-01

    The widespread usage of neonicotinoid insecticides has sparked concern over their effects on non-target organisms. While research has largely focused on terrestrial systems, the low soil binding and high water solubility of neonicotinoids, paired with their extensive use on the landscape, puts aquatic environments at high risk for contamination via runoff events. We assessed the potential threat of these compounds to wetland communities using a combination of field surveys and experimental exposures including concentrations that are representative of what invertebrates experience in the field. In laboratory toxicity experiments, LC50 values ranged from 0.002 ppm to 1.2 ppm for aquatic invertebrates exposed to clothianidin. However, freshwater snails and amphibian larvae showed high tolerance to the chemical with no mortality observed at the highest dissolvable concentration of the insecticide. We also observed behavioral effects of clothianidin. Water bugs, Belostoma flumineum, displayed a dose-dependent reduction in feeding rate following exposure to clothianidin. Similarly, crayfish, Orconectes propinquus, exhibited reduced responsiveness to stimulus with increasing clothianidin concentration. Using a semi-natural mesocosm experiment, we manipulated clothianidin concentration (0.6, 5, and 352 ppb) and the presence of predatory invertebrates to explore community-level effects. We observed high invertebrate predator mortality with increases in clothianidin concentration. With increased predator mortality, prey survival increased by 50% at the highest clothianidin concentration. Thus, clothianidin contamination can result in a top-down trophic cascade in a community dominated by invertebrate predators. In our Indiana field study, we detected clothianidin (max = 176 ppb), imidacloprid (max = 141 ppb), and acetamiprid (max = 7 ppb) in soil samples. In water samples, we detected clothianidin (max = 0.67 ppb), imidacloprid (max = 0.18 ppb), and thiamethoxam (max = 2

  18. Lethal effects of a Mexican Beauveria bassiana (Balsamo) strain against Meccus pallidipennis (Stal).

    PubMed

    Lino, Zumaquero Rios José; Juventino, López-Tlacomulco José; Raúl, Rojas García; Estibaliz, Sansinenea

    2014-01-01

    The entomopathogenic fungus Beauveria bassiana (Balsamo 1835) Vuillemin is an effective alternative control agent against some agricultural pests and biological vectors of important diseases such as Chagas disease. In this work we studied an isolate of Beauveria bassiana from of the town of San Antonio Rayón, Puebla, Mexico and its entomopathogenic effects on Meccus pallidipennis (Stal 1872). Phylogenetic analysis using molecular comparison of the ITS and EF1α genes, showed that the resulting cladogram places the BUAP 04 strain with a relationship closer to the AFAO 9-6 strain, within the diversity of the B. bassiana sensu lato group. Although there was the possibility that BUAP 04 strain was a direct descendant of strains used in campaigns of biologic control, molecular study allowed us to recognize that it was a different fungus due to numerous inserts. A strain isolated from a T. dimiata was evaluated for pathogenicity against another triatoma (Meccus pallidipennis) species obtaining an LC50 of 4.16 × 10(6) spores/mL, confirming that the BUAP 04 strain is virulent for M. pallidipennis and could be a good prospect for formulations to control M. pallidipennis.

  19. Lethal Effect of a Heterologous Murein Hydrolase on Penicillin-Treated Streptococcus sanguis

    PubMed Central

    Horne, Diane; Tomasz, Alexander

    1980-01-01

    Nine strains of Streptococcus sanguis exhibited tolerance to benzylpenicillin: the growth of each strain was susceptible to penicillin with minimal inhibitory concentrations of 0.1 μg/ml or lower, but the bacteriolytic and bactericidal effects were limited in each case. The tolerance of these bacteria was also reflected in the large discrepancies between the minimal inhibitory and minimal bactericidal concentrations for benzylpenicillin. The hypothesis that a natural deficiency of endogenous murein hydrolase (autolysin) in this species accounts for the penicillin tolerance was tested by using a heterologous murein hydrolase, the C-phage-associated lysin. In seven of the strains, addition of the lysin to the culture together with penicillin or other cell wall inhibitors resulted in lysis and rapid loss of viability. The enzyme alone did not appreciably affect normally growing cultures. The irreversible effects of penicillin plus lysin were drastically reduced in the presence of the bacteriostatic agents chloramphenicol and cerulenin. Speculations based on experiments are presented for the mechanisms by which penicillin treatment sensitizes these bacteria to an exogenous lytic enzyme. Similar phenomena requiring cooperation of host factors and penicillin may occur during infection, since somewhat similar although less pronounced results were obtained by addition of human lysozyme to penicillin-treated S. sanguis. PMID:6104471

  20. Lethal effects of a Mexican Beauveria bassiana (Balsamo) strain against Meccus pallidipennis (Stal)

    PubMed Central

    Lino, Zumaquero Rios José; Juventino, López-Tlacomulco José; Raúl, Rojas García; Estibaliz, Sansinenea

    2014-01-01

    The entomopathogenic fungus Beauveria bassiana (Balsamo 1835) Vuillemin is an effective alternative control agent against some agricultural pests and biological vectors of important diseases such as Chagas disease. In this work we studied an isolate of Beauveria bassiana from of the town of San Antonio Rayón, Puebla, Mexico and its entomopathogenic effects on Meccus pallidipennis (Stal 1872). Phylogenetic analysis using molecular comparison of the ITS and EF1α genes, showed that the resulting cladogram places the BUAP 04 strain with a relationship closer to the AFAO 9-6 strain, within the diversity of the B. bassiana sensu lato group. Although there was the possibility that BUAP 04 strain was a direct descendant of strains used in campaigns of biologic control, molecular study allowed us to recognize that it was a different fungus due to numerous inserts. A strain isolated from a T. dimiata was evaluated for pathogenicity against another triatoma (Meccus pallidipennis) species obtaining an LC50 of 4.16 × 106 spores/mL, confirming that the BUAP 04 strain is virulent for M. pallidipennis and could be a good prospect for formulations to control M. pallidipennis. PMID:25242941

  1. Evaluating sub-lethal effects of orchard-applied pyrethroids using video-tracking software to quantify honey bee behaviors.

    PubMed

    Ingram, Erin M; Augustin, Julie; Ellis, Marion D; Siegfried, Blair D

    2015-09-01

    Managed honey bee, Apis mellifera L., colonies are contracted to pollinate fruit and nut orchards improving crop quality and yield. Colonies placed in orchards are potentially exposed to pyrethroid insecticides used for broad-spectrum pest control. Pyrethroids have been reported to pose minimal risk to bees due to their low application rates in the field and putative repellent properties. This repellency is believed to alter foraging behavior with the benefit of preventing bees from encountering a lethal dose in the field. However, sub-lethal exposure to pyrethroids may adversely impact bee behavior potentially resulting in social dysfunction or disruption of foraging. This study quantified behaviors associated with sub-lethal exposure to orchard-applied pyrethroids including, lambda-cyhalothrin, esfenvalerate, and permethrin, using video tracking software, Ethovision XT (Noldus Information Technologies). Bee locomotion, social interaction, and time spent near a food source were measured over a 24-h period. Bees treated with a pyrethroid traveled 30-71% less than control bees. Social interaction time decreased by 43% for bees treated with a high sub-lethal dose of esfenvalerate. Bees exposed to a high sub-lethal dose of permethrin spent 67% less time in social interaction and spent more than 5 times as long in the food zone compared to control bees.

  2. Lethal or protective effects of prolonged treatment with hypoxic cell sensitizers

    SciTech Connect

    Edgren, M.R.

    1995-12-31

    AK-2123 [N-(2-methoxyethyl)-2-(3-nitro-1-triazolyl)acetamide] is a hypoxic cell radiosensitizer which is currently being tested in several oncology clinics and which has a lower toxicity than misonidazole (MISO) in vivo. The positive experiences reported recently certainly warrant further clinical evaluations. The experimental observations reported so far need further experimental studies to clarify the sensitization mechanism, especially as recent intratumoral strategies used in the clinical administration of the sensitizers can result in a large local concentration of the drug that may persist for a prolonged period of time between and after radiation exposures. Model experiments in vitro using V79 cells were performed with AK-2123 under these conditions. Misonidazole (MISO) and metronidazole (METRO), well known hypoxic cell radiosensitizers, were used for comparison of the effects. Clonogenic survival and induction and repair of DNA damage were used as end-points.

  3. Susceptibility to cartap-induced lethal effect and diaphragmatic injury via ocular exposure in rabbits.

    PubMed

    Liao, Jiunn-Wang; Pang, Victor Fei; Jeng, Chian-Ren; Chang, Shao-Kuang; Hwang, Jenn-Sheng; Wang, Shun-Cheng

    2003-11-05

    Cartap is extensively used to control agricultural pests. Pertinent literatures have indicated that it causes no eye irritation [D.E. Ray, Insecticides derived from plants and other organisms, in: W.J. Hayes, E.R. Laws (Eds.), Handbook of Insecticide Toxicology, Classes of Insecticides, vol. 2, Academic Press, New York, 1991, p. 611; C. Tomlin, Cartap, in: C. Tomlin (Ed.), The Insecticide Manual, 12th ed., British Crop Protection Council, Surrey, UK, 2000, p. 144]; however, the instillation of a little cartap through the eye has caused death in rabbits. The aim of this study was to determine the ocular toxicity of cartap in New Zealand White rabbits. Cartap was directly instilled into the low conjunctival sac of eyes, at doses of 0, 5, 7.5, 10 and 12.5 mg/kg body weight. The changes in the enzymes and isoenzymes of creatine kinase (CK), lactate dehydrogenase (LD), as well as pathological changes in the muscles of the heart, thigh and diaphragm were determined in the cartap-treated rabbits. Moreover, the neuromuscular effect of cartap was examined using the isolated rabbit phrenic-nerve diaphragm model. The results indicated that rabbits developed severe signs and they died within 20 min of ocular instillation. The ocular LD50 of cartap was 8.1 mg/kg body weight. Treatment with cartap increased the activities of CK and LD enzymes and their isoenzymes, CK-1, CK-2, and CK-3 in serum, and CK-3 and LD-5 in the diaphragm. Microscopically, hypercontraction bands and the rupture of myofibers of the diaphragm were observed in dead rabbits. Cartap did not affect nerve-evoked twitch but induced irreversible contracture and twitch depression on the isolated rabbit's diaphragm. These results indicate that the rabbit is susceptible to cartap toxicity; the effect of cartap caused contracture and damage to the diaphragm might play a pivotal role in respiratory paralysis and death of rabbits during intoxication.

  4. High risk but not always lethal: the effect of cirrhosis on thermally injured adults.

    PubMed

    Burns, Christopher J; Chung, Kevin K; Aden, James K; Lundy, Jonathan B; Nitzschke, Stephanie L; Renz, Evan M; Cancio, Leopoldo C

    2013-01-01

    The aim of this article was to determine the effect of cirrhosis on mortality in thermally injured adult patients. We conducted a retrospective review of patients admitted to our burn center during 2003 to 2010. Eight hundred eight patients were included in this study, of whom 24 had the diagnosis of cirrhosis established from electronic medical records and/or autopsy reports. The mortality rate for the cirrhotic patients was 50%, and for the noncirrhotic patients it was 14.8%. On logistic regression, age (odds ratio [OR], 1.08; confidence interval [CI], 1.06-1.10), TBSA (OR, 1.08; CI, 1.06-1.10), inhalation injury (OR, 3.17, CI, 1.61-6.25), and cirrhosis (OR, 8.78; CI, 2.97-25.98) had independent effects on mortality. Of the 24 cirrhotic patients in this study, the admission Model for End-Stage Liver Disease score for the patients who survived hospitalization was 12.1 ± 4.0, and for the patients who died it was 13.8 ± 6.0 (P = .4). When comparing patients with 10 to 50% TBSA burn, the mortality rate for cirrhotic patients was 83.3% (10/12), and for the noncirrhotic patients it was only 12.7% (50/394), P < .0001. Adults with cirrhosis are rarely able to survive burn injuries > 10% TBSA. Although we did not detect a significant association between admission Model for End-Stage Liver Disease score and death, the presence of cirrhosis is a high premorbid contributor and, therefore, new strategies are needed to improve outcomes.

  5. Chromosome aberrations and cellular premature senescence as radiation-induced sub-lethal effects: Implications for laser-driven charged-particle radiotherapy

    NASA Astrophysics Data System (ADS)

    Manti, L.; Perozziello, F. M.; Grossi, G.

    2013-07-01

    The use of charged particles significantly reduces the dose absorbed by normal cells due to the inverse dose-depth deposition profile. This is the physical pillar justifying hadrontherapy as the eligible treatment for deepseated tumours. However, a non-negligible amount of radiation is nevertheless absorbed in correspondence with the plateau region of the Bragg curve, which may result in the induction of sub-lethal effects. Very little experimental data exist on the induction of such effects. Moreover, reliable follow-up data on such adverse effects in hadrontherapy patients are limited since this type of treatment has been adopted relatively recently. A fortiori, the dependence of sub-lethal effects on unprecedented factors, such as the exceedingly high dose rates and/or the pulsed nature of beams originated by laser interaction with target materials, is unknown. This warrants investigation prior to a therapeutic use of such beams.

  6. Variations in lethal and sublethal effects of cypermethrin among aquatic stages and species of anuran amphibians.

    PubMed

    Biga, Lindsay M; Blaustein, Andrew R

    2013-12-01

    Despite the use of model species to predict the effects of chemicals in the environment, unpredicted variation in levels of risk to organisms from xenobiotics can be observed. Physiological and morphological differences between species and life stages may lead to differences in sensitivity, while seasonal and spatial variation in pesticide concentrations may affect the level of risk faced by organisms in the environment. Because anurans breed in aquatic habitats subject to contamination by runoff and spraying, they are particularly vulnerable to pesticides. In the present study, embryos, newly hatched larvae, and larvae with limb buds of 3 anuran amphibian species--Pseudacris regilla, Rana cascadae, and Rana aurora--were exposed for 48 h to either 0.5 µg/L or 5.0 µg/L cypermethrin under laboratory conditions. The authors monitored hatching success, larval survival, and measured growth. Additionally, they assayed avoidance behavior 2 wk after exposure or 2 wk after hatching for individuals exposed as embryos. Hatching and survival were not affected in animals of any species exposed as embryos. After exposure as embryos and as newly hatched larvae, however, P. regilla displayed behavioral abnormalities in response to prodding. Cypermethrin increased mortality in P. regilla exposed in both larval stages. Cypermethrin also increased mortality in larval R. cascadae when exposed at the early stage. These results indicate variation in sensitivity to environmentally relevant concentrations of cypermethrin among anuran species and life stages.

  7. Lethal and sublethal effects of embryonic and larval exposure of Hyla versicolor to Stormwater pond sediments.

    PubMed

    Brand, Adrianne B; Snodgrass, Joel W; Gallagher, Matthew T; Casey, Ryan E; Van Meter, Robin

    2010-02-01

    Stormwater ponds are common features of modern stormwater management practices. Stormwater ponds often retain standing water for extended periods of time, develop vegetative characteristics similar to natural wetlands, and attract wildlife. However, because stormwater ponds are designed to capture pollutants, wildlife that utilize ponds might be exposed to pollutants and suffer toxicological effects. To investigate the toxicity of stormwater pond sediments to Hyla versicolor, an anuran commonly found using retention ponds for breeding, we exposed embryos and larvae to sediments in laboratory microcosms. Exposure to pond sediments reduced survival of embryos by approximately 50% but did not affect larval survival. Larvae exposed to stormwater pond sediment developed significantly faster (x = 39 days compared to 42 days; p = 0.005) and were significantly larger at metamorphosis (x = 0.49 g compared to 0.36 g; p < 0.001) than controls that were exposed to clean sand. Substantial amounts (712-2215 mg/l) of chloride leached from pond sediments into the water column of treatment microcosms; subsequently, survival of embryos was negatively correlated (r (2) = 0.50; p < 0.001) with water conductivity during development. Our results, along with the limited number of other toxicological studies of stormwater ponds, suggest that road salt contributes to the degradation of stormwater pond habitat quality for amphibian reproduction and that future research should focus on understanding interactions among road salts and other pollutants and stressors characteristic of urban environments.

  8. Effects of injectable anticholinergic drugs on soman-induced lethality and convulsant/subconvulsant activity

    SciTech Connect

    Harris, L.W.; Anderson, D.R.; Lennox, W.J.; Bowersox, S.L.; Anders, J.C.

    1993-05-13

    FDA approved, injectable preparations of candidate compounds BENZTROPINE (BZT), 1.0 mg/ml; biperiden (BIP), 5.0 mg/ml; dicyclomine (DCL), 10 mg/ml; 1-hyoscyamine (HYO), 0.5 mg/ml; orphenadrine (ORP), 30 mg/ml; scopolamine (SCP), 1.0 mg/ml were tested in parallel with diazepam (DZ, the standard) in male guinea pigs against ongoing soman induced convulsive (CV)/sub-CV activity. Three trained graders concurrently assigned CV/sub-CV scores (12 - convulsions; 0 normal) to each animal. Animals received (im) pyridostigmine (PYR; 26 ug/kg) 30 min before soman (56 ug/kg; 2 LD50), atropine (2 mg/kg) admixed with 2-PAM (25 mg/kg) at one min after soman, and the candidate drug preparation at 5.67 min post soman, a time when CV activity is assured. BIP and SCP demonstrated efficacy over dosage ranges between 10 and 0.3 and 1.0 and 0.13 mg/kg, respectively, while the other preparations were less effective at their respective maximum dosages. At optimal dosages of SCP (0.5 mg/kg) and BIP (10 mg/kg), the CV/sub-CV scores were significantly lower (p < 0.05) than those of DZ.

  9. Toxicity of the pyrethroid pesticide fenvalerate to freshwater catfish Clarias gariepinus: lethality, biochemical effects and role of dietary ascorbic acid.

    PubMed

    Bhattacharya, Madhuban; Kaviraj, Anilava

    2009-08-01

    Static bioassays were made in the laboratory to determine lethal concentration of the pyrethroid pesticide fenvalerate [(RS)-alpha-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate] for the freshwater catfish Clarias gariepinus and effects of sublethal concentrations of the pesticide on some biochemical parameters of the fish. For exposure periods of 24 to 96 h, LC(50) values of fenvalerate ranged from 5.83-4.76 micro g/L and 4.24-2.94 micro g/L, respectively for water and acetone soluble fenvalerate. Two sublethal concentrations of fenvalerate were used in the bioassays for biochemical parameters: 2.1 micro g/L for 24 h and 1.4 micro g/L for 96 h exposure, both concentrations representing 50% of LC(50) value of acetone soluble fenvalerate for the respective exposure period. Hepatosomatic index, liver glycogen, alkaline phosphatase of liver and ascorbic acid of blood, liver, and kidney decreased while haemoglobin (Hb) %, plasma glucose levels and acid phosphatase level of liver increased after 24 h exposure to 2.1 micro g/L fenvalerate. Longer exposure (96 h) to even a lower concentration (1.4 micro g/L) of fenvalerate resulted in reduction of all the parameters (except Hb %) tested as compared with control. Fish previously fed for 60 days with a diet supplemented by a high level of ascorbic acid (100 mg/100 g diet) could reverse most of the effects caused by 24 h exposure to 2.1 micro g/L fenvalerate. A lower level of ascorbic acid (50 mg/ 100 g diet) supplement could not influence these effects of fenvalerate. Even the higher dose of ascorbic acid supplementation (100 mg/100 g diet) could not relieve the stress parameters, except for Hb% and HSI, when the pesticide was applied at 1.4 micro g/L for a longer time period (96 h).

  10. Critical body-residues for lethal and sublethal effects of sediment-associated PAH on benthic copepods

    SciTech Connect

    Lotufo, G.R.

    1995-12-31

    Adult females of the meiobenthic copepod Schizopera knabeni were exposed to sediment-associated fluoranthene for 3, 6, 12, 24, 96, and 240 h. Sediment concentrations ranged from 25 to 1,661 nmol (5--336 {micro}g)/gdw and the TOC was 1.5%. Body burden increased to an apparent steady state after only 6 h. Elimination half-lives were 4.6 and 3.2 h in uncontaminated water and sediment, respectively. Toxic effects were only detected after 240 h as increased mortality and decreased offspring production. Significant mortality was observed only at the highest concentration; the LC50 was 1,011 nmol (204 {micro}g)/dgw. In contrast, offspring production was decreased at much lower concentrations, yielding an IC25 value of 148 nmol (30 {micro}g)/dgw. Lethal critical body residue (CBR) was determined as a 10-d LD50 of 15.5 {micro}mol/g dry tissue. By measuring PAH concentrations in the body and eggs of females, CBRs for reproductive output were determined as IC25 values of 2 and 3.1 {micro}mol/gdw, respectively. PAH sublethal effects on feeding rate were also investigated Adult copepods were exposed to {sup 14}C sediment-associated fluoranthene for 24 h were fed {sup 3}H-labeled algae for 3 h. Ingestion rate was significantly decreased at tissue concentrations as low as 1 {micro}mol/gdw and yielded an IC25 value of 0.6 {micro}mol/gdw. Similar findings were obtained using another species of estuarine copepod, Coullana sp. Non-polar narcotic compounds such as PAH cause a nonspecific disturbance of the functioning of cell membrane which results in decreased overall activity. Measurement of CBR associated with decreased feeding is proposed as a direct method to quantify sublethal narcotizing effects of organic compounds.

  11. Sub-lethal Effects of Chlorpyrifos on Big Brown Bats (Eptesicus fuscus).

    PubMed

    Eidels, Ronny R; Sparks, Daniel W; Whitaker, John O; Sprague, Charles A

    2016-10-01

    We determined dose-response curves for sublethal effects of the organophosphorus (OP) insecticide, chlorpyrifos, on bats. Big brown bats (Eptesicus fuscus, n = 64) were given a single dose of chlorpyrifos (nominal concentrations) of 0, 5, 10, 15, 20, 25, 30, or 60 µg/g body weight and examined at 12 or 24 h after dosing. A second experiment dosed 32 bats with 0 or 60 µg/g body weight and examined 1, 3, 7, or 14 days after dosing. Skin temperature and behavioral changes were recorded, and brain and plasma cholinesterase (ChE) activity were measured. The benchmark dose (BMD10) of chlorpyrifos that altered brain and plasma ChE activity at 24 h was 3.7 and 10.1 µg/g, respectively. The 95 % lower confidence limit for the BMD10 (i.e., BMDL10) was 1.6 and 7.7 µg/g. The best of five models (as determined by AIC) for impaired flight, impaired movement, or presence of tremors provided a BMD10 of 6.2, 12.9, and 7.8 µg/g body weight of chlorpyrifos, respectively. BMDL10 for impaired flight, impaired movement, or presence of tremors was 3.5, 6.6, and 5.3 µg/g body weight, respectively. In the wild, impaired ability to fly or crawl could be life-threatening. Brain and plasma ChE activity remained low for 3 days after dosing. Gradual recovery of enzyme activity was observed by 7 days in survivors. Brain and plasma ChE activity were still significantly lower than that of the control group at 14 days after dosing.

  12. Todralazine Protects Zebrafish from Lethal Effects of Ionizing Radiation: Role of Hematopoietic Cell Expansion

    PubMed Central

    Dimri, Manali; Joshi, Jayadev; Chakrabarti, Rina; Sehgal, Neeta; Sureshbabu, Angara

    2015-01-01

    Abstract The Johns Hopkins Clinical Compound Library (JHCCL), a collection of Food and Drug Administration (FDA)-approved small molecules (1400), was screened in silico for identification of novel β2AR blockers and tested for hematopoietic stem cell (HSC) expansion and radioprotection in zebrafish embryos. Docking studies, followed by the capacity to hasten erythropoiesis, identified todralazine (Binding energy, −8.4 kcal/mol) as a potential HSC-modulating agent. Todralazine (5 μM) significantly increased erythropoiesis in caudal hematopoietic tissue (CHT) in wild-type and anemic zebrafish embryos (2.33- and 1.44-folds, respectively) when compared with untreated and anemic control groups. Todralazine (5 μM) treatment also led to an increased number of erythroid progenitors, as revealed from the increased expression of erythroid progenitor-specific genes in the CHT region. Consistent with these effects, zebrafish embryos, Tg(cmyb:gfp), treated with 5 μM todralazine from 24 to 36 hours post fertilization (hpf) showed increased (approximately two-folds) number of HSCs at the aorta-gonad-mesonephros region (AGM). Similarly, expression of HSC marker genes, runx1 (3.3-folds), and cMyb (1.41-folds) also increased in case of todralazine-treated embryos, further supporting its HSC expansion potential. Metoprolol, a known beta blocker, also induced HSC expansion (1.36- and 1.48-fold increase in runx1 and cMyb, respectively). Todralazine (5 μM) when added 30 min before 20 Gy gamma radiation, protected zebrafish from radiation-induced organ toxicity, apoptosis, and improved survival (80% survival advantage over 6 days). The 2-deoxyribose degradation test further suggested hydroxyl (OH) radical scavenging potential of todralazine, and the same is recapitulated in vivo. These results suggest that todralazine is a potential HSC expanding agent, which might be acting along with important functions, such as antioxidant and free radical scavenging, in

  13. Protective effect of carvacrol on acute lung injury induced by lipopolysaccharide in mice.

    PubMed

    Feng, Xiaosheng; Jia, Aiqing

    2014-08-01

    Carvacrol, the major component of Plectranthus amboinicus, has been known to exhibit anti-inflammatory activities. The aim of this study was to investigate the effects of carvacrol on lipopolysaccharide (LPS)-induced endotoxemia and acute lung injury (ALI) in mice. Mice were injected intraperitoneally (i.p.) with LPS and the mortality of mice for 7 days were observed twice a day. Meanwhile, the protective effect of carvacrol (20, 40 or 80 mg/kg) on LPS-induced endotoxemia were detected. Using an experimental model of LPS-induced ALI, we examined the effect of carvacrol in resolving lung injury. The results showed that carvacrol could improve survival during lethal endotoxemia and attenuate LPS-induced ALI in mice. The anti-inflammatory mechanisms of carvacrol may be due to its ability to inhibit NF-κB and MAPKs signaling pathways, thereby inhibiting inflammatory cytokines TNF-α, IL-6 and IL-1β production.

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

    PubMed

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

    2015-06-15

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

  15. Lethal and sublethal effects of ammonia to juvenile Lampsilis mussels (Unionidae) in sediment and water-only exposures

    USGS Publications Warehouse

    Newton, T.J.; Bartsch, M.R.

    2007-01-01

    We compared the sensitivity of two juvenile unionid mussels (Lampsilis cardium and Lampsilis higginsii) to ammonia in 96-h water-only and sediment tests by use of mortality and growth measurements. Twenty mussels were placed in chambers buried 2.5 cm into reference sediments to approximate pore-water exposure (sediment tests) or elevated above the bottom of the experimental units (water-only tests). In the sediment tests, a pH gradient existed between the overlying water (mean 8.0), sediment-water interface (mean 7.7), and 2.5 cm depth (mean 7.4). We assumed that mussels were exposed to ammonia in pore water and report effect concentrations in pore water, but if they were exposed to the higher pH water, more of the ammonia would be in the toxic un-ionized (NH 3) form. The only differences in toxicity and growth between mussel species occurred in some of the water-only tests. In sediment tests, median lethal concentrations (LC50s) ranged from 124 to 125 ??g NH3-N/L. In water-only tests, LC50s ranged from 157 to 372 ??g NH3-N/L. In sediment tests, median effective concentrations (EC50s based on growth) ranged from 30 to 32 ??g NH3-N/L. Juvenile mussels in the water-only tests grew poorly and did not exhibit a dose-response relation. These data demonstrate that growth is a sensitive and valuable endpoint for studies on ammonia toxicity with juvenile freshwater mussels and that growth should be measured via sediment tests. ?? 2007 SETAC.

  16. The sub-lethal effects and tissue concentration of the human pharmaceutical atenolol in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Steinbach, Christoph; Burkina, Viktoriia; Fedorova, Ganna; Grabicova, Katerina; Stara, Alzbeta; Velisek, Josef; Zlabek, Vladimir; Schmidt-Posthaus, Heike; Grabic, Roman; Kocour Kroupova, Hana

    2014-11-01

    Atenolol is a highly prescribed anti-hypertensive pharmaceutical and a member of the group of β-blockers. It has been detected at concentrations ranging from ng L(-1) to low μg L(-1) in waste and surface waters. The present study aimed to assess the sub-lethal effects of atenolol on rainbow trout (Oncorhynchus mykiss) and to determine its tissue-specific bioconcentration. Juvenile rainbow trout were exposed for 21 and 42 days to three concentration levels of atenolol (1 μg L(-1) - environmentally relevant concentration, 10 μg L(-1), and 1000 μg L(-1)). The fish exposed to 1 μg L(-1) atenolol exhibited a higher lactate content in the blood plasma and a reduced haemoglobin content compared with the control. The results show that exposure to atenolol at concentrations greater than or equal to 10 μg L(-1) significantly reduces both the haematocrit value and the glucose concentration in the blood plasma. The activities of the studied antioxidant enzymes (catalase and superoxide dismutase) were not significantly affected by atenolol exposure, and only the highest tested concentration of atenolol significantly reduced the activity of glutathione reductase. The activities of selected CYP450 enzymes were not affected by atenolol exposure. The histological changes indicate that atenolol has an effect on the vascular system, as evidenced by the observed liver congestion and changes in the pericardium and myocardium. Atenolol was found to have a very low bioconcentration factor (the highest value found was 0.27). The bioconcentration levels followed the order liver>kidney>muscle. The concentration of atenolol in the blood plasma was below the limit of quantification (2.0 ng g(-1)). The bioconcentration factors and the activities of selected CYP450 enzymes suggest that atenolol is not metabolised in the liver and may be excreted unchanged.

  17. Effects of sub-lethal glyphosate concentrations on growth and photosynthetic performance of non-target species Bolboschoenus maritimus.

    PubMed

    Mateos-Naranjo, E; Perez-Martin, A

    2013-11-01

    Glyphosate use has increased over the last decades for the control of invasive plant species in wetland ecosystems. Although glyphosate has been considered 'environmentally' safe, its repeated use could increase the toxicological risk derived from diffuse pollution of surface and groundwater on non-target vegetation. A glasshouse study was designed to determine the effect produced by the addition of different sub-lethal doses of glyphosate herbicides (5-30 mg L(-1)) to the nutrient solution on the growth and photosynthetic apparatus of Bolboschoenus maritimus. Although B. maritimus plants were able to grow and survive after 20 d of exposure to glyphosate, the presence of this herbicide affected their growth, through a direct interaction with the root system. Particularly, at 30 mg L(-1) glyphosate, B. maritimus showed ca. 30% of biomass decrease. The reduction in B. maritimus growth was due to a decrease in net photosynthetic rate (A), which ranged between values ca. 11.5 and 5.5 μmol m(-2)s(-1) CO2 for the control and the highest glyphosate treatment, respectively. The response of A to glyphosate could be largely accounted for by non-stomatal limitations, since stomatal conductance was similar in all glyphosate treatments. Thus, A decrease was prompted by the negative impact of herbicide on photochemical (PSII) apparatus, the reduction in the absorption of essential nutrients, the reduction of photosynthetic pigments and possibly the reduction in Rubisco carboxilation capacity. Moreover, glyphosate excess caused photoinhibitory damage. In conclusion, in this study we have shown that herbicide water pollution could be a source of indirect phytotoxicity for B. maritimus.

  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. Snakebites and ethnobotany in the northwest region of Colombia: Part II: neutralization of lethal and enzymatic effects of Bothrops atrox venom.

    PubMed

    Otero, R; Núñez, V; Jiménez, S L; Fonnegra, R; Osorio, R G; García, M E; Díaz, A

    2000-08-01

    Twelve of 74 ethanolic extracts of plants used by traditional healers for snakebites in the northwest region of Colombia, were active against lethal effect of Bothrops atrox venom when they were i.p. injected into mice (18-20 g). After preincubation of sublethal doses of every extract (0.5-4.0 mg/mouse) with 1.5 i.p. lethal dose 50% (LD50) (99.3 microg) of venom, seven of them demonstrated 100% neutralizing capacity within 48 h. These were the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); rhizomes of Renealmia alpinia (Zingiberaceae) and Heliconia curtispatha (Heliconiaceae); the whole plants of Pleopeltis percussa (Polypodiaceae) and Trichomanes elegans (Hymenophyllaceae); and the ripe fruits of Citrus limon (Rutaceae). The other five extracts showing partial neutralization (45-80%; 10-30% survival rate in the control group receiving the venom alone; P<0.05) were: leaves, branches and stem of Costus lasius (Costaceae); the whole plant of Sida acuta (Malvaceae); rhizomes of Dracontium croatii (Araceae); leaves and branches of Bixa orellana (Bixaceae) and Struthanthus orbicularis (Loranthaceae). When the extracts were independently administered per oral or i.p. route 60 min before an i.m. venom injection (204 microg=1.5 i.m. LD50), C. limon, T. elegans, B. orellana and T. rosea extracts had partial and significant neutralizing capacity against B. atrox venom lethal effect. C. limon extract was also partially effective when it was administered either i.v. 15 min before or i.p. 5 min after an i.m. venom injection. Three of the 12 extracts with anti-lethal effect (C. limon, D. croatii and S. acuta) were devoid of antiphospholipase A2 activity, when they were tested against one minimum indirect hemolytic dose of B. atrox venom (2 microg) in agarose-erythrocyte-egg yolk gels.

  20. Enzymic degradation of plasma arginine using arginine deiminase inhibits nitric oxide production and protects mice from the lethal effects of tumour necrosis factor alpha and endotoxin.

    PubMed Central

    Thomas, J Brandon; Holtsberg, Frederick W; Ensor, C Mark; Bomalaski, John S; Clark, Mike A

    2002-01-01

    Septic shock is mediated in part by nitric oxide (NO) and tumour necrosis factor alpha (TNFalpha). NO is synthesized primarily from extracellular arginine. We tested the ability of an arginine-degrading enzyme to inhibit NO production in mice and to protect mice from the hypotension and lethality that occur after the administration of TNFalpha or endotoxin. Treatment of BALB/c mice with arginine deiminase (ADI) formulated with succinimidyl succinimide polyethylene glycol of M(r) 20000 (ADI-SS PEG(20000)) eliminated all measurable plasma arginine (from normal levels of approximately 155 microM arginine to 2 microM). In addition, ADI-SS PEG(20000) also inhibited the production of NO, as quantified by plasma nitrate+nitrite. Treatment of mice with TNFalpha or endotoxin resulted in a dose-dependent increase in NO production and lethality. Pretreatment of mice with ADI-SS PEG(20000) resulted in increased resistance to the lethal effects of TNFalpha and endotoxin. These observations are consistent with NO production resulting, to some extent, from the metabolism of extracellular arginine. The toxic effects of TNFalpha and endotoxin may be partially inhibited by enzymic degradation of plasma arginine by ADI-SS PEG(20000). Interestingly, pretreatment with ADI-SS PEG(20000) did not inhibit the anti-tumour activity of TNFalpha in vitro or in vivo. This treatment may allow greater amounts of TNFalpha, as well as other cytokines, to be administered while abrogating side effects such as hypotension and death. PMID:11964159

  1. 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

  2. A ΔdinB mutation that sensitizes Escherichia coli to the lethal effects of UV- and X-radiation.

    PubMed

    Lee, Mei-Chong W; Franco, Magdalena; Vargas, Doris M; Hudman, Deborah A; White, Steven J; Fowler, Robert G; Sargentini, Neil J

    2014-01-01

    in protecting cells against the lethal effects of radiation.

  3. Effect of sub-lethal concentrations of endosulfan on phagocytic and hematological parameters in Nile tilapia (Oreochromis niloticus).

    PubMed

    Girón-Pérez, M I; Montes-López, M; García-Ramírez, L A; Romero-Bañuelos, C A; Robledo-Marenco, M L

    2008-03-01

    The effect of endosulfan (6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin-3-oxide), an organochlorine pesticide, was evaluated on phagocytic (phagocytic index and percentage of active cells) and hematological parameters in Nile tilapia. Experimental data showed that an acute exposure to endosulfan (4.0 and 7.0 microg/L) induces a significant decrease in the phagocytic index and the percentage of active cells in peripherical blood of Nile tilapia. However, hemoglobin concentration (Hb), hematocrit (Hto), red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were not significantly altered in fish exposed to endosulfan compared with control group.

