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Sample records for acute lethal effects

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

    PubMed

    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. We 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. The hydrocortisone effect was dose and time related; protection from ara-C increased from 10(-8) to 10(-5) M and was seen after 4 hr exposure but required 8 hr to reach a maximum. We conclude that hydrocortisone can protect blasts from the lethal effects of ara

  2. [Acute lethal alcohol intoxication (author's transl)].

    PubMed

    Kringsholm, B

    1976-01-01

    In 14,744 autopsy cases from an 18-year period 92 cases (of which 7 were ruled out because of decomposition were observed in which death was supposed to be due to direct acute alcoholic intoxication. In the police reports 81 persons were designated as chronic alcoholics or abusers of spirits. The blood alcohol level ranged between 2.04 and 4.92 o/oo. The cases studied were divided into two groups, one with low and the other with high lethal alcohol level. Fatty liver and cirrhosis were found with identical frequency in the two groups, whereas cardiac hypertrophy of obscure origin occurred markedly more often in the group with low lethal blood alcohol level. On the basis the possible mechanism of death in the cases with cardiac hypertrophy is discussed. Finally, the relation between the blood and urine alcohol concentrations observed in 72 cases is discussed. On the assumption that the water phase of the blood was 75 per cent of the total blood, death occurred in the persons without cardiac hypertrophy with fairly identical frequency either in the phase of absorption or the phase of elimination, whereas in the persons with cardiac hypertrophy death most often occurred in the phase of absorption. These statements should, however, be taken with some reservation, partly because the water phase of the blood may vary considerably post mortem (60-90 per cent) and partly because the urine alcohol concentration depends on serval variable factors. PMID:137612

  3. 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.

  4. Long-Term Immunity to Lethal Acute or Chronic Type II Toxoplasma gondii Infection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain▿

    PubMed Central

    Gigley, Jason P.; Fox, Barbara A.; Bzik, David J.

    2009-01-01

    C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized B6 mice chronically infected with ME49 survived for at least 12 months without succumbing to the chronic infection. Potent immunity to type II challenge infections persisted for at least 10 months after vaccination. While the cps1-1 strain-elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 strain-elicited CD8+ immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. In addition, we show that uracil starvation of the cps1-1 strain induces early markers of bradyzoite differentiation. Collectively, these results suggest that more effective immune control of chronic type II infection in the genetically susceptible B6 background is established by vaccination with the nonreplicating type I uracil auxotroph cps1-1 strain. PMID:19797073

  5. Long-term immunity to lethal acute or chronic type II Toxoplasma gondii infection is effectively induced in genetically susceptible C57BL/6 mice by immunization with an attenuated type I vaccine strain.

    PubMed

    Gigley, Jason P; Fox, Barbara A; Bzik, David J

    2009-12-01

    C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized B6 mice chronically infected with ME49 survived for at least 12 months without succumbing to the chronic infection. Potent immunity to type II challenge infections persisted for at least 10 months after vaccination. While the cps1-1 strain-elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 strain-elicited CD8(+) immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. In addition, we show that uracil starvation of the cps1-1 strain induces early markers of bradyzoite differentiation. Collectively, these results suggest that more effective immune control of chronic type II infection in the genetically susceptible B6 background is established by vaccination with the nonreplicating type I uracil auxotroph cps1-1 strain. PMID:19797073

  6. Lethal acute liver failure in a patient treated with sunitinib.

    PubMed

    Guillen, S S; Meijer, M; de Jongh, F E

    2016-01-01

    Sunitinib is a tyrosine kinase inhibitor that is used as an anticancer drug in renal cell carcinoma (RCC), pancreatic neuroendocrine tumours (PNETs) and gastrointestinal stromal tumour. Elevated liver enzymes are frequently observed during treatment but acute liver failure is uncommon. We describe a case of fulminant acute liver failure and acute kidney injury during treatment with sunitinib for metastatic RCC. PMID:26933184

  7. 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. PMID:27074931

  8. Lethal and Sub-lethal Effects of UVB on Juvenile Biomphalaria glabrata (Mollusca: Pulmonata)

    PubMed Central

    Ruelas, Debbie S.; Karentz, Deneb; Sullivan, John T.

    2007-01-01

    Although Schistosoma mansoni occurs mainly in the tropics, where intense levels of solar radiation are present, the impact of ultraviolet (UV) light on schistosome transmission is not known. The purpose of this study was to investigate potential effects of UVB (290–320 nm) on juvenile Biomphalaria glabrata, the snail intermediate host of S. mansoni. Albino and wild type snails were exposed to doses of UVB from UV-fluorescent lamps, and the following were measured: survival, photoreactivation (light-mediated DNA repair), effects on feeding behavior, and morphological tissue abnormalities. Irradiation with UVB is lethal to B. glabrata in a dose-dependent manner. Exposure to white light subsequent to UVB irradiation enhances survival, probably by photoreactivation. The shell offers some, but not complete, protection. Experiments in which UVB transmittance through the shell was blocked with black nail polish suggest that injury to both exposed (headfoot) and shell-enclosed (mantle and visceral mass) tissues contributes to mortality in lethally-irradiated snails. Wild-type (pigmented) snails are less susceptible to lethal effects of UVB than albino snails, and they may be more capable of photoreactivation. UVB exposure inhibits snail feeding behavior, and causes tentacle forks and growths on the headfoot. Thus, UVB may influence the life cycle of S. mansoni by both lethal and sub-lethal damage to the snail intermediate host. However, the ability of snails to photoreactivate may mitigate these effects. PMID:16996081

  9. Nanocomposite Treatment Reduces Disease and Lethality in a Murine Model of Acute Graft-versus-Host Disease and Preserves Anti-Tumor Effects

    PubMed Central

    Resende, Carolina B.; De Paula, Talles P.; Reis, Alesandra C.; Gonçalves, William A.; Vieira, Elias G.; Pinheiro, Maurício V. B.; Souza, Danielle G.; Castor, Marina G. M.; Teixeira, Mauro M.; Pinho, Vanessa

    2015-01-01

    Graft versus host disease (GVHD) is an immunological disorder triggered by bone marrow transplantation that affects several organs, including the gastrointestinal tract and liver. Fullerenes and their soluble forms, fullerols, are nanocomposites with a closed symmetrical structure with anti-inflammatory and anti-oxidant properties. The present study evaluated the effects of treatment with the fullerol (C60(OH)18-20) in the development and pathogenesis of GVHD in a murine model. Mice with experimental GVHD that were treated with the fullerol showed reduced clinical signs of disease and mortality compared with untreated mice. Treatment with the fullerol decreased the hepatic damage associated with reduced hepatic levels of reactive oxygen species, pro-inflammatory cytokines and chemokines (IFN-γ TNF-α, CCL2, CCL3 and CCL5) and reduced leukocyte accumulation. The amelioration of GVHD after treatment with the fullerol was also associated with reduced intestinal lesions and consequent bacterial translocation to the blood, liver and peritoneal cavity. Moreover, the fullerol treatment alleviated the GVHD while preserving effects of the graft against a leukemia cell line (GFP+P815). In summary, the fullerol was effective in reducing the GVHD inflammatory response in mice and may suggest novel ways to treat this disease. PMID:25875016

  10. 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. PMID:24867061

  11. 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. PMID:15880684

  12. Assessing lethal and sub-lethal effects of trichlorfon on different trophic levels.

    PubMed

    Coelho, Sónia; Oliveira, Rhaul; Pereira, Susana; Musso, Carolina; Domingues, Inês; Bhujel, Ram C; Soares, Amadeu M V M; Nogueira, António J A

    2011-06-01

    Trichlorfon (TCF) is one of the most used veterinary pharmaceuticals not only to fight infestations but also as a preventive measure worldwide. The high concentrations used generate concerns about environmental and human health. In this work we assessed the acute toxicity of this compound to non-target organisms belonging to different trophic levels: Danio rerio (early life stages and adults), Daphnia magna and algae (Pseudokirchneriella subcapitata and Chlorella vulgaris), and studied the potential of the biomarkers cholinesterase (ChE), glutathione-S-transferase (GST), lactate dehydrogenase (LDH) and catalase (CAT) to assess sub-lethal effects of trichlorfon in zebrafish and daphnids. The fish embryo test followed the OECD draft guideline FET and was based on the exposure of newly fertilized eggs to 0, 2.5, 5.0, 10, 20, 40, 80 and 160 mg/L of TCF for 5 days; the fish acute test followed the OECD guideline 203 and was based on the exposure of adult fish to 0, 2.5, 5, 10, 20, 40, 60 and 80 mg/L of TCF for 4 days; Daphnia sp. immobilization assay followed the OECD guideline 202 and was based on the exposure of juvenile daphnids to 0, 0.1, 0.3, 0.5, 0.7, 0.9, 1 and 2 μg/L of TCF for 2 days and the algae growth inhibition assay followed the OECD guideline 201 and was based on the exposure of the two species to 0, 1, 3.2, 10, 32, 100 and 300 mg/L of TCF for 4 days. Biomarker levels were measured after 96 h exposure to TCF in zebrafish early life stages and adults and after 48 h exposure in D. magna. Tested organisms seem to have dissimilar sensitivities towards TCF exposure. D. magna (48 h-LC(50)=0.29 μg/L) was the most sensitive organism, followed by early life stages and adults of zebrafish (96 h-LC(50)=25.4 and 28.8 mg/L, respectively) and finally by the algae P. subcapitata (96 h-LC(50)=274.5 mg/L) and C. vulgaris (no effect observed). As daphnids are a source of food for organisms of higher trophic levels, the impairment on its population is prone to have

  13. 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. PMID:26874341

  14. 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. PMID:26352754

  15. 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. PMID:26493272

  16. 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.

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

    PubMed Central

    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

    2009-01-01

    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 alpha beta T cells. Nevertheless, the antibody treatment did not prevent the development of lethal encephalitis. In contrary, the adoptive transfer of primed CD4+ T cells is necessary to prevent lethal encephalitis in mice lacking alpha beta T cell receptor. PMID:19446933

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

    SciTech Connect

    Williams, P.L.

    1988-01-01

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

  19. Acute lethal graft-versus-host disease stimulates cellular proliferation in the adult rat liver.

    PubMed

    Klein, R M; Clancy, J; Stuart, S

    1982-11-01

    The present investigation was designed to analyse the effects of acute lethal graft-versus-host disease (GVHD) in adult (DA x LEW)F1 rats on cellular proliferation within the liver. The influence of the host thymus on GVHD-induced proliferation was also assessed. From 1-28 days after initiation of GVHD [3H]thymidine ([3H]-TdR) was injected i.v. and rats were killed one hour later. Percentage labelled cells (LI) of periportal infiltrating cells (PIC), hepatocytes (H), and sinusoidal lining cells (SC) were counted. Mean values for control rats were 0.3 +/- 0.1% (H), 0.4 +/- 0.1% (SC) and 0.2 +/- 0.1% (PIC). GVHD rats demonstrated a significant increase in LI of PIC (days 1-21), SC (days 2-17) and H (days 2-17). Most labelled cells in PIC were large lymphocytes. Peak LI values were 7.0 +/- 1.0% PIC (day 17), 6.8 +/- 0.9% SC (day 17), and 5.2 +/- 0.9% H (day 7), with all cellular compartments returning to near normal LI values by day 28. Stimulation of cellular proliferation occurred in all three liver cell compartments in neonatally thymectomized (TXM) rats. The intensity of GVHD-induced cell proliferation was significantly decreased at day 7 in all compartments and PIC was dramatically decreased at day 21 in TXM-GVHD rats as compared to non-TXM-GVHD rats. It is hypothesized that the general stimulation of hepatocyte cell proliferation in GVHD is related to the secretion of lymphokines by primarily donor and secondarily host T cells in the periportal infiltrate. PMID:7172201

  20. Lethal and sub-lethal effects of faecal deltamethrin residues on dung-feeding insects.

    PubMed

    Mann, C M; Barnes, S; Offer, B; Wall, R

    2015-06-01

    Endectocides administered to livestock to facilitate pest and parasite control may be excreted in the faeces at concentrations that are toxic to coprophagous insects, including species of ecological importance. Although much research has focused on the effects of macrocyclic lactones, relatively less attention has been given to any similar impacts of the widely used pyrethroid insecticides. Here, the effects of faecal residues of the pyrethroid deltamethrin after application to Holstein-Friesian cattle in a proprietary pour-on formulation are examined. Freshly dropped dung was collected 1, 3, 5 and 7 days after treatment and from an untreated control group. In laboratory bioasssays, female Lucilia sericata (Diptera: Calliphoridae) blow flies matured significantly smaller egg batches and had a lower percentage of eggs hatch after feeding on dung collected for up to 5 days after treatment, compared with flies feeding on dung from untreated cattle. In the field, artificial dung pats were constructed from the collected dung and left on pastureland for 7 days before being retrieved and searched for insects. Significantly more adult Diptera emerged from the faeces of untreated cattle than from the dung of treated cattle collected on days 1 and 3 after treatment. Adult Coleoptera were found in lower numbers in the dung of treated animals compared with control dung, suggesting a repellent effect. The results indicate that deltamethrin residues in cattle faeces have a range of lethal and sub-lethal effects on dung-feeding insects for up to a week after treatment, but that the precise duration and nature of toxicity varies depending on the sensitivity of the insect in question. PMID:25594879

  1. Anthrax Lethal Toxin Induces Acute Diastolic Dysfunction in Rats Through Disruption of the Phospholamban Signaling Network

    PubMed Central

    Golden, Honey B.; Watson, Linley E.; Nizamutdinov, Damir; Feng, Hao; Gerilechaogetu, Fnu; Lal, Hind; Verma, Suresh K.; Mukhopadhyay, Swagoto; Foster, Donald M.; Dillmann, Wolfgang H.; Dostal, D.E.