  4. Non-cancer effects in acute radiation syndrome survivors in Ukraine.

    PubMed

    Belyi, David; Kovalenko, Aleksander; Bazyka, Dmitrij; Bebeshko, Vladimir

    2010-06-01

    The 1986 Chernobyl Nuclear Power Plant accident that occurred is known as the most severe nuclear disaster in the history of humankind. Acute radiation syndrome (ARS) was diagnosed in 237 persons but only 134 of those were confirmed, including 28 patients who died due to lethal total-body gamma-irradiation and severe skin injuries caused by beta/gamma-emitting radionuclides. A small group of ARS survivors offers an interesting observational insight pertinent to the on-going discussions about long-term non-cancer effects of ionizing radiation. This descriptive study summarizes more than 20 y of follow-up, makes attempts to offer a prognosis for the Chernobyl ARS survivors' health, and explores the link between the outcomes of interest and radiation exposure.

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

    PubMed

    Giddings, Jeffrey; Gagne, James; Sharp, Janice

    2016-08-01

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

  6. 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.

  7. Effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    SciTech Connect

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-02-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. /sup 51/Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras.

  8. Acute, chronic and biochemical effects of chlorothalonil on Agalychnis callidryas, Isthmohyla pseudopuma and Smilisca baudinii tadpoles.

    PubMed

    Méndez, Michael; Obando, Priscilla; Pinnock-Branford, Margaret; Ruepert, Clemens; Castillo, Luisa E; Mena, Freylan; Alvarado, Gilbert

    2016-11-01

    Declines of amphibian populations have been a worldwide issue of concern for the scientific community during the last several decades. Efforts are being carried out to elucidate factors related to this phenomenon. Among these factors, pathogens, climate change, and environmental pollution have been suggested as possible causes. Regarding environmental pollutants, some pesticides are persistent in the environment and capable of being transported long distances from their release point. In Costa Rica, some pesticides have been detected in protected areas, at locations where amphibian populations have declined. Information about toxicity of pesticides used in Costa Rican agriculture to amphibians is still scarce, particularly for native species.Toxicity tests with chlorothalonil, a fungicide intensively used in Costa Rica, were carried out exposing tadpoles of three Costa Rican native species: Agalychnis callidryas, Isthmohyla pseudopuma, and Smilisca baudinii in order to evaluate acute and chronic toxicity as well as the biomarkers cholinesterase activity (ChE), glutathione-S transferase activity (GST), and lipid peroxidation (LPO).96-h LC50: 26.6 (18.9-35.8) μg/L to A. callidryas, 25.5 (21.3-29.7) μg/L to I pseudopuma and 32.3 (26.3-39.7) μg/L to S. baudinii were determined for chlorothalonil. These three species of anurans are among the most sensitive to chlorothalonil according to the literature. Besides, GST was induced in S. baudinii after exposure to sub-lethal concentrations of chlorothalonil while evisceration occurred in S. baudinii and A. callidryas tadpoles exposed to lethal concentrations of the fungicide. Chronic exposure to sub-lethal concentrations accelerated development in S. baudinii and caused lesions in tail of S. baudinii and I. pseudopuma tadpoles. Our results demonstrate that chlorothalonil is highly toxic to native amphibian species and that low concentrations can cause biochemical responses related to phase II of biotransformation and

  9. 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

  10. Pharmacological Effects of Niacin on Acute Hyperlipemia.

    PubMed

    la Paz, Sergio Montserrat-de; Bermudez, Beatriz; Naranjo, M Carmen; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

    2016-01-01

    The well-known changes in modern lifestyle habits including over nutrition and physical inactivity have led to striking adverse effects on public health (e.g., obesity, diabetes, and metabolic syndrome) over recent decades. One noticeable consequence is exaggerated and prolonged state of postprandial hyperlipemia due to the ingestion of multiple fat-enriched meals during the course of a day. Postprandial (non-fasting) hyperlipemia is characterized by increased blood levels of exogenous triglycerides (TG) in the form of apolipoprotein (apo) B48-containing TG-rich lipoproteins (TRL), which have a causal role in the pathogenesis and progression of cardiovascular disease (CVD). The cardiovascular benefits of lifestyle modification (healthy diet and exercise) and conventional lipid-lowering therapies (e.g., statins, fibrates, and niacin) could involve their favourable effects on postprandial metabolism. Pharmacologically, niacin has been used as an athero-protective drug for five decades. Studies have since shown that niacin may decrease fasting levels of plasma verylow- density lipoproteins (VLDL), low-density lipoprotein cholesterol (LDL-C), and lipoprotein [a] (Lp[a]), while may increase high-density lipoprotein cholesterol (HDL-C). Herein, the purpose of this review was to provide an update on effects and mechanisms related to the pharmacological actions of niacin on acute hyperlipemia.

  11. Radiation-induced cell lethality of samonella typhimurium ATCC 14028: Cooperative effect of hydroxyl radical and oxygen

    SciTech Connect

    Kim, Y.A.; Thayer, D.W.

    1995-10-01

    The lethality of {gamma}-radiation doses of 0.2 to 1.0 kGy for Salmonella typhimurium ATCC 14028 was measured in the presence of air, N{sub 2} and N{sub 2}O and with the hydroxyl radical scavengers formate and polyethylene glycol (PEG), M{sub r} 8,000. Saturation of cell suspensions with either N{sub 2}O or N{sub 2}/N{sub 2}/N{sub 2}O (1:1, v/v) gas was expected to double the number of hydroxyl radicals (OH{center_dot}) and to produce an equivalent increase in lethality, but this did not occur. Adding 10% (v/v) O{sub 2} to either N{sub 2}/N{sub 2}O gas produced approximately the same {gamma}-irradiation lethality for S. typhimurium as did air. Addition of hydroxyl radical scavengers, 40 mM formate and 1.5% (w/v) PEG, significantly reduced the lethality of {gamma} radiation for S. typhimurium in the presence of air but not in the presence of N{sub 2} or N{sub 2}O gases. Membrane-permeable formate provided slightly better protection than nonpermeable PEG. Cells of S. typhimurium grown under anaerobic conditions were more sensitive to radiation, and were less protected by hydroxyl radical scavengers, especially formate, than when cells grown under aerobic conditions were irradiated in the presence of oxygen. Hydroxyl radical scavengers provided no further protection during irradiation in the absence of oxygen. These results indicated that the increased radiation sensitivity of cells grown under anaerobic conditions may be related to superoxide radicals which could increase intercellular damage during irradiation in the presence of oxygen. However, endogenous superoxide dismutase and catalase activities did not protect cells from the radiation-induced lethality of S. typhimurium. Cytoplasmic extracts protected bacterial DNA in vitro in either the presence of absence of oxygen, and no radiation-induced lipid peroxidation of the cellular components was identified by measuring the levels of 2-thiobarbituric acid. 38 refs., 4 figs., 2 tabs.

  12. Acute effects of solar particle event radiation

    PubMed Central

    Kennedy, Ann R.; Weissman, Drew; Sanzari, Jenine K.; Krigsfeld, Gabriel S.; Wan, X. Steven; Romero-Weaver, Ana L.; Diffenderfer, Eric S.; Lin, L.; Cengel, K.

    2014-01-01

    A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animals exposed to space flight stressors combined with the types of radiation expected during an SPE. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations: gamma rays or electrons). All animal studies described have been approved by the University of PA IACUC. Some conclusions from recent CARR investigations are as follows: (i) the relative biological effectiveness (RBE) values for SPE-like protons compared with standard reference radiations (gammas or electrons) for white blood cells (WBCs) vary greatly between mice, ferrets and pigs, with the RBE values being greater in ferrets than those in mice, and considerably greater in pigs compared with those in ferrets or mice [1, 2]. This trend for the data suggests that the RBE values for WBCs in humans could be considerably greater than those observed in small mammals, and SPE proton radiation may be far more hazardous to humans than previously estimated from small animal studies. (ii) Very low doses of SPE proton radiation (25 cGy) increase blood clotting times in ferrets, and the low SPE-like dose rate has more severe effects than high dose rate radiation [3]. (iii) Results from pig and ferret studies suggest that disseminated intravascular coagulation is a major cause of death at doses near the LD50 level for SPE-like proton and gamma radiation. (iv) Exposure to SPE-like proton or gamma radiation, in combination with

  13. Glucose Effect in the Acute Porphyrias

    MedlinePlus

    ... 2017 Apr 05, 2017 National Porphyria Awareness Week! Mar 23, 2017 National Porphyria Awareness Week is ONE ... 2017 National Porphyria Awareness Week (NPAW) 2017 date: Mar 1, 2017 FDA Meeting for Acute Porphyrias is ...

  14. Effects of sub-lethal teratogen exposure during larval development on egg laying and egg quality in adult Caenorhabditis elegans

    PubMed Central

    Killeen, Alexis; Marin de Evsikova, Caralina

    2016-01-01

    Background: Acute high dose exposure to teratogenic chemicals alters the proper development of an embryo leading to infertility, impaired fecundity, and few viable offspring. However, chronic exposure to sub-toxic doses of teratogens during early development may also have long-term impacts on egg quality and embryo viability. Methods: To test the hypothesis that low dose exposure during early development can impact long-term reproductive health, Caenorhabditis elegans larvae were exposed to 10 teratogens during larval development, and subsequently were examined for the pattern of egg-laying and egg quality (hatched larvae and embryo viability) as gravid adults.  After the exposure, adult gravid worms were transferred to untreated plates and the numbers of eggs laid were recorded every 3 hours, and the day following exposure the numbers of hatched larvae were counted. Re sults: While fecundity and fertility were typically impaired by teratogens, unexpectedly, many teratogens initially increased egg-laying at the earliest interval compared to control but not at later intervals. However, egg quality, as assessed by embryo viability, remained the same because many of the eggs (<50%) did not hatch. Conclusions: Chronic, low dose exposures to teratogens during early larval development have subtle, long-term effects on egg laying and egg quality. PMID:28163903

  15. 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.

  16. Inhalation of diethylamine--acute nasal effects and subjective response

    SciTech Connect

    Lundqvist, G.R.; Yamagiwa, M.; Pedersen, O.F.; Nielsen, G.D. )

    1992-03-01

    Adult volunteers were exposed to 25 ppm (75 mg/m3) diethylamine in a climate chamber for 15 min in order to study the acute nasal reactions to an exposure equivalent to the present threshold limit value-short-term exposure limit. Changes in nasal volume and nasal resistance were measured by acoustic rhinometry and by rhinomanometry. Acute change in nasal volume, usually seen as acute nasal mucosa response to thermal stimuli, was not observed, nor was an acute change in nasal airway resistance. In a subsequent experiment, the aim was to measure acute sensory effects. Exposure to a concentration increasing from 0 to 12 ppm took place for 60 min, equal to an average concentration of 10 ppm (30 mg/m3). A moderate to strong olfactory response and distinct nasal and eye irritation were observed. In spite of considerable individual variation, the results were in agreement with sensory effect estimates obtained from animal studies.

  17. Effects of DDE and PCB (Aroclor 1260) on experimentally poisoned little brown bats (Myotis lucifugus): Lethal brain concentrations

    USGS Publications Warehouse

    Clark, D.R.; Stafford, C.J.

    1981-01-01

    Adult female little brown bats (Myotis lucifugus) were collected in a church attic in North East, Cecil County, Md. Mealworms (Tenebrio molitor) containing organochlorine pollutants were fed to the bats as follows: 5 bats were dosed at 480 ppm DDE, 12 at 150 ppm DDE, 5 at 1000 ppm polychlorinated biphenyl (PCB; Aroclor 1260), and 12 at 15 ppm PCB. Seven other bats were fed untreated mealworms. The objective was to elevate brain levels of DDE and PCB to lethality and measure these concentrations. During 40 d of dosage, one DDE-dosed bat and two PCB-dosed bats died after exhibiting the prolonged tremor that characterizes organochlorine poisoning. After dosage, surviving bats were starved to elevate brain levels of toxicants, and three additional DDE-dosed bats had tremors before dying. The mean brain concentration of DDE diagnostic of death was estimated as 603 ppm, range 540-670 ppm. This mean is 16-18% higher than means for Mexican free-tailed bats (Tadarida brasiliensis) and common grackles (Quiscalus quiscula), and may indicate less sensitivity. Lethal brain concentrations of Aroclor 1260 were 1300 and 1500 ppm. Such values appear to be higher than values (Aroclor 1254) for brown-headed cowbirds (Molothrus ater). During starvation, DDE-dosed bats lost weight about 24% faster than controls. If smaller amounts of stored DDE cause increases in metabolic rates of nonfeeding bats, as during hibernation or migration, the result could be premature energy depletion and increased mortality.

  18. Effect of delayed anthrax vaccine dose on Bacillus anthracis protective antigen IgG response and lethal toxin neutralization activity.

    PubMed

    Pittman, Phillip R; Fisher, Diana; Quinn, Xiaofei; Schmader, Trevor; Barrera-Oro, Julio G

    2013-10-17

    We describe the Bacillus anthracis protective antigen IgG antibody response and the B. anthracis lethal toxin neutralization activity to a delayed dose of anthrax vaccine adsorbed (AVA, BioThrax(®)) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they received a delayed dose of AVA. Overall, 23.6% of subjects showed detectable anti-PA IgG before the boost, compared to 99.2% (P<0.0001) 28 days after the boost. Geometric mean anti-PA IgG concentration (GMC) was 1.66 μg/mL before and 887.82 μg/mL after the boost (P<0.0001). The proportion of individuals with four-fold increase in GMC following the boost ranged from 93.8% to 100%. Robust anti-PA IgG levels and B. anthracis lethal toxin neutralization activity are induced when an AVA dose is delayed as long as two years. These data support continuing with the vaccination schedule when a dose is delayed as long as two years rather than restarting the series.

  19. Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques.

    PubMed

    Warren, Travis K; Whitehouse, Chris A; Wells, Jay; Welch, Lisa; Charleston, Jay S; Heald, Alison; Nichols, Donald K; Mattix, Marc E; Palacios, Gustavo; Kugleman, Jeffrey R; Iversen, Patrick L; Bavari, Sina

    2016-02-01

    Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83-100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI.

  20. Long-term sub-lethal effects of low concentration commercial herbicide (glyphosate/pelargonic acid) formulation in Bryophyllum pinnatum.

    PubMed

    Pokhrel, Lok R; Karsai, Istvan

    2015-12-15

    Potential long-term (~7months) sub-lethal impacts of soil-applied low levels of Roundup herbicide formulation were investigated in a greenhouse environment using the vegetative clones of succulent non-crop plant model, Bryophyllum pinnatum (Lam.) Oken. An eleven day LC50 (concentration that killed 50% of the plants) was found to be 6.25% (~1.25mg glyphosate/mL and 1.25mg pelargonic acid/mL combined), and complete mortality occurred at 12.5%, of the field application rate (i.e., ~20mg glyphosate/mL and 20mg pelargonic acid/mL as active ingredients). While sub-lethal Roundup (1-5%) exposures led to hormesis-characterized by a significant increase in biomass and vegetative reproduction, higher concentrations (≥6.25%) were toxic. A significant interaction between Roundup concentrations and leaf biomass was found to influence the F1 plantlets' biomass. Biomass asymmetry generally increased with increasing Roundup concentrations, indicating that plants were more stressed at higher Roundup treatments but within the low-dose regime (≤5% of the as-supplied formulation). While leaf apex region demonstrated higher reproduction with lower biomass increase, leaf basal area showed lower reproduction with greater biomass increase, in plantlets. The results suggest long-term exposures to drifted low levels of Roundup in soil may promote biomass and reproduction in B. pinnatum.

  1. 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

  2. Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells.

    PubMed

    Flaskos, J; Nikolaidis, E; Harris, W; Sachana, M; Hargreaves, A J

    2011-11-01

    Previous work in our laboratory has shown that sub-lethal concentrations (1-10 μM) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1-10 μM) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH.

  3. Effect of a synbiotic on infantile acute gastroenteritis.

    PubMed

    Gundogdu, Z

    2013-09-01

    Acute gastroenteritis is still a common disease worldwide. Synbiotics are being used to alleviate the effects of acute gastroenteritis-related diarrhoea. The objective of this study was to determine the efficacy of a synbiotic in reducing the duration of diarrhoea in children with acute gastroenteritis. The study has been carried out on data gathered from children with acute gastroenteritis between the age of three months and 14 years seen in paediatric polyclinics between August 2009 and April 2010. While synbiotic group patients got a sachet containing Bifidobacterium lactis 2211 with a minimum of 5×10⁶ cfu active bacteria and 900 mg chicory inulin twice daily for five days together with an oral rehydration solution, the control group only received an oral rehydration solution. Therapy with synbiotic plus an oral rehydration solution shortened the duration of acute diarrhoea in children by approximately one day compared to oral rehydration solution only.

  4. Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells

    SciTech Connect

    Flaskos, J.; Nikolaidis, E.; Harris, W.; Sachana, M.; Hargreaves, A.J.

    2011-11-15

    Previous work in our laboratory has shown that sub-lethal concentrations (1-10 {mu}M) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1-10 {mu}M) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: Black-Right-Pointing-Pointer Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells Black-Right-Pointing-Pointer Acetylcholinesterase exhibits sustained inhibition throughout exposure Black-Right-Pointing-Pointer The levels of neurofilament heavy chain and GAP-43

  5. Hemodynamic effects of acute digitalization several months after acute myocardial infarction.

    PubMed

    Ressl, J; Jandová, R; Jebavý, P; Kasalický, J; Widimský, J

    1975-01-01

    Left ventricular function was investigated at rest and during exercise by heart catheterization in 15 patients 3-5 months after acute myocardial infarction. The effect of 1 mg digoxin i.v. in ten patients was correlated to placebo (saline solution) in five patients. A significant decrease of the left ventricular enddiastolic pressure, increase of left ventricular systolic ejection fraction and a shift of the left ventricular function curve to left upwards was found after digoxin with no changes in the placebo group. This beneficial effect of acute digitalization in patients convalescing from uncomplicated myocardial infarction without clinical signs of manifest heart failure could have therapeutic implication.

  6. Protection of monkeys against the lethal effects of male funnel-web spider (Atrax robustus) venom by immunization with a toxoid.

    PubMed

    Sheumack, D D; Phillips, C A; Mylecharane, E J; Spence, I; Claassens, R; Brown, M R; Comis, A; Howden, M E

    1991-01-01

    A stable toxoid was prepared from robustoxin (the lethal polypeptide neurotoxin in the venom of the male funnel-web spider, Atrax robustus) by polymerization with glutaraldehyde. This material was non-toxic in new-born mice. Administration of the toxoid to three Macaca fascicularis monkeys (50-80 micrograms/kg s.c. at 14-day intervals for 8-12 weeks) produced no toxic effects; anti-robustoxin antibodies were detected in serum samples by immunodiffusion tests within 13-27 days. In vivo evidence of successful protection with the toxoid was obtained by challenging the monkeys with male A. robustus venom (50 micrograms/kg i.v.) under anaesthesia with pentobarbitone (one monkey), or with ketamine, halothane and nitrous oxide, 1-26 weeks after the last injection of the toxoid. Only minor respiratory, cardiovascular and skeletal motor disturbances were produced, and all monkeys recovered fully and uneventfully. Challenge with the same dose of venom in non-immunized or robustoxin N-terminal decapeptide ovalbumin conjugate-treated monkeys resulted in typical lethal neurotoxic effects, culminating in severe hypotension or death from circulatory and respiratory failure within 280 min.

  7. Three years of banning neonicotinoid insecticides based on sub-lethal effects: can we expect to see effects on bees?

    PubMed

    Blacquière, Tjeerd; van der Steen, Jozef J M

    2017-04-03

    The 2013 EU ban of three neonicotinoids used in seed coating of pollinator attractive crops was put in place because of concern about declining wild pollinator populations and numbers of honeybee colonies. It was also concluded that there is an urgent need of good field data to fill knowledge gaps. In the meantime such data have been generated. Based on recent literature we question the existence of recent pollinator declines and their possible link with the use of neonicotinoids. Because of temporal non-coincidence we conclude that declines of wild pollinators and of honeybees are not likely caused by neonicotinoids. Even if bee decline does occur and if there is a causal relationship with the use of neonicotinoids, we argue that it is not possible on such short term to evaluate the effects of the 2013 ban. In order to supply future debate with realistic (field) data and to discourage extrapolating the effects of studies using overdoses that are not of environmental relevance, we propose - in addition to field studies performed by the chemical industry - to use the 'semi-field worst case' treated artificial diet studies approach to free flying colonies in the field. This kind of studies may provide realistic estimates for risk and be useful to study realistic interactions with non-pesticide stressors.

  8. Protective effect of two recombinant ricin subunit vaccines in the New Zealand white rabbit subjected to a lethal aerosolized ricin challenge: survival, immunological response, and histopathological findings.

    PubMed

    McLain, Daniel E; Lewis, Bridget S; Chapman, Jennifer L; Wannemacher, Robert W; Lindsey, Changhong Y; Smith, Leonard A

    2012-03-01

    Ricin, isolated from the castor bean plant Ricinus communis, is included on the Centers for Disease Control and Prevention Category B list of bioterrorism agents, indicating that the toxin is moderately easy to disseminate and could result in moderate morbidity rates. This study evaluated two promising recombinant ricin subunit vaccines, one made using an Escherichia coli codon-optimized gene and the other using a yeast codon-optimized gene in E. coli-based fermentations. Rabbits were vaccinated four times over a period of 6 months and challenged with ∼10 to 30 times the median lethal dose of aerosolized ricin. All unvaccinated control rabbits were either found dead or humanely euthanized within 30 h postchallenge, while the rabbits vaccinated with either vaccine survived the exposure without adverse clinical signs. When the protective antibody responses were analyzed, no significant difference was seen between the two vaccines. However, there was a significant difference in the immune response over time for both vaccines tested. Although clinical pathology was unremarkable, significant histological lesions in the control animals included fibrinonecrotic pneumonia, acute necrotizing lesions in the upper respiratory tract, and necrotizing lymphadenitis in the lymph nodes draining the upper and lower respiratory tract. Vaccine-treated rabbits exhibited resolving lesions associated with ricin exposure, namely chronic inflammation in the upper respiratory tract and lungs, fibrosis, type II pneumocyte hyperplasia, and bronchiolitis obliterans. This study confirmed the safety and efficacy of two recombinant ricin subunit vaccines in rabbits, offering potential protection to warfighters and select populations.

  9. Acute and long term health effects of radiation

    SciTech Connect

    Voelz, G.L.

    1986-11-19

    This paper covers selected aspects of the acute and long term health effects excluding acute radiation syndrome and carcinogenesis, resulting from exposure to ionizing radiation. The changes addressed in this paper are those witnessed within an organ or whole body rather than at the molecular or even cellular level. They include acute and late health effects. Some of these effects are threshold effects, meaning that the dose must exceed a certain threshold before one sees these effects. Less than the threshold dose results in no observable organ or whole body effect. The severity of the effects correlate directly with the amount of cell damage or cell death that has occurred. 15 refs., 4 figs., 8 tabs.

  10. Interaction of Exposure Concentration and Duration in Determining Acute Toxic Effects of Sarin Vapor in Rats

    DTIC Science & Technology

    2002-01-01

    effects occur in the rat and 2) develop models for predicting dose - response effects of low CW agent concentrations as a function of exposure duration. Sarin...effective concentrations for lethality (LC50) and miosis (EC50) in 50% of the exposed population and corresponding dose - response slopes were determined for...exposure duration (i.e., the CT for 50% lethality exposed population and corresponding dose - response slope was not constant over time). A plot of Log (LCt50

  11. Effects of β-glucan polysaccharide revealed by the dominant lethal assay and micronucleus assays, and reproductive performance of male mice exposed to cyclophosphamide.

    PubMed

    Oliveira, Rodrigo Juliano; Pesarini, João Renato; Sparça Salles, Maria José; Nakamura Kanno, Tatiane Yumi; Dos Santos Lourenço, Ana Carolina; da Silva Leite, Véssia; da Silva, Ariane Fernanda; Matiazi, Hevenilton José; Ribeiro, Lúcia Regina; Mantovani, Mário Sérgio

    2014-03-01

    β-glucan is a well-known polysaccharide for its chemopreventive effect. This study aimed to evaluate the chemopreventive ability of β-glucan in somatic and germ cells through the dominant lethal and micronucleus assays, and its influence on the reproductive performance of male mice exposed to cyclophosphamide. The results indicate that β-glucan is capable of preventing changes in DNA in both germ cells and somatic ones. Changes in germ cells were evaluated by the dominant lethal assay and showed damage reduction percentages of 46.46% and 43.79% for the doses of 100 and 150 mg/kg. For the somatic changes, evaluated by micronucleus assay in peripheral blood cells in the first week of treatment, damage reduction percentages from 80.63-116.32% were found. In the fifth and sixth weeks, the percentage ranged from 10.20-52.54% and -0.95-62.35%, respectively. Besides the chemopreventive efficiency it appears that the β-glucan, when combined with cyclophosphamide, is able to improve the reproductive performance of males verified by the significant reduction in rates of post-implantation losses and reabsorption in the mating of nulliparous females with males treated with cyclophosphamide.

  12. The effects of sub-chronic administration of sub-lethal doses of amitraz/xylene on selected reproductive parameters of male Wistar rats

    PubMed Central

    Omoja, V. U.; Anika, S. M.; Asuzu, I. U.

    2016-01-01

    This study investigated the effects of sub-chronic administration of sub-lethal doses of amitraz on some testicular parameters of Albino rats. Twenty-four adult male Albino rats (100 ± 10 g) randomly assigned into four groups were used for the study. Groups A, B and C received 10.0, 2.0 and 0.4 mg/kg amitraz in 10 ml/kg water while group D received equivalent volume of water orally and daily for 84 days. Serum testosterone levels (TESL) were assessed on days 0, 28, 56 and 84. Epididymal sperm reserve (ESR), testicular sperm reserve (TSR), testicular weight index (TWI) and testicular histology were evaluated at the end of the experiment. Results revealed dose-dependent reduction (P<0.05) in the mean TESL, ESR and TSR in the amitraz-treated groups as the dose of the amitraz increased. Histological study revealed testicular degeneration characterized by depopulation of seminiferous tubules and depletion of the spermatogenic cells in rats in group A. It was concluded that sub-chronic administration of sub-lethal doses of amitraz could lead to reduced sperm quantity. PMID:28224014

  13. Effects of β-glucan polysaccharide revealed by the dominant lethal assay and micronucleus assays, and reproductive performance of male mice exposed to cyclophosphamide

    PubMed Central

    Oliveira, Rodrigo Juliano; Pesarini, João Renato; Sparça Salles, Maria José; Nakamura Kanno, Tatiane Yumi; dos Santos Lourenço, Ana Carolina; da Silva Leite, Véssia; da Silva, Ariane Fernanda; Matiazi, Hevenilton José; Ribeiro, Lúcia Regina; Mantovani, Mário Sérgio

    2014-01-01

    β-glucan is a well-known polysaccharide for its chemopreventive effect. This study aimed to evaluate the chemopreventive ability of β-glucan in somatic and germ cells through the dominant lethal and micronucleus assays, and its influence on the reproductive performance of male mice exposed to cyclophosphamide. The results indicate that β-glucan is capable of preventing changes in DNA in both germ cells and somatic ones. Changes in germ cells were evaluated by the dominant lethal assay and showed damage reduction percentages of 46.46% and 43.79% for the doses of 100 and 150 mg/kg. For the somatic changes, evaluated by micronucleus assay in peripheral blood cells in the first week of treatment, damage reduction percentages from 80.63–116.32% were found. In the fifth and sixth weeks, the percentage ranged from 10.20–52.54% and −0.95–62.35%, respectively. Besides the chemopreventive efficiency it appears that the β-glucan, when combined with cyclophosphamide, is able to improve the reproductive performance of males verified by the significant reduction in rates of post-implantation losses and reabsorption in the mating of nulliparous females with males treated with cyclophosphamide. PMID:24688298

  14. A comparison of the potency of trimedoxime and other currently available oximes to reactivate tabun-inhibited acetylcholinesterase and eliminate acute toxic effects of tabun.

    PubMed

    Kassa, Jirí; Kuca, Kamil; Cabal, Jirí

    2005-12-01

    Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) belongs to highly toxic organophosphorus compounds misused as chemical warfare agents for military as well as terroristic purposes. It differs from other highly toxic organophosphates by its chemical structure and by the fact that tabun-inhibited acetylcholinesterase is extraordinarily difficult to reactivate. The potency of trimedoxime and other commonly used oximes (pralidoxime, obidoxime, the oxime HI-6) to reactivate tabun-inhibited acetylcholinesterase and to eliminate tabun-induced acute effects was evaluated using in vitro and in vivo methods. In vitro calculated kinetic parameters of reactivation of tabun-inhibited acetylcholinesterase from rat brain homogenate and in vivo determined percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in poisoned rats show that trimedoxime seems to be the most efficacious reactivator in the case of tabun poisonings. Trimedoxime was also found to be the most efficacious oxime in the elimination of acute lethal toxic effects in tabun-poisoned rats and mice. The oxime HI-6, so efficacious against soman, does not seem to be sufficiently effective oxime to reactivate tabun-inhibited acetylcholinesterase and to counteract acute lethal effects of tabun.

  15. Toxic and sub-lethal effects of oleandrin on biochemical parameters of fresh water air breathing murrel, Channa punctatus (Bloch.).

    PubMed

    Tiwari, Sudhanshu; Singh, Ajay

    2004-04-01

    Active compound oleandrin extracted from Nerium indicum (Lal Kaner) leaf has potent piscicidal activity. The piscicidal activity of oleandrin on freshwater fish C. punctatus was both time and dose dependent. Exposure to sub-lethal doses of oleandrin for 24hr and 96hr to fish caused significant alteration in the level of total protein, total free amino acid, nucleic acid, glycogen, pyruvate, lactate and enzyme protease, phosphatases, alanine aminotransferase, aspartate aminotransferase and acetylcholinesterase activity in liver and muscle tissues. The alterations in all the above biochemical parameters were also significantly time and dose dependent. The results show a significant recovery in all the above biochemical parameters, in both liver and muscle tissues of fish after the 7th day of the withdrawal of treatment. Toxicity persistence test of oleandrin on juvenile Labeo rohita shows that fish seed of common culturing carp can be released into rearing ponds after three days of oleandrin treatment. It supports the view that the oleandrin is safer and may be useful substitute of other piscicides for removing the unwanted freshwater fishes from aquaculture ponds.

  16. 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.

  17. 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.

  18. Does toxic defence in Nycticebus spp. relate to ectoparasites? The lethal effects of slow loris venom on arthropods.

    PubMed

    Grow, Nanda B; Wirdateti; Nekaris, K A I

    2015-03-01

    The venom produced by slow lorises (Nycticebus spp.) is toxic both intra- and inter-specifically. In this study we assessed the ecoparasite repellent properties of their venom. We tested venom from two Indonesian slow loris species: Nycticebus javanicus and Nycticebus coucang. Arthropods directly exposed to brachial gland secretions mixed with saliva from both species were immediately impaired or exhibited reduced activity (76%), and often died as a result (61%). We found no significant difference in the result of 60-min trials between N. coucang and N. javanicus [X(2)(1, n = 140) = 2.110, p = 0.3482]. We found evidence that the degree of lethality of the venom varies according to the arthropod taxa to which it is exposed. While most maggots (84%) were initially impaired from the venom after 10 min, maggots died after a 1 h trial 42% of the time. In contrast, at the end of 1 h trial, spiders died 78% of the time. For all arthropods, the average time to death from exposure was less than 25 min (M = 24.40, SD = 22.60). Ectoparasites including ticks, members of the arachnid order, are known to transmit pathogens to hosts and may be an intended target of the toxic secretions. Our results suggest that one function of slow loris venom is to repel parasites that affect their fitness, and that their topical anointing behaviour may be an adaptive response to ectoparasites.

  19. Effect of sub-lethal doses of vancomycin and oxacillin on biofilm formation by vancomycin intermediate resistant Staphylococcus aureus.

    PubMed

    Mirani, Zulfiqar Ali; Jamil, Nusrat

    2011-04-01

    Biofilms are means of protection to bacteria against antibiotics and antibodies. Catheters and others tube devices used by patients are prone to accumulation of thick layers of biofilms as hiding place for etiologic agents, resulting in substantial morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections. Vancomycin remains the only treatment of choice for MRSA infections. In the present study a vancomycin resistant S. aureus (VRSA) (Labeled as CP2) was isolated from the blood of a post-operative cardiac patient. It harbors a plasmid which carry vanA gene and exhibited low-level vancomycin resistance (MIC 16 μg/ml), high level of oxacillin/methicillin resistance (MIC 500 μg/ml) and was sensitive to teicoplanin. CP2 also found to carry icaA gene on its chromosome. This strain exhibited resistance to triton-X100 induced autolysis under sub-inhibitory concentration of vancomycin and produced some extracellular matrix material that surrounding the cells. These characteristic features have warranted us to study the biofilm formation by CP2 on biomedical indwellings in presence of vancomycin and oxacillin. Our findings suggest that sub-lethal dose of vancomycin induced the biofilm formation by CP2 on nylon and silicon indwellings whereas oxacillin facilitated the biofilm formation on glass surfaces exclusively. This implicates that not only the antibiotics but also the indwelling material influences biofilm formation. Therefore, these implants serve as potential surfaces for bacterial adhesion that lead to biofilm formation, thus provide hiding places for pathogens from the actions of antimicrobials.

  20. 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.

  1. Effects of an Acute Seizure on Associative Learning and Memory

    PubMed Central

    Holley, Andrew J.; Lugo, Joaquin N.

    2015-01-01

    Past studies have demonstrated that inducing several seizures or continuous seizures in neonatal or adult rats results in impairments in learning and memory. The impact of a single acute seizure on learning and memory has not been investigated in mice. In this study, we exposed an adult 129SvEvTac mouse to the inhalant flurothyl until a behavioral seizure was induced. Our study consisted of 4 experiments where we examined the effect of one seizure before or after delay fear conditioning. We also included a separate cohort of animals that was tested in the open field after a seizure to rule out changes in locomotor activity influencing the results of memory tests. Mice that had experienced a single seizure 1 hour, but not 6 hours, prior to training showed a significant impairment in associative conditioning to the conditioned stimulus when compared to controls 24 hours later. There were no differences in freezing one day later for animals that experienced a single seizure 1 hour after associative learning. We also found that an acute seizure reduced activity levels in an open field test 2 hours but not 24 hours later. These findings suggest that an acute seizure occurring immediately before learning can have an effect on the recall of events occurring shortly after that seizure. In contrast, an acute seizure occurring shortly after learning appears to have little or no effect on long-term memory. These findings have implications for understanding the acute effects of seizures on the acquisition of new knowledge. PMID:26655449

  2. Hydrogen peroxide induces protection against lethal effects of cumene hydroperoxide in Escherichia coli cells: an Ahp dependent and OxyR independent system?

    PubMed

    Asad, N R; Asad, L M; Silva, A B; Felzenszwalb, I; Leitão, A C

    1998-06-01

    Pretreatment with 2.5 mM H2O2 protects bacterial cells against cumene hydroperoxide killing. This response is independent of the OxyR system, but possibly involves the participation of Ahp protein, since ahp mutants are not protected. Treatment of bacterial cells with high H2O2 concentrations caused an alteration on the electrophoretic profile of the smaller subunit (22-kDa) of Ahp. This alteration does not require novel gene products and is not dependent on the OxyR protein. In this way, we propose that the modification of the 22-kDa subunit of Ahp by high H2O2 concentration may be responsible for the protection against the lethal effects of cumene hydroperoxide.

  3. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists.

    PubMed

    Mohler, K M; Torrance, D S; Smith, C A; Goodwin, R G; Stremler, K E; Fung, V P; Madani, H; Widmer, M B

    1993-08-01

    Two forms (monomeric or dimeric) of the extracellular, ligand-binding portion of the human p80 cell-surface receptor for TNF were used to antagonize TNF activity in vitro and in vivo. The dimeric sTNFR:Fc molecule was a more potent inhibitor of TNF than the monomeric sTNFR (50 to 1000x), as assessed in vitro by inhibition of TNF binding or bioactivity and in vivo by protection of mice from an otherwise lethal injection of LPS. Surprisingly, the dimeric sTNFR:Fc construct demonstrated a beneficial effect even when administered 3 h after a lethal LPS injection (i.e., after serum TNF levels had peaked and receded). To study the mechanism by which the soluble TNFR functions in vivo, serum TNF levels were examined in mice given LPS in the presence or absence of soluble receptor. Administration of a mortality-reducing dose of sTNFR:Fc ablated the rise in serum TNF bioactivity that normally occurs in response to LPS. However, TNF bioactivity was revealed in these "TNF-negative" serum samples when the L929 bioassay was modified by inclusion of a mAb that blocks the binding of murine TNF to the human soluble TNFReceptor. These results indicate that the absence of direct cytolytic activity in the L929 assay was caused by neutralization of TNF, rather than to an absence of TNF in the serum. Moreover, administration of either monomeric sTNFR or low doses of dimeric sTNFR:Fc actually resulted in increased serum TNF levels compared to mice given LPS but no soluble receptor. However, these "agonistic" doses of soluble receptor did not lead to increased mortality when an LD60 dose of LPS was given. Thus, dimeric sTNFR are effective inhibitors of TNF and under some circumstances function simultaneously as both TNF "carriers" and antagonists of TNF biologic activity.

  4. Effects of sub-lethal high-pressure homogenization treatment on the outermost cellular structures and the volatile-molecule profiles of two strains of probiotic lactobacilli

    PubMed Central

    Tabanelli, Giulia; Vernocchi, Pamela; Patrignani, Francesca; Del Chierico, Federica; Putignani, Lorenza; Vinderola, Gabriel; Reinheimer, Jorge A.; Gardini, Fausto; Lanciotti, Rosalba

    2015-01-01

    Applying sub-lethal levels of high-pressure homogenization (HPH) to lactic acid bacteria has been proposed as a method of enhancing some of their functional properties. Because the principal targets of HPH are the cell-surface structures, the aim of this study was to examine the effect of sub-lethal HPH treatment on the outermost cellular structures and the proteomic profiles of two known probiotic bacterial strains. Moreover, the effect of HPH treatment on the metabolism of probiotic cells within a dairy product during its refrigerated storage was investigated using SPME-GC-MS. Transmission electron microscopy was used to examine the microstructural changes in the outermost cellular structures due to HPH treatment. These alterations may be involved in the changes in some of the technological and functional properties of the strains that were observed after pressure treatment. Moreover, the proteomic profiles of the probiotic strains treated with HPH and incubated at 37°C for various periods showed different peptide patterns compared with those of the untreated cells. In addition, there were differences in the peaks that were observed in the low-mass spectral region (2000–3000 Da) of the spectral profiles of the control and treated samples. Due to pressure treatment, the volatile-molecule profiles of buttermilk inoculated with treated or control cells and stored at 4°C for 30 days exhibited overall changes in the aroma profile and in the production of molecules that improved its sensory profile, although the two different species imparted specific fingerprints to the product. The results of this study will contribute to understanding the changes that occur in the outermost cellular structures and the metabolism of LAB in response to HPH treatment. The findings of this investigation may contribute to elucidating the relationships between these changes and the alterations of the technological and functional properties of LAB induced by pressure treatment. PMID

  5. Effects of sub-lethal high-pressure homogenization treatment on the outermost cellular structures and the volatile-molecule profiles of two strains of probiotic lactobacilli.

    PubMed

    Tabanelli, Giulia; Vernocchi, Pamela; Patrignani, Francesca; Del Chierico, Federica; Putignani, Lorenza; Vinderola, Gabriel; Reinheimer, Jorge A; Gardini, Fausto; Lanciotti, Rosalba

    2015-01-01

    Applying sub-lethal levels of high-pressure homogenization (HPH) to lactic acid bacteria has been proposed as a method of enhancing some of their functional properties. Because the principal targets of HPH are the cell-surface structures, the aim of this study was to examine the effect of sub-lethal HPH treatment on the outermost cellular structures and the proteomic profiles of two known probiotic bacterial strains. Moreover, the effect of HPH treatment on the metabolism of probiotic cells within a dairy product during its refrigerated storage was investigated using SPME-GC-MS. Transmission electron microscopy was used to examine the microstructural changes in the outermost cellular structures due to HPH treatment. These alterations may be involved in the changes in some of the technological and functional properties of the strains that were observed after pressure treatment. Moreover, the proteomic profiles of the probiotic strains treated with HPH and incubated at 37°C for various periods showed different peptide patterns compared with those of the untreated cells. In addition, there were differences in the peaks that were observed in the low-mass spectral region (2000-3000 Da) of the spectral profiles of the control and treated samples. Due to pressure treatment, the volatile-molecule profiles of buttermilk inoculated with treated or control cells and stored at 4°C for 30 days exhibited overall changes in the aroma profile and in the production of molecules that improved its sensory profile, although the two different species imparted specific fingerprints to the product. The results of this study will contribute to understanding the changes that occur in the outermost cellular structures and the metabolism of LAB in response to HPH treatment. The findings of this investigation may contribute to elucidating the relationships between these changes and the alterations of the technological and functional properties of LAB induced by pressure treatment.

  6. 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).

  7. Therapeutic Effect of the Tuber of Alisma orientale on Lipopolysaccharide-Induced Acute Lung Injury

    PubMed Central

    Kwun, Min Jung; Choi, Jun-Yong; Ahn, Kyung-Seop; Oh, Sei-Ryang; Lee, Yong Gyu; Christman, John W.; Sadikot, Ruxana T.

    2013-01-01

    Although Alisma orientale, an ethnic herb, has been prescribed for treating various diseases in Asian traditional medicine, experimental evidence to support its therapeutic effects is lacking. Here, we sought to determine whether A. orientale has a therapeutic effect on acute lung injury (ALI). Ethanol extract of the tuber of A. orientale (EEAO) was prepared and fingerprinted by HPLC for its constituents. Mice received an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) for the induction of ALI. At 2 h after LPS treatment, mice received an intratracheal (i.t.) spraying of various amounts of EEAO to the lung. Bioluminescence imaging of transgenic NF-κB/luciferase reporter mice shows that i.t. EEAO posttreatment suppressed lung inflammation. In similar experiments with C57BL/6 mice, EEAO posttreatment significantly improved lung inflammation, as assessed by H&E staining of lung sections, counting of neutrophils in bronchoalveolar lavage fluid, and semiquantitative RT-PCR analyses of proinflammatory cytokines and Nrf2-dependent genes in the inflamed lungs. Furthermore, EEAO posttreatment enhanced the survival of mice that received a lethal dose of LPS. Together, our results provide evidence that A. orientale has a therapeutic effect on ALI induced by sepsis. PMID:23983806

  8. 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

  9. Little field evidence of direct acute and short-term effects of current pesticides on the grey partridge.

    PubMed

    Millot, Florian; Berny, Philippe; Decors, Anouk; Bro, Elisabeth

    2015-07-01

    Direct lethal and sublethal effects of pesticides on farmland birds' populations are recurring questions and largely debated. In this context, we conducted an innovative study combining radiotelemetry, farmer surveys, residue analyses on carcasses and modelling to assess the unintentional effects of pesticides on terrestrial birds. We chose the grey partridge Perdix perdix as a case study because this typical bird of European cereal ecosystems is highly exposed to pesticides. In this paper we focused on acute and short-term impacts of pesticides on adult mortality during spring and summer in a one-substance approach (multiple exposure were not studied here) but for a large variety of active substances (a.s.) actually used in cultivated farmland of Northern France. The fate and the location of 529 partridges were monitored twice a day from early March to late August 2010 and 2011 on 12 sites (14,500 ha). Their daily potential exposure to 183 a.s. was determined by overlapping birds' habitat use and daily pesticide application data. Based on this procedure, we calculated mortality rates within 10 days following a potential exposure for 157 different a.s.. 5 a.s. were associated with a "10-day mortality rate" higher than 10% but a single one (thiacloprid) is reported to be highly toxic to birds. We recorded 261 mortalities among which 94 carcasses were in suitable condition for residue analyses. We detected at least one a.s in 39.4% of carcasses. However, only 2 mortality cases were attributed to poisoning (carbofuran). Furthermore, modelling results showed that these lethal pesticide-related poisonings decreased the population growth rate by less than 1%. In conclusion, we did not point out important direct acute and short-term effects of pesticides currently used by farmers during the breeding season on the grey partridge. This is discussed with regards to the complexity of potential effects in operational conditions.

  10. OH radicals from the indirect actions of X-rays induce cell lethality and mediate the majority of the oxygen enhancement effect.

    PubMed

    Hirayama, Ryoichi; Ito, Atsushi; Noguchi, Miho; Matsumoto, Yoshitaka; Uzawa, Akiko; Kobashi, Gen; Okayasu, Ryuichi; Furusawa, Yoshiya

    2013-11-01

    We examined OH radical-mediated indirect actions from X irradiation on cell killing in wild-type Chinese hamster ovary cell lines (CHO and AA8) under oxic and hypoxic conditions, and compared the contribution of direct and indirect actions under both conditions. The contribution of indirect action on cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide, which suppresses indirect action by quenching OH radicals without affecting the direct action of X rays on cell killing. The contributions of indirect action on cell killing of CHO cells were 76% and 50% under oxic and hypoxic conditions, respectively, and those for AA8 cells were 85% and 47%, respectively. Therefore, the indirect action on cell killing was enhanced by oxygen during X irradiation in both cell lines tested. Oxygen enhancement ratios (OERs) at the 10% survival level (D10 or LD90) for CHO and AA8 cells were 2.68 ± 0.15 and 2.76 ± 0.08, respectively. OERs were evaluated separately for indirect and direct actions, which gave the values of 3.75 and 2.01 for CHO, and 4.11 and 1.32 for AA8 cells, respectively. Thus the generally accepted OER value of ∼3 is best understood as the average of the OER values for both indirect and direct actions. These results imply that both indirect and direct actions on cell killing require oxygen for the majority of lethal DNA damage, however, oxygen plays a larger role in indirect than for direct effects. Conversely, the lethal damage induced by the direct action of X rays are less affected by oxygen concentration.

  11. Effectiveness of F18+ Fimbrial Antigens Released by a Novel Autolyzed Salmonella Expression System as a Vaccine Candidate against Lethal F18+ STEC Infection

    PubMed Central

    Won, Gayeon; Lee, John H.

    2016-01-01

    Porcine edema disease (ED) caused by Shiga toxin 2e producing Escherichia coli expressing F18ab+ fimbriae (F18ab+STEC) frequently occurs in post-weaned piglets, resulting in a significant economic loss in swine industries worldwide. In the present study, we proposed an efficient prevention scheme against ED in which the attenuated Salmonella Typhimurium inactivated by the E-mediated cell lysis to deliver target antigens, FedF and FedA, which function in fimbrial-mediated adhesion and as a major subunit of F18ab+fimbriae, respectively. The co-expression of FedA and FedF protein with outer membrane protein A signal peptide was confirmed in the resultant strains JOL1460 and JOL1464 by immunoblot analysis. Immunization with the candidate strains in mice led to the significant generation of immunoglobulin (Ig) G, specific to both antigens and secretory IgA specific to FedF (P < 0.05). The titers of IgG isotypes, IgG1 and IgG2a, used as markers for T-helpers (Th)-2 and Th-1lymphocytes, respectively, also significantly increased in the immunized group (P < 0.05). The increase in CD3+CD4+ T lymphocyte subpopulation and in vitro proliferative activity was observed in in vivo stimulated splenocytes, which indicated the immunostimulatory effect of the candidate strains. Moreover, the immunized mice were completely protected from a lethal challenge against wild-type F18+STEC whereas 28% of mice died in the non-immunized group. This study demonstrated that the inactivated Salmonella system could efficiently release FedF and FedA and induce robust immune responses specific to the target antigens, which is sufficient to protect the mice from the lethal challenge. PMID:27920758

  12. Effect of acute pesticide exposure on bee spatial working memory using an analogue of the radial-arm maze

    NASA Astrophysics Data System (ADS)

    Samuelson, Elizabeth E. W.; Chen-Wishart, Zachary P.; Gill, Richard J.; Leadbeater, Ellouise

    2016-12-01

    Pesticides, including neonicotinoids, typically target pest insects by being neurotoxic. Inadvertent exposure to foraging insect pollinators is usually sub-lethal, but may affect cognition. One cognitive trait, spatial working memory, may be important in avoiding previously-visited flowers and other spatial tasks such as navigation. To test this, we investigated the effect of acute thiamethoxam exposure on spatial working memory in the bumblebee Bombus terrestris, using an adaptation of the radial-arm maze (RAM). We first demonstrated that bumblebees use spatial working memory to solve the RAM by showing that untreated bees performed significantly better than would be expected if choices were random or governed by stereotyped visitation rules. We then exposed bees to either a high sub-lethal positive control thiamethoxam dose (2.5 ng‑1 bee), or one of two low doses (0.377 or 0.091 ng‑1) based on estimated field-realistic exposure. The high dose caused bees to make more and earlier spatial memory errors and take longer to complete the task than unexposed bees. For the low doses, the negative effects were smaller but statistically significant, and dependent on bee size. The spatial working memory impairment shown here has the potential to harm bees exposed to thiamethoxam, through possible impacts on foraging efficiency or homing.

  13. Effect of acute pesticide exposure on bee spatial working memory using an analogue of the radial-arm maze

    PubMed Central

    Samuelson, Elizabeth E. W.; Chen-Wishart, Zachary P.; Gill, Richard J.; Leadbeater, Ellouise

    2016-01-01

    Pesticides, including neonicotinoids, typically target pest insects by being neurotoxic. Inadvertent exposure to foraging insect pollinators is usually sub-lethal, but may affect cognition. One cognitive trait, spatial working memory, may be important in avoiding previously-visited flowers and other spatial tasks such as navigation. To test this, we investigated the effect of acute thiamethoxam exposure on spatial working memory in the bumblebee Bombus terrestris, using an adaptation of the radial-arm maze (RAM). We first demonstrated that bumblebees use spatial working memory to solve the RAM by showing that untreated bees performed significantly better than would be expected if choices were random or governed by stereotyped visitation rules. We then exposed bees to either a high sub-lethal positive control thiamethoxam dose (2.5 ng−1 bee), or one of two low doses (0.377 or 0.091 ng−1) based on estimated field-realistic exposure. The high dose caused bees to make more and earlier spatial memory errors and take longer to complete the task than unexposed bees. For the low doses, the negative effects were smaller but statistically significant, and dependent on bee size. The spatial working memory impairment shown here has the potential to harm bees exposed to thiamethoxam, through possible impacts on foraging efficiency or homing. PMID:27958350

  14. Effect of acute pesticide exposure on bee spatial working memory using an analogue of the radial-arm maze.

    PubMed

    Samuelson, Elizabeth E W; Chen-Wishart, Zachary P; Gill, Richard J; Leadbeater, Ellouise

    2016-12-13

    Pesticides, including neonicotinoids, typically target pest insects by being neurotoxic. Inadvertent exposure to foraging insect pollinators is usually sub-lethal, but may affect cognition. One cognitive trait, spatial working memory, may be important in avoiding previously-visited flowers and other spatial tasks such as navigation. To test this, we investigated the effect of acute thiamethoxam exposure on spatial working memory in the bumblebee Bombus terrestris, using an adaptation of the radial-arm maze (RAM). We first demonstrated that bumblebees use spatial working memory to solve the RAM by showing that untreated bees performed significantly better than would be expected if choices were random or governed by stereotyped visitation rules. We then exposed bees to either a high sub-lethal positive control thiamethoxam dose (2.5 ng(-1) bee), or one of two low doses (0.377 or 0.091 ng(-1)) based on estimated field-realistic exposure. The high dose caused bees to make more and earlier spatial memory errors and take longer to complete the task than unexposed bees. For the low doses, the negative effects were smaller but statistically significant, and dependent on bee size. The spatial working memory impairment shown here has the potential to harm bees exposed to thiamethoxam, through possible impacts on foraging efficiency or homing.

  15. The effect of sub-lethal increases in temperature on the growth and population trajectories of three scleractinian corals on the southern Great Barrier Reef.

    PubMed

    Edmunds, Peter J

    2005-12-01

    To date, coral death has been the most conspicuous outcome of warming tropical seas, but as temperatures stabilize at higher values, the consequences for the corals remaining will be mediated by their demographic responses to the sub-lethal effects of temperature. To gain insight into the nature of these responses, here I develop a model to test the effect of increased temperature on populations of three pocilloporid corals at One Tree Island, near the southern extreme of the Great Barrier Reef (GBR). Using Seriatopora hystrix, S. caliendrum and Pocillopora damicornis as study species, the effects of temperature on growth were determined empirically, and the dynamics of their populations determined under natural temperatures over a 6-month period between 1999 and 2000 [defined as the study year (SY)]. The two data sets were combined in a demographic test of the possibility that the thermal regime projected for the southern GBR in the next 55-83 years--warmer by 3 degrees C than the study year (the SY+3 regime), which is equivalent to 1.4 degrees C warmer than the recent warm year of 1998--would alter coral population trajectories through the effects on coral growth alone; the analyses first were completed by species, then by family after pooling among species. Laboratory experiments showed that growth rates (i.e., calcification) varied significantly among species and temperatures, and displayed curvilinear thermal responses with growth maxima at approximately 27.1 degrees C. Based on these temperature-growth responses, the SY+3 regime is projected to: (1) increase annualized growth rates of all taxa by 24-39%, and defer the timing of peak growth from the summer to the autumn and spring, (2) alter the intrinsic rate of population growth (lambda) for S. hystrix (lambda decreases 26%) and S. caliendrum (lambda increases 5%), but not for P. damicornis, and (3) have a minor effect on lambda (a 0.3% increase) for the Pocilloporidae, largely because lambda varies more

  16. 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.

  17. 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.

  18. Radioprotective effect of Rapana thomasiana hemocyanin in gamma induced acute radiation syndrome.

    PubMed

    Kindekov, Ivan; Mileva, Milka; Krastev, Dimo; Vassilieva, Vladimira; Raynova, Yuliana; Doumanova, Lyuba; Aljakov, Mitko; Idakieva, Krassimira

    2014-05-04

    The radioprotective effect of Rapana thomasiana hemocyanin (RtH) against radiation-induced injuries (stomach ulcers, survival time and endogenous haemopoiesis) and post-radiation recovery was investigated in male albino mice (C3H strain). Radiation course was in a dose of 7.5 Gy (LD 100/30 - dose that kills 100% of the mice at 30 days) from (137)Cs with a dose of 2.05 Gy/min. Radiation injuries were manifested by inducing а hematopoietic form of acute radiation syndrome. RtH was administered intraperitoneally in a single dose of 50, 100, 150 and 200 mg/kg body weight (b. w.) once a day for five consecutive days before irradiation. The results obtained showed that radiation exposure led to (1) 100% mortality rate, (2) ulceration in the stomach mucosa and (3) decrease formation of spleen colonies as a marker of endogenous haemopoiesis. Administration of RtH at a dose of 200 mg/kg provided better protection against radiation-induced stomach ulceration, mitigated the lethal effects of radiation exposure and recovered endogenous haemopoiesis versus irradiated but not supplemented mice. It could be expected that RtH will find a use in mitigating radiation induced injury and enhanced radiorecovery.

  19. Effect of acute ethanol and acute allopregnanolone on spatial memory in adolescent and adult rats.

    PubMed

    Chin, Vivien S; Van Skike, Candice E; Berry, Raymond B; Kirk, Roger E; Diaz-Granados, Jamie; Matthews, Douglas B

    2011-08-01

    The effects of ethanol differ in adolescent and adult rats on a number of measures. The evidence of the effects of ethanol on spatial memory in adolescents and adults is equivocal. Whether adolescents are more or less sensitive to ethanol-induced impairment of spatial memory acquisition remains unclear; with regard to the effects of acute ethanol on spatial memory retrieval there is almost no research looking into any age difference. Thus, we examined the effects of acute ethanol on spatial memory in the Morris Watermaze in adolescents and adults. Allopregnanolone (ALLO) is a modulator of the GABA(A) receptor and has similar behavioral effects as ethanol. We sought to also determine the effects of allopreganolone on spatial memory in adolescent and adults. Male adolescent (post natal [PN]28-30) and adult (PN70-72) rats were trained in the Morris Watermaze for 6 days and acute doses of ethanol (saline, 1.5 and 2.0 g/kg) or ALLO (vehicle, 9 and 18 mg/kg) were administered on Day 7. A probe trial followed on Day 8. As expected, there were dose effects; higher doses of both ethanol and ALLO impaired spatial memory. However, in both the ethanol and ALLO conditions adolescents and adults had similar spatial memory impairments. The current results suggest that ethanol and ALLO both impair hippocampal-dependent spatial memory regardless of age in that once learning has occurred, ethanol or ALLO does not differentially impair the retrieval of spatial memory in adolescents and adults. Given the mixed results on the effect of ethanol on cognition in adolescent rats, additional research is needed to ascertain the factors critical for the reported differential results.

  20. 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

  1. Acute Stressor Effects on Goal-Directed Action in Rats

    ERIC Educational Resources Information Center

    Braun, Stephanie; Hauber, Wolfgang

    2013-01-01

    Here we examined effects of acute stressors that involve either systemic coadministration of corticosterone/yohimbine (3 mg/kg each) to increase glucocorticoid/noradrenaline activity (denoted as "pharmacological" stressor) or one or several distinct restraint stressors (denoted as "single" vs. "multiple" stressor) on…

  2. Effects of Acute Exercise on Long-Term Memory

    ERIC Educational Resources Information Center

    Labban, Jeffrey D.; Etnier, Jennifer L.

    2011-01-01

    In this study, we tested the effect of acute exercise on long-term memory, specifically the timing of exercise relative to the memory challenge. We assessed memory via paragraph recall, in which participants listened to two paragraphs (exposure) and recounted them following a 35-min delay. Participants (n = 48) were randomly assigned to one of…

  3. Effects of melatonin on gallbladder neuromuscular function in acute cholecystitis.

    PubMed

    Gomez-Pinilla, Pedro J; Camello, Pedro J; Pozo, María J

    2007-10-01

    Gallbladder stasis is associated to experimental acute cholecystitis. Impaired contractility could be, at least in part, the result of inflammation-induced alterations in the neuromuscular function. This study was designed to determine the changes in gallbladder neurotransmission evoked by acute inflammation and to evaluate the protective and therapeutic effects of melatonin. Experimental acute cholecystitis was induced in guinea pigs by common bile duct ligation for 2 days, and then the neuromuscular function was evaluated using electrical field stimulation (EFS; 5-40 Hz). In a group of animals with the bile duct ligated for 2 days, a deligation of the duct was performed, and after 2 days, the neuromuscular function was studied. The EFS-evoked isometric gallbladder contraction was significantly lower in cholecystitic tissue. In addition, inflammation changed the pharmacological profile of these contractions that were insensitive to tetrodotoxin but sensitive to atropine and omega-conotoxin, indicating that acute cholecystitis affects action potential propagation in the intrinsic nerves. Nitric oxide (NO)-mediated neurotransmission was reduced by inflammation, which also increased the reactivity of sensitive fibers. Melatonin treatment prevented qualitative changes in gallbladder neurotransmission, but it did not improve EFS-induced contractility. The hormone recovered gallbladder neuromuscular function once the biliary obstruction was resolved, even when the treatment was started after the onset of gallbladder inflammation. These findings show for the first time the therapeutic potential of melatonin in the recovery of gallbladder neuromuscular function during acute cholecystitis.

  4. Is racecadotril effective for acute diarrhea in children? -First update.

    PubMed

    Sáez, Josefina; Cifuentes, Lorena

    2016-05-06

    This article updates the December 2015 Living FRISBEE (Living FRISBEE: Living FRIendly Summary of the Body of Evidence using Epistemonikos), based on the detection of two systematic reviews not identified in the previous version. Gastroenteritis or acute watery diarrhea is usually a self-limited disease, but it is still associated to substantial healthcare costs and remains a frequent demand for medical care. Racecadotril, an intestinal enkephalinase inhibitor, has been used as treatment because it would decrease the duration of acute diarrhea and fluid loss. However there is still no evidence supporting its routine use. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including nine randomized trials relevant for our question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded racecadotril probably reduces the duration of acute diarrhea in pediatric patients, without increasing adverse effects.

  5. Lethal and sublethal effects of the water-soluble fraction of Cook Inlet crude oil on Pacific herring (clupea harengus pallasi) reproduction. Final report

    SciTech Connect

    Rice, S.D.; Babcock, M.M.; Brodersen, C.C.; Carls, M.G.; Gharrett, J.A.

    1986-01-01

    The proposed sale of continental shelf leases for petroleum development in Bristol Bay, Alaska, is generating concern about the possible effects on valuable fishery resources, such as Pacific herring (Clupea harengus pallasi), in the area. The inshore spawning strategy of herring makes them particularly vulnerable to the effects of an oil spill. Using the water-soluble fraction (WSF) of Cook Inlet crude oil, the effects of lethal and sublethal exposures on prespawn adult Pacific herring, eggs, yolk-sac larvae, and feeding larvae as well as on hatching success of eggs from exposed adults were studied. The effects of feeding oil-contaminated prey to herring larvae were also examined. The life stage at which the reproductive success of Pacific herring seems most likely to be impaired by oil is feeding larvae. Even if oil is present at levels too low to threaten the survival of herring, the fisheries could be impacted because the rapid bioaccumulation of oil hydrocarbons in the edible muscle and ovarian tissues could make the herring unmarketable.

  6. Effects of dehydroepiandrosterone on obesity and glucose-6-phosphate dehydrogenase activity in the lethal yellow mouse (strain 129/Sv-Ay/Aw).

    PubMed

    Granholm, N H; Staber, L D; Wilkin, P J

    1987-04-01

    We investigated the anti-obesity effects of the adrenal androgen, dehydroepiandrosterone (DHEA), on genetically predisposed obese lethal yellow mice (Ay/Aw). Secondly, we tested the hypothesis that DHEA promotes its anti-obesity effects by decreasing the activity of glucose-6-phosphate dehydrogenase (G6PDH). We subjected four genotype-sex combinations of yellow and agouti (control) mice to four dietary treatments and determined weight changes, food consumption, and G6PDH activity. Although G6PDH activities of yellow mice were considerably decreased in the 0.4% DHEA treatment group, they were elevated in the 0.0 and 0.1% DHEA treatment groups. In contrast, G6PDH activities of DHEA-treated control agouti mice remained relatively constant. These studies confirm that DHEA prevents the Ay gene from promoting excess fat deposition via some mechanism(s) other than reduced dietary intake. However, the overall absence of agreement between weight change (gain or loss) and G6PDH activity suggests that the anti-obesity activity of DHEA is not mediated via G6PDH. Since yellow obese (Ay/Aw) mice were found to be more susceptible to DHEA's effects than their agouti (Aw/Aw) littermates, Ay appears to induce an altered metabolism in Ay/Aw mice which is more susceptible to the effects of DHEA than the normal metabolism of Aw/Aw mice.

  7. Effects of acute hypoxia on cerebrovascular responses to carbon dioxide.

    PubMed

    Ogoh, Shigehiko; Nakahara, Hidehiro; Ueda, Shinya; Okazaki, Kazunobu; Shibasaki, Manabu; Subudhi, Andrew W; Miyamoto, Tadayoshi

    2014-06-01

    In normoxic conditions, a reduction in arterial carbon dioxide tension causes cerebral vasoconstriction, thereby reducing cerebral blood flow and modifying dynamic cerebral autoregulation (dCA). It is unclear to what extent these effects are altered by acute hypoxia and the associated hypoxic ventilatory response (respiratory chemoreflex). This study tested the hypothesis that acute hypoxia attenuates arterial CO2 tension-mediated regulation of cerebral blood flow to help maintain cerebral O2 homeostasis. Eight subjects performed three randomly assigned respiratory interventions following a resting baseline period, as follows: (1) normoxia (21% O2); (2) hypoxia (12% O2); and (3) hypoxia with wilful restraint of the respiratory chemoreflex. During each intervention, 0, 2.0, 3.5 or 5.0% CO2 was sequentially added (8 min stages) to inspired gas mixtures to assess changes in steady-state cerebrovascular CO2 reactivity and dCA. During normoxia, the addition of CO2 increased internal carotid artery blood flow and middle cerebral artery mean blood velocity (MCA Vmean), while reducing dCA (change in phase = -0.73 ± 0.22 rad, P = 0.005). During acute hypoxia, internal carotid artery blood flow and MCA Vmean remained unchanged, but cerebrovascular CO2 reactivity (internal carotid artery, P = 0.003; MCA Vmean, P = 0.031) and CO2-mediated effects on dCA (P = 0.008) were attenuated. The effects of hypoxia were not further altered when the respiratory chemoreflex was restrained. These findings support the hypothesis that arterial CO2 tension-mediated effects on the cerebral vasculature are reduced during acute hypoxia. These effects could limit the degree of hypocapnic vasoconstriction and may help to regulate cerebral blood flow and cerebral O2 homeostasis during acute periods of hypoxia.

  8. Lipids as tumoricidal components of human α-lactalbumin made lethal to tumor cells (HAMLET): unique and shared effects on signaling and death.

    PubMed

    Ho, James C S; Storm, Petter; Rydström, Anna; Bowen, Ben; Alsin, Fredrik; Sullivan, Louise; Ambite, Inès; Mok, K H; Northen, Trent; Svanborg, Catharina

    2013-06-14

    Long-chain fatty acids are internalized by receptor-mediated mechanisms or receptor-independent diffusion across cytoplasmic membranes and are utilized as nutrients, building blocks, and signaling intermediates. Here we describe how the association of long-chain fatty acids to a partially unfolded, extracellular protein can alter the presentation to target cells and cellular effects. HAMLET (human α-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded α-lactalbumin and oleic acid (OA). As OA lacks independent tumoricidal activity at concentrations equimolar to HAMLET, the contribution of the lipid has been debated. We show by natural abundance (13)C NMR that the lipid in HAMLET is deprotonated and by chromatography that oleate rather than oleic acid is the relevant HAMLET constituent. Compared with HAMLET, oleate (175 μm) showed weak effects on ion fluxes and gene expression. Unlike HAMLET, which causes metabolic paralysis, fatty acid metabolites were less strongly altered. The functional overlap increased with higher oleate concentrations (500 μm). Cellular responses to OA were weak or absent, suggesting that deprotonation favors cellular interactions of fatty acids. Fatty acids may thus exert some of their essential effects on host cells when in the deprotonated state and when presented in the context of a partially unfolded protein.

  9. [Effects of imidazolium chloride ionic liquids on the acute toxicity and weight of earthworm].

    PubMed

    Huang, Ruo-Nan; Fan, Jun-Jie; Tu, Hong-Zhi; Tang, Ling-Yan; Liu, Hui-Jun; Xu, Dong-Mei

    2013-04-01

    Standard contact filter paper test of OECD and artificial soil test were used to study the acute lethal effect of three imidazolium chloride ionic liquids, 1-butyl- 3-methylimidazolium chloride ([Bmim] Cl), 1-hexyl- 3-methylimidazolium chloride ([Hmim] Cl), and 1-octyl- 3-methylimidazolium chloride ([Omim] Cl) on earthworm (Eisenia fetida), and the weight of the earthworms was measured after subtle exposure. The 24 h-LC50 values of [Bmim] Cl, [Hmim] Cl and [Omim] Cl using the contact filter paper method were 109.60, 50.38 and 7.94 microg x cm(-2), respectively. The 48 h-LC50 values were 98.52, 39.14 and 3.61 microg x cm(-2), respectively. Using the artificial soil method, the 7 d-LC50 values of [Bmim] Cl, [Hmim] Cl and [Omim] Cl were 447.78, 245.56 and 180.51 mg x kg(-1), respectively, and the 14 d-LC50 values were 288.42, 179.75, 150.35 mg x kg(-1), respectively. There were differences in poisoning symptoms of the three ionic liquids on earthworms. The growth of Eisenia fetida was inhibited and declined with increasing ionic liquid concentration. The toxicity of ionic liquids on Eisenia fetida increased with the length of carbon chain.

  10. Acute effects of tea consumption on attention and mood.

    PubMed

    Einöther, Suzanne J; Martens, Vanessa E

    2013-12-01

    Tea has historically been associated with mood and performance benefits, such as relaxation and concentration. This review summarizes the research on the acute effects of tea, and its ingredients theanine and caffeine, on attention and mood. Consistent with abundant research on the benefits of caffeine, the performance benefits of tea were identified in a number of studies, with particularly consistent evidence for improved attention. Tea consumption also consistently improved self-reported alertness and arousal, whereas effects on pleasure or relaxation were less consistent. In addition to the research on caffeine in real-life performance, 2 recent studies have provided a broader perspective on tea's effects on psychological function in that they showed beneficial effects in related areas such as work performance and creativity. These studies showed the validity of laboratory findings by supporting the idea that tea consumption has acute benefits on both mood and performance in real-life situations.

  11. The effects of citicoline on acute ischemic stroke: a review.

    PubMed

    Overgaard, Karsten

    2014-08-01

    Early reopening of the occluded artery is, thus, important in ischemic stroke, and it has been calculated that 2 million neurons die every minute in an ischemic stroke if no effective therapy is given; therefore, "Time is Brain." In massive hemispheric infarction and edema, surgical decompression lowers the risk of death or severe disability defined as a modified Rankin Scale score greater than 4 in selected patients. The majority, around 80%-85% of all ischemic stroke victims, does not fulfill the criteria for revascularization therapy, and also for these patients, there is no effective acute therapy. Also there is no established effective acute treatment of spontaneous intracerebral bleeding. Therefore, an effective therapy applicable to all stroke victims is needed. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11,000 patients with various neurologic disorders, including acute ischemic stroke (AIS). The conclusion is that citicoline is safe to use and may have a beneficial effect in AIS patients and most beneficial in less severe stroke in older patients not treated with recombinant tissue plasminogen activator. No other neuroprotective agent had any beneficial effect in confirmative clinical trials or had any positive effect in the subgroup analysis. Citicoline is the only drug that in a number of different clinical stroke trials continuously had some neuroprotective benefit.

  12. The Acute and Chronic Biochemical and Behavioral Effects of Cyclotrimethylenetrinitramine

    DTIC Science & Technology

    1975-03-31

    Behavioral Studies - Barbiturate slieptimes were determined using hexabar- bital according to the standard technique used in our labora- tory, in which rats...the in vitro study (Table 4 D). - These results show that CMT does not produce an acute effect on Ouptake of duration over 6 hours. Nor does chronic...results of a study of the toxic effects of cyclomethylenetrinitramine on the brain after chronic admin.istration to male rats. In 1973 the Department

  13. Valdecoxib provides effective pain relief following acute ankle sprain.

    PubMed

    Diaz, J A; Cuervo, C; Valderrama, A M; Kohles, J

    2006-01-01

    We sought to determine whether valdecoxib is as effective as diclofenac in treating acute ankle sprain. Patients (n=202) with acute first- and second-degree ankle sprain were randomized to valdecoxib (40 mg twice daily on day 1 followed by 40 mg once daily on days 2-7) or diclofenac (75 mg twice daily). The primary efficacy end-point was the Patient's Assessment of Ankle Pain visual analogue scale (VAS, 0-100 mm) value on day 4. Valdecoxib was as efficacious as diclofenac in treating the signs and symptoms of acute ankle sprain. The mean VAS reduction in ankle pain on day 4 was not different between groups; the two-sided 95% confidence interval for the between-group difference was within the prespecified limit for non-inferiority (10 mm). There were no significant differences between groups for all secondary efficacy end-points. The two treatments were similarly effective and well tolerated for treatment of acute ankle sprain.