    2013-01-01

    Background Anthrax lethal toxin (LT), secreted by Bacillus anthracis, causes severe cardiac dysfunction by unknown mechanisms. LT specifically cleaves the docking domains of MAPKK (MEKs); thus, we hypothesized that LT directly impairs cardiac function through dysregulation of MAPK signaling mechanisms. Methods and Results In a time-course study of LT toxicity, echocardiography revealed acute diastolic heart failure accompanied by pulmonary regurgitation and left atrial dilation in adult Sprague-Dawley rats at time points corresponding to dysregulated JNK, phospholamban (PLB) and protein phosphatase 2A (PP2A) myocardial signaling. Using isolated rat ventricular myocytes, we identified the MEK7-JNK1-PP2A-PLB signaling axis to be important for regulation of intracellular calcium (Ca2+i) handling, PP2A activation and targeting of PP2A-B56α to Ca2+i handling proteins, such as PLB. Through a combination of gain-of-function and loss-of-function studies, we demonstrated that over-expression of MEK7 protects against LT-induced PP2A activation and Ca2+i dysregulation through activation of JNK1. Moreover, targeted phosphorylation of PLB-Thr17 by Akt improved sarcoplasmic reticulum Ca2+i release and reuptake during LT toxicity. Co-immunoprecipitation experiments further revealed the pivotal role of MEK7-JNK-Akt complex formation for phosphorylation of PLB-Thr17 during acute LT toxicity. Conclusions Our findings support a cardiogenic mechanism of LT-induced diastolic dysfunction, by which LT disrupts JNK1 signaling and results in Ca2+i dysregulation through diminished phosphorylation of PLB by Akt and increased dephosphorylation of PLB by PP2A. Integration of the MEK7-JNK1 signaling module with Akt represents an important stress-activated signalosome that may confer protection to sustain cardiac contractility and maintain normal levels of Ca2+i through PLB-T17 phosphorylation. PMID:23907041

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

    PubMed Central

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

    2014-01-01

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

  3. 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.

  4. Effects of gas supersaturation on lethality and avoidance responses in juvenile rock carp (Procypris rabaudi Tchang)*

    PubMed Central

    Huang, Xiang; Li, Ke-feng; Du, Jun; Li, Ran

    2010-01-01

    Laboratory experiments were conducted to determine the effects of total dissolved gas (TDG) supersaturation on acute lethality and avoidance responses in juvenile rock carp (Procypris rabaudi Tchang). The juvenile rock carp were exposed to water with different levels of supersaturation (105%, 115%, 120%, 125%, 130%, 135%, 140%, and 145%) and depth of 0.20 m at 25 °C for 60 h. Median lethal time (LT50) was used to assess the lethal responses corresponding to different levels of gas supersaturation. The results show that half of the juvenile rock carp died at the 120%, 125%, 130%, 135%, 140%, and 145% levels of supersaturation, and the LT50 corresponding to different levels of supersaturation was 18.7, 15.4, 8.2, 6.6, 3.5, and 1.7 h. When the level of supersaturated water is below 115%, the mortality is negligible. Avoidance responses were observed 5 min after the fish were put into equilibrated water (99%, 0.08 m deep) and water with different supersaturated levels (105%, 115%, 125%, 135%, and 145%, 0.08 m deep) at 25 °C. The fish exhibited strong avoidance responses in supersaturated water when the gas supersaturation was above 135%. However, they exhibited an obvious preference to supersaturated water when the gas supersaturation was below 115%. Thus, the juvenile rock carp can likely survive in water with a supersaturated level of 115%. PMID:20872989

  5. Replication of an acutely lethal simian immunodeficiency virus activates and induces proliferation of lymphocytes.

    PubMed Central

    Fultz, P N

    1991-01-01

    A variant of simian immunodeficiency virus from sooty mangabey monkeys (SIVsmm), termed SIVsmmPBj14, was previously identified and shown to induce acute disease and death within 1 to 2 weeks of inoculation of pig-tailed macaques and mangabey monkeys (P. N. Fultz, H. M. McClure, D. C. Anderson, and W. M. Switzer, AIDS Res. Hum. Retroviruses 5:397-409, 1989). SIVsmmPBj14 differed from its parent virus, SIVsmm9, not only in pathogenicity but also in multiple in vitro properties. As a first approach to understanding the biological and molecular mechanisms responsible for the acute disease and death induced by this variant, virus-host cell interactions of SIVsmmPBj14 and SIVsmm9 were studied. Initial rates of replication of the two viruses were identical in primary peripheral blood mononuclear cells (PBMC) from normal pig-tailed macaques and mangabey monkeys, but SIVsmmPBj14 infection always resulted in higher yields of virus than did SIVsmm9 infection, as assessed by levels of reverse transcriptase activity in culture supernatants. Surprisingly, despite its cytopathicity for macaque and mangabey CD4+ cells, replication of SIVsmmPBj14 was accompanied by up to 10-fold increases in number of viable cells compared with cell numbers in uninfected or SIVsmm9-infected cultures. Furthermore, SIVsmmPBj14 was shown to infect and replicate in resting PBMC just as efficiently as in mitogen-stimulated PBMC, irrespective of whether exogenous interleukin-2 (IL-2) or antibodies that neutralized IL-2 were added to culture media. Accumulation of virus in culture supernatants of resting PBMC preceded by several days the appearance of activated cells which expressed the IL-2 receptor alpha subunit (CD25), suggesting that activation of cells was not essential for replication. The ability to activate and to induce simian PBMC to proliferate appeared specific for the acutely lethal variant because incorporation of [3H]thymidine by PBMC from naive animals was observed only upon incubation

  6. ACUTE LETHAL CONCENTRATIONS OF CAFFEINE ON NON-TARGET FRESHWATER ORGANISMS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite the recent detection of caffeine in US streams, studies investigating caffeine's toxic effects on non-target freshwater organisms lack acute data for several standard surrogate species and chronic data for any freshwater species. The present study describes the mortality rate at different c...

  7. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats.

    PubMed

    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

  8. 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

  9. Airway Tissue Plasminogen Activator Prevents Acute Mortality Due to Lethal Sulfur Mustard Inhalation

    PubMed Central

    Veress, Livia A.; Anderson, Dana R.; Hendry-Hofer, Tara B.; Houin, Paul R.; Rioux, Jacqueline S.; Garlick, Rhonda B.; Loader, Joan E.; Paradiso, Danielle C.; Smith, Russell W.; Rancourt, Raymond C.; Holmes, Wesley W.; White, Carl W.

    2015-01-01

    Rationale: Sulfur mustard (SM) is a chemical weapon stockpiled today in volatile regions of the world. SM inhalation causes a life-threatening airway injury characterized by airway obstruction from fibrin casts, which can lead to respiratory failure and death. Mortality in those requiring intubation is more than 80%. No therapy exists to prevent mortality after SM exposure. Our previous work using the less toxic analog of SM, 2-chloroethyl ethyl sulfide, identified tissue plasminogen activator (tPA) an effective rescue therapy for airway cast obstruction (Veress, L. A., Hendry-Hofer, T. B., Loader, J. E., Rioux, J. S., Garlick, R. B., and White, C. W. (2013). Tissue plasminogen activator prevents mortality from sulfur mustard analog-induced airway obstruction. Am. J. Respir. Cell Mol. Biol. 48, 439–447). It is not known if exposure to neat SM vapor, the primary agent used in chemical warfare, will also cause death due to airway casts, and if tPA could be used to improve outcome. Methods: Adult rats were exposed to SM, and when oxygen saturation reached less than 85% (median: 6.5 h), intratracheal tPA or placebo was given under isoflurane anesthesia every 4 h for 48 h. Oxygen saturation, clinical distress, and arterial blood gases were assessed. Microdissection was done to assess airway obstruction by casts. Results: Intratracheal tPA treatment eliminated mortality (0% at 48 h) and greatly improved morbidity after lethal SM inhalation (100% death in controls). tPA normalized SM-associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress. Moreover, tPA treatment resulted in greatly diminished airway casts, preventing respiratory failure from airway obstruction. Conclusions: tPA given via airway more than 6 h after exposure prevented death from lethal SM inhalation, and normalized oxygenation and ventilation defects, thereby rescuing from respiratory distress and failure. Intra-airway tPA should be considered as a life

  10. Demographic Toxicokinetic-Toxicodynamic Modeling of Lethal Effects.

    PubMed

    Gergs, André; Gabsi, Faten; Zenker, Armin; Preuss, Thomas G

    2016-06-01

    The aquatic effect assessment of chemicals is largely based on standardized measures of toxicity determined in short-term laboratory tests which are designed to reduce variability. For this purpose, uniform individuals of a species are kept under environmental and chemical exposure conditions which are as constant as possible. In nature, exposure often appears to be pulsed, effects might last longer than a few days, sensitivity might vary among different sized organisms and populations are usually size or age structured and are subject to demographic processes. To overcome this discrepancy, we tested toxicokinetic-toxicodynamic models of different complexities, including body size scaling approaches, for their ability to represent lethal effects observed for Daphnia magna exposed to triphenyltin. The consequences of the different toxicokinetic and toxicodynamic assumptions for population level responses to pulsed exposure are tested by means of an individual based model and are evaluated by confronting model predictions with population data for various pulsed exposure scenarios. We provide an example where increased model complexity reduces the uncertainty in model outputs. Furthermore, our results emphasize the importance of considering population demography in toxicokinetics and toxicodynamics for understanding and predicting potential chemical impacts at higher levels of biological organization. PMID:27158745

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

    PubMed Central

    Bell, M L; Davis, D L

    2001-01-01

    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. PMID:11427388

  12. 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. PMID:11427388

  13. 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. PMID:27262939

  14. 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

  15. BIOASSAY PROTOCOL FOR LETHAL AND SUBLETHAL EFFECTS OF FUNGAL PATHOGENS ON CHRYSOPERLA CARNEA

    EPA Science Inventory

    This practice describes procedures for evaluating the lethal and sub-lethal effects of exposure to fungal pathogens on larvae and adults of the predatory insect Chrysoperla carnea (Stephens). his practice was developed and tested with the fungal insect pathogen Beauveria bassiana...