  14. 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)

  15. Pretreatment of mice with lipopolysaccharide (LPS) or IL-1β exerts dose-dependent opposite effects on Shiga toxin-2 lethality

    PubMed Central

    Palermo, M; Alves-Rosa, F; Rubel, C; Fernández, G C; Fernández-Alonso, G; Alberto, F; Rivas, M; Isturiz, M

    2000-01-01

    Haemolytic uraemic syndrome (HUS) has been closely associated with infection with a group of Shiga toxin-producing enterohaemorrhagic Eschericchia coli in young children. Shiga toxins (Stx) have been implicated as pathogenic agents of HUS by binding to the surface receptor of endothelial cells. LPS is a central product of the Gram-negative bacteria and several reports have documented that both LPS and Stx are important for disease development. In this study the reciprocal interactions between LPS and Stx2 are analysed in a mouse model. The results demonstrated that LPS was able to reduce or enhance Stx2 toxicity, depending on the dose and the timing of the injection. The involvement of the main early cytokines induced by LPS, tumour necrosis factor alpha (TNF-α) and IL-1β, in those LPS opposite effects on Stx2 toxicity was evaluated. Stx2 toxicity was enhanced by in vivo injection of murine TNF-α and low doses of murine IL-1β. However, at higher doses of IL-1β which induced corticosteroid increase in serum, Stx2 lethality was decreased. Considering that dexamethasone and IL-1β reproduce the LPS protective effects, it is suggested that endogenous corticosteroids secondary to the inflammatory response induced by LPS, mediate the protection against Stx2. It can be concluded that the fine equilibrium between proinflammatory and anti-inflammatory activities strongly influences Stx2 toxicity. PMID:10606967

  16. Towards the quantification of the effect of acid treatment on the heat tolerance of Escherichia coli K12 at lethal temperatures.

    PubMed

    Velliou, E G; Van Derlinden, E; Cappuyns, A M; Nikolaidou, E; Geeraerd, A H; Devlieghere, F; Van Impe, J F

    2011-06-01

    The aim of this work is to investigate the effect of acid treatment -before and during heat inactivation- on the heat resistance of Escherichia coli K12 MG1655 cells at lethal temperatures. E. coli cells were grown in Brain Heart Infusion broth until they reached the stationary phase (≈10(9) cfu/mL). Approximately 30 min before thermal inactivation the early stationary phase cells were added in Brain Heart Infusion broth with a specific pH value, achieved with addition of either acetic (50% (v/v)), lactic (50% (v/v)) or hydrochloric acid (30% (v/v)), and inactivation experiments took place at 54 °C and 58 °C. The inactivation dynamics are analysed using the inactivation model of Geeraerd et al. (2000). This enables to define the induced thermotolerance of E. coli as a prolongation of the shoulder and/or a reduction of the inactivation rate. Generally, addition of acids increased the heat resistance of E. coli. The induced resistance depends on the type of acid and on the quantity added, i.e. different levels of acidification lead to a different level of heat resistance. This work provides additional knowledge on the reaction of bacterial cultures to heat after acid treatment -before and during heat treatment- and, therefore, it contributes to an improved understanding of the effect of acid exposure on the bacterial heat resistance.

  17. Acute Administration of Dopaminergic Drugs has Differential Effects on Locomotion in Larval Zebrafish

    PubMed Central

    Irons, T.D.; Kelly, P.; Hunter, D.L.; MacPhail, R.C.; Padilla, S.

    2013-01-01

    Altered dopaminergic signaling causes behavioral changes in mammals. In general, dopaminergic receptor agonists increase locomotor activity, while antagonists decrease locomotor activity. In order to determine if zebrafish (a model organism becoming popular in pharmacology and toxicology) respond similarly, the acute effects of drugs known to target dopaminergic receptors in mammals were assessed in zebrafish larvae. Larvae were maintained in 96-well microtiter plates (1 larva/well). Non-lethal concentrations (0.2–50 µM) of dopaminergic agonists (apomorphine, SKF-38393, and quinpirole) and antagonists (butaclamol, SCH-23390, and haloperidol) were administered at 6 days post-fertilization (dpf). An initial experiment identified the time of peak effect of each drug (20–260 minutes post-dosing, depending on the drug). Locomotor activity was then assessed for 70 minutes in alternating light and dark at the time of peak effect for each drug to delineate dose-dependent effects. All drugs altered larval locomotion in a dose-dependent manner. Both the D1- and D2-like selective agonists (SKF-38393 and quinpirole, respectively) increased activity, while the selective antagonists (SCH-23390 and haloperidol, respectively) decreased activity. Both selective antagonists also blunted the response of the larvae to changes in lighting conditions at higher doses. The nonselective drugs had biphasic effects on locomotor activity: apomorphine increased activity at the low dose and at high doses, while butaclamol increased activity at low to intermediate doses, and decreased activity at high doses. This study demonstrates that (1) larval zebrafish locomotion can be altered by dopamine receptor agonists and antagonists, (2) receptor agonists and antagonists generally have opposite effects, and (3) drugs that target dopaminergic receptors in mammals appear, in general, to elicit similar locomotor responses in zebrafish larvae. PMID:23274813

  18. Sub-lethal effects of dietary neonicotinoid insecticide exposure on honey bee queen fecundity and colony development

    NASA Astrophysics Data System (ADS)

    Wu-Smart, Judy; Spivak, Marla

    2016-08-01

    Many factors can negatively affect honey bee (Apis mellifera L.) health including the pervasive use of systemic neonicotinoid insecticides. Through direct consumption of contaminated nectar and pollen from treated plants, neonicotinoids can affect foraging, learning, and memory in worker bees. Less well studied are the potential effects of neonicotinoids on queen bees, which may be exposed indirectly through trophallaxis, or food-sharing. To assess effects on queen productivity, small colonies of different sizes (1500, 3000, and 7000 bees) were fed imidacloprid (0, 10, 20, 50, and 100 ppb) in syrup for three weeks. We found adverse effects of imidacloprid on queens (egg-laying and locomotor activity), worker bees (foraging and hygienic activities), and colony development (brood production and pollen stores) in all treated colonies. Some effects were less evident as colony size increased, suggesting that larger colony populations may act as a buffer to pesticide exposure. This study is the first to show adverse effects of imidacloprid on queen bee fecundity and behavior and improves our understanding of how neonicotinoids may impair short-term colony functioning. These data indicate that risk-mitigation efforts should focus on reducing neonicotinoid exposure in the early spring when colonies are smallest and queens are most vulnerable to exposure.

  19. Sub-lethal effects of dietary neonicotinoid insecticide exposure on honey bee queen fecundity and colony development

    PubMed Central

    Wu-Smart, Judy; Spivak, Marla

    2016-01-01

    Many factors can negatively affect honey bee (Apis mellifera L.) health including the pervasive use of systemic neonicotinoid insecticides. Through direct consumption of contaminated nectar and pollen from treated plants, neonicotinoids can affect foraging, learning, and memory in worker bees. Less well studied are the potential effects of neonicotinoids on queen bees, which may be exposed indirectly through trophallaxis, or food-sharing. To assess effects on queen productivity, small colonies of different sizes (1500, 3000, and 7000 bees) were fed imidacloprid (0, 10, 20, 50, and 100 ppb) in syrup for three weeks. We found adverse effects of imidacloprid on queens (egg-laying and locomotor activity), worker bees (foraging and hygienic activities), and colony development (brood production and pollen stores) in all treated colonies. Some effects were less evident as colony size increased, suggesting that larger colony populations may act as a buffer to pesticide exposure. This study is the first to show adverse effects of imidacloprid on queen bee fecundity and behavior and improves our understanding of how neonicotinoids may impair short-term colony functioning. These data indicate that risk-mitigation efforts should focus on reducing neonicotinoid exposure in the early spring when colonies are smallest and queens are most vulnerable to exposure. PMID:27562025

  20. Sub-lethal effects of dietary neonicotinoid insecticide exposure on honey bee queen fecundity and colony development.

    PubMed

    Wu-Smart, Judy; Spivak, Marla

    2016-08-26

    Many factors can negatively affect honey bee (Apis mellifera L.) health including the pervasive use of systemic neonicotinoid insecticides. Through direct consumption of contaminated nectar and pollen from treated plants, neonicotinoids can affect foraging, learning, and memory in worker bees. Less well studied are the potential effects of neonicotinoids on queen bees, which may be exposed indirectly through trophallaxis, or food-sharing. To assess effects on queen productivity, small colonies of different sizes (1500, 3000, and 7000 bees) were fed imidacloprid (0, 10, 20, 50, and 100 ppb) in syrup for three weeks. We found adverse effects of imidacloprid on queens (egg-laying and locomotor activity), worker bees (foraging and hygienic activities), and colony development (brood production and pollen stores) in all treated colonies. Some effects were less evident as colony size increased, suggesting that larger colony populations may act as a buffer to pesticide exposure. This study is the first to show adverse effects of imidacloprid on queen bee fecundity and behavior and improves our understanding of how neonicotinoids may impair short-term colony functioning. These data indicate that risk-mitigation efforts should focus on reducing neonicotinoid exposure in the early spring when colonies are smallest and queens are most vulnerable to exposure.

  1. Effect of fractionated versus unfractionated total body irradiation on the growth of the BN acute myelocytic leukemia

    SciTech Connect

    Hagenbeek, A.; Martens, A.C.M.

    1981-08-01

    The efficacy of various total body irradiation (TBI) regimens prior to bone marrow transplantation was evaluated in a rat model for acute myelocytic leukemia (Dq = 85.1 cGy gamma ; N = 3.7). Using high dose rate gamma-irradiation (115 cGy/min), fractionated TBI with large total daily doses (400 to 600 cGy), either given as acute doses or as split doses at 8 hr intervals, was most effective. Split doses (2 fractions per day) offered no additional advantage. At the most, a 4 log leukemic cell kill was induced. No lethal toxicity was observed. Nine-hundred cGy flash TBI had a similar anti-tumor effect, but with this regimen almost half of the rats died from radiation-induced toxicity (lungs and gastro-intestinal tract). The results are explained in terms of differences between normal and leukemic cells as regards (a) repair of sublethal damage; and (b) repopulation. Low dose rate continuous gamma-irradiation (0.26 cGy/min) with total doses ranging from 900 to 2000 cGy was also quite effective. Maximally a 4 log cell kill was obtained. With 2000 cGy, 50% of the rats died from the gastro-intestinal tract-syndrome. In addition to the major role played by chemotherapy, TBI is mainly of importance in sterilizing the various sanctuaries in the body which contain leukemic cells anatomically resistant to most cytostatic agents.

  2. Acute effects of cannabis on breath-holding duration.

    PubMed

    Farris, Samantha G; Metrik, Jane

    2016-08-01

    Distress intolerance (an individual's perceived or actual inability to tolerate distressing psychological or physiological states) is associated with cannabis use. It is unknown whether a biobehavioral index of distress intolerance, breath-holding duration, is acutely influenced (increased or decreased) by cannabis. Such information may further inform understanding of the expression of psychological or physiological distress postcannabis use. This within-subjects study examined whether smoked marijuana with 2.7%-3.0% delta-9-tetrahydrocannabinol (THC), relative to placebo, acutely changed duration of breath holding. Participants (n = 88; 65.9% male) were nontreatment-seeking frequent cannabis users who smoked placebo or active THC cigarette on two separate study days and completed a breath-holding task postsmoking. Controlling for baseline breath-holding duration and participant sex, THC produced significantly shorter breath-holding durations relative to placebo. There was a significant interaction of drug administration × frequency of cannabis use, such that THC decreased breath-holding time among less frequent but not among more frequent users. Findings indicate that cannabis may exacerbate distress intolerance (via shorter breath-holding durations). As compared to less frequent cannabis users, frequent users display tolerance to cannabis' acute effects including increased ability to tolerate respiratory distress when holding breath. Objective measures of distress intolerance are sensitive to contextual factors such as acute drug intoxication, and may inform the link between cannabis use and the expression of psychological distress. (PsycINFO Database Record

  3. Effect of solcoseryl on antitumour action and acute toxicity of some antineoplastic drugs.

    PubMed

    Danysz, A; Sołtysiak-Pawluczuk, D; Czyzewska-Szafran, H; Jedrych, A; Jastrzebski, Z

    1991-01-01

    The in vivo effect of Solcoseryl on the antitumour activity and acute toxicity of some antineoplastic drugs was examined. It was found that Solcoseryl does not inhibit the antineoplastic effectiveness of the drugs against transplantable P 388 leukaemia in mice. Studies of the effect of Solcoseryl on acute toxicity of selected antineoplastic drugs in mice revealed that the biostimulator could exert a modifying influence. The prior administration of Solcoseryl significantly decreases the acute toxicity of methotrexate but has no effect on acute toxicity of 5-fluorouracil, increases the acute toxicity of bleomycin and vinblastine and has no effect on acute toxicity of methotrexate and mitoxantron. On the other hand, Solcoseryl administered simultaneously with the antineoplastic drugs increases acute toxicity of 5-fluorouracil, bleomycin and mitoxantron. The protective effect of the biostimulator noted exclusively against acute toxicity of 5-fluorouracil was also observed after multiple administration of this anticancer drug.

  4. 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.

  5. 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

  6. Perceived Control Alters the Effect of Acute Stress on Persistence

    PubMed Central

    Bhanji, Jamil P.; Kim, Eunbin S.; Delgado, Mauricio R.

    2015-01-01

    We often encounter setbacks while pursuing our goals. Success requires that we cope with these negative outcomes and choose to persist in spite of them. For example, learners may be more likely to continue a course after failing an assessment if they control their emotional reactions to the setback and study harder. However, the ability to effectively cope with the negative emotion inherent in such setbacks can be compromised by acute stress present in daily life (e.g., struggles in the household), which can subsequently lead to problems with persisting with a goal. The present study examined whether increasing the perception of control over setbacks (e.g., belief that a setback was caused by a correctable mistake rather than uncontrollable factors) can guard against the influence of a prior acute stressor on reactions to setbacks. Participants underwent a socially-evaluated cold water stress or a non-stress control procedure. Afterwards, they performed a behavioral task designed to measure persistence through controllable and uncontrollable setbacks. We observed that exposure to an acute stressor led to a detrimental effect on decision making by decreasing persistence behavior. Importantly, we also observed that the perception of control protected against the effect of preexisting stress and helped promote persistence. That is, stress impaired persistence through uncontrollable setbacks, but the impairment was alleviated by presenting setbacks as controllable. The findings demonstrate a potential avenue for improving the maintenance of goals aimed at behavior change, which can be susceptible to effects of stress. PMID:26726915

  7. Acute effects of aerobic exercise promote learning.

    PubMed

    Perini, Renza; Bortoletto, Marta; Capogrosso, Michela; Fertonani, Anna; Miniussi, Carlo

    2016-05-05

    The benefits that physical exercise confers on cardiovascular health are well known, whereas the notion that physical exercise can also improve cognitive performance has only recently begun to be explored and has thus far yielded only controversial results. In the present study, we used a sample of young male subjects to test the effects that a single bout of aerobic exercise has on learning. Two tasks were run: the first was an orientation discrimination task involving the primary visual cortex, and the second was a simple thumb abduction motor task that relies on the primary motor cortex. Forty-four and forty volunteers participated in the first and second experiments, respectively. We found that a single bout of aerobic exercise can significantly facilitate learning mechanisms within visual and motor domains and that these positive effects can persist for at least 30 minutes following exercise. This finding suggests that physical activity, at least of moderate intensity, might promote brain plasticity. By combining physical activity-induced plasticity with specific cognitive training-induced plasticity, we favour a gradual up-regulation of a functional network due to a steady increase in synaptic strength, promoting associative Hebbian-like plasticity.

  8. Delayed Hippocampal Effects From a Single Exposure of Prepubertal Guinea Pigs to sub-lethal dose of Chlorpyrifos: A Magnetic Resonance Imaging and Spectroscopy Study

    PubMed Central

    Mullins, Roger J.; Xu, Su; Pereira, Edna F.R.; Mamczarz, Jacek; Albuquerque, Edson X.; Gullapalli, Rao P.

    2013-01-01

    This study was designed to test the hypothesis that in vivo Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) can detect in adulthood the neurotoxic effects of a single exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos. Twelve female guinea pigs were given either a single dose of chlorpyrifos (0.6xLD50 or 300 mg/kg, sc) or peanut oil (vehicle; 0.5 ml/kg, sc) at 35–40 days of age. One year after the exposure, the animals were tested in the Morris water maze. Three days after the end of the behavioral testing, the metabolic and structural integrity of the brain of the animals was examined by means of MRI/MRS. In the Morris water maze, the chlorpyrifos-exposed guinea pigs showed significant memory deficit. Although no significant anatomical differences were found between the chlorpyrifos-exposed guinea pigs and the control animals by in vivo MRI, the chlorpyrifos-exposed animals showed significant decreases in hippocampal myo-inositol concentration using MRS. The present results indicate that a single sub-lethal exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos can lead to long-term memory deficits that are accompanied by significant reductions in the levels of hippocampal myo-inositol. PMID:23411083

  9. Delayed hippocampal effects from a single exposure of prepubertal guinea pigs to sub-lethal dose of chlorpyrifos: a magnetic resonance imaging and spectroscopy study.

    PubMed

    Mullins, Roger J; Xu, Su; Pereira, Edna F R; Mamczarz, Jacek; Albuquerque, Edson X; Gullapalli, Rao P

    2013-05-01

    This study was designed to test the hypothesis that in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS) can detect in adulthood the neurotoxic effects of a single exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos. Twelve female guinea pigs were given either a single dose of chlorpyrifos (0.6×LD50 or 300mg/kg, sc) or peanut oil (vehicle; 0.5ml/kg, sc) at 35-40 days of age. One year after the exposure, the animals were tested in the Morris water maze. Three days after the end of the behavioral testing, the metabolic and structural integrity of the brain of the animals was examined by means of MRI/MRS. In the Morris water maze, the chlorpyrifos-exposed guinea pigs showed significant memory deficit. Although no significant anatomical differences were found between the chlorpyrifos-exposed guinea pigs and the control animals by in vivo MRI, the chlorpyrifos-exposed animals showed significant decreases in hippocampal myo-inositol concentration using MRS. The present results indicate that a single sub-lethal exposure of prepubertal guinea pigs to the organophosphorus pesticide chlorpyrifos can lead to long-term memory deficits that are accompanied by significant reductions in the levels of hippocampal myo-inositol.

  10. A novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic H1N1 influenza viruses in mice.

    PubMed

    Shao, Hongxia; Ye, Jianqiang; Vincent, Amy L; Edworthy, Nicole; Ferrero, Andrea; Qin, Aijian; Perez, Daniel R

    2011-09-01

    The HA protein of the 2009 pandemic H1N1 viruses (H1N1pdm) is antigenically closely related to the HA of classical North American swine H1N1 influenza viruses (cH1N1). Since 1998, through mutation and reassortment of HA genes from human H3N2 and H1N1 influenza viruses, swine influenza strains are undergoing substantial antigenic drift and shift. In this report we describe the development of a novel monoclonal antibody (S-OIV-3B2) that shows high hemagglutination inhibition (HI) and neutralization titers not only against H1N1pdm, but also against representatives of the α, β, and γ clusters of swine-lineage H1 influenza viruses. Mice that received a single intranasal dose of S-OIV-3B2 were protected against lethal challenge with either H1N1pdm or cH1N1 virus. These studies highlight the potential use of S-OIV-3B2 as effective intranasal prophylactic or therapeutic antiviral treatment for swine-lineage H1 influenza virus infections.

  11. Proteomic analysis of differentiating neuroblastoma cells treated with sub-lethal neurite inhibitory concentrations of diazinon: Identification of novel biomarkers of effect

    SciTech Connect

    Harris, W.; Sachana, M.; Flaskos, J.; Hargreaves, A.J.

    2009-10-15

    In previous work we showed that sub-lethal levels of diazinon inhibited neurite outgrowth in differentiating N2a neuroblastoma cells. Western blotting analysis targeted at proteins involved in axon growth and stress responses, revealed that such exposure led to a reduction in the levels of neurofilament heavy chain, microtubule associated protein 1 B (MAP 1B) and HSP-70. The aim of this study was to apply the approach of 2 dimensional polyacrylamide gel electrophoresis and mass spectrometry to identify novel biomarkers of effect. A number of proteins were found to be up-regulated compared to the control on silver-stained gels. These were classified in to 3 main groups of proteins: cytosolic factors, chaperones and the actin-binding protein cofilin, all of which are involved in cell differentiation, survival or metabolism. The changes observed for cofilin were further confirmed by quantitative Western blotting analysis with anti-actin and anti-cofilin antibodies. Indirect immunofluorescence staining with the same antibodies indicated that the microfilament network was disrupted in diazinon-treated cells. Our data suggest that microfilament organisation is disrupted by diazinon exposure, which may be related to increased cofilin expression.

  12. Effects of acute exercise on long-term memory.

    PubMed

    Labban, Jeffrey D; Etnier, Jennifer L

    2011-12-01

    In this study, we tested the effect of acute exercise on long-term memory, specifically the timing of exercise relative to the memory challenge. We assessed memory via paragraph recall, in which participants listened to two paragraphs (exposure) and recounted them following a 35-min delay. Participants (n = 48) were randomly assigned to one of three groups: exercise prior to exposure, exercise after exposure, or no-exercise. Exercise consisted of 30 min on a cycle ergometer including 20 min at moderate intensity. Only the exercise prior group recalled significantly more than the control group (p < .05). Differences among the exercise groups failed to reach significance (p = .09). Results indicated that acute exercise positively influenced recall and that exercise timing relative to memory task may have an impact on this effect.

  13. The Protective Effects of Buzui on Acute Alcoholism in Mice

    PubMed Central

    Wen, Da-Chao; Gao, Shu-di; Hu, Xiao-yu; Yi, Cheng

    2016-01-01

    This study was designed to investigate the role of a traditional buzui recipe in anti-inebriation treatment. Buzui consists of Fructus Schisandrae Chinensis, Fructus Chebulae, Fructus Mume, Fructus Crataegi, Endothelium Corneum Gigeriae Galli, and Excrementum Bombycis. The buzui mixture was delivered by gavage, and ethanol was delivered subsequent to the final treatment. The effects of buzui on the righting reflex, inebriation rates, and the survival curve are depicted. Blood alcohol concentrations, alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels, and alkaline phosphatase (ALP) levels were recorded. The activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and superoxide dismutase (SOD), as well as malonaldehyde (MDA) levels, were also measured. Our results demonstrated that a traditional buzui recipe showed significant effects on promoting wakefulness and the prevention of acute alcohol intoxication, accelerating the metabolism of alcohol in the liver and reducing the oxidative damage caused by acute alcoholism. PMID:26884793

  14. The effect of menthol on acute experimental colitis in rats.

    PubMed

    Ghasemi-Pirbaluti, Masoumeh; Motaghi, Ehsan; Bozorgi, Homan

    2017-03-18

    Menthol is an aromatic compound with high antiinflammatory activity. The purpose of the current research is to investigate the effectiveness of menthol on acetic acid induced acute colitis in rats. Animals were injected with menthol (20 and 50 and 80mg/kg, i.p.) 24h prior to induction of colitis for 3 consecutive days. Menthol at medium and higher doses similar to dexamethasone as a reference drug significantly reduced body weight loss, macroscopic damage score, ulcer area, colon weight, colon length and improved hematocrit in rats with colitis. The histopathological examination also confirmed anti-colitic effects of menthol. Menthol also reduced significantly the colonic levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6) and myeloperoxidase (MPO) activity in inflamed colons. Thus, the findings of the current study provide evidence that menthol may be beneficial in patients suffering from acute ulcerative colitis.

  15. Spaceflight Sensorimotor Analogs: Simulating Acute and Adaptive Effects

    NASA Technical Reports Server (NTRS)

    Taylor, Laura C.; Harm, Deborah L.; Kozlovskaya, Inessa; Reschke, Millard F.; Wood, Scott J.

    2009-01-01

    Adaptive changes in sensorimotor function during spaceflight are reflected by spatial disorientation, motion sickness, gaze destabilization and decrements in balance, locomotion and eye-hand coordination that occur during and following transitions between different gravitational states. The purpose of this study was to conduct a meta-synthesis of data from spaceflight analogs to evaluate their effectiveness in simulating adaptive changes in sensorimotor function. METHODS. The analogs under review were categorized as either acute analogs used to simulate performance decrements accompanied with transient changes, or adaptive analogs used to drive sensorimotor learning to altered sensory feedback. The effectiveness of each analog was evaluated in terms of mechanisms of action, magnitude and time course of observed deficits compared to spaceflight data, and the effects of amplitude and exposure duration. RESULTS. Parabolic flight has been used extensively to examine effects of acute variation in gravitational loads, ranging from hypergravity to microgravity. More recently, galvanic vestibular stimulation has been used to elicit acute postural, locomotor and gaze dysfunction by disrupting vestibular afferents. Patient populations, e.g., with bilateral vestibular loss or cerebellar dysfunction, have been proposed to model acute sensorimotor dysfunction. Early research sponsored by NASA involved living onboard rotating rooms, which appeared to approximate the time course of adaptation and post-exposure recovery observed in astronauts following spaceflight. Exposure to different bed-rest paradigms (6 deg head down, dry immersion) result in similar motor deficits to that observed following spaceflight. Shorter adaptive analogs have incorporated virtual reality environments, visual distortion paradigms, exposure to conflicting tilt-translation cues, and exposure to 3Gx centrifugation. As with spaceflight, there is considerable variability in responses to most of the analogs

  16. The acute (cerebro)vascular effects of statins.

    PubMed

    Prinz, Vincent; Endres, Matthias

    2009-08-01

    The introduction of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, i.e., statins, constitutes a milestone in the prevention of cardio- and cerebrovascular disease. The effects of statins extend far beyond their effects on cholesterol levels: pleiotropic effects include vasoprotective mechanisms, comprising improved endothelial function, increased bioavailability of nitric oxide, immunomodulatory and antiinflammatory properties, stabilization of atherosclerotic plaques, as well as antioxidant and stem cell-regulating capacities. Large clinical trials have clearly demonstrated that statins reduce the risk of myocardial infarction and stroke. Recent experimental and clinical data have demonstrated that in addition to risk reduction, statins may also improve outcome after stroke and myocardial infarction, even when statins were administered after the event. Moreover, abrupt discontinuation of statin therapy after acute cardio- or cerebrovascular events may impair vascular function and increase morbidity and mortality. Beyond stroke, statin treatment also has been shown to provide protective effects in critically ill patients, e.g., after major surgery, sepsis, or in patients at high-vascular risk. However, although large randomized controlled trials are missing, ongoing trials will clarify the impact of acute statin treatment in these conditions. Although evidence is presently limited, acute statin therapy is emerging as a new therapeutic avenue for the treatment of the critically ill. Until now, statins were only available as oral drugs. An IV formulation may be warranted for acute treatment of severely ill patients, for example, those who are unable to swallow or scheduled for surgery. Hydrophilic statins would be suitable for an IV formulation and have been safely tested in healthy volunteers.

  17. Effect of roxithromycin on acute toxoplasmosis in mice.

    PubMed Central

    Chang, H R; Pechere, J C

    1987-01-01

    Roxithromycin effectively treated acute peritoneal murine toxoplasmosis. After five doses, starting 24 h after challenge, the 100 and 50% survival doses were 540 and 336 mg/kg per day, respectively. After 14 doses, starting 3 h after challenge, the 50% survival dose was 360 mg/kg per day. Toxoplasma gondii was recovered from the brain in 59 and 28% of surviving mice treated with 5 and 14 doses, respectively. PMID:3662475

  18. Effects of Acute Stress on Decision Making.

    PubMed

    Wemm, Stephanie E; Wulfert, Edelgard

    2017-03-01

    The study examined the effects of a social stressor (Trier Social Stress Test) on 24 male and 32 female college students' affective and physiological reactivity and their subsequent performance on a decision-making task (Iowa Gambling Task). The 56 participants were randomly assigned to a social stressor or a control condition. Compared to controls, participants in the stress condition responded with higher heart rates and skin conductance responses, reported more negative affect, and on the decision-making task made less advantageous choices. An exploratory regression analysis revealed that among men higher levels of heart rate were positively correlated with riskier choices on the Iowa Gambling Task, whereas for women this relationship was curvilinear. Exploratory correlational analyses showed that lower levels of skin conductance within the stress condition were associated with greater levels of substance use and gambling. The results suggest that the presence of a stressor may generally result in failure to attend to the full range of possible consequences of a decision. The relationship pattern between the degree of stress responding and successful decision making may be different for men and women.

  19. Oral Toxicity of Okadaic Acid in Mice: Study of Lethality, Organ Damage, Distribution and Effects on Detoxifying Gene Expression

    PubMed Central

    Vieira, Andres C.; Rubiolo, Juan A.; López-Alonso, Henar; Cifuentes, José Manuel; Alfonso, Amparo; Bermúdez, Roberto; Otero, Paz; Vieytes, Mercedes R.; Vega, Félix V.; Botana, Luis M.

    2013-01-01

    In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produce lesions in liver, small intestine and forestomach. Because several reports differ in the damage detected in different organs, and on okadaic acid distribution after consumption, we determined the toxicity of this compound after oral administration to mice. After 24 hours, histopathological examination showed necrotic foci and lipid vacuoles in the livers of intoxicated animals. By immunohistochemical analysis, we detected this toxin in the liver and kidneys of intoxicated animals. Okadaic acid induces oxidative stress and can be activated in vitro into reactive compounds by the post-mitochondrial S9 fraction, so we studied the okadaic effect on the gene expression of antioxidant and phase II detoxifying enzymes in liver. We observed a downregulation in the expression of these enzymes and a reduction of protein expression of catalase and superoxide dismutase 1 in intoxicated animals. PMID:24217398

  20. Possible ameliorative effects of kolaviron against reproductive toxicity in sub-lethally whole body gamma-irradiated rats.

    PubMed

    Adaramoye, Oluwatosin A; Adedara, Isaac A; Farombi, E Olatunde

    2012-05-01

    Ionizing radiation is one of the environmental factors that may contribute to reproductive dysfunction by a mechanism involving oxidative stress. We investigated the possible ameliorative effects of kolaviron (KV) (a biflavonoid from the seeds of Garcinia kola) on sperm characteristics, testicular lipid peroxidation (LPO) and antioxidant status after a whole body γ-irradiation in Wistar rats. Vitamin C (VC) served as standard antioxidant in this study. The study consists of four groups of 6 rats each. Group I received corn oil, whereas group II received a single dose of γ-radiation (5 Gy). The animals in groups III and IV were pretreated with KV (250 mg/kg) and VC (250 mg/kg) by oral gavage five times in a week, respectively, for 6 weeks prior to and 8 weeks after exposure to γ-radiation. Gamma-irradiation resulted in a significant (p<0.05) decrease in body weight and relative testes weight. Also, γ-irradiation significantly (p<0.05) decreased the activities of superoxide dismutase, catalase and glutathione S-transferase as well as glutathione level, but markedly elevated malondialdehyde levels in the serum and testes. Irradiated rats showed testicular degeneration with concomitant decrease in sperm motility and viability. Although sperm abnormalities significantly increased, it has no effect on the epididymal sperm count. KV and VC significantly (p<0.05) decreased the body weight loss and increased relative testes weights of the rats. Furthermore, supplementation of KV and VC ameliorated radiation-induced toxicity by increasing the activities of antioxidant enzymes, decreased LPO and abrogated testicular degeneration. Taken together, γ-irradiation caused reproductive dysfunction by depleting the antioxidant defence system in the rats, while administration of KV or VC ameliorated the radiation-induced testicular toxicity.

  1. The Therapeutic Effect of Pamidronate on Lethal Avian Influenza A H7N9 Virus Infected Humanized Mice

    PubMed Central

    Liu, Yinping; Xiang, Zheng; Liu, Ming; Chan, Kwok-Hung; Lau, Siu-Ying; Lam, Kwok-Tai; To, Kelvin Kai-Wang; Chan, Jasper Fuk-Woo; Li, Lanjuan; Chen, Honglin; Lau, Yu-Lung; Yuen, Kwok-Yung; Tu, Wenwei

    2015-01-01

    A novel avian influenza virus H7N9 infection occurred among human populations since 2013. Although the lack of sustained human-to-human transmission limited the epidemics caused by H7N9, the late presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against H7N9 in urgent demands. In this study, we evaluated the potential of pamidronate, a pharmacological phosphoantigen that can specifically boost human Vδ2-T-cell, on treating H7N9 virus-infected humanized mice. Our results showed that intraperitoneal injection of pamidronate could potently decrease the morbidity and mortality of H7N9-infected mice through controlling both viral replication and inflammation in affected lungs. More importantly, pamidronate treatment starting from 3 days after infection could still significantly ameliorate the severity of diseases in infected mice and improve their survival chance, whereas orally oseltamivir treatment starting at the same time showed no therapeutic effects. As for the mechanisms underlying pamidronate-based therapy, our in vitro data demonstrated that its antiviral effects were partly mediated by IFN-γ secreted from human Vδ2-T cells. Meanwhile, human Vδ2-T cells could directly kill virus-infected host cells in a perforin-, granzyme B- and CD137-dependent manner. As pamidronate has been used for osteoporosis treatment for more than 20 years, pamidronate-based therapy represents for a safe and readily available option for clinical trials to treat H7N9 infection. PMID:26285203

  2. The effects of blood pressure on rebleeding when using ExcelArrest™ in a porcine model of lethal femoral injury

    PubMed Central

    Hirst, HaYong; Brinkman, John; Beasley, Amy; Crocker, Richard; O’Sullivan, Joseph

    2011-01-01

    Background: Uncontrolled hemorrhage is one of the leading causes of death in both combat and civilian trauma. This study was designed to compare the arterial blood pressures at which rebleeding occurred when a hemostatic agent, ExcelArrest™, was used compared with a standard pressure dressing. Materials and Methods: This study was a prospective, experimental, and mixed research design. Swine were assigned to one of two groups: ExcelArrest™ (n=5) or a control consisting of standard pressure dressings (n=5). Investigators generated a complex groin injury. The femoral artery and vein were transected and allowed to bleed for 60 s in each pig. After 60 s, ExcelArrest™ was poured into the wound. The control group underwent the same procedures, but without treatment with the hemostatic agent. After 5 min of direct pressure, a standard pressure dressing was applied. After 30 min, dressings were removed and the systolic blood pressure (SBP) was increased incrementally using intravenous phenylephrine until rebleeding occurred. Statistical Analysis: A multivariate ANOVA and a least significant difference were used to analyze the data. Results: ExcelArrest™ was more effective in preventing rebleeding compared to a standard pressure dressing (P<0.05). The means and standard deviations in mmHg for SBP and mean arterial pressure (MAP) for rebleeding were as follows: ExcelArrest™ (SBP=206.4, SD±11.6; MAP=171.4, SD±12.5); for the control group (SBP=89.40±3.58, MAP=58.60±12.86). Conclusions: ExcelArrest™ was more effective in preventing rebleeding compared to the standard dressing with elevated blood pressures. There may be protective benefits in using this hemostatic agent against elevated blood pressures provided by ExcelArrest™. PMID:21769207

  3. The Therapeutic Effect of Pamidronate on Lethal Avian Influenza A H7N9 Virus Infected Humanized Mice.

    PubMed

    Zheng, Jian; Wu, Wai-Lan; Liu, Yinping; Xiang, Zheng; Liu, Ming; Chan, Kwok-Hung; Lau, Siu-Ying; Lam, Kwok-Tai; To, Kelvin Kai-Wang; Chan, Jasper Fuk-Woo; Li, Lanjuan; Chen, Honglin; Lau, Yu-Lung; Yuen, Kwok-Yung; Tu, Wenwei

    2015-01-01

    A novel avian influenza virus H7N9 infection occurred among human populations since 2013. Although the lack of sustained human-to-human transmission limited the epidemics caused by H7N9, the late presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against H7N9 in urgent demands. In this study, we evaluated the potential of pamidronate, a pharmacological phosphoantigen that can specifically boost human Vδ2-T-cell, on treating H7N9 virus-infected humanized mice. Our results showed that intraperitoneal injection of pamidronate could potently decrease the morbidity and mortality of H7N9-infected mice through controlling both viral replication and inflammation in affected lungs. More importantly, pamidronate treatment starting from 3 days after infection could still significantly ameliorate the severity of diseases in infected mice and improve their survival chance, whereas orally oseltamivir treatment starting at the same time showed no therapeutic effects. As for the mechanisms underlying pamidronate-based therapy, our in vitro data demonstrated that its antiviral effects were partly mediated by IFN-γ secreted from human Vδ2-T cells. Meanwhile, human Vδ2-T cells could directly kill virus-infected host cells in a perforin-, granzyme B- and CD137-dependent manner. As pamidronate has been used for osteoporosis treatment for more than 20 years, pamidronate-based therapy represents for a safe and readily available option for clinical trials to treat H7N9 infection.