  16. Effect of lethality on the extinction and on the error threshold of quasispecies.

    PubMed

    Tejero, Hector; Marín, Arturo; Montero, Francisco

    2010-02-21

    In this paper the effect of lethality on error threshold and extinction has been studied in a population of error-prone self-replicating molecules. For given lethality and a simple fitness landscape, three dynamic regimes can be obtained: quasispecies, error catastrophe, and extinction. Using a simple model in which molecules are classified as master, lethal and non-lethal mutants, it is possible to obtain the mutation rates of the transitions between the three regimes analytically. The numerical resolution of the extended model, in which molecules are classified depending on their Hamming distance to the master sequence, confirms the results obtained in the simple model and shows how an error catastrophe regime changes when lethality is taken in account. PMID:19833133

  17. Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus▿

    PubMed Central

    McCray, Paul B.; Pewe, Lecia; Wohlford-Lenane, Christine; Hickey, Melissa; Manzel, Lori; Shi, Lei; Netland, Jason; Jia, Hong Peng; Halabi, Carmen; Sigmund, Curt D.; Meyerholz, David K.; Kirby, Patricia; Look, Dwight C.; Perlman, Stanley

    2007-01-01

    The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies. PMID:17079315

  18. 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.

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

    PubMed Central

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

    2014-01-01

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

  20. Effect of temperature and heating rate on apparent lethal concentrations of pyrolysis products

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Solis, A. N.; Marcussen, W. H.; Furst, A.

    1976-01-01

    The apparent lethal concentrations for 50 percent of the test animals of the pyrolysis products from twelve polymeric materials were studied as a function of temperature and heating rate. The materials were polyethylene, nylon 6, ABS, polycarbonate, polyether sulfone, polyaryl sulfone, wool fabric, aromatic polyamide fabric, polychloroprene foam, polyvinyl fluoride film, Douglas fir, and red oak. The apparent lethal concentration values of most materials vary significantly with temperature and heating rate. The apparent lethal concentration values, based on weight of sample charged, appears to effectively integrate the thermophysical, thermochemical, and physiological responses from a known quantity of material under specified imposed conditions.

  1. 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.

  2. 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. PMID:27461039

  3. USE OF LETHALITY DATA DURING CATEGORICAL REGRESSION MODELING OF ACUTE REFERENCE EXPOSURES

    EPA Science Inventory

    Categorical regression is being considered by the U.S. EPA as an additional tool for derivation of acute reference exposures (AREs) to be used for human health risk assessment for exposure to inhaled chemicals. Categorical regression is used to calculate probability-response fun...

  4. 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

  5. Clinical effects and lethal and forensic aspects of propofol.

    PubMed

    Levy, Richard J

    2011-01-01

    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 postmortem 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

  6. 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

  7. 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.

  8. 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. PMID:20850107

  9. 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. PMID:26367124

  10. 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

  11. 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

  12. 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.

  13. 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. PMID:26621540

  14. Protection of Escherichia coli from the Lethal Effect of Colicins by High Osmotic Pressure

    PubMed Central

    Beppu, Teruhiko; Arima, Kei

    1967-01-01

    The sensitivity of Escherichia coli to the lethal effect of colicin E2 was reduced by elevation of osmotic pressure of the incubation medium. Optimal protection of the cells from the lethal effect of colicin E2 was achieved with 0.6 to 0.8 m NaCl or with 0.8 m sucrose containing 0.01 m MgSO4. Under such conditions, the degradation of deoxyribonucleic acid caused by colicin E2 was also suppressed markedly. It was concluded that a high concentration of sucrose with Mg++ might prevent the action of the adsorbed colicin E2. A similar protection was observed against the lethal effect of colicin K. PMID:5335904

  15. 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

  16. Lethal and sublethal effects of cyantraniliprole on Bactrocera dorsalis (Hendle) (Diptera: Tephiritidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The oriental fruit fly, Bactrocera dorsalis (Hendel) is one of the most important and damaging fruit pests in the world. Studies were conducted with a novel anthranilic diamide insecticide (i.e. DuPontTM CyazypyrTM) cyantraniliprole to determine its lethal and sublethal effects on B. dorsalis. An in...

  17. Effects of total dissolved gas supersaturated water on lethality and catalase activity of Chinese sucker (Myxocyprinus asiaticus Bleeker)*

    PubMed Central

    Chen, Shi-chao; Liu, Xiao-qing; Jiang, Wen; Li, Ke-feng; Du, Jun; Shen, Dan-zhou; Gong, Quan

    2012-01-01

    Total dissolved gas (TDG) supersaturation caused by dam sluicing can result in gas bubble trauma (GBT) in fish and threaten their survival. In the present study, Chinese suckers (Myxocyprinus asiaticus Bleeker) were exposed to TDG supersaturated water at levels ranging from 120% to 145% for 48 h. The median lethal concentration (LC50) and the median lethal time (LT50) were determined to evaluate acute lethal effects on Chinese suckers. The results showed that the LC50 values of 4, 6, 8, and 10 h were 142%, 137%, 135%, and 130%, respectively. The LT50 values were 3.2, 4.7, 7.8, 9.2, and 43.4 h, respectively, when TDG supersaturated levels were 145%, 140%, 135%, 130%, and 125%. Furthermore, the biological responses in Chinese suckers were studied by assaying the catalase (CAT) activities in gills and muscles at the supersaturation level of 140% within LT50. The CAT activities in the gills and muscle tissues exhibited a regularity of a decrease after an increase. CAT activities in the muscles were increased significantly at 3/5LT50 (P<0.05) and then came back to the normal level. However, there were no significant differences between the treatment group (TDG level of 140%) and the control group (TDG level of 100%) on CAT activities in the gills before 3/5LT50 (P>0.05), but the activities were significantly lower than the normal level at 4/5LT50 and LT50 (P<0.05). PMID:23024046

  18. Effects of total dissolved gas supersaturated water on lethality and catalase activity of Chinese sucker (Myxocyprinus asiaticus Bleeker).

    PubMed

    Chen, Shi-chao; Liu, Xiao-qing; Jiang, Wen; Li, Ke-feng; Du, Jun; Shen, Dan-zhou; Gong, Quan

    2012-10-01

    Total dissolved gas (TDG) supersaturation caused by dam sluicing can result in gas bubble trauma (GBT) in fish and threaten their survival. In the present study, Chinese suckers (Myxocyprinus asiaticus Bleeker) were exposed to TDG supersaturated water at levels ranging from 120% to 145% for 48 h. The median lethal concentration (LC(50)) and the median lethal time (LT(50)) were determined to evaluate acute lethal effects on Chinese suckers. The results showed that the LC(50) values of 4, 6, 8, and 10 h were 142%, 137%, 135%, and 130%, respectively. The LT(50) values were 3.2, 4.7, 7.8, 9.2, and 43.4 h, respectively, when TDG supersaturated levels were 145%, 140%, 135%, 130%, and 125%. Furthermore, the biological responses in Chinese suckers were studied by assaying the catalase (CAT) activities in gills and muscles at the supersaturation level of 140% within LT(50). The CAT activities in the gills and muscle tissues exhibited a regularity of a decrease after an increase. CAT activities in the muscles were increased significantly at 3/5LT(50) (P<0.05) and then came back to the normal level. However, there were no significant differences between the treatment group (TDG level of 140%) and the control group (TDG level of 100%) on CAT activities in the gills before 3/5LT(50) (P>0.05), but the activities were significantly lower than the normal level at 4/5LT(50) and LT(50) (P<0.05). PMID:23024046

  19. Effect of UV irradiation on lethal infection of mice with Candida albicans.

    PubMed

    Denkins, Y M; Kripke, M L

    1993-02-01

    Exposure of mice to UV radiation inhibits the induction and elicitation of the delayed-type hypersensitivity (DTH) response to Candida albicans. To determine whether UV irradiation also affects the pathogenesis of systemic C. albicans infection, C3H mice were exposed to a single dose of 48 kJ/m2 UV-B radiation from FS40 sunlamps 5 days before or 5 days after sensitization with formalin-fixed C. albicans and challenged intravenously (i.v.) with a lethal dose of viable fungi 6 days after sensitization (11 or 1 days after UV irradiation). Exposing unsensitized mice to UV radiation 11 days before lethal challenge had no effect on survival, but the survival time of mice exposed to UV radiation 1 day before challenge was reduced by more than 50%. In the latter group, decreased survival time correlated with persistence of C. albicans in the brain and progressive growth of C. albicans in the kidneys. Sensitization of unirradiated mice with formalin-fixed C. albicans extended their survival time following lethal i.v. challenge with viable C. albicans. Exposing the mice to UV radiation 5 days before sensitization did not abrogate this beneficial effect of sensitization on survival, even though it significantly reduced the DTH response. Thus, immunity to systemic infection did not depend on the ability of the mice to exhibit a DTH response to C. albicans. The beneficial effect of sensitization on survival after lethal infection was abrogated, however, in mice exposed to UV radiation 1 day before lethal challenge with C. albicans. Furthermore, these mice were unable to contain the progressive growth of C. albicans in the kidneys, in contrast to sensitized, unirradiated mice. PMID:8451288

  20. [Lethal effect of Cuban Myrtaceae on Aedes aegypti (Diptera Cuilicidae)].

    PubMed

    Aguilera, Lucita; Navarro, Agustín; Tacoronte, Juan E; Leyva, Maureen; Marquetti, María C

    2003-01-01

    The biological activity of the essential foliar oils from 2 Cuban endemic Myrtaceae: Eugenia melanadenia and Psidium rotundatum on A. aegypti larvae was evaluated for the first time at the laboratory level. The probit-log analysis of the results showed the larvicidal effect of both oils with values of CL50 = 0.0085% and CL95 = 0.0104% for E. melanadenia and CL50 = 0.0063% and CL95 = 0.0071% for O. rotundatum. Besides, the diagnostic concentration for both essential oils are given and the possible implications of these findings on field populations of A. aegypti are suggessted. PMID:15849965

  1. Recombinant expression of Bacillus anthracis lethal toxin components of Indian isolate in Escherichia coli and determination of its acute toxicity level in mouse model.

    PubMed

    Nagendra, Suryanarayana; Vanlalhmuaka; Verma, Sarika; Tuteja, Urmil; Thavachelvam, Kulanthaivel

    2015-12-15

    Bacillus anthracis lethal toxin (LeTx) is the principle factor responsible for toxaemia and anthrax related death. Lethal toxin consist of two proteins viz protective antigen (PA) and lethal factor which combines in a typical fashion similar to other toxins belonging to A-B toxin super family. The amount of LeTx required to kill a particular organism generally differs among strains owing to their geographical distributions and genetic variation. In the present study, we have cloned PA and LF genes from B. anthracis clinical isolate of Indian origin and expressed them in soluble form employing Escherichia coli expression system. Both the proteins were purified to near homogeneity level using Immobilized metal ion affinity chromatography (IMAC). Further we have used equal ratio of both the proteins to form LeTx and determined its acute toxicity level in Balb/c mice by graphical method of Miller and Tainter. The LD50 value of LeTx by intravenous (i.v) route was found to be 0.97 ± 0.634 mg kg(-1) Balb/c mice. This study highlights the expression of recombinant LeTx from E. coli and assessing its acute toxicity level in experimental mouse model. PMID:26472254

  2. 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. PMID:2728023

  3. Lethal effect of mitomycin C on Haemophilus influenzae.

    PubMed Central

    Small, G D; Setlow, J K; Kooistra, J; Shapanka, R

    1976-01-01

    The sensitivity of ultraviolet-sensitive strains to inactivation by mitomycin C (MC) is at the most only a factor of two greater than that of the wild type. The presence of inducible prophage has very little effect on the sensitivity. Genes which control excision of ultraviolet-induced pyrimidine dimers also control repair of MC-induced cross-links, as measured by resistance of denatured deoxyribonucleic acid (DNA) from treated cells to S1 nuclease digestion. However, endonucleolytic breaks in MC-damaged DNA, as judged by decreased single-strand molecular weight upon incubation of treated cells, are independent of these genes and probably are caused by monoadducts. After long periods of incubation there is a return to the molecular weight of untreated DNA. DNA degradation after MC treatment of various strains is not correlated with sensitivity to inactivation. Stationary-phase cells of all strains are more than twice as sensitive to MC as exponentially growing cells, and the sensitivity difference agrees with the measured difference in the number of cross-links after MC treatment of cells in the two growth stages. Evidence has been obtained that these phenomena result from differences in uptake of MC, which can be influenced by cyclic adenosine monophosphate. Small deviations in MC sensitivity from that of the wild type observed in mutants lacking the adenosine 5'-triphosphate-dependent nuclease are postulated to result from differences in MC uptake. These mutants, although no more ultraviolet sensitive than the wild type, are more sensitive to streptomycin, which also must be taken up by the cell to be effective. PMID:173712

  4. Evaluating the lethal and pre-lethal effects of a range of fungi against adult Anopheles stephensi mosquitoes

    PubMed Central

    2012-01-01

    Background Insecticide resistance is seriously undermining efforts to eliminate malaria. In response, research on alternatives to the use of chemical insecticides against adult mosquito vectors has been increasing. Fungal entomopathogens formulated as biopesticides have received much attention and have shown considerable potential. This research has necessarily focused on relatively few fungal isolates in order to ‘prove concept’. Further, most attention has been paid to examining fungal virulence (lethality) and not the other properties of fungal infection that might also contribute to reducing transmission potential. Here, a range of fungal isolates were screened to examine variation in virulence and how this relates to additional pre-lethal reductions in feeding propensity. Methods The Asian malaria vector, Anopheles stephensi was exposed to 17 different isolates of entomopathogenic fungi belonging to species of Beauveria bassiana, Metarhizium anisopliae, Metarhizium acridum and Isaria farinosus. Each isolate was applied to a test substrate at a standard dose rate of 1×109 spores ml-1 and the mosquitoes exposed for six hours. Subsequently the insects were removed to mesh cages where survival was monitored over the next 14 days. During this incubation period the mosquitoes’ propensity to feed was assayed for each isolate by offering a feeding stimulant at the side of the cage and recording the number probing. Results and conclusions Fungal isolates showed a range of virulence to A. stephensi with some causing >80% mortality within 7 days, while others caused little increase in mortality relative to controls over the study period. Similarly, some isolates had a large impact on feeding propensity, causing >50% pre-lethal reductions in feeding rate, whereas other isolates had very little impact. There was clear correlation between fungal virulence and feeding reduction with virulence explaining nearly 70% of the variation in feeding reduction. However, there

  5. Protective effect of picolinic acid on mice intracerebrally infected with lethal doses of Candida albicans.

    PubMed Central

    Blasi, E; Mazzolla, R; Pitzurra, L; Barluzzi, R; Bistoni, F

    1993-01-01

    We have studied the effects of picolinic acid (PLA), a product of tryptophan degradation, on mouse susceptibility to intracerebral infection with Candida albicans. We show that intraperitoneal administration of PLA significantly enhances the median survival time of mice inoculated with the lethal challenge. Furthermore, intracerebral administration of this agent induces a protective state against the local lethal infection, the phenomenon depending upon the administration schedule and doses of PLA employed. According to survival data, yeast growth in the brain as well as yeast colonization of the kidneys are drastically reduced in PLA-treated mice compared with those for untreated controls. Northern (RNA) blot analysis of brain tissues demonstrates that mRNA levels specific for tumor necrosis factor and interleukin 1 are augmented and induced, respectively, after inoculation of PLA. These results indicate that PLA has a protective effect likely involving elicitation of a cytokine response in vivo against fungal infections. Images PMID:7506894

  6. 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

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

    PubMed

    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

  8. Lethal and sublethal effects of lufenuron on sugarcane borer Diatraea flavipennella and its parasitoid Cotesia flavipes.

    PubMed

    Fonseca, Ana Paula Pereira; Marques, Edmilson Jacinto; Torres, Jorge Braz; Silva, Liliane Marques; Siqueira, Herbert Álvaro Abreu

    2015-11-01

    The combination of chemical and biological controls is a historic goal of integrated pest management, but has rarely been achieved due to lethal and sublethal impact of insecticides on natural enemies altering their performance. In this context, the susceptibility of the yellow sugarcane borer, Diatraea flavipennella (Lepidoptera: Crambidae), to the insect growth regulator lufenuron and the consequent effects upon its endoparasitoid Cotesia flavipes (Hymenoptera: Braconidae) encountering exposed but surviving larvae were studied. Neonate and 10-day-old larvae were subjected to one of seven concentrations of lufenuron (1.56, 3.12, 6.25, 12.5, 25.0, 50.0 and 100 mg a.i./L). Further, effects of lufenuron to the host larvae and to the parasitoid were assessed using low lethal LC20 and LC50. Lufenuron at concentrations up to 12.5 mg a.i./L allowed partial survival of borer larvae; and concentrations over 12.5 mg a.i./L caused 100 % larval mortality before pupation in both ages. Neonate larvae exhibited lower pupal weights only at concentrations 12.5 mg a.i./L; while 10-day-old larvae treated with the LC50 exhibited delayed development. Egg viability was reduced for adult borers from surviving larvae of both ages treated with low lethal concentrations. The parasitoid C. flavipes successfully parasitized surviving low lethal treated larvae. Among the studied life history characteristics of C. flavipes, only a delayed development was observed. The results showed that lufenuron can be effective against D. flavipennella at concentrations over 25 mg a.i./L, and that surviving larvae can be successfully parasitized by C. flavipes. The insecticide lufenuron and the parasitoid C. flavipes seem to be compatible for sugarcane borer control. PMID:26250937

  9. Association of immunological disorders in lethal side effect of NSAIDs on beta-glucan-administered mice.

    PubMed

    Takahashi, H; Ohno, N; Adachi, Y; Yadomae, T

    2001-07-01

    (1-->3)-beta-D-Glucan (beta-glucan) is a biological response modifier that regulates host immune response. We have found that the combination of a beta-glucan and a non-steroidal anti-inflammatory drug (NSAID), indomethacin (IND), induced lethal toxicity in mice [Yoshioka et al. (1998) FEMS Immunol. Med. Microbiol., 21, 171-179]. This study was undertaken to analyze the mechanism of the lethal side effect. Combination of a beta-glucan and IND increased the number of leukocytes, especially macrophages and neutrophils, in various organs and these cells were activated. The activated state of these cells was supported by the enhanced production of interferon-gamma in the presence of IND in vitro culture of the peritoneal exudate cells. Intestinal bacterial flora was translocated into the peritoneal cavity in these mice to cause peritonitis. Comparing the toxicity of various NSAIDs, nabumetone, a partially cyclooxygenase-2-selective NSAID with weaker toxicity to the gastrointestinal tract, did not exhibit a lethal side effect. These facts strongly suggested that gastrointestinal damage by NSAIDs was more severe in beta-glucan-administered mice, resulting in peritonitis by enteric bacteria and leading to death. PMID:11476975

  10. 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.

  11. 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

  12. Toxicological dose assessment and acute health effect criteria

    SciTech Connect

    Stalker, A.C.; White, B.

    1992-01-01

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

  13. Toxicological dose assessment and acute health effect criteria

    SciTech Connect

    Stalker, A.C.; White, B.

    1992-09-01

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

  14. Lethal and sublethal effects of imidacloprid on Osmia lignaria and clothianidin on Megachile rotundata (Hymenoptera: Megachilidae).

    PubMed

    Abbott, V A; Nadeau, J L; Higo, H A; Winston, M L

    2008-06-01

    We examined lethal and sublethal effects of imidacloprid on Osmia lignaria (Cresson) and clothianidin on Megachile rotundata (F.) (Hymenoptera: Megachilidae). We also made progress toward developing reliable methodology for testing pesticides on wild bees for use in pesticide registration by using field and laboratory experiments. Bee larvae were exposed to control, low (3 or 6 ppb), intermediate (30 ppb), or high (300 ppb) doses of either imidacloprid or clothianidin in pollen. Field experiments on both bee species involved injecting the pollen provisions with the corresponding pesticide. Only O. lignaria was used for the laboratory experiments, which entailed both injecting the bee's own pollen provisions and replacing the pollen provision with a preblended pollen mixture containing imidacloprid. Larval development, emergence, weight, and mortality were monitored and analyzed. There were no lethal effects found for either imidacloprid or clothianidin on O. lignaria and M. rotundata. Minor sublethal effects were detected on larval development for O. lignaria, with greater developmental time at the intermediate (30 ppb) and high doses (300 ppb) of imidacloprid. No similar sublethal effects were found with clothianidin on M. rotundata. We were successful in creating methodology for pesticide testing on O. lignaria and M. rotundata; however, these methods can be improved upon to create a more robust test. We also identified several parameters and developmental stages for observing sublethal effects. The detection of sublethal effects demonstrates the importance of testing new pesticides on wild pollinators before registration. PMID:18613579

  15. Pharmacological antagonism of lethal effects induced by O-isobutyl S-[2-(diethylamino)ethyl]methylphosphonothioate.

    PubMed

    Chang, F C T; Hoffman, B E; DeBus, S

    2002-08-01

    O-Isobutyl S-[2-(diethylamino)ethyl]methylphosphonothioate (VR) is a structural isomer of a more widely known chemical warfare agent O-ethyl S-[2(diisopropylamino)ethyl]methylphosphonothioate (VX). VR has the potential of being used as military threat/sabotage/terrorist agent. The development of a sound medical countermeasure will undoubtedly enhance not only our medical readiness and ability in VR casualty management, but also our defense posture against the deployment of VR in both combat and politically volatile environments. Acute exposure to a lethal dose of VR has been shown to cause cholinergic hyperfunction, incapacitation, seizures, convulsions, cardiorespiratory depression and death. In this study, pharmacological antagonism of VR-induced cardiorespiratory failure and lethality was investigated in guinea pigs chronically instrumented for concurrent recordings of electrocorticogram, diaphragmatic EMG, Lead II ECG, heart rate and neck skeletal muscle EMG. Thirty (30) min prior to intoxication with a 2 x LD50 dose of VR (22.6 micrograms/kg, s.c.), animals were pretreated with pyridostigmine (0.026 mg/kg, i.m.). Immediately after VR intoxication, animals were given pralidoxime chloride (2-PAM; 25 mg/kg, i.m.) and atropine sulfate (2, 8 or 16 mg/kg, i.m.). In animals that displayed seizures and convulsions, diazepam (5 mg/kg, i.m.) was administered 10 min following the onset of epileptiform activities. Responses to pretreatment/therapy modality were evaluated at 24 h post-VR. All animals survived the 2 x LD50 VR challenge. With the exception of an increased heart rate in response to atropine, the myocardial and diaphragmatic (respiratory) activity profiles appeared normal throughout the course of intoxication and recovery. Animals receiving 2 mg/kg atropine all developed fasciculations, seizures, signs of excessive mucoid/salivary secretion, and needed diazepam adjunct therapy. One-half (50%) of the animals receiving 8 mg/kg atropine developed seizure

  16. Pseudomonas aeruginosa UV-A-induced lethal effect: influence of salts, nutritional stress and pyocyanine.

    PubMed

    Fernández, R O; Pizarro, R A

    1999-05-01

    The presence of NaCl in plating media shows an important protection against the Pseudomonas aeruginosa UV-A-induced lethal effect, contrasting with the known sensitizing action of salts on UV-A-irradiated Escherichia coli cells. MgSO4 exhibits a similar protection, but lower concentrations than for NaCl are needed to achieve the same effect. NaCl protection from lethal effects involves an osmotic mechanism, while MgSO4 could act by a different process. On the other hand, when cells grown in a complete medium are then incubated for 20 min in a synthetic medium and irradiated with UV-A, a very marked protection is obtained. This protection is dependent on protein synthesis, since treatment with tetracycline, during the nutritional stress, blocks its induction. These results offer a new example of cross-protection among different stressing agents. In our experimental conditions, natural phenazines of P. aeruginosa are not present in the cells, ruling out the possibility that these pigments act as photosensitizers. Conversely, pyocyanine (the major phenazine produced by this microorganism) prevents the UV-A killing effect in a concentration-dependent way when present in the irradiation media. Finally, UV-A irradiation induces, as in E. coli, the accumulation of guanosine tetraphosphate and guanosine pentaphosphate, although the physiological meaning of this finding has yet to be determined. PMID:10443032

  17. 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. PMID:25655818

  18. Lethal and sublethal effects of an insect growth regulator, pyriproxyfen, on obliquebanded leafroller (Lepidoptera: Tortricidae).