  4. Glucocorticoid therapy-induced memory deficits: acute versus chronic effects.

    PubMed

    Coluccia, Daniel; Wolf, Oliver T; Kollias, Spyros; Roozendaal, Benno; Forster, Adrian; de Quervain, Dominique J-F

    2008-03-26

    Conditions with chronically elevated glucocorticoid levels are usually associated with declarative memory deficits. Considerable evidence suggests that long-term glucocorticoid exposure may cause cognitive impairment via cumulative and long-lasting influences on hippocampal function and morphology. However, because elevated glucocorticoid levels at the time of retention testing are also known to have direct impairing effects on memory retrieval, it is possible that such acute hormonal influences on retrieval processes contribute to the memory deficits found with chronic glucocorticoid exposure. To investigate this issue, we examined memory functions and hippocampal volume in 24 patients with rheumatoid arthritis who were treated either chronically (5.3 +/- 1.0 years, mean +/- SE) with low to moderate doses of prednisone (7.5 +/- 0.8 mg, mean +/- SE) or without glucocorticoids. In both groups, delayed recall of words learned 24 h earlier was assessed under conditions of either elevated or basal glucocorticoid levels in a double-blind, placebo-controlled crossover design. Although the findings in this patient population did not provide evidence for harmful effects of a history of chronic prednisone treatment on memory performance or hippocampal volume per se, acute prednisone administration 1 h before retention testing to either the steroid or nonsteroid group impaired word recall. Thus, these findings indicate that memory deficits observed under chronically elevated glucocorticoid levels result, at least in part, from acute and reversible glucocorticoid effects on memory retrieval.

  5. 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.

  6. Effects of acute hippocampal stimulation on EEG dynamics.

    PubMed

    Nair, Sandeep P; Sackellares, J Chris; Shiau, Deng-Shan; Norman, Wendy M; Dance, Linda K; Pardalos, Panos M; Principe, Jose C; Carney, Paul R

    2006-01-01

    Progressive preictal dynamical convergence and postictal divergence of dynamical EEG descriptors among brain regions has been reported in human temporal lobe epilepsy (TLE) and in a rodent model of TLE. There are also reports of anticonvulsant effects of high frequency stimulation of the hippocampus in humans. We postulate that this anticonvulsant effect is due to dynamical resetting by the electrical stimulation. The following study investigated the effects of acute hippocampal electrical stimulation on dynamical transitions in the brain of a spontaneously seizing animal model of TLE to test the hypothesis of divergence in dynamical values by electrical stimulation of the hippocampus.

  7. Ethyl Formate Fumigation of Dry and Semidry Date Fruits: Experimental Kinetics, Modeling, and Lethal Effect on Carob Moth.

    PubMed

    Bessi, Haithem; Bellagha, Sihem; Lebdi, Kaouthar Grissa; Bikoba, Veronique; Mitcham, Elizabeth J

    2015-06-01

    Ethyl formate (EF) was studied as a fumigant agent with the objective to replace methyl bromide (MB) for date fruit disinfestations. Date fruits Phoenix dactylifera 'Deglet Nour' with different initial moisture content (16% for dry dates, 20% for semidry dates, and a mixture of the two types) were separately fumigated with EF at different concentrations: 28.6, 57.3, 85.9, and 114.6 g/m3 for 2 h. Experimental data of EF sorption during fumigation was successfully fitted to Peleg's model. This model allows the prediction of the effects of date moisture content and EF concentration on sorption behavior. Samples with different moisture content showed similar EF sorption behavior. Dates were artificially infested with carob moth (Ectomyelois ceratoniae (Zeller)) at different life stages. Eggs, third- and fifth-instars, and pupae were exposed to 28.6, 57.3, 85.9, and 114.6 g/m3 EF for 2 h. Among these life stages, fifth-instars were the most resistant to EF fumigation. A 2-h fumigation with 114.6 g/m3 EF provided complete control of eggs, third-instars, and pupae of carob moth, and generated 91.6% mortality of fifth-instars. A longer fumigation time or higher EF concentration may provide complete control of all life stages of carob moth.

  8. [Protective effect of oral administration of several traditional Kampo-medicines on lethal Candida infection in immunosuppressed mice].

    PubMed

    Abe, S; Ishibashi, H; Tansho, S; Hanazawa, R; Komatsu, Y; Yamaguchi, H

    2000-01-01

    The protective effects of a "hozai" type of Kampo medicine, Juzen-taiho-to (Shi-quan-da-bu-tang, TJ-48), Hochu-ekki-to (Bu-zhong-yi-qi-tang, TJ-41) or Ninjin-yoei-to (Ren-shen-yang-rong-tang, TJ-108) on experimental candidiasis in immunosuppressed mice were investigated. ICR mice, which were immunosuppressed by injection of cyclophosphamide or prednisolone, were given these medicines orally andchallenged intravenously with Candida albicans (day 0). Treatments with a daily dose of 1 g/kg/day of TJ-48 or that of 1 or 2 g/kg/day of TJ-108 for 4 consecutive days from day-4 significantly prolonged the survival time of the Candida-infected mice pretreated with cyclophosphamide. Treatments with a daily dose of 1 g/kg/day of TJ-48 for 4 consecutive days from day 0, but not from day -4, significantly prolonged the life span of the Candida-infected mice pretreated with prednisolone. On the basis of these results and previous findings, characteristics of these kampo medicines as therapeutic agents against candidiasis in immunosuppressed hosts were discussed.

  9. Histopathology and the lethal effect of Cry proteins and strains of Bacillus thuringiensis Berliner in Spodoptera frugiperda J.E. Smith Caterpillars (Lepidoptera, Noctuidae).

    PubMed

    Knaak, N; Franz, A R; Santos, G F; Fiuza, L M

    2010-08-01

    Among the phytophagous insects which attack crops, the fall armyworm, Spodoptera frugiperda (J.E. Smith, 1797) (Lepidoptera, Noctuidae) is particularly harmful in the initial growth phase of rice plants. As a potential means of controlling this pest, and considering that the entomopathogen Bacillus thuringiensis Berliner demonstrates toxicity due to synthesis of the Cry protein, the present study was undertaken to evaluate this toxic effect of B. thuringiensis thuringiensis 407 (pH 408) and B. thuringiensis kurstaki HD-73 on S. frugiperda. The following method was used. Both bacterial strains were evaluated in vitro in 1st instar S. frugiperda caterpillars, by means of histopathological assays. The Cry1Ab and Cry1Ac proteins, codified by the respective strains of B. thuringiensis, were evaluated in vivo by bioassays of 1st instar S. frugiperda caterpillars in order to determine the Mean Lethal Concentration (LC50). The results of the histopathological analysis of the midget of S. frugiperda caterpillars demonstrate that treatment with the B. thuringiensis thuringiensis strain was more efficient, because the degradations of the microvilosities started 9 hours after treatment application (HAT), while in the B. thuringiensis kurstaki the same effect was noticed only after 12 HAT. Toxicity data of the Cry1Ab and Cry1Ac proteins presented for the target-species LC50 levels of 9.29 and 1.79 microgxcm-2 respectively. The strains and proteins synthesised by B. thuringiensis thuringiensis and B. thuringiensis kurstaki are effective in controlling S. frugiperda, and may be used to produce new biopesticides or the genes may be utilised in the genetic transformation of Oryza sativa L.

  10. Physiological Stress Responses in Amphibian Larvae to Multiple Stressors Reveal Marked Anthropogenic Effects even below Lethal Levels.

    PubMed

    Burraco, Pablo; Gomez-Mestre, Ivan

    Natural and anthropogenic disturbances cause profound alterations in organisms, inducing physiological adjustments to avoid, reduce, or remedy the impact of disturbances. In vertebrates, the stress response is regulated via neuroendocrine pathways, including the hypothalamic-pituitary-interrenal axis that regulates the secretion of glucocorticoids. Glucocorticoids have cascading effects on multiple physiological pathways, affecting the metabolic rate, reactive oxygen species production, or immune system. Determining the extent to which natural and anthropogenic environmental factors induce stress responses in vertebrates is of great importance in ecology and conservation biology. Here we study the physiological stress response in spadefoot toad tadpoles (Pelobates cultripes) against three levels of a series of natural and anthropogenic stressors common to many aquatic systems: salinity (0, 6, and 9 ppt), herbicide (0, 1, and 2 mg/L acid equivalent of glyphosate), water acidity (pH 4.5, 7.0, and 9.5), predators (absent, native, and invasive), and temperature (21°, 25°, and 29°C). The physiological stress response was assessed examining corticosterone levels, standard metabolic rate, activity of antioxidant enzymes, oxidative cellular damage in lipids, and immunological status. We found that common stressors substantially altered the physiological state of tadpoles. In particular, salinity and herbicides cause dramatic physiological changes in tadpoles. Moreover, tadpoles reduced corticosterone levels in the presence of natural predators but did not do so against invasive predators, indicating a lack of innate recognition. Corticosterone and the antioxidant enzyme glutathione reductase were the most sensitive parameters to stress in this study. Anthropogenic perturbations of aquatic systems pose serious threats to larval amphibians even at nonlethal concentrations, judging from the marked physiological stress responses generated, and reveal the importance of

  11. Lethal effects of water quality on threatened California salamanders but not on co-occurring hybrid salamanders.

    PubMed

    Ryan, Maureen E; Johnson, Jarrett R; Fitzpatrick, Benjamin M; Lowenstine, Linda J; Picco, Angela M; Shaffer, H Bradley

    2013-02-01

    Biological invasions and habitat alteration are often detrimental to native species, but their interactions are difficult to predict. Interbreeding between native and introduced species generates novel genotypes and phenotypes, and human land use alters habitat structure and chemistry. Both invasions and habitat alteration create new biological challenges and opportunities. In the intensively farmed Salinas Valley, California (U.S.A.), threatened California tiger salamanders (Ambystoma californiense) have been replaced by hybrids between California tiger salamander and introduced barred tiger salamanders (Ambystoma tigrinum mavortium). We conducted an enclosure experiment to examine the effects habitat modification and relative frequency of hybrid and native California tiger salamanders have on recruitment of salamanders and their prey, Pacific chorus frogs (Pseudacris regilla). We tested whether recruitment differed among genetic classes of tiger salamanders (hybrid or native) and pond hydroperiod (seasonal or perennial). Roughly 6 weeks into the experiment, 70% (of 378 total) of salamander larvae died in 4 out of 6 ponds. Native salamanders survived (n = 12) in these ponds only if they had metamorphosed prior to the die-offs. During die-offs, all larvae of native salamanders died, whereas 56% of hybrid larvae died. We necropsied native and hybrid salamanders, tested water quality, and queried the California Department of Pesticide Regulation database to investigate possible causes of the die-offs. Salamander die-offs, changes in the abundance of other community members (invertebrates, algae, and cyanobacteria), shifts in salamander sex ratio, and patterns of pesticide application in adjacent fields suggest that pesticide use may have contributed to die-offs. That all survivors were hybrids suggests that environmental stress may promote rapid displacement of native genotypes.

  12. Uptake, metabolism and sub-lethal effects of BDE-47 in two estuarine invertebrates with different trophic positions.

    PubMed

    Díaz-Jaramillo, M; Miglioranza, K S B; Gonzalez, M; Barón, E; Monserrat, J M; Eljarrat, E; Barceló, D

    2016-06-01

    Two microcosm types -sediment-biota and biota-biota- were constructed to simulate different pathways of BDE-47 uptake, metabolism and oxidative stress effects in two key estuarine invertebrates (polychaete Laeonereis acuta and crab Cyrtograpsus angulatus). In the sediment-biota experiment, both species were exposed to spiked sediments; an environmentally reported and a high concentration of BDE-47 for 2 weeks. In the biota-biota experiment, crabs were fed with polychaetes pre-exposed to BDE-47 in the sediment-biota experiment. The sediment-biota experiment first revealed that polychaetes significantly accumulated BDE-47 (biota-sediment accumulation factor >2; p < 0.05) to a much greater extent than the crab organs (muscle, hepatopancreas, gills) at both sediment concentrations. For oxidative stress responses, polychaete and crab tissues exposed to spiked sediment showed a significant increase (p < 0.05) of only glutathione S-transferase (GST) activity with respect to controls in both BDE-47 concentrations. No lipid peroxidation (TBARS) or total antioxidant capacity (ACAP) changes were evident in the species or organs exposed to either BDE-47 sediment concentration. The biota-biota experiment showed that feeding crabs with pre-exposed polychaetes caused BDE-47 accumulation in organs as well as significant amounts of BDE-47 eliminated through feces (p < 0.05). Unlike the sediment-biota exposure, crabs fed with pre-exposed BDE-47 polychaetes showed the most conspicuous oxidative stress responses. Significant changes in GST and ACAP in both hepatopancreas and gills, in addition to enhanced TBARS levels in the hepatopancreas with respect to controls (p < 0.05), revealed that BDE-47 assimilated by invertebrates represents a potential source of toxicity to their predators. No methoxylated metabolites (MeO-PBDEs) were detected during BDE-47 metabolism in the invertebrates in either of the two different exposure types. In contrast, hydroxylated metabolites (OH

  13. 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.

  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. Lethal and Sublethal Effects of Insecticides on the Biological Attributes of Zygogramma bicolorata Pallister (Coleoptera: Chrysomelidae): a Biocontrol Agent of Parthenium hysterophorus L.

    PubMed

    Hasan, F; Ansari, M S

    2017-01-31

    Acute toxicity and sublethal effects of six commonly used insecticides, i.e., malathion, carbaryl, imidacloprid, cypermethrin, dimethoate, and monocrotophos, were evaluated through biological and life table parameters of Zygogramma bicolorata Pallister in laboratory. Concentration of these insecticides was within the minimum ranges of recommended field rate. Among the insecticides tested for acute toxicity, monocrotophos and imidacloprid caused the highest mortality of third instars and prolonged the development time of treated larvae. Fecundity and egg viability were also reduced in monocrotophos-treated group. Sublethal toxicity (carryover effect) of insecticides was evaluated through life table analysis of F1 progenies developed from surviving third instars treated for acute toxicity experiment. Survivorship was prolonged to 117 days in carbaryl treated group. Monocrotophos prolonged the overall immature development time compared to other insecticidal treatments and untreated control. Moreover, the lowest female survival, and the lowest value of life indices parameters, i.e., m x , R 0, r m, and λ, was evident in monocrotophos-exposed groups compared to that in other tested insecticides. However, mean generation time (T c) and doubling time (DT) were significantly prolonged in the insecticide-treated groups compared to those in the untreated group. A significantly greater number of females were produced in control groups than those in treated with malathion and sex ratio (proportion of male) was computed as 0.34 and 0.37, respectively. Based on the present study, it can be concluded that none of the tested insecticides can be classified as safe to Z. bicolorata. However, comparisons among the tested insecticides showed that malathion was less toxic compared to other insecticides tested.

  16. The effects of acute sleep deprivation during residency training.

    PubMed

    Bartle, E J; Sun, J H; Thompson, L; Light, A I; McCool, C; Heaton, S

    1988-08-01

    Verbal and symbol concentration, learning, problem solving, clear thinking, manual skills, and memory were tested in 42 surgical residents to assess the effects of acute sleep deprivation on specific neuropsychological parameters. A series of eight neuropsychological tests--digit symbols, digit vigilance, story memory, trail making, PASAT, Raven matrices, delayed story, and pegboard--and a questionnaire on mood states were completed by the residents both when fatigued (less than 4 hours of sleep: mean, 2.0 +/- 1.5 hours) and when rested (more than 4 hours of sleep: mean, 6.5 +/- 1.0 hours), with at least 7 days between tests. In order to eliminate the effects of learning from the first test series, randomization of residents was performed so that one half were first evaluated when rested and one half when fatigued. ANOVA, multiple regression analysis, and the Student t test were used to assess differences. In the acute sleep-deprived state, residents were less vigorous and more fatigued, depressed, tense, confused, and angry (p less than 0.05) than they were in rested state. Despite these changes in mood, however, the responses on all of the functional tests were no different statistically in those who were rested and those who were fatigued (even in those with less than 2 hours' sleep). We conclude that acute sleep deprivation of less than 4 hours alters mood state but does not change performance in test situations in which concentration, clear thinking, and problem solving are important.

  17. Effects of acute ingestion of salbutamol during submaximal exercise.

    PubMed

    Collomp, K; Candau, R; Collomp, R; Carra, J; Lasne, F; Préfaut, C; De Ceaurriz, J

    2000-10-01

    To assess the eventual effects of acute oral salbutamol intake on performance and metabolism during submaximal exercise, nine healthy volunteers completed two cycling trials at a power corresponding to 80-85% VO2max, after either placebo (Pla) or salbutamol (Sal, 6 mg) treatment, according to a double-blind randomized protocol. Blood samples were collected both at rest and during exercise (5 min-, 10 min-, 15 min-exhaustion) for C-peptide, FFA, lactate and blood glucose measurements. Cycling performance was significantly improved in the Sal vs. Pla trials (p < 0.05). After Sal intake, resting C-peptide, lactate, FFA and blood glucose values were higher whereas exercise lactate and free fatty acid concentrations were greater during and at the conclusion of the exercise period (p < 0.05). These results suggest that acute salbutamol ingestion improved performance during submaximal exercise probably through an enhancement of the overall contribution to energy production from both aerobic and anaerobic metabolisms.

  18. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. Evaluating the stress response as a bioindicator of sub-lethal effects of crude oil exposure in wild house sparrows (Passer domesticus).

    PubMed

    Lattin, Christine R; Ngai, Heather M; Romero, L Michael

    2014-01-01

    Petroleum can disrupt endocrine function in humans and wildlife, and interacts in particularly complex ways with the hypothalamus-pituitary-adrenal (HPA) axis, responsible for the release of the stress hormones corticosterone and cortisol (hereafter CORT). Ingested petroleum can act in an additive fashion with other stressors to cause increased mortality, but it is not clear exactly why--does petroleum disrupt feedback mechanisms, stress hormone production, or both? This laboratory study aimed to quantify the effects of ingested Gulf of Mexico crude oil on the physiological stress response of house sparrows (Passer domesticus). We examined baseline and stress-induced CORT, negative feedback, and adrenal sensitivity in house sparrows given a 1% oil or control diet (n = 12 in each group). We found that four weeks on a 1% oil diet did not alter baseline CORT titers or efficacy of negative feedback, but significantly reduced sparrows' ability to secrete CORT in response to a standardized stressor and adrenocorticotropin hormone injection, suggesting that oil damages the steroid-synthesizing cells of the adrenal. In another group of animals on the same 1% oil (n = 9) or control diets (n = 8), we examined concentrations of eight different blood chemistry parameters, and CORT in feathers grown before and during the feeding experiments as other potential biomarkers of oil exposure. None of the blood chemistry parameters differed between birds on the oil and control diets after two or four weeks of feeding, nor did feather CORT differ between the two groups. Overall, this study suggests that the response of CORT to stressors, but not baseline HPA function, may be a particularly sensitive bioindicator of sub-lethal chronic effects of crude oil exposure.

  1. Countermeasures for Space Radiation Induced Malignancies and Acute Biological Effects

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann

    The hypothesis being evaluated in this research program is that control of radiation induced oxidative stress will reduce the risk of radiation induced adverse biological effects occurring as a result of exposure to the types of radiation encountered during space travel. As part of this grant work, we have evaluated the protective effects of several antioxidants and dietary supplements and observed that a mixture of antioxidants (AOX), containing L-selenomethionine, N-acetyl cysteine (NAC), ascorbic acid, vitamin E succinate, and alpha-lipoic acid, is highly effective at reducing space radiation induced oxidative stress in both in vivo and in vitro systems, space radiation induced cytotoxicity and malignant transformation in vitro [1-7]. In studies designed to determine whether the AOX formulation could affect radiation induced mortality [8], it was observed that the AOX dietary supplement increased the 30-day survival of ICR male mice following exposure to a potentially lethal dose (8 Gy) of X-rays when given prior to or after animal irradiation. Pretreatment of animals with antioxidants resulted in significantly higher total white blood cell and neutrophil counts in peripheral blood at 4 and 24 hours following exposure to doses of 1 Gy and 8 Gy. Antioxidant treatment also resulted in increased bone marrow cell counts following irradiation, and prevented peripheral lymphopenia following 1 Gy irradiation. Supplementation with antioxidants in irradiated animals resulted in several gene expression changes: the antioxidant treatment was associated with increased Bcl-2, and decreased Bax, caspase-9 and TGF-β1 mRNA expression in the bone marrow following irradiation. These results suggest that modulation of apoptosis may be mechanistically involved in hematopoietic system radioprotection by antioxidants. Maintenance of the antioxidant diet was associated with improved recovery of the bone marrow following sub-lethal or potentially lethal irradiation. Taken together

  2. Effects of acute bouts of exercise on cognition.

    PubMed

    Tomporowski, Phillip D

    2003-03-01

    A review was conducted of studies that assessed the effects of acute bouts of physical activity on adults' cognitive performance. Three groups of studies were constituted on the basis of the type of exercise protocol employed. Each group was then evaluated in terms of information-processing theory. It was concluded that submaximal aerobic exercise performed for periods up to 60 min facilitate specific aspects of information processing; however, extended exercise that leads to dehydration compromises both information processing and memory functions. The selective effects of exercise on cognitive performance are explained in terms of Sanders' [Acta Psychol. 53 (1983) 61] cognitive-energetic model.

  3. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

    PubMed Central

    Amin, Bahareh; Nakhsaz, Alireza; Hosseinzadeh, Hossein

    2015-01-01

    Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST). Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg) and crocetin (20 and 40 mg/kg) produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg). Crocetin (12.5, 25 and 50 mg/kg) was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration. PMID:26468466

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

    PubMed

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

    2009-11-01

    Clopyralid (3,6-dichloro-2-pyridinecarboxylic acid) is a pyridine herbicide frequently used to control invasive, noxious weeds in the northwestern United States. Clopyralid exhibits low acute toxicity to fish, including the rainbow trout (Oncorhynchus mykiss) and the threatened bull trout (Salvelinus confluentus). However, there are no published chronic toxicity data for clopyralid and fish that can be used in ecological risk assessments. We conducted 30-day chronic toxicity studies with juvenile rainbow trout exposed to the acid form of clopyralid. The 30-day maximum acceptable toxicant concentration (MATC) for growth, calculated as the geometric mean of the no observable effect concentration (68 mg/L) and the lowest observable effect concentration (136 mg/L), was 96 mg/L. No mortality was measured at the highest chronic concentration tested (273 mg/L). The acute:chronic ratio, calculated by dividing the previously published 96-h acutely lethal concentration (96-h ALC(50); 700 mg/L) by the MATC was 7.3. Toxicity values were compared to a four-tiered exposure assessment profile assuming an application rate of 1.12 kg/ha. The Tier 1 exposure estimation, based on direct overspray of a 2-m deep pond, was 0.055 mg/L. The Tier 2 maximum exposure estimate, based on the Generic Exposure Estimate Concentration model (GEENEC), was 0.057 mg/L. The Tier 3 maximum exposure estimate, based on previously published results of the Groundwater Loading Effects of Agricultural Management Systems model (GLEAMS), was 0.073 mg/L. The Tier 4 exposure estimate, based on published edge-of-field monitoring data, was estimated at 0.008 mg/L. Comparison of toxicity data to estimated environmental concentrations of clopyralid indicates that the safety factor for rainbow trout exposed to clopyralid at labeled use rates exceeds 1000. Therefore, the herbicide presents little to no risk to rainbow trout or other salmonids such as the threatened bull trout.

  5. Remote effects of acute kidney injury in a porcine model.

    PubMed

    Gardner, David S; De Brot, Simone; Dunford, Louise J; Grau-Roma, Llorenc; Welham, Simon J M; Fallman, Rebecca; O'Sullivan, Saoirse E; Oh, Weng; Devonald, Mark A J

    2016-02-15

    Acute kidney injury (AKI) is a common and serious condition with no specific treatment. An episode of AKI may affect organs distant from the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we tested the hypothesis that early effects of AKI on distant organs is by immune cell infiltration, leading to inflammatory cytokine production, extravasation, and edema. In 29 pigs exposed to either sham surgery or renal ischemia-reperfusion (control, n = 12; AKI, n = 17), we assessed remote organ (liver, lung, brain) effects in the short (from 2- to 48-h reperfusion) and longer term (5 wk later) using immunofluorescence (for leukocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (e.g., electrolytes), blood hematology and chemistry (e.g., liver enzymes), and PCR (for inflammatory markers). AKI elicited significant, short-term (∼24 h) increments in enzymes indicative of acute liver damage (e.g. , AST: ALT ratio; P = 0.02) and influenced tissue biochemistry in some remote organs (e.g., lung tissue [Ca(2+)] increased; P = 0.04). These effects largely resolved after 48 h, and no further histopathology, edema, apoptosis, or immune cell infiltration was noted in the liver, lung, or hippocampus in the short and longer term. AKI has subtle biochemical effects on remote organs in the short term, including a transient increment in markers of acute liver damage. These effects resolved by 48 h, and no further remote organ histopathology, apoptosis, edema, or immune cell infiltration was noted.

  6. Toxoplasma gondii: the effect of fluconazole combined with sulfadiazine and pyrimethamine against acute toxoplasmosis in murine model.

    PubMed

    Martins-Duarte, Érica S; de Souza, Wanderley; Vommaro, Rossiane C

    2013-03-01

    Toxoplasma gondii is an important opportunistic pathogen for immunocompromised patients and responsible for toxoplasmic encephalitis, which is often lethal. Treatment for this infection is limited to a restricted therapeutic arsenal. In this work we tested the combination of fluconazole with the current treatment for acute toxoplasmosis on the murine model in vivo. Different experimental groups were treated with combinations of sulfadiazine plus pyrimethamine with fluconazole and pyrimethamine with fluconazole. Fluconazole is an important antifungal triazole used against others CNS related opportunistic pathogens such as Cryptococcus neoformans and Candida spp. The combinations of fluconazole plus sulfadiazine and pyrimethamine or fluconazole plus pyrimethamine were remarkably effective against T. gondii in vivo. The 10-day treatment with 10mg/kg/day of fluconazole combined with 40/1mg/kg/day sulfadiazine and pyrimethamine resulted in 93% survival of CF1 mice acutely infected with the highly virulent T. gondii RH strain, versus 36% of mice treated with just sulfadiazine and pyrimethamine. Combinations of fluconazole with lower doses of sulfadiazine and pyrimethamine or with just pyrimethamine were also efficient in reducing the mortality of mice compared with the treatment without fluconazole. The results obtained are promising for the treatment of human toxoplasmosis and point to the need to extend these studies to other murine models.

  7. Effects of sub-lethal and chronic lead concentrations on blood and liver ALA-D activity and hematological parameters in Nile tilapia.

    PubMed

    Dos Santos, Carlucio Rocha; Cavalcante, Ana Luiza Michel; Hauser-Davis, Rachel Ann; Lopes, Renato Matos; Mattos, Rita De Cássia Oliveira Da Costa

    2016-07-01

    Liver and blood δ-aminolevulinic acid dehydratase (ALA-D) inhibition by exposure to sub-lethal lead concentrations over time in Nile tilapia (Oreochromis niloticus) were investigated. All three lead concentrations (1mgkg(-1), 10mgkg(-1) and 100mgkg(-1)) significantly inhibited ALA-D activity in blood (319±29.2; 180±14.6 and 172±19µmols(-1)h(-1)L(-1) respectively) and liver (302±5.84; 201±41.4 and 93±22.1µmols(-1)h(-1)L(-1)) 24h after injection relative to controls (blood: 597±37.0µmols(-1)h(-1)L(-1); liver: 376±23.1µmols(-1)h(-1)L(-1)). Blood ALA-D was greatly inhibited in all but the highest lead dose. Fish were then exposed to 1mgkg(-1) lead for 9 days, and presented short-term hyperglycemia, decreased hemoglobin and hematocrit values and time-dependent blood ALA-D activity inhibition, corroborating blood ALA-D activity as being more suitable for investigating lead effects, showing dose and time-dependent ALA-D inhibition after lead exposure. The results of the present study also demonstrated that fish size affects blood ALA-D activity, as fish from the 24-h assay, which were slightly smaller (approximately 200g), showed higher ALA-D inhibition in response to lead exposure when compared to the fish from the 9-day assay (approximately 500g). Thus, fish size should always be taken into account both in the field and in laboratory settings, and efforts should be made to obtain uniform fish size samples for biomarker studies.

  8. Effects of diazoxide in experimental acute necrotizing pancreatitis

    PubMed Central

    de Oliveira Andrade, Roberta; Kunitake, Tiago; Koike, Marcia Kiyomi; Machado, Marcel C C; Souza, Heraldo Possolo

    2017-01-01

    OBJECTIVE: We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis. METHODS: Male Wistar rats (200–400 g) were divided randomly into two groups. Fifteen minutes before surgery, animals received physiological (0.9%) saline (3 mL/kg) (control group) or 45 mg/kg diazoxide (treatment group) via the intravenous route. Acute pancreatitis was induced by injection of 2.5% sodium taurocholate via the biliopancreatic duct. Mortality (n=38) was observed for 72 h and analyzed by the Mantel–Cox Log-rank test. To study pancreatic lesions and systemic inflammation, rats (10 from each group) were killed 3 h after acute pancreatitis induction; ascites volume was measured and blood as well as pancreases were collected. Pancreatic injury was assessed according to Schmidt’s scale. Cytokine expression in plasma was evaluated by the multiplex method. RESULTS: Mortality at 72 h was 33% in the control group and 60% in the treatment group (p=0.07). Ascites volumes and plasma levels of cytokines between groups were similar. No difference was observed in edema or infiltration of inflammatory cells in pancreatic tissues from either group. However, necrosis of acinar cells was lower in the treatment group compared to the control group (3.5 vs. 3.75, p=0.015). CONCLUSIONS: Treatment with diazoxide can reduce necrosis of acinar cells in an experimental model of acute pancreatitis, but does not affect the inflammatory response or mortality after 72 h. PMID:28273237

  9. Acute effects of ethanol on renal folate clearance in rats

    SciTech Connect

    Eisenga, B.H.; McMartin, K.E.

    1986-03-05

    Studies of the renal clearance of folic acid in primates demonstrate net reabsorption of folate by a saturable system. The acute administration of ethanol to rats causes a significant increase in urinary folate excretion. The mechanism for this effect is unknown and thus the effect of acute administration of ethanol on the renal absorption and urinary clearance of folate was studied in rats. Folic acid was administered to male Sprague-Dawley rats via continuous intravenous infusion in doses ranging from 3-75 micromoles/kg and renal clearance relative to inulin was determined. The effects of various dose levels of ethanol on these parameters were then determined. At a dose of 15 micromoles/kg, the renal clearance of folate relative to that of inulin was about 0.65 mg/min. At a plasma ethanol level about 100 mg/dl, the renal clearance of folate was not markedly altered. These results suggests that there is net reabsorption of folate in the rat kidney and that moderate doses of ethanol have little effect on renal effect on renal folate reabsorption.

  10. 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

  11. The inhibitory effect of Zingiber corallinum Hance essential oil on drug-resistant bacteria and evaluation of its acute toxicity

    PubMed Central

    Yang, Ce; Zhou, Lin-Lin; Wang, Hai-Yan; Huang, Su-Na; Liu, Qing; Hu, Shi-Lin; Li, Ting-Rong; Chen, Yan-Bing; Jiang, Jian-Xin

    2011-01-01

    Summary Background The excessive and irregular use of antibiotics could result in the generation and diffusion of drug-resistant bacteria. The aim of this study was to investigate the inhibitory effect of Zingiber corallinum Hance essential oil (ZCHO) on drug-resistant bacteria, especially on drug-resistant Acinetobacter baumannii. Material/Methods Susceptibility testing was used to evaluate the effect of ZCHO on growth inhibition of drug-resistant bacteria by paper disk method. Mice orally administered with ZCHO were used to observe acute toxicity and to determine median lethal dose (LD50) of ZCHO. Broth dilution method was used to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ZCHO on drug-resistant Acinetobacter baumannii. Results ZCHO exhibited an obvious inhibitory effect not only on gram-negative drug-resistant bacteria including Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Acinetobacter baumannii, but also on gram-positive drug-resistant bacteria including Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus. The ZCHO containing 79% terpinen-4-ol revealed better bacteriostatic effect than ZCHO with 34% terpinen-4-ol. The LD50 of ZCHO was 1790.427 mg/kg. The MIC and MBC of ZCHO on drug-resistant Acinetobacter baumannii were 1457.81 mg/L. Conclusions ZCHO has obvious bacteriostasis and bactericidal effects, especially against drug-resistant Acinetobacter baumannii. Therefore, ZCHO is a promising natural bioactive component with antibacterial effect and satisfactory safety due to its low toxicity. PMID:21525802

  12. 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.

  13. Dietary taurine supplementation ameliorates the lethal effect of phenanthrene but not the bioaccumulation in a marine teleost, red sea bream, Pagrus major.

    PubMed

    Hano, Takeshi; Ito, Mana; Ito, Katsutoshi; Kono, Kumiko; Ohkubo, Nobuyuki

    2017-03-01

    The present study was performed to evaluate the effect of dietary taurine on the hepatic metabolic profiles of red sea bream (Pagrus major) and on phenanthrene (a polyaromatic hydrocarbon) toxicity and bioaccumulation. The fish were fed a diet supplemented with 0% (TAU0%), 0.5% (TAU0.5%), or 5% (TAU5%) taurine for 40-55d and subjected to phenanthrene acute toxicity and bioaccumulation tests. Taurine deficiency in feed severely affected the hepatic metabolic profiles of fish, which indicated a complementary physiological response to taurine deficiency. For the acute toxicity test, fish were fed the test diets for 55d and were then exposed to 0-893µg/L phenanthrene for 96h. Tolerance to phenanthrene was significantly improved by 0.5% of taurine inclusion in feed relative to TAU0%, but not by 5.0% inclusion. Reduced glutathione in the liver, which acts as an oxygen-free radical scavenger, was associated with a reduction in the toxicity of phenanthrene. For the bioaccumulation test, fish were fed the test diets for 40d and were thereafter chronically exposed to 20µg/L phenanthrene for 13d followed by depuration for 3d. The activity of hepatic biomarker, ethoxyresorufin-O-deethylase, was increased by phenanthrene exposure in the taurine inclusion groups. However, phenanthrene concentrations in the liver and muscle of fish fed TAU5.0% tended to be higher than those of fish fed TAU0% and TAU0.5% during the exposure period. These results indicate that 0.5% of taurine inclusion in feed plays an important role in the alleviation of phenanthrene toxicity but not bioaccumulation. Furthermore, larger amount of taurine inclusion (TAU5%) did not show marked beneficial effects against phenanthrene exposure. This study provides insight about a major concern of environmental contaminants into aquatic environment and can be effectively used for improvement of aquaculture.

  14. 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.

  15. 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.

  16. The acute toxic effects of imidazolium-based ionic liquids with different alkyl-chain lengths and anions on zebrafish (Danio rerio).

    PubMed

    Zhang, Cheng; Zhu, Lusheng; Wang, Jinhua; Wang, Jun; Zhou, Tongtong; Xu, Yaqi; Cheng, Chao

    2017-06-01

    With the increasing applications of ionic liquids (ILs), the toxicity of ILs has drawn increasing attention in recent years, especially the influences of different anions and alkyl-chain lengths on the acute toxicity to aquatic organisms. We performed a study on the acute toxicity of 1-alkyl-3-methylimidazolium nitrate ([Cnmim]NO3 (n=2, 4, 6, 8, 10, 12)), 1-hexyl-3-methylimidazolium ILs ([C6mim]R (R=Cl(-), Br(-), BF4(-), PF6(-))) to zebrafish (Danio rerio). We also evaluated the sensibility of the investigated animals and the stability of ILs in water via high performance liquid chromatography (HPLC, Agilent 1260, Agilent Technologies Inc., USA) to prove the reliability of the present study. The results illustrated that the test zebrafish (Danio rerio) were sensitive to the reference toxicant and that the investigated ILs in water were stable. The 50% lethal concentration (LC50) was used to represent the acute toxicity to zebrafish (Danio rerio). The present study showed that the highest toxic IL is [C12mim]NO3 and the lowest toxic IL is [C2mim]NO3 on Danio rerio. The LC50s for ILs with different anions had similar values. Accordingly, we believe that ILs with different alkyl-chain lengths cause greater effects than other anions on acute toxicity to aquatic organisms. Furthermore, the present study can also provide scientific methods for future studies to select and assess ILs.