    PubMed

    Sial, Ashfaq A; Brunner, Jay F

    2010-04-01

    The obliquebanded leafroller, Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae), is one of the most destructive pests of tree fruit in Washington. The development of insecticide resistance in C. rosaceana has led us to explore new management tactics. The use of very low doses of insecticides that have strong sublethal effects represents an environmentally friendly option to improve existing integrated pest management (IPM) strategies. We tested the insect growth regulator pyriproxyfen to determine its lethal and sublethal effects on growth and development of C. rosaceana. A leaf-disk bioassay was used to test seven concentrations of pyriproxyfen ranging from 0 to 30 ppm on fifth-instar C. rosaceana. Male and female larvae were assessed separately for mortality as well as other parameters of growth and development. The LC, values for males and females were 2.4 and 4.8 ppm, respectively. The response to pyriproxyfen was concentration-dependent: only 5-6% of the larvae treated with the highest concentration emerged as morphologically normal adults compared with 86% emergence in the controls. The pupation and adult emergence was significantly delayed at concentrations higher than 1 ppm. The weights of C. rosaceana pupae and adults were significantly increased, whereas fecundity and fertility were significantly reduced at a sublethal concentration of 0.3 ppm. We conclude that both lethal and sublethal effects might exhibit significant impacts on the population dynamics of C. rosaceana in tree fruit orchards treated with low concentrations of pyriproxyfen. PMID:20429446

  19. Dominant Maternal-Effect Mutations Causing Embryonic Lethality in Caenorhabditis Elegans

    PubMed Central

    Mains, P. E.; Sulston, I. A.; Wood, W. B.

    1990-01-01

    We undertook screens for dominant, temperature-sensitive, maternal-effect embryonic-lethal mutations of Caenorhabditis elegans as a way to identify certain classes of genes with early embryonic functions, in particular those that are members of multigene families and those that are required in two copies for normal development. The screens have identified eight mutations, representing six loci. Mutations at three of the loci result in only maternal effects on embryonic viability. Mutations at the remaining three loci cause additional nonmaternal (zygotic) effects, including recessive lethality or sterility and dominant male mating defects. Mutations at five of the loci cause visible pregastrulation defects. Three mutations appear to be allelic with a recessive mutation of let-354. Gene dosage experiments indicate that one mutation may be a loss-of-function allele at a haploin sufficient locus. The other mutations appear to result in gain-of-function ``poison'' gene products. Most of these become less deleterious as the relative dosage of the corresponding wild-type allele is increased; we show that relative self-progeny viabilities for the relevant hermaphrodite genotypes are generally M/+/+ > M/+ > M/M/+ > M/Df > M/M, where M represents the dominant mutant allele. PMID:2379819

  20. 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.

  1. Glucose Effect in the Acute Porphyrias

    MedlinePlus

    ... You are here Home Diet and Nutrition The glucose effect in acute porphyrias The disorders Acute Intermittent ... are treated initially with the administration of carbohydrate/glucose. This therapy has its basis in the ability ...

  2. Variation in lethality and effects of two Australian chirodropid jellyfish venoms in fish.

    PubMed

    Kintner, Anna H; Seymour, Jamie E; Edwards, Susan L

    2005-11-01

    The North Queensland chirodropid box jellyfish Chironex fleckeri and Chiropsalmus sp. share similar nematocyst composition and the same prey of Acetes australis shrimps in their early medusa stages; however, as C. fleckeri individuals reach larger size, the animals add fish to their diet and their complement of nematocyst types changes, allowing larger doses of venom to be delivered to prey. This study demonstrated that the venoms of the two species differ as well: despite similar effects previously documented in crustacean prey models, the two had widely different cardiac and lethal effects in fish, with C. fleckeri being substantially more potent in its ability to cause death. Comparisons between the venom delivery abilities of the two species showed that the change in nematocysts of C. fleckeri cannot alone account for its ontogenetic shift to prey fish; instead, its prey ecology clearly necessitates it having venom capable of acting efficiently to cause death in fish. Although this venom is almost certainly produced at greater metabolic cost to the animal than the less-lethal venom of Chiropsalmus sp., owing to its greater molecular protein complexity, it confers the advantage of increased caloric intake from fish prey, facilitating larger size and potentially greater reproductive output of C. fleckeri over Chiropsalmus sp. PMID:16165181

  3. 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.

  4. In vitro–differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations

    PubMed Central

    Carlson, Michael J.; West, Michelle L.; Coghill, James M.; Panoskaltsis-Mortari, Angela; Blazar, Bruce R.

    2009-01-01

    The morbidity and mortality associated with graft-host-disease (GVHD) is a significant obstacle to the greater use of allogeneic stem cell transplantation. Donor T cells that predominantly differentiate into TH1/Tc1 T cells and generate pro-inflammatory cytokines such as interferon-γ (IFN-γ) mediate GVHD. Although numerous studies have described a pathogenic role for IFN-γ, multiple reports have demonstrated that the lack of IFN-γ paradoxically exacerbated GVHD lethality. This has led to speculation that another subset of T cells may significantly contribute to GVHD mortality. Several groups have demonstrated a new lineage of CD4+ T helper cell development distinct from TH1 or TH2 differentiation. This lineage is characterized by production of interleukin (IL)–17A, IL-17F, IL-22, and IL-21 and has been termed TH17 cells. Here, we demonstrate that a highly purified population of TH17 cells is capable of inducing lethal GVHD, hallmarked by extensive pathologic cutaneous and pulmonary lesions. Upon transfer, these cells migrate to and expand in GVHD target organs and secondary lymphoid tissues. Finally, we demonstrate differential roles for tumor necrosis factor-α (TNF-α) and IL-17A in the clinical manifestations of GVHD induced by TH17 cells. Our studies demonstrate that cells other than TH1/Tc1 can mediate acute GVHD. PMID:18957685

  5. 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. PMID:25243466

  6. 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

  7. The Effect of Less-Lethal Weapons on Injuries in Police Use-of-Force Events

    PubMed Central

    Kaminski, Robert J.; Smith, Michael R.

    2009-01-01

    Objectives. We investigated the effect of the use of less-lethal weapons, conductive energy devices (CEDs), and oleoresin capsicum (OC) spray on the prevalence and incidence of injuries to police officers and civilians in encounters involving the use of force. Methods. We analyzed data from 12 police departments that documented injuries to officers and civilians in 24 380 cases. We examined monthly injury rates for 2 police departments before and after their adoption of CEDs. Results. Odds of injury to civilians and officers were significantly lower when police used CED weapons, after control for differences in case attributes and departmental policies restricting use of these weapons. Monthly incidence of injury in 2 police departments declined significantly, by 25% to 62%, after adoption of CED devices. Conclusions. Injuries sustained during police use-of-force events affect thousands of police officers and civilians in the United States each year. Incidence of these injuries can be reduced dramatically when law enforcement agencies responsibly employ less-lethal weapons in lieu of physical force. PMID:19846686

  8. 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 ℃. PMID:26801888

  9. Lethal effects of Clostridium perfringens epsilon toxin are potentiated by alpha and perfringolysin-O toxins in a mouse model.

    PubMed

    Fernandez-Miyakawa, Mariano E; Jost, B Helen; Billington, Stephen J; Uzal, Francisco A

    2008-03-18

    Epsilon toxin (ETX) is the most important virulence factor of Clostridium perfringens type D. Two other important toxins, alpha toxin (CPA) and perfringolysin-O (PFO), are encoded and potentially produced by most C. perfringens type D isolates. The biological effects of these toxins are dissimilar although they are all lethal. Since the possible interaction of these toxins during infection is unknown, the effects of CPA and PFO on the lethal activity of ETX were studied in a mouse model. Mice were injected intravenously or intragastrically with CPA or PFO with or without ETX. Sublethal doses of CPA or PFO did not affect the lethality of ETX when either was injected together with the latter intravenously. However, sublethal or lethal doses of CPA or PFO resulted in reduction of the survival time of mice injected simultaneously with ETX when compared with the intravenous effect of ETX injected alone. When PFO was inoculated intragastrically with ETX, a reduction of the survival time was observed. CPA did not alter the survival time when inoculated intragastrically with ETX. The results of the present study suggest that both CPA and PFO have the potential to enhance the ETX lethal effects during enterotoxemia in natural hosts such as sheep and goats. PMID:17997054

  10. Effect of vanillin on toxicant-induced lethality in the Drosophila melanogaster DNA repair test.

    PubMed

    Furlanetto, Magda Patrícia; Sinigaglia, Marialva; Amaral, Viviane Souza do; Dihl, Rafael Rodrigues; de Andrade, Heloísa Helena Rodrigues

    2007-01-01

    Vanillin (VA) modulates the genotoxicity of chemical and physical agents in a complex manner. Previous studies indicate that VA inhibits the mutagenicity but increases the mitotic homologous recombination caused by at least some genotoxic agents. In the present study, we have evaluated the effects of VA on the repair of lethal damage produced by three genotoxins, N-ethyl-N-nitrosourea (ENU), ethyl methanesulfonate (EMS), and mitomycin C (MMC), using the DNA repair test (DRT) in Drosophila melanogaster. VA, 0.25% and 0.5% (w/v), increased the toxicity of MMC and EMS in repair-deficient flies, as measured by a decrease in the proportion of male to female progeny in the DRT; sex ratios decreased from 18-48% for MMC and 21-97% for EMS. These effects may be caused by the inhibition of nonhomologous DNA end joining caused by VA. In contrast to the results with MMC and EMS, VA protected against the lethality of ENU in repair-defective flies, as measured by a 43-207% increase in the survival of male flies in the DRT. It was inferred that the protective effect was due to VA modulating stages prior to the induction of ENU lesions in DNA, including modulating the antioxidant properties of VA and/or to its interference with the metabolic activation and/or detoxification of specific genotoxins. The results from this study indicate that the characterization of VA as a promising agent for preventing damage to genes and chromosomes should be tempered by observations that VA can increase the toxicity of chemical agents. PMID:17177210

  11. 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

  12. 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…

  13. A Toxin-Antitoxin Module in Bacillus subtilis Can Both Mitigate and Amplify Effects of Lethal Stress

    PubMed Central

    Wu, Xiangli; Wang, Xiuhong; Drlica, Karl; Zhao, Xilin

    2011-01-01

    Background Bacterial type-2 (protein-protein) toxin-antitoxin (TA) modules are two-gene operons that are thought to participate in the response to stress. Previous work with Escherichia coli has led to a debate in which some investigators conclude that the modules protect from stress, while others argue that they amplify lethal stress and lead to programmed cell death. To avoid ambiguity arising from the presence of multiple TA modules in E. coli, the effect of the sole type-2 toxin-antitoxin module of Bacillus subtilis was examined for several types of lethal stress. Methodology/Principal Findings Genetic knockout of the toxin gene, ndoA (ydcE), conferred protection to lethal stressors that included kanamycin, moxifloxacin, hydrogen peroxide, and UV irradiation. However, at low doses of UV irradiation the ndoA deficiency increased lethality. Indeed, gradually increasing UV dose with the ndoA mutant revealed a crossover response – from the mutant being more sensitive than wild-type cells to being less sensitive. For high temperature and nutrient starvation, the toxin deficiency rendered cells hypersensitive. The ndoA deficiency also reduced sporulation frequency, indicating a role for toxin-antitoxin modules in this developmental process. In the case of lethal antimicrobial treatment, deletion of the toxin eliminated a surge in hydrogen peroxide accumulation observed in wild-type cells. Conclusions A single toxin-antitoxin module can mediate two opposing effects of stress, one that lowers lethality and another that raises it. Protective effects are thought to arise from toxin-mediated inhibition of translation based on published work. The enhanced, stress-mediated killing probably involves toxin-dependent accumulation of reactive oxygen species, since a deficiency in the NdoA toxin suppressed peroxide accumulation following antimicrobial treatment. The type and perhaps the level of stress appear to be important for determining whether this toxin will have a

  14. 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. PMID:20855511

  15. 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

  16. 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

    2014-05-01

    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. PMID:24619441

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

    PubMed Central

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

    2014-01-01

    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. PMID:24619441

  18. 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

  19. Genetic loci with parent-of-origin effects cause hybrid seed lethality in crosses between Mimulus species.

    PubMed

    Garner, Austin G; Kenney, Amanda M; Fishman, Lila; Sweigart, Andrea L

    2016-07-01

    In flowering plants, F1 hybrid seed lethality is a common outcome of crosses between closely related diploid species, but the genetic basis of this early-acting and potentially widespread form of postzygotic reproductive isolation is largely unknown. We intercrossed two closely related species of monkeyflower, Mimulus guttatus and Mimulus tilingii, to characterize the mechanisms and strength of postzygotic reproductive isolation. Then, using a reciprocal backcross design, we performed high-resolution genetic mapping to determine the genetic architecture of hybrid seed lethality and directly test for loci with parent-of-origin effects. We found that F1 hybrid seed lethality is an exceptionally strong isolating barrier between Mimulus species, with reciprocal crosses producing < 1% viable seeds. This form of postzygotic reproductive isolation appears to be highly polygenic, indicating that multiple incompatibility loci have accumulated rapidly between these closely related Mimulus species. It is also primarily caused by genetic loci with parent-of-origin effects, suggesting a possible role for imprinted genes in the evolution of Mimulus hybrid seed lethality. Our findings suggest that divergence in loci with parent-of-origin effects, which is probably driven by genomic coevolution within lineages, might be an important source of hybrid incompatibilities between flowering plant species. PMID:26924810

  20. Serum amyloid A protects murine macrophages from lethal toxin-mediated death.

    PubMed

    Rose, Kira; Long, Paul; Shankar, Malini; Ballard, Jimmy D; Webb, Carol F

    2012-01-01

    Lethal toxin, a key virulence factor produced by Bacillus anthracis, induces cell death, in part by disrupting numerous signaling pathways, in mouse macrophages. However, exposure to sublethal doses of lethal toxin allows some cells to survive. Because these pro-survival signaling events occur within a few hours after exposure to sublethal doses, we hypothesized that acute phase proteins might influence macrophage survival. Our data show that serum amyloid A (SAA) is produced in response to lethal toxin treatment. Moreover, pre-treatment of macrophages with exogenous SAA protected macrophages from lethal toxin-mediated death. Exogenous SAA activated the p38 mitogen activated protein kinase (MAP) kinase pathway, while lethal toxin mutants incapable of p38 activation were incapable of causing cell death. Chemical inhibition of the p38 activation pathway abrogated the protective effects of SAA. These data show that SAA affords protection against lethal toxin in mouse macrophages and link this response to the p38 pathway. PMID:22082566

  1. Overexpression of the human HAP1 protein sensitizes cells to the lethal effect of bioreductive drugs.

    PubMed

    Prieto-Alamo, M J; Laval, F

    1999-03-01

    Abasic sites (AP sites) are generated in DNA either directly by DNA-damaging agents or by DNA glycosylases acting during base excision repair. These sites are repaired in human cells by the HAP1 protein, which, besides its AP-endonuclease activity, also possesses a redox function. To investigate the ability of HAP1 protein to modulate cell resistance to DNA-damaging agents, CHO cells were transfected with HAP1 cDNA, resulting in stable expression of the protein in the cell nuclei. The sensitivity of the transfected cells to the toxic effect of various agents, e.g. methylmethane sulfonate, bleomycin and H2O2, was not modified. However, the transfected cells became more sensitive to killing by mitomycin C, porfiromycin, daunorubicin and aziridinyl benzoquinone, drugs that are activated by reduction. To test whether the redox function of HAP1 protein was involved in this increased cytotoxicity, we have constructed a mutated HAP1 protein endowed with normal AP-endonuclease activity but deleted for redox function. When this mutated protein was expressed in the cells, elevated AP-endonuclease activity was measured, but sensitization to the lethal effects of compounds requiring bioreduction was no longer observed. These results suggest that HAP1 protein, besides its involvement in DNA repair, is able to activate bioreduction of alkylating drugs used in cancer chemotherapy. PMID:10190555

  2. 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. PMID:26804506

  3. Metagenomic Detection of Viral Pathogens in Spanish Honeybees: Co-Infection by Aphid Lethal Paralysis, Israel Acute Paralysis and Lake Sinai Viruses

    PubMed Central

    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. PMID:23460860

  4. 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

  5. Effectiveness of modified steroid-antibiotic therapies for lethal sepsis in the dog.

    PubMed

    Beller, B K; Archer, L T; Passey, R B; Flournoy, D J; Hinshaw, L B

    1983-11-01

    Dogs permanently recover (survive at least seven days) from lethal doses of Escherichia coli when treated early with intravenous (IV) intermittent infusions of methylprednisolone sodium succinate and gentamicin sulfate. We evaluated the therapeutic effectiveness of constant or bolus IV infusion of methylprednisolone combined with gentamicin or netilmicin sulfate. Four groups of anesthetized dogs were infused for one hour with E coli and treated as follows (% survival indicated): no treatment (0%); constant infusion of methylprednisolone and gentamicin (100%); bolus infusion of methylprednisolone and gentamicin (57%); and constant infusion of methylprednisolone and netilmicin (83%). Constant or bolus infusion of methylprednisolone was begun 15 minutes after E coli infusion was started. Gentamicin or netilmicin administration was begun when all organisms had been infused. The probability of recovery from shock was significantly increased when dogs were treated with constant infusion of methylprednisolone and intermittent infusions of gentamicin or netilmicin, but was only moderately increased when treated with intermittent bolus infusions of methylprednisolone and intermittent infusions of gentamicin. PMID:6357146

  6. Effects of prior administration of steroids upon recovery from lethal sepsis.

    PubMed

    Hinshaw, L B; Beller, B K; Chang, A C; Passey, R B; Lahti, R A; Flournoy, D J; Lane, M M; Archer, L T

    1986-10-01

    The effects upon survival of large doses of steroid administered to dogs prior to challenging them with lethal sepsis was evaluated in this study. Dogs were given 30 milligrams per kilogram of body weight per day of methylprednisolone sodium succinate for one, two or eight days and then were infused with 9.72 +/- 0.35 X 10(9) Escherichia coli per kilogram of body weight. All dogs in group 1 (n equals six) not given steroid died within 25 hours. Of the dogs in group 2 (n equals 12) given one or two doses of steroid previously, 42 per cent permanently survived (more than seven days). All dogs in group 3 (n equals five) given eight daily doses of steroid prior to infusion of Escherichia coli died within 17 hours. Dogs in group 4 (n equals six) were given eight daily doses of steroid prior to infusion of Escherichia coli and treated on the day of infusion of Escherichia coli with a regimen of methylprednisolone and gentamicin sulfate which results in a 100 per cent survival rate when given to dogs that have not received prior treatment with steroid. Thirty-three per cent of the dogs in group 4 permanently survived. One or two daily large doses of steroid did not detrimentally affect survival of the dogs. Eight days of steroid administration suppressed endogenous cortisol production. When the dogs were treated with six hours of steroid-antibiotic therapy, survival benefits were limited. PMID:2945272

  7. Sub-lethal effects caused by the cocaine metabolite benzoylecgonine to the freshwater mussel Dreissena polymorpha.

    PubMed

    Parolini, Marco; Pedriali, Alessandra; Riva, Consuelo; Binelli, Andrea

    2013-02-01

    Illicit drugs have been recognized as emerging environmental pollutants that could represent a potential risk for aquatic communities. Even if many studies have shown the occurrence of several drugs of abuse and their metabolites in freshwaters in the High ng/L to Low μg/L range worldwide, no information on their potentially harmful effects on non-target organisms is available. The aim of this study was to investigate sub-lethal effects induced by the main metabolite of cocaine, the benzoylecgonine (BE), on the freshwater bivalve Dreissena polymorpha. Mussels were exposed under semi-static conditions for 14 days to two environmentally relevant BE concentrations (0.5 μg/L and 1 μg/L) and induced adverse effects were evaluated through the application of a suite of ten different biomarkers. We applied on bivalve hemocytes the single cell gel electrophoresis (SCGE) assay, the DNA diffusion assay and the micronucleus test (MN test) to investigate DNA injuries, while the neutral red retention assay (NRRA) was used to assess BE cytotoxicity. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities, as well as the lipid peroxidation (LPO) and protein carbonyl content (PCC), were measured as oxidative stress indices in zebra mussel homogenates. Significant decrease in lysosomal membrane stability and imbalances of defense enzyme activities were found at both exposure concentrations, suggesting the involvement of oxidative stress in BE toxicity. Significant increases in LPO and PCC, as well as in primary (DNA strand breaks) and fixed DNA damage (apoptotic and micronucleated cell frequency), were found at the highest BE treatment, confirming that adverse effects to macromolecules were due to the increase of BE-induced oxidative stress. PMID:23266551

  8. 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. PMID:26132327

  9. 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

  10. Methionine excess in diet induces acute lethal hepatitis in mice lacking cystathionine γ-lyase, an animal model of cystathioninuria.

    PubMed

    Yamada, Hidenori; Akahoshi, Noriyuki; Kamata, Shotaro; Hagiya, Yoshifumi; Hishiki, Takako; Nagahata, Yoshiko; Matsuura, Tomomi; Takano, Naoharu; Mori, Masatomo; Ishizaki, Yasuki; Izumi, Takashi; Kumagai, Yoshito; Kasahara, Tadashi; Suematsu, Makoto; Ishii, Isao

    2012-05-01

    Physiological roles of the transsulfuration pathway have been recognized by its contribution to the synthesis of cytoprotective cysteine metabolites, such as glutathione, taurine/hypotaurine, and hydrogen sulfide (H(2)S), whereas its roles in protecting against methionine toxicity remained to be clarified. This study aimed at revealing these roles by analyzing high-methionine diet-fed transsulfuration-defective cystathionine γ-lyase-deficient (Cth(-/-)) mice. Wild-type and Cth(-/-) mice were fed a standard diet (1 × Met: 0.44%) or a high-methionine diet (3 × Met or 6 × Met), and hepatic conditions were monitored by serum biochemistry and histology. Metabolome analysis was performed for methionine derivatives using capillary electrophoresis- or liquid chromatography-mass spectrometry and sulfur-detecting gas chromatography. The 6 × Met-fed Cth(-/-) (not 1 × Met-fed Cth(-/-) or 6 × Met-fed wild type) mice displayed acute hepatitis, which was characterized by markedly elevated levels of serum alanine/aspartate aminotransferases and serum/hepatic lipid peroxidation, inflammatory cell infiltration, and hepatocyte ballooning; thereafter, they died of gastrointestinal bleeding due to coagulation factor deficiency. After 1 week on 6 × Met, blood levels of ammonia/homocysteine and hepatic levels of methanethiol/3-methylthiopropionate (a methionine transamination product/methanethiol precursor) became significantly higher in Cth(-/-) mice than in wild-type mice. Although hepatic levels of methionine sulfoxide became higher in 6 × Met-fed wild-type mice and Cth(-/-) mice, those of glutathione, taurine/hypotaurine, and H(2)S became lower and serum levels of homocysteine became much higher in 6 × Met-fed Cth(-/-) mice than in wild-type mice. Thus, transsulfuration plays a critical role in the detoxification of excessive methionine by circumventing aberrant accumulation of its toxic transamination metabolites, including ammonia, methanethiol, and 3-methylthiopropionate

  11. 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.

  12. 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.