  17. 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.

  18. The effects of acute nicotine on contextual safety discrimination.

    PubMed

    Kutlu, Munir G; Oliver, Chicora; Gould, Thomas J

    2014-11-01

    Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories. Given the high rate of cigarette smoking in patients with PTSD, as well as the recent finding that an acute dose of nicotine impairs extinction of contextual fear memory, we conducted a series of experiments to investigate the effect of acute nicotine in an animal model of contextual safety discrimination. Following saline or nicotine (at 0.0275, 0.045, 0.09 and 0.18 mg/kg) administration, C57BL/6J mice were trained in a contextual discrimination paradigm, in which the subjects received presentations of conditioned stimuli (CS) that co-terminated with a foot-shock in one context (context A (CXA)) and only CS presentations without foot-shock in a different context (context B (CXB)). Therefore, CXA was designated as the 'dangerous context', whereas CXB was designated as the 'safe context'. Our results suggested that saline-treated animals showed a strong discrimination between dangerous and safe contexts, while acute nicotine dose-dependently impaired contextual safety discrimination (Experiment 1). Furthermore, our results demonstrate that nicotine-induced impairment of contextual safety discrimination learning was not a result of increased generalized freezing (Experiment 2) or contingent on the common CS presentations in both contexts (Experiment 3). Finally, our results show that increasing the temporal gap between CXA and CXB during training abolished the impairing effects of nicotine (Experiment 4). The findings of this study may help link nicotine exposure to the safety learning deficits seen in anxiety disorder and PTSD patients.

  19. 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

  20. 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.

  1. [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.

  2. 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.

  3. Protective effects of endothelin-1 on acute pancreatitis in rats.

    PubMed

    Kogire, M; Inoue, K; Higashide, S; Takaori, K; Echigo, Y; Gu, Y J; Sumi, S; Uchida, K; Imamura, M

    1995-06-01

    Endothelin-1, a 21-residue peptide isolated from vascular endothelial cells, has a broad spectrum of actions. To clarify the involvement of endothelin-1 in acute pancreatitis, we examined the effects of endothelin-1 and its receptor antagonist BQ-123 on cerulein-induced pancreatitis in rats. Rats were infused intravenously with heparin-saline (control), endothelin-1 (100 pmol/kg/hr), cerulein (5 micrograms/kg/hr), or cerulein plus endothelin-1 for 3.5 hr. In another experiment, cerulein or cerulein plus BQ-123 (3 mg/kg/hr) was infused. Infusion of cerulein caused hyperamylasemia and pancreatic edema. Endothelin-1, when infused with cerulein, decreased the extent of pancreatic edema with a significant increase in the pancreatic dry- to wet-weight ratio. Histological changes induced by cerulein were markedly attenuated when endothelin-1 was given with cerulein. In contrast, endothelin-receptor blockade with BQ-123 further augmented pancreatic edema caused by cerulein. The extent of inflammatory cell infiltration was greater than BQ-123 was given with cerulein. Endothelin-1 or BQ-123 had no influence on hyperamylasemia. This study suggests that endothelin-1 has protective effects on experimental acute pancreatitis.

  4. Acute effects of a glucose energy drink on behavioral control.

    PubMed

    Howard, Meagan A; Marczinski, Cecile A

    2010-12-01

    There has been a dramatic rise in the consumption of glucose energy drinks (e.g., Amp, Monster, and Red Bull) in the past decade, particularly among high school and college students. However, little laboratory research has examined the acute objective and subjective effects of energy drinks. The purpose of this study was to investigate the acute effects of a glucose energy drink (Red Bull) on cognitive functioning. Participants (N = 80) were randomly assigned to one of five conditions: 1.8 ml/kg energy drink, 3.6 ml/kg energy drink, 5.4 ml/kg energy drink, placebo beverage, or no drink. Participants completed a well-validated behavioral control task (the cued go/no-go task) and subjective measures of stimulation, sedation, and mental fatigue both before and 30 minutes following beverage administration. The results indicated that compared with the placebo and no drink conditions, the energy drink doses decreased reaction times on the behavioral control task, increased subjective ratings of stimulation and decreased ratings of mental fatigue. Greatest improvements in reaction times and subjective measures were observed with the lowest dose and improvements diminished as the dose increased. The findings suggest that energy drink consumption can improve cognitive performance on a behavioral control task, potentially explaining the dramatic rise in popularity of these controversial new beverages.

  5. 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.

  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. Comparative study of the lethal effects of near-UV light (360 nm) and 8-methoxypsoralen plus near-UV on plasmid DNA

    SciTech Connect

    Paramio, J.M.; Bauluz, C.; de Vidania, R. )

    1991-01-01

    The authors have studied the lethality produced on pBR322 by near-UV radiation and by 8-Methoxypsoralen plus near-UV (PUV treatment). Samples of pBR322 DNA were irradiated with increasing fluences of 360 nm-light either in the absence or presence of 400 molecules of 8-Methoxypsoralen (8-MOP) per plasmid molecule. They have estimated to what extent the global lethality of PUVA treatment is due to the presence of psoralen adducts in DNA or to radiation itself. In order to analyse the involvement of DNA repair mechanisms in the removal of plasmid lesions, several strains of E. coli (differing in their repair capacities) they are used as recipients of the treated plasmids. Results showed that excision and recombination participate in the repair of near-UV-induced plasmid lesions. Repair of PUV-induced lesions showed an even greater requirement of the excision pathway. Besides, a slight increase on plasmid mutation frequencies was observed after near-UV or PUV treatment in wild type and uvrA cells. Estimation of the contribution of 8-MOP to the global lethality of PUV treatment showed that only the excision pathway was involved in removing psoralen adducts from plasmid DNA, suggesting the involvement of the recombinational pathway in the repair of near-UV-derived lesions.

  8. The effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    SciTech Connect

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-02-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. /sup 51/Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras. These results raise the possibility that the fulminant GVHD seen in human marrow transplantation is in part due to the major contamination of bone marrow with peripheral blood that results from the techniques currently used for human bone marrow harvest.

  9. Side effects of using nitrates to treat heart failure and the acute coronary syndromes, unstable angina and acute myocardial infarction.

    PubMed

    Thadani, Udho; Ripley, Toni L

    2007-07-01

    Nitrates are potent venous dilators and anti-ischemic agents. They are widely used for the relief of chest pain and pulmonary congestion in patients with acute coronary syndromes and heart failure. Nitrates, however, do not reduce mortality in patients with acute coronary syndromes. Combination of nitrates and hydralazine when given in addition to beta-blockers and angiotensin-converting enzyme (ACE) inhibitors reduce mortality and heart failure hospitalizations in patients with heart failure due to left ventricular systolic dysfunction who are of African-American origin. Side effects during nitrate therapy are common but are less well described in the literature compared with the reported side effects in patients with stable angina pectoris. The reported incidence of side effects varies highly among different studies and among various disease states. Headache is the most commonly reported side effect with an incidence of 12% in acute heart failure, 41-73% in chronic heart failure, 3-19% in unstable angina and 2-26% in acute myocardial infarction. The reported incidence of hypotension also differs: 5-10% in acute heart failure, 20% in chronic heart failure, 9% in unstable angina and < 1-48% in acute myocardial infarction, with the incidence being much higher with concomitant nitrate therapy plus angiotensin-converting enzyme inhibitors. Reported incidence of dizziness is as low as 1% in patients with acute myocardial infarction to as high as 29% in patients with heart failure. Severe headaches and/or symptomatic hypotension may necessitate discontinuation of nitrate therapy. Severe life threatening hypotension or even death may occur when nitrates are used in patients with acute inferior myocardial infarction associated with right ventricular dysfunction or infarction, or with concomitant use of phosphodiesterase-5 inhibitors or N-acetylcysteine. Despite the disturbing observational reports in the literature that continuous and prolonged use of nitrates may lead to

  10. Synthetic lethal interactions for the development of cancer therapeutics: biological and methodological advancements.

    PubMed

    Mizuarai, Shinji; Kotani, Hidehito

    2010-12-01

    Synthetic lethal interaction is defined as a combination of two mutations that is lethal when present in the same cell; each individual mutation is non-lethal. Synthetic lethal interactions attract attention in cancer research fields since the discovery of synthetic lethal genes with either oncogenes or tumor suppressor genes (TSGs) provides novel cancer therapeutic targets. Due to the selective lethal effect on cancer cells harboring specific genetic alterations, it is expected that targeting synthetic lethal genes would provide wider therapeutic windows compared with cytotoxic chemotherapeutics. Here, we review the current status of the application of synthetic lethal screening in cancer research fields from biological and methodological viewpoints. Very recent studies seeking to identify synthetic lethal genes with K-RAS and p53, which are known to be the most frequently occurring oncogenes and TSGs, respectively, are introduced. Among the accumulating amount of research on synthetic lethal interactions, the synthetic lethality between BRCA1/2 and PARP1 inhibition has been clinically proven. Thus, both preclinical and clinical data showing a preferential anti-tumor effect on BRCA1/2 deficient tumors by a PARP1 inhibitor are the best examples of the synthetic lethal approach of cancer therapeutics. Finally, methodological progress regarding synthetic lethal screening, including barcode shRNA screening and in vivo synthetic lethal screening, is described. Given the fact that an increasing number of synthetic lethal genes for major cancerous genes have been validated in preclinical studies, this intriguing approach awaits clinical verification of preferential benefits for cancer patients with specific genetic alterations as a clear predictive factor for tumor response.

  11. Acute and neuropathic orofacial antinociceptive effect of eucalyptol.

    PubMed

    Melo Júnior, José de Maria de Albuquerque de; Damasceno, Marina de Barros Mamede Vidal; Santos, Sacha Aubrey Alves Rodrigues; Barbosa, Talita Matias; Araújo, João Ronielly Campêlo; Vieira-Neto, Antonio Eufrásio; Wong, Deysi Viviana Tenazoa; Lima-Júnior, Roberto César Pereira; Campos, Adriana Rolim

    2017-04-01

    Terpenes have a wide range of pharmacological properties, including antinociceptive action. The anti-inflammatory and antinociceptive effects of eucalyptol are well established. The purpose of this study was to evaluate the antinociceptive effect of eucalyptol on acute and neuropathic orofacial pain in rodent models. Acute orofacial and corneal nociception was induced with formalin, capsaicin, glutamate and hypertonic saline in mice. In another series, animals were pretreated with capsazepine or ruthenium red to evaluate the involvement of TRPV1 receptors in the effect of eucalyptol. In a separate experiment, perinasal tissue levels of IL-1β, TNF-α and IFN-γ were measured. Rats were pretreated with eucalyptol before induction of temporomandibular joint pain with formalin or mustard oil. In another experiment, rats were submitted to infraorbital nerve transection (IONX) to induce chronic pain, followed by induction of mechanical hypersensitivity using Von Frey hairs. Locomotor performance was evaluated with the open-field test, and molecular docking was conducted on the TRPV1 channel. Pretreatment with eucalyptol significantly reduced formalin-induced nociceptive behaviors in all mouse strains, but response was more homogenous in the Swiss strain. Eucalyptol produced antinociceptive effects in all tests. The effect was sensitive to capsazepine but not to ruthenium red. Moreover, eucalyptol significantly reduced IFN-γ levels. Matching the results of the experiment in vivo, the docking study indicated an interaction between eucalyptol and TRPV1. No locomotor activity changes were observed. Our study shows that eucalyptol may be a clinically relevant aid in the treatment of orofacial pain, possibly by acting as a TRPV1 channel antagonist.

  12. Acute off-target effects of neural circuit manipulations.

    PubMed

    Otchy, Timothy M; Wolff, Steffen B E; Rhee, Juliana Y; Pehlevan, Cengiz; Kawai, Risa; Kempf, Alexandre; Gobes, Sharon M H; Ölveczky, Bence P

    2015-12-17

    Rapid and reversible manipulations of neural activity in behaving animals are transforming our understanding of brain function. An important assumption underlying much of this work is that evoked behavioural changes reflect the function of the manipulated circuits. We show that this assumption is problematic because it disregards indirect effects on the independent functions of downstream circuits. Transient inactivations of motor cortex in rats and nucleus interface (Nif) in songbirds severely degraded task-specific movement patterns and courtship songs, respectively, which are learned skills that recover spontaneously after permanent lesions of the same areas. We resolve this discrepancy in songbirds, showing that Nif silencing acutely affects the function of HVC, a downstream song control nucleus. Paralleling song recovery, the off-target effects resolved within days of Nif lesions, a recovery consistent with homeostatic regulation of neural activity in HVC. These results have implications for interpreting transient circuit manipulations and for understanding recovery after brain lesions.

  13. Comparison of the effects of erdosteine and N-acetylcysteine on apoptosis regulation in endotoxin-induced acute lung injury.

    PubMed

    Demiralay, Rezan; Gürsan, Nesrin; Ozbilim, Gülay; Erdogan, Gülgün; Demirci, Elif

    2006-01-01

    This study was carried out to investigate comparatively the frequency of apoptosis in lung epithelial cells after intratracheal instillation of endotoxin [lipopolysaccharide (LPS)] in rats and the role of tumor necrosis factor alpha (TNF-alpha) on apoptosis, and the effects of erdosteine and N-acetylcysteine on the regulation of apoptosis. Female Wistar rats were given oral erdosteine (10-500 mg kg(-1)) or N-acetylcysteine (10-500 mg kg(-1)) once a day for 3 consecutive days. Then the rats were intratracheally instilled with LPS (5 mg kg(-1)) to induce acute lung injury. The rats were killed at 24 h after LPS administration. Lung tissue samples were stained with hematoxylin-eosin for histopathological assessments. The apoptosis level in the lung bronchial and bronchiolar epithelium was determined using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Cytoplasmic TNF-alpha was evaluated by immunohistochemistry. Pretreatment with erdosteine and pretreatment with N-acetylcysteine at a dose of 10 mg kg(-1) had no protective effect on LPS-induced lung injury. When the doses of drugs increased, the severity of the lung damage caused by LPS decreased. It was found that as the pretreatment dose of erdosteine was increased, the rate of apoptosis induced by LPS in lung epithelial cells decreased and this decrease was statistically significant in doses of 300 mg kg(-1) and 500 mg kg(-1). Pretreatment with N-acetylcysteine up to a dose of 500 mg kg(-1) did not show any significant effect on apoptosis regulation. It was noticed that both antioxidants had no significant effect on the local production level of TNF-alpha. These findings suggest that erdosteine could be a possible therapeutic agent for acute lethal lung injury and its mortality.

  14. Age-related differences in pulmonary effects of acute and ...

    EPA Pesticide Factsheets

    Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects.Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers ofpulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that ado

  15. Inhibitory effect of anethole in nonimmune acute inflammation.

    PubMed

    Domiciano, Talita Perdigão; Dalalio, Márcia Machado de Oliveira; Silva, Expedito Leite; Ritter, Alessandra Mileni Versuti; Estevão-Silva, Camila Fernanda; Ramos, Fernando Seara; Caparroz-Assef, Silvana Martins; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

    2013-04-01

    Anethole [1-methoxy-4-(1-propenyl)benzene] occurs naturally as a major component of the essential oil of star anise (Illicium verum Hook.f., family Illiciaceae), comprising more than 90 % of its volatile components. Studies showed that this substance has antioxidant, antibacterial, antifungal, and anesthetic properties. In this study, the anti-inflammatory properties of anethole in animal models of nonimmune acute inflammation such as croton oil-induced ear edema and carrageenan-induced pleurisy were investigated. The investigated parameters were edema formation, leukocyte migration, and inflammatory mediators involved. Oral administration of anethole at a dose of 250 and 500 mg/kg reduced both the volume of pleural exudates and the number of migrated leukocytes. Levels of nitric oxide (NO) and prostaglandins (PGE2) in the inflammatory exudate were reduced by treatment with anethole, but levels of tumor necrosis factor-α and interleukin-1β were not significantly altered. In ear edema, the oral treatment with anethole inhibited the formation of exudate and the activity of myeloperoxidase, but not after topical administration. These results suggest that the anethole may be effective in controlling some nonimmune acute inflammation-related disease, probably by an inhibitory action on production and/or release of PGE2 and NO.

  16. Effect of dexamethasone on brain oedema following acute ischemic stroke.

    PubMed

    Shaikh, A K; Mohammad, Q D; Ullah, M A; Ahsan, M M; Rahman, A; Shakoor, M A

    2011-07-01

    A randomized clinical trial was conducted to asses the effects of dexamethasone on brain oedema following acute ischemic stroke in the departments of Medicine of different hospitals from July, 2003 to December, 2006. A total of 60 patients were included in the study. They were divided into two groups keeping the similarity regarding the age, sex and severity of the stroke between two groups. There were 30 patients in experimental group and 30 in control group. The level of consciousness was compared by Glasgow Coma Scale (GCS) on 3rd, 7th and 10th day of intervention and improvement was found in both the groups, but the improvement of level of consciousness was statistically significant in Dexamethasone treated group. The volume of hypodense area did not differ significantly in two groups in CT scans before and after treatment (p=0.74). The study results demonstrate that Dexamethasone improves the level of consciousness in acute ischemic stroke associated with brain oedema but did not reduce volume of hypodense area.

  17. Effects of clotrimazol on the acute necrotizing pancreatitis in rats.

    PubMed

    Cekic, Arif Burak; Alhan, Etem; Usta, Arif; Türkyılmaz, Serdar; Kural, Birgül Vanizor; Erçin, Cengiz

    2013-12-01

    This study aims to investigate the influence of clotrimazol (CLTZ) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. Rats were divided into five groups as sham + saline, sham + CLTZ, sham + polyethylene glycol, ANP + saline, and ANP + CLTZ. ANP in rats was induced by glycodeoxycholic acid. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density (FCD), renal/hepatic functions, and changes in some enzyme markers for pancreatic and lung tissue were investigated during ANP in rats. The use of CLTZ after the induction of ANP resulted in a significant decrease in the mortality rate, pancreatic necrosis, and serum activity of amylase, alanine aminotransferase, interleukin-6, lactate dehydrogenase in bronchoalveolar lavage fluid, serum concentration of urea, and tissue activity of myeloperoxidase, and malondialdehyde in the pancreas and lung and a significant increase in concentrations of calcium, blood pressure, urine output, pO2, and FCD. This study showed that CLTZ demonstrated beneficial effect on the course of ANP in rats. Therefore, it may be used in the treatment of acute pancreatitis.

  18. Diurnal Spectral Sensitivity of the Acute Alerting Effects of Light

    PubMed Central

    Rahman, Shadab A.; Flynn-Evans, Erin E.; Aeschbach, Daniel; Brainard, George C.; Czeisler, Charles A.; Lockley, Steven W.

    2014-01-01

    Study Objectives: Previous studies have demonstrated short-wavelength sensitivity for the acute alerting response to nocturnal light exposure. We assessed daytime spectral sensitivity in alertness, performance, and waking electroencephalogram (EEG). Design: Between-subjects (n = 8 per group). Setting: Inpatient intensive physiologic monitoring unit. Participants: Sixteen healthy young adults (mean age ± standard deviation = 23.8 ± 2.7 y). Interventions: Equal photon density exposure (2.8 × 1013 photons/cm2/s) to monochromatic 460 nm (blue) or 555 nm (green) light for 6.5 h centered in the middle of the 16-h episode of wakefulness during the biological day. Results were compared retrospectively to 16 individuals who were administered the same light exposure during the night. Measurements and Results: Daytime and nighttime 460-nm light exposure significantly improved auditory reaction time (P < 0.01 and P < 0.05, respectively) and reduced attentional lapses (P < 0.05), and improved EEG correlates of alertness compared to 555-nm exposure. Whereas subjective sleepiness ratings did not differ between the two spectral conditions during the daytime (P > 0.05), 460-nm light exposure at night significantly reduced subjective sleepiness compared to 555-nm light exposure at night (P < 0.05). Moreover, nighttime 460-nm exposure improved alertness to near-daytime levels. Conclusions: The alerting effects of short-wavelength 460-nm light are mediated by counteracting both the circadian drive for sleepiness and homeostatic sleep pressure at night, but only via reducing the effects of homeostatic sleep pressure during the day. Citation: Rahman SA; Flynn-Evans EE; Aeschbach D; Brainard GC; Czeisler CA; Lockley SW. Diurnal spectral sensitivity of the acute alerting effects of light. SLEEP 2014;37(2):271-281. PMID:24501435

  19. Protective effects of rhubarb on experimental severe acute pancreatitis

    PubMed Central

    Zhao, Yu-Qing; Liu, Xiao-Hong; Ito, Tetsuhide; Qian, Jia-Ming

    2004-01-01

    AIM: To investigate the effects of rhubarb on severe acute pancreatitis (SAP) in rats. METHODS: Severe acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 μg/kg body weight) plus 5-h restraint water-immersion stress. Rhubarb (75-150 mg/kg) was orally fed before the first cerulein injection. The degree of pancreatic edema, serum amylase level, local pancreatic blood flow (PBF), and histological alterations were investigated. The effects of rhubarb on pancreatic exocrine secretion in this model were evaluated by comparing with those of somatostatin. RESULTS: In the Cerulein + Stress group, severe edema and diffuse hemorrhage in the pancreas were observed, the pancreatic wet weight (11.60 ± 0.61 g/Kg) and serum amylase (458 490 ± 43 100 U/L) were markedly increased (P < 0.01 vs control). In the rhubarb (150 mg/kg) treated rats, necrosis and polymorphonuclear neutrophil (PMN) infiltration in the pancreas were significantly reduced (P < 0.01), and a marked decrease (50%) in serum amylase levels was also observed (P < 0.01). PBF dropped to 38% (93 ± 5 mL/min per 100 g) of the control in the Cerulein + Stress group and partly recovered in the Cerulein + Stress + Rhubarb 150 mg group (135 ± 12 mL/min per 100 g) (P < 0.01). The pancreatic exocrine function was impaired in the SAP rats. The amylase levels of pancreatic juice were reduced in the rats treated with rhubarb or somatostatin, comparing with that of untreated SAP group. The bicarbonate concentration of pancreatic juice was markedly elevated only in the rhubarb-treated group (P < 0.01). CONCLUSION: Rhubarb can exert protective effects on SAP, probably by inhibiting the inflammation of pancreas, improving pancreatic microcirculation, and altering exocrine secretion. PMID:15052683

  20. An Investigation of the Interaction Effects of Acute Self-Esteem and Perceived Competence on Conformity.

    DTIC Science & Technology

    1978-12-22

    On the basis of previous research on conformity it was predicted that subjects who were subjected to acute self - esteem manipulations and perceived...a demonstration of the interaction effects of acute self - esteem and perceived competence. Acute self - esteem manipulations (high, low or no) were...role in conformity. The main effect of self - esteem and the interaction of self - esteem and perceived competence did not prove significant. Results were

  1. Effect of acute smoke exposure on hepatic protein synthesis.

    PubMed

    Garrett, R J; Jackson, M A

    1979-05-01

    In vivo hepatic protein synthesis was monitored in female rats under control and smoke-exposed conditions. During the 15 min period after i.v. administration of [3H]proline protein synthesis was 206 +/- 35 nmol of proline per mg of DNA for sham-control animals. When animals were subjected to acute exposure to cigarette smoke, protein synthesis was inhibited and the extent of inhibition was positively correlated with the dosage of smoke (32%, 15 puffs; 66%, 60 puffs). The inhibitory effect of whole smoke on protein synthesis was unaltered by passing the smoke through either charcoal or cambridge filters. Carbon monoxide in smoke is not removed by either type of filter. At a level comparable to that in cigarette smoke carbon monoxide depressed hepatic protein synthesis to the same extent as did whole or filtered smoke.

  2. Investigation of acute stroke: what is the most effective strategy?

    PubMed Central

    Dunbabin, D. W.; Sandercock, P. A.

    1991-01-01

    Techniques of investigation of acute stroke syndromes have progressed rapidly in recent years, outpacing developments in effective stroke treatment. The clinician is thus faced with a variety of tests, each with different cost implications and each altering management to a greater or lesser extent. This review will concentrate on the basic tests which should be performed for all strokes (full blood count, ESR, biochemical screen, blood glucose, cholesterol, syphilis serology, chest X-ray and electrocardiogram). Additional tests may be required in selected cases: CT scan to diagnose 'non-stroke' lesions, to exclude cerebral haemorrhage if anti-haemostatic therapy is planned, and to detect strokes which may require emergency intervention (such as cerebellar stroke with hydrocephalus); echocardiography to detect cardiac sources of emboli; and in a few cases lumbar puncture and specialized haematological tests. Other tests, which are currently research tools, may be suitable for widespread use in the future including NMR, SPECT and PET scanning. PMID:2062773

  3. Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance

    PubMed Central

    Baker, Lindsay B.; Rollo, Ian; Stein, Kimberly W.; Jeukendrup, Asker E.

    2015-01-01

    Intermittent sports (e.g., team sports) are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1–2 h). Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1) potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2) the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3) what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports). Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30–60 g/h in the form of a 6%–7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before and during a

  4. Acute effects of coffee on QT interval in healthy subjects

    PubMed Central

    2011-01-01

    The coronary endothelial function is recognized to have an important role in the physiology of the diastolic ventricular relaxation, a phase of the heart cycle that influences the electrocardiographic QT interval. Endothelial function is investigated in vivo by flow mediated dilation (FMD) in the brachial artery and has proven to be a strong predictor of both coronary endothelial function and cardiovascular events. It has been reported that coffee acutely induces FMD changes. In particular, the brachial artery FMD seems to decrease after caffeinated coffee (CC) and to increase after decaffeinated coffee (DC) ingestion. Since the cardiovascular effects of coffee are still a debated matter, this study aimed at investigating with a randomized, double-blind crossover design, if the QT interval of adult healthy subjects (19 males and 21 females) changes in the hour following CC or DC ingestion. Both systolic and diastolic blood pressure were higher in the hour following the ingestion of CC; the heart rate significantly increased 30 minutes after CC ingestion. A significant increase of the QT duration was observed one hour after DC ingestion (398.9 ± 3.8 vs 405.3 ± 3.7 msec; P < 0.05), not after CC. The QT interval corrected for heart rate did not significantly change following CC or DC ingestion. In conclusion, despite CC and DC previously demonstrated to influence the FMD they do not seem to induce a significant unfavourable acute change of the left ventricular repolarization. Further investigations are required to elucidate the effects of coffee in subjects with cardiovascular diseases. PMID:21288364

  5. Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance.

    PubMed

    Baker, Lindsay B; Rollo, Ian; Stein, Kimberly W; Jeukendrup, Asker E

    2015-07-14

    Intermittent sports (e.g., team sports) are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1-2 h). Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1) potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2) the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3) what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports). Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30-60 g/h in the form of a 6%-7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before and during a game

  6. 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.

  7. 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

  8. Acute toxicities and sublethal effects of some conventional insecticides on Trichogramma chilonis (Hymenoptera: Trichogrammatidae).

    PubMed

    Wang, De-Sen; He, Yu-Rong; Guo, Xiang-Ling; Luo, Yong-Li

    2012-08-01

    The acute toxicity of 10 conventional insecticides to adult of Trichogramma chilonis Ishii (Hymenoptera: Trichogrammatidae) was bioassayed by membrane method, and then their sublethal effects on the parasitoid were evaluated in the laboratory. Based on sublethal concentration (LC30) values at 8 h after treatment, we determined that adult T. chilonis were the most susceptible to chlorfenapyr, followed by fipronil, spinosad, avermectins, beta-cypermethrin, and cartap, with lethal concentration (LC)30 values of 0.3133, 0.3269, 1.5408, 3.2961, 6.1469, and 9.021 mg/liter, respectively. The field-recommended concentrations of chlorfluazuron, indoxacarb, Bacillus thuringiensis, and tebufenozide caused <30% mortality of treated adults; therefore, they were used to evaluate sublethal effects on the parasitoid. After treatment with sublethal concentration of fipronil and avermectins, the longevity of treated females (1.2 and 1.6 d) was significantly shortened and fecundity (34.7 and 1.6) was remarkably decreased; consequently, the life-table parameters (R0, r(m), lambda, and T) of T. chilonis were statistically lower than those in the control. Cartap and spinosad also reduced longevity (8 and 7.9 d) and fecundity (110.77 and 117.2) of treated adults, but cartap enhanced the female percentage of F1 offspring (61.6%), resulting a statistical higher R0, r(m), and lambda of treated T. chilonis. In contrast, chlorfluazuron and tebufenozide increased longevity (16.4 and 15.4 d) and fecundity (248 and 256.9) of treated adults but slightly decreased the female percentage of F1 offspring (31.4 and 38.1%). Although chlorfenapyr showed no adverse influence on longevity and fecundity, it remarkably reduced the female percentage of F1 offspring (13.5%), leading to a lower R0, r(m), and lambda of treated T. chilonis. Indoxacarb, B. thuringiensis, and beta-cypermethrin had no obvious sublethal effects on the longevity and fecundity of treated adults. Based on these results, we consider B

  9. WHY DO THE ACUTE BEHAVIORAL EFFECTS OT TOLUENE IN RATS DEPEND ON THE ROUTE OF EXPOSURE?

    EPA Science Inventory

    Despite evidence suggesting that the acute effects of organic solvents are related to their concentration in the brain, we have observed route-dependent differences in the acute behavioral effects of toluene. Whereas inhaled toluene disrupts the performance of rats on a visual si...

  10. Acute and Chronic Effects of Cocaine on the Spontaneous Behavior of Pigeons

    ERIC Educational Resources Information Center

    Pinkston, Jonathan W.; Branch, Marc N.

    2010-01-01

    The present experiment examined the effects of acute and daily cocaine on spontaneous behavior patterns of pigeons. After determining the acute effects of a range of doses, 9 pigeons were divided into three groups that received one of three doses of cocaine daily, either 1.0, 3.0, or 10.0 mg/kg cocaine. Measures were taken of spontaneous…

  11. Effects of acute restraint stress on set-shifting and reversal learning in male rats.

    PubMed

    Thai, Chester A; Zhang, Ying; Howland, John G

    2013-03-01

    Exposure to acute stress alters cognition; however, few studies have examined the effects of acute stress on executive functions such as behavioral flexibility. The goal of the present experiments was to determine the effects of acute periods of stress on two distinct forms of behavioral flexibility: set-shifting and reversal learning. Male Sprague-Dawley rats were trained and tested in an operant-chamber-based task. Some of the rats were exposed to acute restraint stress (30 min) immediately before either the set-shifting test day or the reversal learning test day. Acute stress had no effect on set-shifting, but it significantly facilitated reversal learning, as assessed by both trials to criterion and total errors. In a second experiment, the roles of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the acute-stress-induced facilitation of reversal learning were examined. Systemic administration of the GR-selective antagonist RU38486 (10 mg/kg) or the MR-selective antagonist spironolactone (50 mg/kg) 30 min prior to acute stress failed to block the facilitation on reversal learning. The present results demonstrate a dissociable effect of acute stress on set-shifting and reversal learning and suggest that the facilitation of reversal learning by acute stress may be mediated by factors other than corticosterone.

  12. Antidepressant Effects of Mallotus oppositifolius in Acute Murine Models

    PubMed Central

    Kukuia, Kennedy K. E.; Mante, Priscilla K.; Ameyaw, Elvis O.; Adongo, Donatus W.

    2014-01-01

    Objective. Hydroalcoholic extract of leaves of Mallotus oppositifolius (MOE), a plant used for CNS conditions in Ghana, was investigated for acute antidepressant effects in the forced swimming (FST) and tail suspension tests (TST). Results. In both FST and TST, MOE (10, 30, and 100 mg kg−1) significantly decreased immobility periods and frequencies. A 3-day pretreatment with 200 mg kg−1, i.p., para-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor, reversed the decline in immobility and the increase of swimming score induced by MOE in the modified FST. Pretreatment with reserpine alone (1 mg kg−1), α-methyldopa alone (400 mg kg−1, i.p.), or a combination of both drugs failed to reverse the decline in immobility or the increase in swimming score caused by the extract in the modified FST. The extract potentiated the frequency of head twitch responses induced by 5-hydroxytryptamine. Pretreatment with d-serine (600 mg kg−1, i.p.), glycine/NMDA agonist, abolished the behavioural effects of MOE while d-cycloserine (2.5 mg kg−1, i.p.), a glycine/NMDA partial agonist, potentiated it in both TST and modified FST. Conclusion. The extract exhibited antidepressant effects in mice which is mediated by enhancement of serotoninergic neurotransmission and inhibition of glycine/NMDA receptor activation. PMID:25045543

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

    PubMed

    Magozzi, Sarah; Calosi, Piero

    2015-01-01

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

  14. [Effect of citicoline on the development of chronic epileptization of the brain (pentylenetetrazole kindling) and acute seizures reaction of kindled mice C57Bl/6].

    PubMed

    Kuznetzova, L V; Karpova, M N; Zinkovsky, K A; Klishina, N V

    2014-01-01

    In experiments on mice C57Bl/6 was studied effects of citicoline (500 mg/kg, i.p.) on development of chronically epileptization of the brain--pentylenetetrazole (PTZ) kindling (30 mg/kg PTZ, i.p. during 24 days) and on acute generalized seizures (i.v., 1% solution of PTZ with the speed of 0.01 ml/s). It was shown that daily injection of citicoline an hour before the introduction of PTZ had no effect on development of chronically epileptization of the brain --PTZ-kindling (the latency of seizures appearance and their severity). However, citicoIine posses anticonvulsive effects on acute seizures in kindled mice. In animals with increased seizure susceptibility of the brain caused by kindling and severity of seizures 2-3 points injection citicoline after 14 days of kindling had anticonvulsive effect, increasing the threshold clonic seizures. Injection of citicoline during 24 days of kindled animals and severity of seizures 3-5 points caused the increase of thresholds as clonic and tonic phase of seizures with lethal outcome. Thus, the anticonvulsant effect of citicoline more pronounced in the long-term use.

  15. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: effects of epinephrine and oxygen therapies.

    PubMed

    Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G; Xu, Fadi; Russell, Robert G; Sopori, Mohan L

    2014-01-15

    Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes including weakened response to hypoxia. We now show that LD50 sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD50 sarin-exposed animals were administered the bronchodilator epinephrine, >90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD50 sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin.

  16. Chronic and acute effects of endurance training on telomere length.

    PubMed

    Borghini, Andrea; Giardini, Guido; Tonacci, Alessandro; Mastorci, Francesca; Mercuri, Antonella; Mrakic-Sposta, Simona; Sposta, Simona Mrakic; Moretti, Sarah; Andreassi, Maria Grazia; Pratali, Lorenza

    2015-09-01

    Telomere shortening is considered a cellular marker of health status and biological ageing. Exercise may influence the health and lifespan of an individual by affecting telomere length (TL). However, it is unclear whether different endurance exercise levels may have beneficial or detrimental effects on biological aging. The aims of the study were to assess both chronic and acute effects of endurance training on TL after an exceptional and extreme trail race. TL was assessed in 20 endurance athletes (17 males; age = 45.4 ± 9.2 years) and 42 age- and gender-matched sedentary controls (32 males; age = 45.9 ± 9.5 years) with quantitative real-time PCR at baseline conditions. Of the 20 runners enrolled in the 'Tor des Géants ®' ultra-distance trail race, 15 athletes (12 males; age = 47.2 ± 8.5 years) were re-evaluated at the intermediate point and 14 athletes (11 males; age = 47.1 ± 8.8 years) completed the competition and were analysed at the final point. Comparison between the two groups (endurance athletes vs. sedentary controls) revealed a significant difference in TL (1.28 ± 0.4 vs. 1.02 ± 0.3, P = 0.005). TL was better preserved in elder endurance runners compared with the same age control group (1.3 ± 0.27 vs. 0.91 ± 0.21, P = 0.003). TL was significantly reduced at the intermediate (0.88 ± 0.36 vs. 1.11 ± 0.34, P = 0.002) and final point compared with baseline measurements (0.86 ± 0.4 vs. 1.11 ± 0.34, P = 0.0006) for athletes engaged in the ultra-marathon race. Our data suggest that chronic endurance training may provide protective effects on TL attenuating biological aging. Conversely, acute exposure to an ultra-distance endurance trail race implies telomere shortening probably caused by oxidative DNA damage.

  17. Acute effects of stochastic resonance whole body vibration

    PubMed Central

    Elfering, Achim; Zahno, Jasmine; Taeymans, Jan; Blasimann, Angela; Radlinger, Lorenz

    2013-01-01

    AIM: To investigate the acute effects of stochastic resonance whole body vibration (SR-WBV) training to identify possible explanations for preventive effects against musculoskeletal disorders. METHODS: Twenty-three healthy, female students participated in this quasi-experimental pilot study. Acute physiological and psychological effects of SR-WBV training were examined using electromyography of descending trapezius (TD) muscle, heart rate variability (HRV), different skin parameters (temperature, redness and blood flow) and self-report questionnaires. All subjects conducted a sham SR-WBV training at a low intensity (2 Hz with noise level 0) and a verum SR-WBV training at a higher intensity (6 Hz with noise level 4). They were tested before, during and after the training. Conclusions were drawn on the basis of analysis of variance. RESULTS: Twenty-three healthy, female students participated in this study (age = 22.4 ± 2.1 years; body mass index = 21.6 ± 2.2 kg/m2). Muscular activity of the TD and energy expenditure rose during verum SR-WBV compared to baseline and sham SR-WBV (all P < 0.05). Muscular relaxation after verum SR-WBV was higher than at baseline and after sham SR-WBV (all P < 0.05). During verum SR-WBV the levels of HRV were similar to those observed during sham SR-WBV. The same applies for most of the skin characteristics, while microcirculation of the skin of the middle back was higher during verum compared to sham SR-WBV (P < 0.001). Skin redness showed significant changes over the three measurement points only in the middle back area (P = 0.022). There was a significant rise from baseline to verum SR-WBV (0.86 ± 0.25 perfusion units; P = 0.008). The self-reported chronic pain grade indicators of pain, stiffness, well-being, and muscle relaxation showed a mixed pattern across conditions. Muscle and joint stiffness (P = 0.018) and muscular relaxation did significantly change from baseline to different conditions of SR-WBV (P < 0.001). Moreover

  18. Mitigation Effect of an FGF-2 Peptide on Acute Gastrointestinal Syndrome After High-Dose Ionizing Radiation

    SciTech Connect

    Zhang Lurong; Sun Weimin; Wang Jianjun; Zhang Mei; Yang Shanmin; Tian Yeping; Vidyasagar, Sadasivan; Pena, Louis A.; Zhang Kunzhong; Cao Yongbing; Yin Liangjie; Wang Wei; Zhang Lei; Schaefer, Katherine L.; Saubermann, Lawrence J.; Swarts, Steven G.; Fenton, Bruce M.; Keng, Peter C.; Okunieff, Paul

    2010-05-01

    Purpose: Acute gastrointestinal syndrome (AGS) resulting from ionizing radiation causes death within 7 days. Currently, no satisfactory agent exists for mitigation of AGS. A peptide derived from the receptor binding domain of fibroblast growth factor 2 (FGF-P) was synthesized and its mitigation effect on AGS was examined. Methods and Materials: A subtotal body irradiation (sub-TBI) model was created to induce gastrointestinal (GI) death while avoiding bone marrow death. After 10.5 to 16 Gy sub-TBI, mice received an intramuscular injection of FGF-P (10 mg/kg/day) or saline (0.2 ml/day) for 5 days; survival (frequency and duration) was measured. Crypt cells and their proliferation were assessed by hematoxylin, eosin, and BrdU staining. In addition, GI hemoccult score, stool formation, and plasma levels of endotoxin, insulin, amylase, interleukin (IL)-6, keratinocyte-derived chemokine (KC) monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF)-alpha were evaluated. Results: Treatment with FGF-P rescued a significant fraction of four strains of mice (33-50%) exposed to a lethal dose of sub-TBI. Use of FGF-P improved crypt survival and repopulation and partially preserved or restored GI function. Furthermore, whereas sub-TBI increased plasma endotoxin levels and several pro-inflammation cytokines (IL-6, KC, MCP-1, and TNF-alpha), FGF-P reduced these adverse responses. Conclusions: The study data support pursuing FGF-P as a mitigator for AGS.

  19. Sensory and Cognitive Effects of Acute Exposure to Hydrogen Sulfide

    PubMed Central

    Fiedler, Nancy; Kipen, Howard; Ohman-Strickland, Pamela; Zhang, Junfeng; Weisel, Clifford; Laumbach, Robert; Kelly-McNeil, Kathie; Olejeme, Kelechi; Lioy, Paul

    2008-01-01

    Background Some epidemiologic studies have reported compromised cognitive and sensory performance among individuals exposed to low concentrations of hydrogen sulfide (H2S). Objectives We hypothesized a dose–response increase in symptom severity and reduction in sensory and cognitive performance in response to controlled H2S exposures. Methods In separate exposure sessions administered in random order over three consecutive weeks, 74 healthy subjects [35 females, 39 males; mean age (± SD) = 24.7 ± 4.2; mean years of education = 16.5 ± 2.4], were exposed to 0.05, 0.5, and 5 ppm H2S. During each exposure session, subjects completed ratings and tests before H2S exposure (baseline) and during the final hour of the 2-hr exposure period. Results Dose–response reduction in air quality and increases in ratings of odor intensity, irritation, and unpleasantness were observed. Total symptom severity was not significantly elevated across any exposure condition, but anxiety symptoms were significantly greater in the 5-ppm than in the 0.05-ppm condition. No dose–response effect was observed for sensory or cognitive measures. Verbal learning was compromised during each exposure condition. Conclusions Although some symptoms increased with exposure, the magnitude of these changes was relatively minor. Increased anxiety was significantly related to ratings of irritation due to odor. Whether the effect on verbal learning represents a threshold effect of H2S or an effect due to fatigue across exposure requires further investigation. These acute effects in a healthy sample cannot be directly generalized to communities where individuals have other health conditions and concomitant exposures. PMID:18197303

  20. The acute effect of local homicides on children's cognitive performance

    PubMed Central

    Sharkey, Patrick

    2010-01-01

    This study estimates the acute effect of exposure to a local homicide on the cognitive performance of children across a community. Data are from a sample of children age 5–17 y in the Project on Human Development in Chicago Neighborhoods. The effect of local homicides on vocabulary and reading assessments is identified by exploiting exogenous variation in the relative timing of homicides and interview assessments among children in the same neighborhood but assessed at different times. Among African-Americans, the strongest results show that exposure to a homicide in the block group that occurs less than a week before the assessment reduces performance on vocabulary and reading assessments by between ∼0.5 and ∼0.66 SD, respectively. Main results are replicated using a second independent dataset from Chicago. Findings suggest the need for broader recognition of the impact that extreme acts of violence have on children across a neighborhood, regardless of whether the violence is witnessed directly. PMID:20547862

  1. Genetic effects of acute spermatogonial X-irradiation of the laboratory rat.

    PubMed

    Chambers, J R; Chapman, A B

    1977-02-01

    The genetic effects of one generation of spermatogonial X-irradiation in rats, by a single dose of 600r in one experiment and by a fractionated dose of 450r in another, were measured in three generations of their descendants. Estimates of dominant lethal mutation rates--(2 to 3) X 10-4/gamete/r--from litter size differences between irradiated and nonirradiated stock were consistent with previous estimates from rats and mice. Similar consistency was found for estimates of sex-linked recessive mutation rates--(1 to 2) X 10-4 chromosome/r--from male proportions within strains; however, when measured in crossbreds the proportion of males was higher in the irradiated than in the nonirradiated lines. This inconsistency in results is in keeping with the contradictory results reported for recessive sex-linked lethal mutation rates in mice. The effects used to estimate recessive lethal mutation rates which were unusually high--(2 to 14) X 10-4/gamete/r--were not significant. Other factors that could have contributed to the observed effects are postulated.

  2. [Effect of lethal doses of plants of the Agavaceae family on the cardiac activity and oviposition of Biophalaria havanensis (Mollusca: Planobidae)].

    PubMed

    Díaz Garcés, R; Ferrer López, J R

    1996-01-01

    Work was carried out with lethal doses of 3 agavaceas, Agave legrelliana, Agave fourcroydes and Agave franzosinii, and it was determined the influences of LD50 and LD90 of agavaceas on the cardiac activity reduction. As a result, it was found that A. fourcryodes has the aqueous extract influencing the most on the reduction of heart rate. LD90 of agavaceas also affects the embrionary development of eggs having between 1 and 7 days of oviposition. The greatest affectation was found among the first. A. fourcroydes and A. legrelliana, respectively, influence the most on the reduction of the amount of eggs. The number of eggs ovipositted by mollucs surviving the application of LD90 from A. franzosinii is lower, as well as the number of hatched eggs.

  3. Toxicity of biodiesel, diesel and biodiesel/diesel blends: comparative sub-lethal effects of water-soluble fractions to microalgae species.

    PubMed

    Pereira, Solange A; Araújo, Vinicius Queiroz; Reboucas, Marcio V; Vieira, Fernanda Seabra V; de Almeida, Marcos Vinicio A; Chinalia, Fabio A; Nascimento, Iracema Andrade

    2012-02-01

    The water-soluble-fractions (WSF) from biodiesel and biodiesel/diesel blends were compared to diesel in their sub-lethal toxicity to microalgae. Chemical analyses of aromatics, non-aromatics hydrocarbons and methanol were carried out in the WSF, the former showing positive correlation with increasing diesel concentrations (B100 < B5 < B3 < B2 < D). Biodiesel interacted with the aqueous matrix, generating methanol, which showed lower toxicity than the diesel contaminants in blends. The WSF caused 50% culture growth inhibition (IC50-96 h) at concentrations varying from 2.3 to 85.6%, depending on the tested fuels and species. However, the same species sensitivity trend (S. costatum > N. oculata > T. chuii > P. subcapitata) was observed for all the tested fuels.

  4. Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?

    PubMed

    Moraga, Felipe; Ahumada, Vanessa; Crovari, Fernando

    2016-01-26

    Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, growing evidence has been published about the use of antibiotics as the exclusive treatment for acute appendicitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including one pertinent randomized trial. We generated a summary of findings following the GRADE approach. We concluded the use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy and probably increases major complications compared with appendectomy.

  5. Acute Effect of Hookah Smoking on the Human Coronary Microcirculation.

    PubMed

    Nelson, Michael D; Rezk-Hanna, Mary; Rader, Florian; Mason, O'Neil R; Tang, Xiu; Shidban, Sarah; Rosenberry, Ryan; Benowitz, Neal L; Tashkin, Donald P; Elashoff, Robert M; Lindner, Jonathan R; Victor, Ronald G

    2016-06-01

    Hookah (water pipe) smoking is a major new understudied epidemic affecting youth. Because burning charcoal is used to heat the tobacco product, hookah smoke delivers not only nicotine but also large amounts of charcoal combustion products, including carbon-rich nanoparticles that constitute putative coronary vasoconstrictor stimuli and carbon monoxide, a known coronary vasodilator. We used myocardial contrast echocardiography perfusion imaging with intravenous lipid shelled microbubbles in young adult hookah smokers to determine the net effect of smoking hookah on myocardial blood flow. In 9 hookah smokers (age 27 ± 5 years, mean ± SD), we measured myocardial blood flow velocity (β), myocardial blood volume (A), myocardial blood flow (A × β) as well as myocardial oxygen consumption (MVO2) before and immediately after 30 minutes of ad lib hookah smoking. Myocardial blood flow did not decrease with hookah smoking but rather increased acutely (88 ± 10 to 120 ± 19 a.u./s, mean ± SE, p = 0.02), matching a mild increase in MVO2 (6.5 ± 0.3 to 7.6 ± 0.4 ml·minute(-1), p <0.001). This was manifested primarily by increased myocardial blood flow velocity (0.7 ± 0.1 to 0.9 ± 0.1 second(-1), p = 0.01) with unchanged myocardial blood volume (133 ± 7 to 137 ± 7 a.u., p = ns), the same pattern of coronary microvascular response seen with a low-dose β-adrenergic agonist. Indeed, with hookah, the increased MVO2 was accompanied by decreased heart rate variability, an indirect index of adrenergic overactivity, and eliminated by β-adrenergic blockade (i.v. propranolol). In conclusion, nanoparticle-enriched hookah smoke either is not an acute coronary vasoconstrictor stimulus or its vasoconstrictor effect is too weak to overcome the physiologic dilation of coronary microvessels matching mild cardiac β-adrenergic stimulation.

  6. Effects of sub-lethal heroin administration on thyroid stimulating hormone (TSH), thyroid hormones (T3, T4) and thyroid gland of Mus norvegicus.

    PubMed

    Bhoir, Kaminidevi K; Suryawanshi, S A; Pandey, A K

    2009-11-01

    Serum TSH level of control Mus norvegicus fluctuated between 498.20 +/- 21.92 and 506.80 +/- 22.35 ng ml(-1), thyroxine (T4) between 68.17 +/- 3.46 and 69.03 +/- 4.12 microg dl(-1) and triiodothyronine (T3) between 4.76 +/- 0.52 and 5.00 +/- 0.66 microg dl(-1). Sub-lethal heroin administration induced a significant decline in the levels of all the three hormones at 24 hr and 15 days post-administration. Decline in the levels of these hormones registered the lowest values (p<0.001) by day 30 of the treatment. Thyroid gland of control rat consisted of spherical, round follicles lined with low cuboidal and columnar epithelial cells and lumina filled with eosinophilic colloid. Ultrastructurally, the thyroid follicular cells showed the presence of round nuclei, polymorphic mitochondria, Golgi complex as well as lysosomes located on the apical side of the nucleus and cytoplasm with different sizes of lipid droplets and smooth along with rough endoplasmic reticulum. Basal lamina of the follicular cells was often in association with the endothelium of the capillaries. Sub-lethal heroin administration for 30 days elicited degenerative changes in the follicular epithelial cells as evident by the vacuolization of cytoplasm, pycnotic nuclei and reduced colloidal content. Ultrastructurally, the thyroid follicular cells showed indented nuclei with heavy deposition of chromatin material on the inner membrane of nucleus and dilated rough endoplasmic reticulum. Along with RBC infiltration, vesiculated mitochondria owing to the loss of cristae were also seen. Diffused electron-dense material was seen at the periphery of the cell body. Heroin treatment caused cellular necrosis as revealed by the fragmentation of cytoplasmic materials in follicular epithelial cells of the gland.

  7. Interaction of exposure concentration and duration in determining acute toxic effects of sarin vapor in rats.

    PubMed

    Mioduszewski, R; Manthei, J; Way, R; Burnett, D; Gaviola, B; Muse, W; Thomson, S; Sommerville, D; Crosier, R

    2002-04-01

    Sarin (GB) vapor exposure is associated with both systemic and local toxic effects occurring primarily via the inhalation and ocular routes. The objective of these studies was to develop models for predicting dose-response effects of GB vapor concentrations as a function of exposure duration. Thus, the probability of GB vapor-induced lethality was estimated in rats exposed to various combinations of exposure concentration and duration. Groups of male and female Sprague-Dawley rats were exposed to one of a series of GB vapor concentrations for a single duration (5-360 min) in a whole-body dynamic chamber. The onset of clinical signs and changes in blood cholinesterase activity were measured with each exposure. Separate effective concentrations for lethality in 50% of the exposed population (LC50) and corresponding dose-response slopes were determined for each exposure duration by the Bliss probit method. Contrary to that predicted by Haber's rule, the interaction of LC50 x time (LCT50) values increased with exposure duration (i.e., the CT for 50% lethality in the exposed population and corresponding dose-response slope was not constant over time). A plot of log (LCT50) versus log (exposure time) showed significant curvature. Predictive models derived from multifactor probit analysis of results describing the relationship between exposure conditions and probability of lethality in the rat are discussed. Overall, female rats were more sensitive to GB vapor toxicity than male rats over the range of exposure concentration and duration studied. Miosis was the initial clinical sign noted after the start of GB vapor exposure. Although blood cholinesterase activity was significantly inhibited by GB vapor exposure, poor correlation between cholinesterase inhibition and exposure conditions or cholinesterase inhibition and severity of clinical signs was noted.

  8. 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

  9. Acute effects of tianeptine on circulating neurotransmitters and cardiovascular parameters.

    PubMed

    Lechin, Fuad; van der Dijs, Bertha; Hernández, Gerardo; Orozco, Beatriz; Rodríguez, Simon; Baez, Scarlet

    2006-03-01

    Tianeptine is a serotonin-uptake enhancer drug whose antidepressant effectiveness is based on its ability to reduce rather than increase serotonin availability at the synaptic cleft. This paradoxical neuropharmacological mechanism has raised doubt among neuropharmacologists and psychiatrists as to the role of tianeptine as a trusty-reliable antidepressant drug. This controversial issue led us to investigate the acute effects of a single, oral dose (12.5 mg) of this drug on circulating neurotransmitters and cardiovascular parameters in 50 healthy subjects. The drug provoked a striking and significant reduction of plasma noradrenaline (NA) and plasma serotonin (f-5-HT) while it increased plasma dopamine (DA) and platelet serotonin (p-5-HT) concentrations within the 4-h study period. No adrenaline (Ad) changes were registered. The NA/Ad ratio and the f-5-HT/p-5-HT ratio showed significant reduction throughout the test. Finally, although diastolic blood pressure (DBP) showed significant decrease, neither systolic blood pressure (SBP) nor heart rate (HR) showed significant change. These findings are consistent with the postulation that tianeptine reduces both neural sympathetic activity and parasympathetic activity without affecting adrenal sympathetic activity, enabling us to discuss the possible mechanisms involved in the antidepressant effects of tianeptine. The well-known fact that major depressed patients always show raised NA plus lower than normal p-5-HT levels, both disorders which are normalized by tianeptine, gives neurochemical support to the clinical improvement triggered by the drug in these patients. Summarizing, the results presented in this study demonstrate that tianeptine triggers significant reduction of circulating noradrenaline and plasma serotonin while increasing circulating dopamine and platelet serotonin. Other possible neuropharmacological effects are also discussed.

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

    USGS Publications Warehouse

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

    2009-01-01

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

  11. Safety and effectiveness of transdermal nicotine patch in smokers admitted with acute coronary syndromes.

    PubMed

    Meine, Trip J; Patel, Manesh R; Washam, Jeffrey B; Pappas, Paul A; Jollis, James G

    2005-04-15

    An analysis of smokers admitted with acute coronary syndrome who received transdermal nicotine therapy and those who did not was performed. Propensity analysis was used to match patients. Transdermal nicotine therapy appears safe and does not have an effect on the mortality of patients with acute coronary syndromes.

  12. 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.

  13. Protection from lethal and sub-lethal whole body exposures of mice to γ-radiation by Acorus calamus L.: studies on tissue antioxidant status and cellular DNA damage.

    PubMed

    Sandeep, Divyasree; Nair, Cherupally Krishnan Krishnan

    2012-01-01

    The radioprotecting activity of Acorus calamus extract after whole body exposure of mice to lethal and sub-lethal doses of γ-irradiation in terms of radiation induced mortality and damages to cellular DNA and tissue antioxidant levels were studied. A. calamus extract (250 mg/kg body weight) was orally administered to mice 1 h prior to whole body γ-radiation exposure. The antioxidant levels in the tissue homogenates of brain, liver and kidney of the irradiated mice were determined and cellular DNA damage was monitored by comet assay. Effect of administration of the extract on survival of the animals exposed to acute lethal dose of 10 Gy whole body γ-radiations was also monitored. Administration of the extract significantly increased the activities of major enzymes of the antioxidant defense system specially SOD, catalase and GPx and levels of GSH in 2, 6 and 10 Gy irradiated mice and decreased the formation MDA. The extract also decreased DNA strand breaks. The survival rate was found to be increased up to 5%. These studies highlight the role of A. calamus extract as good source of natural radioprotecting agent and its therapeutic implications for radiation-induced injuries.

  14. Effects of lysine-induced acute renal failure in dogs.

    PubMed

    Asanuma, Kentaro; Adachi, Kenji; Sugimoto, Tetsuro; Chiba, Shuichi

    2006-05-01

    This study investigates the effects of lysine-induced acute renal failure. Female dogs received a lysine hydrochloride (lysine) of 4500 mg/kg/day (3.75 ml/kg/hr) for 3 consecutive days. The dogs were observed for clinical signs. Body weights were recorded, food consumption and water consumption calculated, and urinalysis and blood biochemistry were performed daily. Plasma samples for amino acid determinations were obtained from all dogs, which were necropsied on Day 3. Histopathological examinations were done on all test animals. Compound-related findings include the following. Blood biochemistry results showed increases in ammonia, blood urea nitrogen, blood urea nitrogen/creatinine ratio, and creatinine. Urinary changes consisted of increases in urine volume, total protein, albumin, gamma-glutamyl transpeptidase, and N-acetyl-beta-D-glucosaminidase. In addition, macroscopic findings consisted of pale, congested capsule; microscopic findings consisted of hypertrophy of proximal convoluted tubule (mainly S1 segment), and degeneration/desquamation of urinary tubule (mainly S3 segment with hyaline casts) in the kidney. From these findings, it can be concluded that lysine is nephrotoxic in dogs. Nephrotoxicity of lysine may relate to direct tubular toxicity and to tubular obstruction.

  15. Acute effects of cigarette smoking on pattern electroretinogram.

    PubMed

    Gundogan, Fatih C; Durukan, A Hakan; Mumcuoglu, Tarkan; Sobaci, Gungor; Bayraktar, M Zeki

    2006-09-01

    In this study, acute effects of cigarette smoking on the pattern electroretinogram (PERG) were investigated. First, variability of the PERG was studied in a group of young male smokers (26 right eyes of 26 subjects). Then PERGs were investigated in a group of habitual smokers (17 right eyes of 17 subjects) in separate real smoking and sham smoking sessions. On each session PERGs were recorded pre-smoking (PS), immediately after smoking (IAS) and 5 min after smoking (5th) conditions. Real smoking significantly increased P50 amplitudes and decreased N95 latencies. Regarding P50 amplitudes in the real smoking sessions, the differences were significant between PS and IAS (PS: 3.3 +/- 0.5 muV, IAS: 3.7 +/- 0.7microV, P = 0.015) and between PS-5th (PS: 3.3 +/- 0.5microV, 5th: 4.1 +/- 0.9microV, P = 0.039). There was significant difference (P = 0.024) between N95 latencies of PS (98.5 +/- 6.9 ms) and IAS (94.7 +/- 5.1 ms) in the real smoking sessions. No statistically significant difference was observed in sham smoking sessions. Our results indicated, for the first time, that cigarette smoking may influence PERG amplitude and latency significantly in habitual smokers.

  16. Effects of acute spinalization on neurons of postural networks

    PubMed Central

    Zelenin, Pavel V.; Lyalka, Vladimir F.; Hsu, Li-Ju; Orlovsky, Grigori N.; Deliagina, Tatiana G.

    2016-01-01

    Postural limb reflexes (PLRs) represent a substantial component of postural corrections. Spinalization results in loss of postural functions, including disappearance of PLRs. The aim of the present study was to characterize the effects of acute spinalization on two populations of spinal neurons (F and E) mediating PLRs, which we characterized previously. For this purpose, in decerebrate rabbits spinalized at T12, responses of interneurons from L5 to stimulation causing PLRs before spinalization, were recorded. The results were compared to control data obtained in our previous study. We found that spinalization affected the distribution of F- and E-neurons across the spinal grey matter, caused a significant decrease in their activity, as well as disturbances in processing of posture-related sensory inputs. A two-fold decrease in the proportion of F-neurons in the intermediate grey matter was observed. Location of populations of F- and E-neurons exhibiting significant decrease in their activity was determined. A dramatic decrease of the efficacy of sensory input from the ipsilateral limb to F-neurons, and from the contralateral limb to E-neurons was found. These changes in operation of postural networks underlie the loss of postural control after spinalization, and represent a starting point for the development of spasticity. PMID:27302149

  17. Protective effect of vitamin E against acute kidney injury.

    PubMed

    Liu, Pengfei; Feng, Yetong; Wang, Yi; Zhou, Yulai; Zhao, Lei

    2015-01-01

    It has been well-known for many years now that vitamin E is an essential nutrient; however, some of the physiological functions of this vitamin are still far from being understood. In recent years, a series of preclinical and clinical studies proposed a protective role of vitamin E on acute kidney injury (AKI), which has a high morbidity rate and mortality rate in clinical investigations. Based on the benefits associated with vitamin E, such as strong antioxidant function, low toxicity, rare side-effects, and low cost, this therapy strategy has garnered an extensive amount of interest in the scientific community for the development of new therapy modes against AKI. In this review, a concise overview of the application of vitamin E in the treatment of AKI is provided as well as a summary of a series of published data regarding the combination therapy modes and detailed therapy mechanisms of vitamin E-based therapy against AKI. At present, there are critical points of this therapy mode that are still in need of further clarification, meaning the current understanding of the role of vitamin E in the treatment of AKI remains incomplete. However, the development of more reliable pharmacological or biotechnical strategies with vitamin E for the eventual treatment of patients with AKI may guide the next chapter of vitamin E research.

  18. Cerebral blood flow effects of acute intravenous heroin administration.

    PubMed

    Kosel, Markus; Noss, Roger S; Hämmig, Robert; Wielepp, Peter; Bundeli, Petra; Heidbreder, Rebeca; Kinser, Jane A; Brenneisen, Rudolf; Fisch, Hans-Ulrich; Kayser, Sarah; Schlaepfer, Thomas E

    2008-04-01

    We examined acute effects of intravenous diacetylmorphine (heroin) administration - which induces a characteristic biphasic response: A short rush-sensation associated with intense pleasurable feelings followed by a subjectively different period of euphoria on cerebral blood flow. This was assessed in nine male heroin dependent patients participating in a heroin maintenance program in a setting resembling everyday pattern of heroin abuse. 99mTc-HMPAO was administered 45 s (rush) and 15 min (euphoria) after administration of i.v. heroin and 45 s after administration of saline (placebo). Plasma concentration of diacetylmorphine and its metabolites were measured with high-pressure liquid chromatography (HPLC). Compared to the euphoria condition, rush was associated with blood flow increase in the left posterior cerebellar lobe, left anterior cingulate gyrus and right precuneus. Our results are in line with recent reports indicating that the cerebellum is an important component in functional brain systems subserving sensory and motor integration, learning, modulation of affect, motivation and social behaviour, which all play important roles in reinforcing properties of opioids.

  19. Protective Effects of Hydrogen Gas on Experimental Acute Pancreatitis

    PubMed Central

    Zhou, Hao-xin; Han, Bing; Hou, Li-Min; An, Ting-Ting; Jia, Guang; Cheng, Zhuo-Xin; Ma, Yong; Zhou, Yi-Nan; Kong, Rui; Wang, Shuang-Jia; Wang, Yong-Wei; Sun, Xue-Jun; Pan, Shang-Ha; Sun, Bei

    2016-01-01

    Acute pancreatitis (AP) is an inflammatory disease mediated by damage to acinar cells and pancreatic inflammation. In patients with AP, subsequent systemic inflammatory responses and multiple organs dysfunction commonly occur. Interactions between cytokines and oxidative stress greatly contribute to the amplification of uncontrolled inflammatory responses. Molecular hydrogen (H2) is a potent free radical scavenger that not only ameliorates oxidative stress but also lowers cytokine levels. The aim of the present study was to investigate the protective effects of H2 gas on AP both in vitro and in vivo. For the in vitro assessment, AR42J cells were treated with cerulein and then incubated in H2-rich or normal medium for 24 h, and for the in vivo experiment, AP was induced through a retrograde infusion of 5% sodium taurocholate into the pancreatobiliary duct (0.1 mL/100 g body weight). Wistar rats were treated with inhaled air or 2% H2 gas and sacrificed 12 h following the induction of pancreatitis. Specimens were collected and processed to measure the amylase and lipase activity levels; the myeloperoxidase activity and production levels; the cytokine mRNA expression levels; the 8-hydroxydeoxyguanosine, malondialdehyde, and glutathione levels; and the cell survival rate. Histological examinations and immunohistochemical analyses were then conducted. The results revealed significant reductions in inflammation and oxidative stress both in vitro and in vivo. Furthermore, the beneficial effects of H2 gas were associated with reductions in AR42J cell and pancreatic tissue damage. In conclusion, our results suggest that H2 gas is capable of ameliorating damage to the pancreas and AR42J cells and that H2 exerts protective effects both in vitro and in vivo on subjects with AP. Thus, the results obtained indicate that this gas may represent a novel therapy agent in the management of AP. PMID:27115738

  20. Protective Effects of Hydrogen Gas on Experimental Acute Pancreatitis.

    PubMed

    Zhou, Hao-Xin; Han, Bing; Hou, Li-Min; An, Ting-Ting; Jia, Guang; Cheng, Zhuo-Xin; Ma, Yong; Zhou, Yi-Nan; Kong, Rui; Wang, Shuang-Jia; Wang, Yong-Wei; Sun, Xue-Jun; Pan, Shang-Ha; Sun, Bei

    2016-01-01

    Acute pancreatitis (AP) is an inflammatory disease mediated by damage to acinar cells and pancreatic inflammation. In patients with AP, subsequent systemic inflammatory responses and multiple organs dysfunction commonly occur. Interactions between cytokines and oxidative stress greatly contribute to the amplification of uncontrolled inflammatory responses. Molecular hydrogen (H2) is a potent free radical scavenger that not only ameliorates oxidative stress but also lowers cytokine levels. The aim of the present study was to investigate the protective effects of H2 gas on AP both in vitro and in vivo. For the in vitro assessment, AR42J cells were treated with cerulein and then incubated in H2-rich or normal medium for 24 h, and for the in vivo experiment, AP was induced through a retrograde infusion of 5% sodium taurocholate into the pancreatobiliary duct (0.1 mL/100 g body weight). Wistar rats were treated with inhaled air or 2% H2 gas and sacrificed 12 h following the induction of pancreatitis. Specimens were collected and processed to measure the amylase and lipase activity levels; the myeloperoxidase activity and production levels; the cytokine mRNA expression levels; the 8-hydroxydeoxyguanosine, malondialdehyde, and glutathione levels; and the cell survival rate. Histological examinations and immunohistochemical analyses were then conducted. The results revealed significant reductions in inflammation and oxidative stress both in vitro and in vivo. Furthermore, the beneficial effects of H2 gas were associated with reductions in AR42J cell and pancreatic tissue damage. In conclusion, our results suggest that H2 gas is capable of ameliorating damage to the pancreas and AR42J cells and that H2 exerts protective effects both in vitro and in vivo on subjects with AP. Thus, the results obtained indicate that this gas may represent a novel therapy agent in the management of AP.

  1. Acute effect of ephedrine on 24-h energy balance

    NASA Technical Reports Server (NTRS)

    Shannon, J. R.; Gottesdiener, K.; Jordan, J.; Chen, K.; Flattery, S.; Larson, P. J.; Candelore, M. R.; Gertz, B.; Robertson, D.; Sun, M.

    1999-01-01

    Ephedrine is used to help achieve weight control. Data on its true efficacy and mechanisms in altering energy balance in human subjects are limited. We aimed to determine the acute effect of ephedrine on 24-h energy expenditure, mechanical work and urinary catecholamines in a double-blind, randomized, placebo-controlled, two-period crossover study. Ten healthy volunteers were given ephedrine (50 mg) or placebo thrice daily during each of two 24-h periods (ephedrine and placebo) in a whole-room indirect calorimeter, which accurately measures minute-by-minute energy expenditure and mechanical work. Measurements were taken of 24-h energy expenditure, mechanical work, urinary catecholamines and binding of (+/-)ephedrine in vitro to human beta1-, beta2- and beta3-adrenoreceptors. Twenty-four-hour energy expenditure was 3.6% greater (8965+/-1301 versus 8648+/-1347 kJ, P<0.05) with ephedrine than with placebo, but mechanical work was not different between the ephedrine and placebo periods. Noradrenaline excretion was lower with ephedrine (0.032+/-0.011 microg/mg creatinine) compared with placebo (0.044+/-0.012 microg/mg creatinine) (P<0.05). (+/-)Ephedrine is a relatively weak partial agonist of human beta1- and beta2-adrenoreceptors, and had no detectable activity at human beta3-adrenoreceptors. Ephedrine (50 mg thrice daily) modestly increases energy expenditure in normal human subjects. A lack of binding of ephedrine to beta3-adrenoreceptors and the observed decrease in urinary noradrenaline during ephedrine treatment suggest that the thermogenic effect of ephedrine results from direct beta1-/beta2-adrenoreceptor agonism. An indirect beta3-adrenergic effect through the release of noradrenaline seems unlikely as urinary noradrenaline decreased significantly with ephedrine.

  2. Acute Toxicity Investigation and Anti-diarrhoeal Effect of the Chloroform-Methanol Extract of the Leaves of Persea americana.

    PubMed

    Christian E, Odo; Okwesili Fc, Nwodo; Parker E, Joshua; Okechukwu Pc, Ugwu

    2014-01-01

    Persea americana is a plant used by traditional medicine practitioners to treat ailments including diarrhoea and diabetes mellitus in Nigeria. Hence, the chloroform and the methanol fractions of the chloroform-methanol extract of the leaves of P. americana were evaluated for their acute toxicity as well as anti-diarrhoeal effects in Wistar rats to substantiate this claim. The chloroform and methanol fractions [at graded doses of 100 and 200 mg/Kg body weight (b.w) of each] were studied for their anti-diarrhoeal effects in terms of the reductions in the wetness of faeces and the frequency of defaecation of castor oil-induced diarrhoea. To understand the mechanism of their anti-diarrhoeal effects, their actions were further evaluated on castor oil-induced enteropooling (intestinal fluid accumulation). The median lethal dose (LD50) of the methanol fraction was found to be less than 5000 mg/Kg b.w. At the two doses, the chloroform and the methanol fractions showed dose-dependent significant (p < 0.05) reductions in the wetness of faeces and the frequency of defaecation with the 200 mg/Kg b.w of the chloroform fraction being the most effective. Results of the fractions were comparable with those of the standard anti-diarrhoeal drug, hyoscine butylbromide (3 mg/Kg b.w). Both fractions produced remarkable (p < 0.05) dose-related inhibition of castor oil-induced enteropooling as shown by the significant (p < 0.05) decreases in the weight and volume of the intestinal contents. Experimental findings show that the chloroform-methanol extract of the leaves of P. americana possesses significant anti-diarrhoeal effect and may be a potent source of anti-diarrhoeal drug(s) in future.

  3. Involvement of free radicals followed by the activation of phospholipase A2 in the mechanism that underlies the combined effects of methamphetamine and morphine on subacute toxicity or lethality in mice: comparison of the therapeutic potential of fullerene, mepacrine, and cooling.

    PubMed

    Mori, Tomohisa; Ito, Shinobu; Namiki, Mizuho; Suzuki, Tadashi; Kobayashi, Shizuko; Matsubayashi, Kenji; Sawaguchi, Toshiko

    2007-07-17

    An increase in polydrug abuse is a major problem worldwide. The coadministration of methamphetamine and morphine increased subacute toxicity or lethality in rodents. However, the underlying mechanisms by which lethality is increased by the coadministration of methamphetamine and morphine are not yet fully understood. Coadministered methamphetamine and morphine induced lethality by more than 80% in BALB/c mice, accompanied by the rupture of cells in the kidney and liver, and an increase in poly (ADP-ribose) polymerase (PARP)-immunoreactive cells in the heart, kidney and liver. The lethal effect and the increase in the incidence of rupture or PARP-immunoreactive cells induced by the coadministration of methamphetamine and morphine was significantly attenuated by pretreatment with mepacrine (phospholipase A(2) inhibitor) or fullerene (a radical scavenger), or by cooling from 30 to 90 min after drug administration. Furthermore, based on the results of the electron spin resonance spin-trapping technique, hydroxyl radicals were increased by the administration of methamphetamine and morphine, and these increased hydroxyl radicals were potently attenuated by fullerene and cooling. These results suggest that hydroxyl radicals plays an important role in the increased lethality induced by the coadministration of methamphetamine plus morphine. The potency of cooling or drugs for decreasing the subacute toxicity or lethality induced by the coadministration of methamphetamine and morphine was in the order fullerene=cooling>mepacrine. These results indicate that fullerene and cooling are beneficial for preventing death that is induced by the coadministration of methamphetamine and morphine.

  4. Effect of fluid ingestion on orthostatic responses following acute exercise

    NASA Technical Reports Server (NTRS)

    Davis, J. E.; Fortney, S. M.