  13. Effect of ketoconazole on lethal action of amphotericin B on Leishmania mexicana promastigotes.

    PubMed Central

    Ramos, H; Saint-Pierre-Chazalet, M; Bolard, J; Cohen, B E

    1994-01-01

    The effect of ergosterol depletion by ketoconazole on the leishmanicidal activity of the pore-forming antibiotic amphotericin B (AmB) was investigated. Leishmania mexicana promastigotes were lysed within minutes by the addition of micromolar concentrations of AmB (0.5 microM) but became insensitive to AmB after growth in the presence of ketoconazole (0.25 microM, 90 h). Lipid chromatographic analysis indicated that under such conditions, ketoconazole depleted the major Leishmania sterols, dehydroepisterol and ergosterol. Plasma membrane vesicles prepared from ketoconazole-treated promastigotes exhibited a much reduced enhancement of their salt permeability after the addition of AmB at concentrations as high as 5 microM. This finding clearly indicates that upon ketoconazole treatment, the capacity of pore formation by the antibiotic is substantially impaired. The reduction of desmethyl sterols by ketoconazole was accompanied by a significant increase of 14-alpha-methyl sterols, but exogenous cholesterol remained unchanged. This ability of Leishmania promastigotes to incorporate cholesterol from the external medium may explain why ketoconazole-treated cells exhibited a much decreased but significative response to AmB when they were exposed to high AmB concentrations (2.5 or 5.0 microM). Parallel measurements by using a fluorescence energy transfer method indicated that binding of AmB to ketoconazole-treated Leishmania promastigotes and heat-transformed leishmanias was also decreased but to different extents, a finding that may be related to the differences in their sterol content. The results obtained clearly indicate that the specific interaction of AmB with desmethyl sterols, such as dehydroepisterol, ergosterol, and even exogenous cholesterol, is an absolute requirement for the lethal action exerted by this polyene antibiotic on L. mexicana promastigotes. PMID:8067741

  14. 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.

  15. Induction of lethal bystander effects in human breast cancer cell cultures by DNA-incorporated Iodine-125 depends on phenotype

    PubMed Central

    Akudugu, John M.; Azzam, Edouard I.; Howell, Roger W.

    2013-01-01

    Purpose This study uses a three-dimensional cell culture model to investigate lethal bystander effects in human breast cancer cell cultures (MCF-7, MDA-MB-231) treated with 125I-labeled 5-iodo-2′-deoxyuridine (125IdU). These breast cancer cell lines respectively form metastatic xenografts in nude mice in an estrogen-dependent and independent manner. Materials and methods In the present study, these cells were cultured in loosely-packed three-dimensional architecture in a Cytomatrix™ carbon scaffold. Cultures were pulse-labeled for 3 h with 125IdU to selectively irradiate a minor fraction of cells, and simultaneously co-pulse-labeled with 0.04 mM 5-ethynyl-2′-deoxyuridine (EdU) to identify the radiolabeled cells using Click-iT® EdU and flow cytometry. The cultures were then washed and incubated for 48 h. The cells were then harvested, serially diluted, and seeded for colony formation. Aliquots of cells were subjected to flow cytometry to determine the percentage of cells labeled with 125IdU/EdU. Additional aliquots were used to determine the mean 125I activity per labeled cell. The percentage of labeled cells was about 15% and 10% for MCF-7 and MDA-MB-231 cells, respectively. This created irradiation conditions wherein the cross-dose to unlabeled cells was small relative to the self-dose to labeled cells. The surviving fraction relative to EdU-treated controls was measured. Results Survival curves indicated significant lethal bystander effect in MCF-7 cells, however, no significant lethal bystander effect was observed in MDA-MB-231 cells. Conclusions These studies demonstrate the capacity of 125IdU to induce lethal bystander effects in human breast cancer cells and suggest that the response depends on phenotype. PMID:22489958

  16. Separation of sublethal and lethal effects of the bactericidal/permeability increasing protein on Escherichia coli.

    PubMed Central

    Mannion, B A; Weiss, J; Elsbach, P

    1990-01-01

    Binding of the bactericidal/permeability increasing protein (BPI) of granulocytes to Escherichia coli promptly produces several discrete outer envelope alterations and growth arrest without major impairment of bacterial structure or biosynthetic capabilities, raising the question whether these early effects of BPI are sufficient to cause bacterial death. In this study, the bactericidal action of BPI was examined more closely. We have found that bovine or human serum albumin blocks bacterial killing without preventing BPI binding or an increase in outer membrane permeability. Moreover, addition of serum albumin after BPI results in growth resumption without displacement of bound BPI and without (early) repair of the envelope alterations. These effects are opposite to those produced by Mg2+ (80 mM), which displaces greater than 85% of bound BPI and rapidly initiates outer envelope repair without restoration of bacterial growth. The extent of rescue by serum albumin depends on the time and pH of preincubation of BPI with E. coli: e.g., for E. coli J5 treated with human BPI, t1/2 = 79 min at pH 7.4 and 10 min at pH 6.0. The serum albumin effects on BPI action are the same in wild-type E. coli and in a mutant strain lacking an activatable phospholipase, indicating that serum albumin does not act by sequestering membrane-damaging products of bacterial phospholipid hydrolysis. The progression from reversible to irreversible growth arrest, revealed by the subsequent addition of serum albumin at different times, is paralleled by a decrease in amino acid uptake and an increase in the permeability of the cytoplasmic membrane to o-nitrophenyl-beta-D-galactoside. These findings demonstrate at least two stages in the action of BPI: (a) an early, reversible, sublethal stage in which BPI has effects on the outer envelope and causes growth arrest, and (b) time- and pH-dependent progression to a lethal stage, apparently involving cytoplasmic membrane damage, possibly caused by

  17. Lethal and sublethal effects of selected PPCPs on the freshwater rotifer, Plationus patulus.

    PubMed

    Martinez Gomez, Diana A; Baca, Sarah; Walsh, Elizabeth J

    2015-04-01

    Pharmaceuticals and personal care products (PPCPs) have been reported in surface waters around the world. The continuous input of these pollutants into freshwaters and their potential effects on aquatic life are of increasing concern. The rotifer Plationus patulus, a basal member of riverine food webs, was used to test acute and chronic toxicity of 4 PPCPs (acetamidophenol, caffeine, fluoxetine, triclosan). A population from a remote site in Mexico (reference population) and one from an urbanized stretch of the Rio Grande were exposed. Acute toxicity tests show that both populations were more sensitive to fluoxetine. Chronic exposure to acetamidophenol (10 mg/L, 15 mg/L, and 20 mg/L) inhibited reference population growth, whereas Rio Grande population growth was inhibited only at 15 mg/L and 20 mg/L. Population growth was inhibited at 200 mg/L and 300 mg/L of caffeine for both populations. Chronic exposure to fluoxetine (0.020 mg/L) significantly inhibited population growth for the Rio Grande population only. Triclosan (0.05 mg/L, 0.075 mg/L, 0.10 mg/L) had the most deleterious effects, significantly reducing both populations' growth rates. Sublethal effects of chronic exposure to PPCPs included decreased egg production and increased egg detachment. A mixed exposure (6 PPCPs, environmentally relevant concentrations) did not affect population growth in either population. However, the continuous introduction of a broad suite of PPCPs to aquatic ecosystems still may present a risk to aquatic communities. Environ Toxicol Chem 2015;34:913-922. © 2014 SETAC. PMID:25557148

  18. B7-H3 expression in donor T cells and host cells negatively regulates acute graft-versus-host disease lethality.

    PubMed

    Veenstra, Rachelle G; Flynn, Ryan; Kreymborg, Katharina; McDonald-Hyman, Cameron; Saha, Asim; Taylor, Patricia A; Osborn, Mark J; Panoskaltsis-Mortari, Angela; Schmitt-Graeff, Annette; Lieberknect, Elisabeth; Murphy, William J; Serody, Jonathan S; Munn, David H; Freeman, Gordon J; Allison, James P; Mak, Tak W; van den Brink, Marcel; Zeiser, Robert; Blazar, Bruce R

    2015-05-21

    Members of the B7 family have been shown to be important for regulating immune responses by providing either positive or negative costimulatory signals. The function of B7-H3 has been controversial. We show that B7-H3 is upregulated in graft-versus-host disease (GVHD) target organs, including the colon, liver, and lung. Infusion of allogeneic donor T cells into B7-H3(-/-) vs wild-type (WT) recipients resulted in increased GVHD lethality associated with increased T-cell proliferation, colonic inflammatory cytokines, and destruction of epithelial barriers. Allogeneic B7-H3(-/-) vs WT donor T cells also had increased T-cell proliferation and GVHD lethality associated with increased proliferation and cytokine secretion in the spleen, intraepithelial lymphocyte inflammatory cytokines, and intestinal permeability. Both resting and activated regulatory T cells (Tregs) lack B7-H3 messenger RNA. Consistent with these data, GVHD was augmented in recipients of B7-H3(-/-) Treg-depleted grafts. In two delayed lymphocyte infusion (DLI) models, T cells lacking B7-H3 are capable of providing graft-versus-leukemia (GVL) effects. We conclude that B7-H3 is responsible for providing a negative costimulatory signal. Our studies provide support for developing and testing new therapies directed toward the B7-H3 pathway, including approaches to augment host B7-H3 early after bone marrow transplantation to prevent GVHD and to develop potent antagonistic antibodies later after transplant to facilitate DLI-mediated GVL without GVHD complications. PMID:25814530

  19. Sub-lethal effects of fenbutatin oxide on prey location by the predatory mite Iphiseiodes zuluagai (Acari: Phytoseiidae).

    PubMed

    Teodoro, Adenir V; Pallini, Angelo; Oliveira, Claudinei

    2009-04-01

    We used a Y-tube olfactometer to assess the sub-lethal effects of the acaricide fenbutatin oxide on the olfactory response of the predatory mite Iphiseiodes zuluagai towards odours from: (1) air or undamaged coffee plants; (2) undamaged or red spider mite Oligonychus ilicis-infested coffee plants; (3) undamaged or false spider mite Brevipalpus phoenicis-infested coffee plants. Predatory mite adult females were exposed to residues of fenbutatin oxide or distilled water on leaf discs during a period of 72 h prior experiments. When exposed to distilled water (control treatments), predatory mites significantly preferred undamaged plants over air, O. ilicis-infested plants over undamaged plants, and they did not prefer B. phoenicis-infested plants over undamaged plants. However, predatory mites that had been exposed to residues of fenbutatin oxide were neither attracted towards undamaged plants nor to O. ilicis-infested plants. Thus, fenbutatin oxide affected negatively the olfactory response of I. zuluagai. We conclude that sub-lethal-effect studies should be considered in pesticide selectivity programs since the ability of predatory mites to locate their prey may be negatively affected by non-lethal concentrations of pesticides. PMID:19009359

  20. Effect of diet on hyperthermia-induced cell lethality and prostaglandin release.

    PubMed

    Wainberg, R H; Walden, T L; Stebler, B A; Yatvin, M B

    1991-05-01

    Hyperthermia-induced cell lethality is thought to be mediated through injury to the cell membrane. Membrane perturbation results in the release of prostaglandins (PG) and leukotrienes (LT). These compounds are potent biological mediators and may modify the tumor microenvironment and therapeutic efficacy. Membrane composition and PG/LT release are influenced by the dietary fatty acids. The relationship between these variables and response to hyperthermia was examined in vitro using murine P388 leukemia cells grown as an ascites in mice provided either saturated fatty acid diet (SFA; 16% beef tallow) or unsaturated fatty acid diet (UFA; 16% safflower oil). Cells were harvested and exposed in vitro to either 37 degrees C or 43.5 degrees C for periods up to 2 hours. Hyperthermic exposure for 2 hours resulted in 40% cell lethality in SFA cells and 55% in UFA cells. The phospholipid and total cholesterol content was higher (33% and 50% respectively) in the UFA versus the SFA cells. Hyperthermia produced a six-fold increase in prostaglandin E2 PGE2 release by SFA cells and a 4.5-fold increase by UFA cells. No LTC4 was detected. Alteration of dietary fat affects cell lethality and PG release following hyperthermic treatment. The increase in phospholipid and cholesterol content of UFA cells may be a response to reduced membrane fluidity. PMID:1862229

  1. [Effects of sub-lethal dosages abamectin on food intake and digestive enzyme activities of silkworm Bombyx mori L].