    1997-01-01

    Orthostatic tolerance is impaired following an acute bout of exercise. This study examined the effect of fluid ingestion following treadmill exercise in restoring the cardiovascular responses to an orthostatic stress. Five men (age, 29.6 +/- 3.4 yrs) were exposed to a graded lower body negative (LBNP) pressure protocol (0 to -50 mmHg) during euhydration without exercise (C), 20 minutes after exercise dehydration (D), 20 minutes after exercise and fluid ingestion (FI20), and 60 minutes after exercise and fluid ingestion (FI60). Fluid ingestion (mean +/- SE) consisted of water-ingestion equivalent to 50% of the body weight lost during exercise (520 +/- 15 ml). Exercise dehydration resulted in significantly higher heart rates (119 +/- 8 vs 82 +/- 7 bpm), lower systolic blood pressures (95 +/- 1.7 vs 108 +/- 2.3 mmHg), a smaller increase in leg circumference (3.7 +/- 4 vs 6.9 +/- 1.0 mm), and an attenuated increase in total peripheral resistance (2.58 +/- 1.2 vs 4.28 +/- 0.9 mmHg/L/min) at -50 mmHg LBNP compared to the C condition. Fluid ingestion (both 20 and 60), partially restored the heart rate, systolic blood pressure, and total peripheral resistance responses to LBNP, but did not influence the change in leg circumference during LBNP (4 +/- 0.3 for R20 and 2.8 +/- 0.4 mm for R60). These data illustrate the effectiveness of fluid ingestion on improving orthostatic responses following exercise, and suggest that dehydration is a contributing factor to orthostatic intolerance following exercise.

  5. ORAL 1-O-OCTADECYL-2-O-BENZYL-SN-GLYCERO-3-CIDOFOVIR TARGETS THE LUNG AND IS EFFECTIVE AGAINST A LETHAL RESPIRATORY CHALLENGE WITH ECTROMELIA VIRUS IN MICE

    PubMed Central

    Hostetler, Karl Y.; Beadle, James R.; Trahan, Julissa; Aldern, Kathy A.; Owens, Gelita; Schriewer, Jill; Melman, Lora; Buller, R. Mark

    2007-01-01

    Hexadecyloxypropyl-cidofovir (HDP-CDV) has been shown to be orally active against lethal infection with orthopoxviruses including, mousepox, cowpox, vaccinia and rabbitpox. The alkoxyalkyl group provides oral absorption and reduces greatly the amount of drug reaching the kidney, the site of CDV’s dose limiting toxicity. However, the amount of HDP-CDV detected in lung, an important site of early poxvirus replication, is low and the reduction of viral titers in surviving animals is reduced moderately compared with the liver where poxvirus titers are virtually undetectable. We synthesized a novel glycerol ester of CDV, 1-O-octadecyl-2-O-benzyl-sn-glycero-3-CDV (ODBG-CDV), and compared its oral pharmacokinetics with that of HDP-CDV. Surprisingly, ODBG-CDV levels in lung are much higher and liver levels are reduced, suggesting that the compound is transported in small intestinal lymph instead the portal vein. ODBG-CDV has excellent in vitro activity in cells infected with ectromelia virus (ECTV). In mice infected with a lethal aerosol or intranasal challenge of ECTV, HDP-CDV and ODBG-CDV are equally effective in preventing death from disease. Other drugs esterified to 1-O-octadecyl-2-O-benzyl-sn-glycerol or 1-O-octadecyl-2-O-benzyl-sn-glycerol-3-phosphate may provide lung targeting for treatment of microbial or neoplastic diseases while reducing first pass removal by the liver during oral absorption. PMID:17123638

  6. Oral 1-O-octadecyl-2-O-benzyl-sn-glycero-3-cidofovir targets the lung and is effective against a lethal respiratory challenge with ectromelia virus in mice.

    PubMed

    Hostetler, Karl Y; Beadle, James R; Trahan, Julissa; Aldern, Kathy A; Owens, Gelita; Schriewer, Jill; Melman, Lora; Buller, R Mark

    2007-03-01

    Hexadecyloxypropyl-cidofovir (HDP-CDV) has been shown to be orally active against lethal infection with orthopoxviruses including, mousepox, cowpox, vaccinia and rabbitpox. The alkoxyalkyl group provides oral absorption and reduces greatly the amount of drug reaching the kidney, the site of CDV's dose limiting toxicity. However, the amount of HDP-CDV detected in lung, an important site of early poxvirus replication, is low and the reduction of viral titers in surviving animals is reduced moderately compared with the liver where poxvirus titers are virtually undetectable. We synthesized a novel glycerol ester of CDV, 1-O-octadecyl-2-O-benzyl-sn-glycero-3-CDV (ODBG-CDV), and compared its oral pharmacokinetics with that of HDP-CDV. Surprisingly, ODBG-CDV levels in lung are much higher and liver levels are reduced, suggesting that the compound is transported in small intestinal lymph instead the portal vein. ODBG-CDV has excellent in vitro activity in cells infected with ectromelia virus (ECTV). In mice infected with a lethal aerosol or intranasal challenge of ECTV, HDP-CDV and ODBG-CDV are equally effective in preventing death from disease. Other drugs esterified to 1-O-octadecyl-2-O-benzyl-sn-glycerol or 1-O-octadecyl-2-O-benzyl-sn-glycerol-3-phosphate may provide lung targeting for treatment of microbial or neoplastic diseases while reducing first pass removal by the liver during oral absorption.

  7. The effects of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone on proinflammatory signaling pathways and CLP-induced lethal sepsis in mice.

    PubMed

    Tham, Chau Ling; Lam, Kok Wai; Rajajendram, Revathee; Cheah, Yoke Kqueen; Sulaiman, Mohd Roslan; Lajis, Nordin H; Kim, Min Kyu; Israf, Daud A

    2011-02-10

    We previously showed that 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC), suppressed the synthesis of various proinflammatory mediators. In this study we explain the mechanism of action of BHMC in lipopolysaccharide (LPS)-induced U937 monocytes and further show that BHMC prevents lethality of CLP-induced sepsis. BHMC showed dose-dependent inhibitory effects on p38, JNK and ERK 1/2 activity as determined by inhibition of phosphorylation of downstream transcription factors ATF-2, c-Jun and Elk-1 respectively. Inhibition of these transcription factors subsequently caused total abolishment of AP-1-DNA binding. BHMC inhibited p65 NF-κB nuclear translocation and DNA binding of p65 NF-κB only at the highest concentration used (12.5μM) but failed to alter phosphorylation of JNK, ERK1/2 and STAT-1. Since the inhibition of p38 activity was more pronounced we evaluated the possibility that BHMC may bind to p38. Molecular docking experiments confirmed that BHMC fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We also show that BHMC was able to improve survival from lethal sepsis in a murine caecal-ligation and puncture (CLP) model.

  8. Acute Effects of Eccentric Overload on Concentric Front Squat Performance.

    PubMed

    Munger, Cameron N; Archer, David C; Leyva, Whitney D; Wong, Megan A; Coburn, Jared W; Costa, Pablo B; Brown, Lee E

    2017-01-30

    Eccentric overload is used to enhance performance. The purpose of this study was to investigate the acute effects of eccentric overload on concentric front squat performance. Twenty resistance-trained males (age=23.80±1.82yrs, ht=176.95±5.21cm, mass=83.49±10.43kg, 1 Repetition Maximum [1RM] front squat=131.02±21.32kg) volunteered. A dynamic warm-up and warm-up sets of front squat were performed. Eccentric hooks were added to the barbell. They descended for 3 seconds, until eccentric hooks released, and performed the concentric phase as fast as possible. There were three randomly-ordered conditions with the concentric phase always at 90% 1RM and the eccentric phase at 105%, 110%, and 120% of 1RM. Two repetitions were performed for each condition. A repeated measures ANOVA was used to determine differences. For peak velocity, there were main effects for time and condition (P<0.05), where post (1.01±0.10m/s) was greater than pre (0.96±0.11m/s) and 120% (1.03±1.11m/s) was greater than 105% (0.99±0.13m/s). For peak power, there was a main effect for condition where 120% (2225.00±432.37W) was greater than 105% (2021.84±563.53W). For peak ground reaction force, there were main effects for time and condition, where post was greater than pre and 120% was greater than 105%. For rate of force development, there was no interaction or main effects. Eccentric overload enhanced concentric velocity and power, therefore it can be used by strength coaches and athletes during the power phase of a training program. It can also be used to prescribe supramaximal loads and could be a tool to supplement the clean exercise because the front squat is a precursor.

  9. 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.

  10. Assessment of metals exposure and sub-lethal effects in voles and small birds captured near the DeLong Mountain Regional Transportation System Road, Cape Krusenstern National Monument, Alaska, 2006

    USGS Publications Warehouse

    Brumbaugh, William G.; Mora, Miguel A.; May, Thomas W.

    2008-01-01

    Voles (n=6) and small ground-nesting birds (n=12) were live-captured near the DeLong Mountain Regional Transportation System haul road in Cape Krusenstern National Monument in northwest Alaska in 2006 to assess metals exposure and sub-lethal biological effects. Similar numbers of animals were captured from a reference site in southern Cape Krusenstern National Monument for comparison. Histopathological examination of selected organs, blood analysis, and analysis for aluminum, barium, cadmium, lead, and zinc concentrations in liver and blood samples were performed. Voles and small birds captured from near the haul road had about 20 times greater blood and liver lead concentrations and about 3 times greater cadmium concentrations when compared to those from the reference site. Barium and zinc tissue concentrations of animals collected from different sites were not remarkably different, and aluminum concentrations were below the reporting limits in most samples. There was no clear evidence of serious sub-lethal biological effects such as lesions in internal organs or DNA damage in blood in any of the animals. Accordingly, blood and liver lead concentrations in animals captured near the haul road generally were less than tissue concentration thresholds associated with serious biological effects reported from other studies; however, subtle effects resulting from lead exposure, such as the suppression of the activity of certain enzymes, cannot be ruled out for those animals nearest the haul road. Notably, liver lead concentrations of voles and small birds at the reference location were considerably less than those previously reported for similar animals at reference sites in other parts of the United States, Canada, and Europe. Results from this reconnaissance-level study indicate that voles and small birds inhabiting this area are not suffering serious biological effects as a result of metals exposure; however, continued monitoring of lead and other metals is

  11. Hospital admissions for asthma and acute bronchitis in El Paso, Texas: Do age, sex, and insurance status modify the effects of dust and low wind events?

    PubMed Central

    Staniswalis, Joan G.; Bulathsinhala, Priyangi; Peng, Yanlei; Gill, Thomas E.

    2013-01-01

    Background El Paso County (Texas) is prone to still air inversions and is one of the dust “hot spots” in North America. In this context, we examined the sub-lethal effects of airborne dust and low wind events on human respiratory health (i.e., asthma and acute bronchitis) between 2000 and 2003, when 110 dust and 157 low wind events occurred. Because environmental conditions may not affect everyone the same, we explored the effects of dust and low wind within three age groups (children, adults, and the elderly), testing for effect modifications by sex and insurance status, while controlling for weather and air pollutants. Methods We used a case-crossover design using events matched with referent days on the same day-of-the-week, month, and year with conditional logistic regression to estimate the probability of hospital admission, while controlling for apparent temperature (lag 1), nitrogen dioxide, and particulate matter of 2.5 micrometers or less. Results Children (aged 1–17) were 1.19 (95% confidence interval: 1.00–1.41) times more likely to be hospitalized for asthma three days after a low wind event, and 1.33 (95% CI: 1.01–1.75) times more likely to be hospitalized for acute bronchitis one day after a dust event than on a clear day. Girls were more sensitive to acute bronchitis hospitalizations after dust events (1.83, 95% CI: 1.09–3.08) than boys, but less sensitive than boys to acute bronchitis hospitalizations after low wind events (0.68, 95% CI: 0.46–1.00). We found general trends with regard to dust and low wind events being associated with increased odds of hospitalization for asthma and bronchitis amongst all ages and adults (aged 18–64). Adults covered by Medicaid and adults without health insurance had higher risks of hospitalization for asthma and acute bronchitis after both low wind and dust event Conclusions Results suggest that there were respiratory health effects associated with dust and low wind events in El Paso, with stronger

  12. Acute stress does not affect the impairing effect of chronic stress on memory retrieval

    PubMed Central

    Ozbaki, Jamile; Goudarzi, Iran; Salmani, Mahmoud Elahdadi; Rashidy-Pour, Ali

    2016-01-01

    Objective(s): Due to the prevalence and pervasiveness of stress in modern life and exposure to both chronic and acute stresses, it is not clear whether prior exposure to chronic stress can influence the impairing effects of acute stress on memory retrieval. This issue was tested in this study. Materials and Methods: Adult male Wistar rats were randomly assigned to the following groups: control, acute, chronic, and chronic + acute stress groups. The rats were trained with six trials per day for 6 consecutive days in the water maze. Following training, the rats were either kept in control conditions or exposed to chronic stress in a restrainer 6 hr/day for 21 days. On day 22, a probe test was done to measure memory retention. Time spent in target and opposite areas, platform location latency, and proximity were used as indices of memory retention. To induce acute stress, 30 min before the probe test, animals received a mild footshock. Results: Stressed animals spent significantly less time in the target quadrant and more time in the opposite quadrant than control animals. Moreover, the stressed animals showed significantly increased platform location latency and proximity as compared with control animals. No significant differences were found in these measures among stress exposure groups. Finally, both chronic and acute stress significantly increased corticosterone levels. Conclusion: Our results indicate that both chronic and acute stress impair memory retrieval similarly. Additionally, the impairing effects of chronic stress on memory retrieval were not influenced by acute stress. PMID:27635201

  13. 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

  14. Acute and chronic effects of ketamine on semantic priming: modeling schizophrenia?

    PubMed

    Stefanovic, Ana; Brandner, Brigitta; Klaassen, Elissa; Cregg, Roman; Nagaratnam, Mayavaty; Bromley, Lesley M; Das, Ravi K; Rossell, Susan L; Morgan, Celia J A; Curran, H Valerie

    2009-04-01

    Acute administration of the N-methyl-D-aspartate receptor antagonist ketamine induces schizophrenia-like symptoms in healthy volunteers; furthermore, a window on ketamine's chronic effects is provided by regular recreational users. The current study utilized both acute ketamine administration in healthy volunteers and chronic ketamine abusers to investigate semantic processing, one of the key cognitive deficits in schizophrenia. Semantic processing was examined using a semantic priming paradigm. In experiment 1, acute effects of low (75 ng/mL) and high (150 ng/mL) ketamine doses were compared in a placebo-controlled double-blind independent group design with 48 participants. In experiment 2, 19 regular recreational ketamine users were compared with 19 ketamine-naive polydrug controls and 26 non-drug-using controls. In both experiments, semantic priming parameters were manipulated to distinguish between ketamine's effects on (1) automatic and strategic processing and (2) the facilitation and inhibition components of semantic priming for strongly (directly) related primes and targets. Acute effects of ketamine on semantic priming for weakly (indirectly) related primes and targets were also assessed in experiment 1. Acutely, ketamine impaired the employment of strategic mechanisms but not automatic processing within both the direct and indirect semantic priming tasks. Acute ketamine administration also induced clear schizophrenia-like symptoms. Schizotypy traits in the cognitive and perceptual domains tended to correlate with increased semantic priming in long-term ketamine users. In summary, acute and chronic ketamine-induced changes partially mirrored the findings on semantic priming in schizophrenia.

  15. Acute exposure to acid fog. Effects on mucociliary clearance

    SciTech Connect

    Laube, B.L.; Bowes, S.M. III; Links, J.M.; Thomas, K.K.; Frank, R. )

    1993-05-01

    Submicrometric sulfuric acid (H2SO4) aerosol can affect mucociliary clearance without eliciting irritative symptoms or changes in pulmonary function. The effect of larger fog droplets containing H2SO4 on mucociliary clearance is unknown. We quantified mucociliary clearance from the trachea (n = 4) and small airways (n = 7) of young healthy male adults after an acute exposure to H2SO4 fog (MMAD = 10.3 microns; pH = 2.0; liquid water content = 481 +/- 65 mg/m3; osmolarity = 30 mOsm). Acid fog (AF) or saline fog (SF) (10.9 microns; 492 +/- 116 mg/m3; 30 mOsm) was administered for 40 min of unencumbered breathing (no mouth-piece) at rest and for 20 min of exercise sufficient to produce oronasal breathing. Fog exposures were followed by a methacholine (MCh) challenge (a measure of airway reactivity) or inhalation of technetium-99M radioaerosol (MMAD = 3.4 microns) on 2 study days each. Changes in symptoms and forced ventilatory function were also assessed. Clearance was quantified from computer-assisted analyses of gamma camera images of the lower respiratory tract in terms of %removal/min of the radiolabel from the trachea 25 min after inhalation and from the outer zone of the right lung after 1.9 to 3 h. Symptoms, forced ventilatory function, and MCh response were unaffected by either fog. Tracheal clearance was more rapid in four of four subjects after AF (0.83 +/- 1.58% removal/min) compared with that after SF (-0.54 +/- 0.85% removal/min). Outer zone clearance was more rapid in six of seven subjects after AF (0.22 +/- 0.15% removal/min) compared with that after SF (0.01 +/- 0.09% removal/min).

  16. Effects of Montelukast in an Experimental Model of Acute Pancreatitis

    PubMed Central

    Angı, Serkan; Eken, Hüseyin; Kılıç, Erol; Karaköse, Oktay; Balci, Gürhan; Somuncu, Erkan

    2016-01-01

    Background We evaluated the hematological, biochemical, and histopathological effects of Montelukast on pancreatic damage in an experimental acute pancreatitis model created by cerulein in rats before and after the induction of pancreatitis. Materials/Methods Forty rats were divided into 4 groups with 10 rats each. The study groups were: the Cerulein (C) group, the Cerulein + early Montelukast (CMe) group, the Cerulein + late Montelukast (CMl) group, and the Control group. The pH, pO2, pCO2, HCO3, leukocyte, hematocrit, pancreatic amylase, and lipase values were measured in the arterial blood samples taken immediately before rats were killed. Results There were statistically significant differences between the C group and the Control group in the values of pancreatic amylase, lipase, blood leukocyte, hematocrit, pH, pO2, pCO2, HCO3, and pancreatic water content, and also in each of the values of edema, inflammation, vacuolization, necrosis, and total histopathological score (P<0.05). When the CMl group and C group were compared, no statistically significant differences were found in any parameter analyzed. When the CMe group was compared with the C group, pancreatic amylase, lipase, pH, PO2, pCO2, HCO3, pancreatic water content, histopathological edema, inflammation, and total histopathological score values were significantly different between the groups (P<0.05). Finally, when the CMe group and the Control group were compared, significant differences were found in all except 2 (leukocyte and pO2) parameters (P<0.05). Conclusions Leukotriene receptor antagonists used in the late phases of pancreatitis might not result in any benefit; however, when they are given in the early phases or prophylactically, they may decrease pancreatic damage. PMID:27479458

  17. Predicting the acute behavioral effects in rats inhaling toluene (or up to 24 hrs: Inhaled vs. internal dose metrics.

    EPA Science Inventory

    The acute toxicity oftoluene, a model volatile organic compound (VOC), depends on the concentration (C) and duration (t) ofexposure, and guidelines for acute exposures have traditionally used ext relationships to extrapolate protective and/or effective concentrations across durat...

  18. [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.

  19. Acute Effects of Fine Particulate Air Pollution on ST Segment Height: A Longitudinal Study

    EPA Science Inventory

    Background: The mechanisms for the relationship between particulate air pollution and cardiac disease are not fully understood. Air pollution-induced myocardial ischemia is one of the potentially important mechanisms. Methods: We investigate the acute effects and the time cours...

  20. Protective Effect of Pretreatment with Acenocoumarol in Cerulein-Induced Acute Pancreatitis.

    PubMed

    Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Dembiński, Marcin; Cieszkowski, Jakub; Kuśnierz-Cabala, Beata; Olszanecki, Rafał; Tomaszewska, Romana; Ambroży, Tadeusz; Dembiński, Artur

    2016-10-12

    Coagulation is recognized as a key player in inflammatory and autoimmune diseases. The aim of the current research was to examine the effect of pretreatment with acenocoumarol on the development of acute pancreatitis (AP) evoked by cerulein.

  1. Acute and chronic effects of rat colon after photodynamic therapy and radiotherapy: a comparative study

    NASA Astrophysics Data System (ADS)

    Sassy, T.; Breiter, N.; Sroka, Ronald; Ernst, Helmut

    1994-03-01

    After clinical photodynamic therapy (PDT) and radiotherapy (RT) of the colon carcinoma acute and late damages on adjacent normal tissue were seen. Therefore it was the aim of this experimental study to investigate these damages on normal colon tissue of rats after PDT in comparison with RT. Within the first hours after PDT the endoscopic examination showed a severe acute damage. The histopathological examination showed that the acute ulceration depends on the energy density applied within the first three days. This study indicates different progresses of acute effects after PDT and RT, respectively. Late damages were observed only by RT in contrast to PDT. Synthetic diet prevents acute damages after PDT. However, the synthetic diet after RT can prevent the late damage for the duration of the diet administration.

  2. Effect of sesame oil against acetaminophen-induced acute oxidative hepatic damage in rats.

    PubMed

    Chandrasekaran, Victor Raj Mohan; Wan, Chang-Hsin; Liu, Li-Lian; Hsu, Dur-Zong; Liu, Ming-Yie

    2008-08-01

    Acetaminophen (APAP) overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of sesame oil on APAP-induced acute liver injury. Male Wistar rats were given APAP (1,000 mg/kg; orally) to induce acute liver injury. Acetaminophen significantly increased aspartate transaminase, alanine transaminase, lipid peroxidation, and superoxide anion and hydroxyl radical generation levels; it also induced glutathione depletion. Sesame oil (8 mL/kg; orally) did not alter the gastric absorption of APAP, but it inhibited all the parameters altered by APAP and protected the rats against APAP-induced acute liver injury. We hypothesize that sesame oil maintained the intracellular glutathione levels, reduced reactive oxygen species levels, and inhibited lipid peroxidation in rats with APAP-induced acute liver injury.

  3. Using silicone passive samplers to detect polycyclic aromatic hydrocarbons from wildfires in streams and potential acute effects for invertebrate communities.

    PubMed

    Schäfer, Ralf Bernhard; Hearn, Laurence; Kefford, Ben J; Mueller, Jochen F; Nugegoda, Dayanthi

    2010-08-01

    Silicone rubber passive samplers spiked with 4 deuterated performance reference compounds were deployed for 29-33 days to estimate the concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) in 9 streams in Victoria, Australia, following a wildfire. Silicone rubber strips of 2 thicknesses were used to obtain information on the status of uptake of the chemicals of interest at retrieval. In addition, we monitored the stream macroinvertebrate community for potential effects of PAHs or other fire organics. All selected PAHs were detected in the passive samplers and the sampling rates ranged from 0.5 to 50 L/day significantly varying between sites but not compounds, presumably due to differences in current velocity. The estimated water concentrations were 0.1-10 ng/L for total PAHs with phenanthrene, pyrene and fluoranthene accounting for 91% of the total concentration. All PAHs were a factor of 1000 or more below the reported 48-h median lethal concentrations (48-h LC50) for Daphnia magna. Two sites located closest to the fires exhibited elevated concentrations compared to the other sites and the passive samplers in these sites remained in the integrative uptake regime for all compounds, suggesting precipitation-associated PAH input. No acute toxic effects of PAHs or other fire organics on the invertebrate community were detected using a biotic index for organic toxicants (SPEAR), whereas a non-specific biotic index (SIGNAL) decreased in two sites indicating impacts from changes in other environmental parameters. We conclude (1) that silicone-based passive samplers with two different area-to-volume ratios represent a promising tool for determining organic toxicants and (2) that PAHs from wildfires are unlikely to be a common main cause for fire-related ecological effects in streams adjacent to burnt regions.

  4. Effect of acute and delayed hyperbaric oxygen therapy on cyanide whole blood levels during acute cyanide intoxication.

    PubMed

    Lawson-Smith, P; Jansen, E C; Hilsted, L; Johnsen, A H; Hyldegaard, O

    2011-01-01

    Cyanide and carbon monoxide, which are often found in fire victims, are toxic gases emitted from fires. Cyanide and carbon monoxide have similar molecular structure. Cyanide binds to the enzyme cytochrome oxidase a, a3 similar to carbon monoxide, thus blocking the mitochondrial respiration chain causing depletion of adenosine triphosphate. Hyperbaric oxygen (HBO2) is recommended for treating carbon monoxide poisoning. The therapeutic effect is due to a high oxygen pressure removing carbon monoxide from the cells. We hypothesise that HBO2 induces changes in whole-blood-cyanide by a competitive mechanism forcing cyanide out of cellular tissues. A rat model was developed to study this effect. Female Sprague Dawley rats were anesthetized with a fentanyl + fluanizone combination and midazolam given subcutaneously (s.c.). Rats were poisoned with 5.4 mg/kg KCN injected intra-peritoneally in Group 1 and intra-arterially in Group 2. Blood samples were taken immediately after poisoning, and at one and a half, three and five hours. Blood was drawn from a jugular vein in Group 1 and from a femoral artery in Group 2. Group 1 rats were divided into a control group of 12 rats without HBO2, 10 rats had acute HBO2 immediately after poisoning and a group of 10 rats had HBO2 one and a half hours after poisoning. Group 2 rats were divided into a control group and an acute HBO2 group, with 10 rats in both groups. Whole-blood-cyanide concentrations were measured using the Conway method based on diffusion and the subsequent formation of cyanocobalamin measured by a spectrophotometer. Results showed that whole-blood-cyanide concentration in Group 1 controls and acute HBO2 initially rose and then fell towards zero. In rats treated with delayed HBO2, the reduction in whole-blood-cyanide concentration was significantly less as compared to controls and acute HBO2-treated rats. Group 2 controls whole-blood-cyanide concentration decreased towards zero throughout the observation period. However

  5. Effect of the selective pressure of sub-lethal level of heavy metals on the fate and distribution of ARGs in the catchment scale.

    PubMed

    Xu, Yan; Xu, Jian; Mao, Daqing; Luo, Yi

    2017-01-01

    Our previous study demonstrated that high levels of antibiotic resistance genes (ARGs) in the Haihe River were directly attributed to the excessive use of antibiotics in animal agriculture. The antibiotic residues of the Xiangjiang River determined in this study were much lower than those of the Haihe River, but the relative abundance of 16 detected ARGs (sul1, sul2 and sul3, qepA, qnrA, qnrB, qnrD and qnrS, tetA, tetB, tetW, tetM, tetQ and tetO, ermB and ermC), were as high as the Haihe River particularly in the downstream of the Xiangjiang River which is close to the extensive metal mining. The ARGs discharged from the pharmaceutical wastewater treatment plant (PWWTP) are a major source of ARGs in the upstream of the Xiangjiang River. In the downstream, selective stress of heavy metals rather than source release had a significant influence on the distinct distribution pattern of ARGs. Some heavy metals showed a positive correlation with certain ARG subtypes. Additionally, there is a positive correlation between individual ARG subtypes and heavy metal resistance genes, suggesting that heavy metals may co select the ARGs on the same plasmid of antibiotic resistant bacteria. The co-selection mechanism between specific metal and antibiotic resistance was further confirmed by these isolations encoding the resistance genotypes to antibiotics and metals. To our knowledge, this is the first study on the fate and distribution of ARGs under the selective pressure exerted by heavy metals in the catchment scale. These results are beneficial to understand the fate, and to discern the contributors of ARGs from either the source release or the selective pressure by sub-lethal levels of environmental stressors during their transport on a river catchment scale.

  6. Comparison of intermittent and continuous exposures to inorganic mercury in the mussel, Mytilus edulis: accumulation and sub-lethal physiological effects.

    PubMed

    Amachree, Dokuboba; Moody, A John; Handy, Richard D

    2014-11-01

    Aquatic organisms are often subject to intermittent exposure to pollutants in real ecosystems. This study aimed to compare mercury accumulation and the physiological responses of mussels, Mytilus edulis during continuous and intermittent exposure to the metal. Mussels were treated in a semi-static, triplicated design to either a control (no added Hg) or 50 µg l(-1) Hg as HgCl2 in continuous (daily) or intermittent (2 day exposure, 2 days in clean seawater alternately) exposure for 14 days. A time-dependent increase in Hg accumulation was observed in the continuous exposure, while the intermittent treatment showed step-wise changes in Hg concentrations with the exposure profile, especially in the gills. At the end of the experiment, tissue Hg concentrations were significantly increased in the continuous compared to the intermittent exposure for digestive gland (4 fold), gonad and remaining soft tissue (>2 fold), but not for the gill and adductor muscle. There was no observed oxidative damage at the end of the experiment as measured by the thiobarbituric acid reactive substances (TBARS) concentrations in tissues from all treatments. However, total glutathione was significantly decreased in the gill and digestive gland of both the continuous and intermittent exposure by the end of the experiment. The neutral red retention ability of the haemocytes was not affected, but total haemocyte counts were significantly decreased (<2 fold) in the intermittent compared to the continuous exposure. Histopathological examinations showed less pathology in the gill, but more inflammation in the digestive gland of mussels for the intermittent compared to the continuous exposure. Overall, the results showed that Hg accumulation from intermittent exposure was less than that of the continuous exposure regime, but the sub-lethal responses are sometimes more severe than expected in the former.

  7. Median lethal dose determination for percutaneous exposure to soman and VX in guinea pigs and the effectiveness of decontamination with M291 SDK or SANDIA foam.

    PubMed

    Clarkson, Edward D; Schulz, Susan M; Railer, Roy F; Smith, Kelly H

    2012-08-03

    Soman (GD) and VX are chemical warfare agents that can be absorbed through the skin. We determined the median lethal dose (MLD) for the cutaneous application of GD and VX in anesthetized haired guinea pigs and then tested the ability of a currently fielded decontamination kit, the M291 Skin Decontamination Kit (SDK), and decontaminating foam made by SANDIA Labs to decontaminate areas that have been exposed to cutaneous applications of GD and VX. The fur of guinea pigs was clipped on the left flank 24h prior to exposure. Animals were anesthetized and 5 min later neat GD or neat VX was applied. The MLD for percutaneous exposure to GD was 11.6 mg/kg, and to VX it was 0.10mg/kg. To test the ability of the M291 SDK, either GD or VX was applied and removed 1 min later with the pads of the M291 SDK clasped in a pair of forceps and wiped across the flank of the animal. The MLDs for GD and VX removed with the M291 SDK pads were 76.9 mg/kg and 0.87 mg/kg, respectively. When neat GD or neat VX was applied and removed 1 min later in the same manner with gauze soaked in SANDIA foam (MDF-100), the MLDs were 412 mg/kg and 10.4 mg/kg respectively. These data demonstrate that GD and VX are significantly less potent when applied cutaneously than previously reported for subcutaneous injections and indicate that improvement is needed on the limited protective ratio provided by the M291 SDK.

  8. Differential role of CYP2E1-mediated metabolism in the lethal and vestibulotoxic effects of cis-crotononitrile in the mouse

    SciTech Connect

    Boadas-Vaello, Pere; Diez-Padrisa, Nuria; Llorens, Jordi

    2007-12-15

    Several alkylnitriles are toxic to sensory systems, including the vestibular system, through yet undefined mechanisms. This study addressed the hypothesis that the vestibular toxicity of cis-crotononitrile depends on CYP2E1-mediated bioactivation. Wild-type (129S1) and CYP2E1-null female mice were exposed to cis-crotononitrile at 0, 2, 2.25 or 2.5 mmol/kg (p.o.) in either a baseline condition or following exposure to 1% acetone in drinking water to induce CYP2E1 expression. The exposed animals were assessed for vestibular toxicity using a behavioral test battery and through surface observation of the vestibular sensory epithelia by scanning electron microscopy. In parallel groups, concentrations of cis-crotononitrile and cyanide were assessed in whole blood. Contrary to our hypothesis, CYP2E1-null mice were slightly more susceptible to the vestibular toxicity of cis-crotononitrile than were control 129S1 mice. Similarly, rather than enhance vestibular toxicity, acetone pretreatment actually reduced it slightly in 129S1 controls, although not in CYP2E1-null mice. In addition, significant differences in mortality were recorded, with the greatest mortality occurring in 129S1 mice after acetone pretreatment. The highest mortality recorded in the 129S1 + acetone mice was associated with the lowest blood concentrations of cis-crotononitrile and the highest concentrations of cyanide at 6 h after nitrile exposure, the time when deaths were initially recorded. We conclude that cis-crotononitrile is a CYP2E1 substrate as hypothesized, but that CYP2E1-mediated metabolism of this nitrile is not necessary for vestibular toxicity; rather, this metabolism constitutes a major pathway for cyanide release and subsequent lethality.

  9. Specific Effects of Acute Moderate Exercise on Cognitive Control

    ERIC Educational Resources Information Center

    Davranche, Karen; McMorris, Terry

    2009-01-01

    The main issue of this study was to determine whether cognitive control is affected by acute moderate exercise. Twelve participants [4 females (VO[subscript 2 max]=42 ml/kg/min) and 8 males (VO[subscript 2 max]=48 ml/kg/min)] performed a Simon task while cycling at a carefully controlled workload intensity corresponding to their individual…

  10. Impulsivity, aggression and brain structure in high and low lethality suicide attempters with borderline personality disorder

    PubMed Central

    Soloff, Paul; White, Richard; Diwadkar, Vaibhav A.

    2014-01-01

    Impulsivity and aggressiveness are trait dispositions associated with the vulnerability to suicidal behavior across diagnoses. They are associated with structural and functional abnormalities in brain networks involved in regulation of mood, impulse and behavior. They are also core characteristics of borderline personality disorder (BPD), a disorder defined, in part, by recurrent suicidal behavior. We assessed the relationships between personality traits, brain structure and lethality of suicide attempts in 51 BPD attempters using multiple regression analyses on structural MRI data. BPD was diagnosed by the Diagnostic Interview for Borderline Patients-revised, impulsivity by the Barratt Impulsiveness Scale (BIS), aggression by the Brown-Goodwin Lifetime History of Aggression (LHA), and high lethality by a score of 4 or more on the Lethality Rating Scale (LRS). Sixteen High Lethality attempters were compared to 35 Low Lethality attempters, with no significant differences noted in gender, co-morbidity, childhood abuse, BIS or LHA scores. Degree of medical lethality (LRS) was negatively related to gray matter volumes across multiple fronto-temporal-limbic regions. Effects of impulsivity and aggression on gray matter volumes discriminated High from Low Lethality attempters and differed markedly within lethality groups. Lethality of suicide attempts in BPD may be related to the mediation of these personality traits by specific neural networks. PMID:24656768

  11. 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.

  12. Younger rats are more susceptible to the lethal effects of sarin than adult rats: 24 h LC50 for whole-body (10 and 60 min) exposures.

    PubMed

    Wright, Linnzi K M; Lumley, Lucille A; Lee, Robyn B; Taylor, James T; Miller, Dennis B; Muse, William T; Emm, Edward J; Whalley, Christopher E

    2017-04-01

    Chemical warfare nerve agents (CWNA) inhibit acetylcholinesterase and are among the most lethal chemicals known to man. Children are predicted to be vulnerable to CWNA exposure because of their smaller body masses, higher ventilation rates and immature central nervous systems. While a handful of studies on the effects of CWNA in younger animals have been published, exposure routes relevant to battlefield or terrorist situations (i.e. inhalation for sarin) were not used. Thus, we estimated the 24 h LC50 for whole-body (10 and 60 min) exposure to sarin using a stagewise, adaptive dose design. Specifically, male and female Sprague-Dawley rats were exposed to a range of sarin concentrations (6.2-44.0 or 1.6-12.5 mg/m³) for either 10 or 60 min, respectively, at six different times during their development (postnatal day [PND] 7, 14, 21, 28, 42 and 70). For male and female rats, the lowest LC50 values were observed for PND 14 and the highest LC50 values for PND 28. Sex differences were observed only for PND 42 for the 10 min exposures and PND 21 and 70 for the 60 min exposures. Thus, younger rats (PND 14) were more susceptible than older rats (PND 70) to the lethal effects of whole-body exposure to sarin, while adolescent (PND 28) rats were the least susceptible and sex differences were minimal. These results underscore the importance of controlling for the age of the animal in research on the toxic effects associated with CWNA exposure.