    PubMed

    Zhu, Jiu-sheng; Wang, Jing; Gao, Hai-yan; Qin, Shu; Qiao, Xiong-wu; Han, Ju-cai

    2008-11-01

    Mulberry leaves treated with sub-lethal dosages (LC5, LC10 and LC20) abameetin were fed to the 5th instar larvae of silkworm (Bombyx mori L.), and the food intake and digestive enzyme activities of the larvae were studied by using gravimetric method and measuring enzyme activities. The results showed that sub-lethal dosages abameetin significantly inhibited the growth and food intake of the larvae, with their body mass and its increase rate as well as their relative growth rate being significantly lower than the control, and accompanied with the decreases of food intake, its relative consumption rate, and feces amount. The efficiency of the conversion of ingested food (ECI) and that of the conversion of digested food (EDI) also reduced, but the approximate digestibility (AD) increased significantly. The amylase and sucrase activities in the midgut of the larvae treated with abameetin decreased significantly for a longer time at the beginning, and then recovered to the same as or a higher level than the control, whereas the trehalase activity decreased significantly for a shorter time at the beginning, then increased significantly, and finally recovered to the normal. It was suggested that sub-lethal dosages abameetin had definite toxicity to the silkworm, and the toxic effect was increased with increasing dosage, which could result in the turbulence of silkworm's digestive system, and further, affect its food intake and its growth and development. PMID:19238858

  2. Lethal effects on different marine organisms, associated with sediment-seawater acidification deriving from CO2 leakage.

    PubMed

    Basallote, M D; Rodríguez-Romero, A; Blasco, J; DelValls, A; Riba, I

    2011-08-01

    CO(2) leakages during carbon capture and storage in sub-seabed geological structures could produce potential impacts on the marine environment. To study lethal effects on marine organisms attributable to CO(2) seawater acidification, a bubbling CO(2) system was designed enabling a battery of different tests to be conducted, under laboratory conditions, employing various pH treatments (8.0, 7.5, 7.0, 6.5, 6.0, and 5.5). Assays were performed of three exposure routes (seawater, whole sediment, and sediment elutriate). Individuals of the clam (Ruditapes philippinarum) and early-life stages of the gilthead seabream, Sparus aurata, were exposed for 10 days and 72 h, respectively, to acidified clean seawater. S. aurata larvae were also exposed to acidified elutriate samples, and polychaete organisms of the specie Hediste diversicolor and clams R. philippinarum were also exposed for 10 days to estuarine whole sediment. In the fish larvae elutriate test, 100 % mortality was recorded at pH 6.0, after 48 h of exposure. Similar results were obtained in the clam sediment exposure test. In the other organisms, significant mortality (p < 0.05) was observed at pH values lower than 6.0. Very high lethal effects (calculating L[H(+)]50, defined as the H(+) concentration that causes lethal effects in 50 % of the population exposed) were detected in association with the lowest pH treatment for all the species. The implication of these results is that a severe decrease of seawater pH would cause high mortality in marine organisms of several different kinds and life stages. The study addresses the potential risks incurred due to CO(2) leakages in marine environments. PMID:22828884

  3. Effects of chronic sub-lethal oxidative stress on biofilm formation by Azotobacter vinelandii.

    PubMed

    Villa, Federica; Remelli, William; Forlani, Fabio; Gambino, Michela; Landini, Paolo; Cappitelli, Francesca

    2012-01-01

    This work showed that perturbations of the physiological steady-state level of reactive oxygen species (ROS) affected biofilm genesis and the characteristics of the model bacterium Azotobacter vinelandii. To get a continuous endogenous source of ROS, a strain exposed to chronic sub-lethal oxidative stress was deprived of the gene coding for the antioxidant rhodanese-like protein RhdA (MV474). In this study MV474 biofilm showed (i) a seven-fold higher growth rate, (ii) induction of catalase and alkyl-hydroxyl-peroxidase enzymes, (iii) higher average thicknesses due to increased production of a polysaccharide-rich extracellular matrix and (iv) less susceptibility to hydrogen peroxide than the wild-type strain (UW136). MV474 showed increased swimming and swarming activity and the swarming colonies experienced a higher level of oxidative stress compared to UW136. A continuous exogenous source of ROS increased biofilm formation in UW136. Overall, chronic sub-lethal oxidative events promoted sessile behavior in A. vinelandii. PMID:22871137

  4. 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. PMID:7933272

  5. Effect of Sub-Lethal Exposure to Ultraviolet Radiation on the Escape Performance of Atlantic Cod Larvae (Gadus morhua)

    PubMed Central

    Fukunishi, Yuichi; Browman, Howard I.; Durif, Caroline M. F.; Bjelland, Reidun M.; Skiftesvik, Anne Berit

    2012-01-01

    The amount of ultraviolet (UV) radiation reaching the earth's surface has increased due to depletion of the ozone layer. Several studies have reported that UV radiation reduces survival of fish larvae. However, indirect and sub-lethal impacts of UV radiation on fish behavior have been given little consideration. We observed the escape performance of larval cod (24 dph, SL: 7.6±0.2 mm; 29 dph, SL: 8.2±0.3 mm) that had been exposed to sub-lethal levels of UV radiation vs. unexposed controls. Two predators were used (in separate experiments): two-spotted goby (Gobiusculus flavescens; a suction predator) and lion's mane jellyfish (Cyanea capillata; a “passive" ambush predator). Ten cod larvae were observed in the presence of a predator for 20 minutes using a digital video camera. Trials were replicated 4 times for goby and 5 times for jellyfish. Escape rate (total number of escapes/total number of attacks ×100), escape distance and the number of larvae remaining at the end of the experiment were measured. In the experiment with gobies, in the UV-treated larvae, both escape rate and escape distance (36%, 38±7.5 mm respectively) were significantly lower than those of control larvae (75%, 69±4.7 mm respectively). There was a significant difference in survival as well (UV: 35%, Control: 63%). No apparent escape response was observed, and survival rate was not significantly different, between treatments (UV: 66%, Control: 74%) in the experiment with jellyfish. We conclude that the effect and impact of exposure to sub-lethal levels of UV radiation on the escape performance of cod larvae depends on the type of predator. Our results also suggest that prediction of UV impacts on fish larvae based only on direct effects are underestimations. PMID:22536406

  6. 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. PMID:27160634

  7. Sub-lethal stress effects on virulence gene expression in Enterococcus faecalis.

    PubMed

    Lenz, Christian A; Hew Ferstl, Carrie M; Vogel, Rudi F

    2010-05-01

    Enterococci are ubiquitous lactic acid bacteria commonly associated with the human digestive tract as commensal organisms. Additionally, these organisms have a long history of use in foods improving flavor as well as providing protective mechanisms as either a probiotic or antimicrobial additive. However, Enterococcus faecalis accounts for up to 10% of all nosocomial infections of the bloodstream, wounds, urinary tract and heart. Knowledge about the regulation of virulence factors is limited and the involvement of environmental signals contributing to E. faecalis pathogenicity is poorly documented. In this study, two clinical E. faecalis isolates, TMW 2.63 and OG1RF, as well as one food isolate, TMW 2.629, were subjected to six sub-lethal food- and host-related stresses including 6.8% NaCl, 200 ppm nitrite, 51 degrees C, 80 MPa, pH 4.1 and 0.08% bile salts (cholic acid:chenodeoxycholic acid 1:1), respectively, reducing their growth rate to 10%. Relative gene expression of 15 stress and virulence-associated genes including dnaK, groEL, ctsR, clpPBCEX, gls24, efaAfs, ace, fsrB, gelE, sprE and cylB, was quantified by using real time PCR and Lightcycler((R)) technology (reference conditions: BHI broth, 37 degrees C, pH = 7.4). Apart from strain-dependent differences, sub-lethal environmental stress was capable of provoking significant alterations in the expression of virulence-associated genes in E. faecalis from clinical as well as food origins of isolation. These results help to avoid preconditioning enterococci in food production processes and to understand the complex mechanisms in E. faecalis' switch to pathogenicity. PMID:20227595

  8. 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

  9. 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

  10. 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. PMID:24944572

  11. 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

  12. 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. PMID:26421727

  13. 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. PMID:21186925

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

    USGS Publications Warehouse

    Clark, D.R., Jr.; 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.

  15. Cell contact-dependent lethal effect of the dinoflagellate Heterocapsa circularisquama on phytoplankton-phytoplankton interactions

    NASA Astrophysics Data System (ADS)

    Yamasaki, Yasuhiro; Zou, Yanan; Go, Jyoji; Shikata, Tomoyuki; Matsuyama, Yukihiko; Nagai, Kiyohito; Shimasaki, Yohei; Yamaguchi, Kenichi; Oshima, Yuji; Oda, Tatsuya; Honjo, Tsuneo

    2011-01-01

    We used bi-algal culture experiments to investigate and verify the roles of growth interaction between Heterocapsa circularisquama and Prorocentrum dentatum in monospecific bloom formation. Growth of H. circularisquama was slightly inhibited when inoculated at 10 2 cells mL -1 along with P. dentatum at 10 4 cells mL -1. In other combinations of inoculation densities, P. dentatum density rapidly decreased to extremely low levels in the presence of H. circularisquama. We used a mathematical model to simulate growth and interactions of H. circularisquama and P. dentatum in bi-algal cultures. The model indicates that one species will always inhibit the growth of the other and that the relative initial cell densities of the species are critical in determining the outcome. When cultured together under conditions without cell contact, growth of H. circularisquama and P. dentatum was not inhibited. As with P. dentatum, the growth of Heterosigma akashiwo and Skeletonema costatum was inhibited in intact cell suspensions with H. circularisquama, but a nontoxic species, Heterocapsa triquetra, did not affect the growth of P. dentatum or the other species. Similarly, cell suspensions of H. circularisquama showed hemolytic activity toward rabbit erythrocytes, but those of H. triquetra did not. In addition, the cell-free supernatant of H. circularisquama cultures showed no significant hemolytic activity. These results suggest that H. circularisquama causes lethality in P. dentatum by direct cell contact in which live-cell-mediated hemolytic activity might be a contributing factor.

  16. Sub-Lethal Effects of Pesticide Residues in Brood Comb on Worker Honey Bee (Apis mellifera) Development and Longevity

    PubMed Central

    Wu, Judy Y.; Anelli, Carol M.; Sheppard, Walter S.

    2011-01-01

    Background Numerous surveys reveal high levels of pesticide residue contamination in honey bee comb. We conducted studies to examine possible direct and indirect effects of pesticide exposure from contaminated brood comb on developing worker bees and adult worker lifespan. Methodology/Principal Findings Worker bees were reared in brood comb containing high levels of known pesticide residues (treatment) or in relatively uncontaminated brood comb (control). Delayed development was observed in bees reared in treatment combs containing high levels of pesticides particularly in the early stages (day 4 and 8) of worker bee development. Adult longevity was reduced by 4 days in bees exposed to pesticide residues in contaminated brood comb during development. Pesticide residue migration from comb containing high pesticide residues caused contamination of control comb after multiple brood cycles and provided insight on how quickly residues move through wax. Higher brood mortality and delayed adult emergence occurred after multiple brood cycles in contaminated control combs. In contrast, survivability increased in bees reared in treatment comb after multiple brood cycles when pesticide residues had been reduced in treatment combs due to residue migration into uncontaminated control combs, supporting comb replacement efforts. Chemical analysis after the experiment confirmed the migration of pesticide residues from treatment combs into previously uncontaminated control comb. Conclusions/Significance This study is the first to demonstrate sub-lethal effects on worker honey bees from pesticide residue exposure from contaminated brood comb. Sub-lethal effects, including delayed larval development and adult emergence or shortened adult longevity, can have indirect effects on the colony such as premature shifts in hive roles and foraging activity. In addition, longer development time for bees may provide a reproductive advantage for parasitic Varroa destructor mites. The impact of

  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. The membrane stress response buffers the lethal effects of lipid disequilibrium by reprogramming the protein homeostasis network

    PubMed Central

    Thibault, Guillaume; Shui, Guanghou; Kim, Woong; McAlister, Graeme C.; Ismail, Nurzian; Gygi, Steven P.; Wenk, Markus R.; Ng, Davis T.W.

    2012-01-01

    SUMMARY Lipid composition can differ widely among organelles and even between leaflets of a membrane. Lipid homeostasis is critical because disequilibrium can have disease outcomes. Despite their importance, mechanisms maintaining lipid homeostasis remain poorly understood. Here, we establish a model system to study the global effects of lipid imbalance. Quantitative lipid profiling was integral to monitor changes to lipid composition and for system validation. Applying global transcriptional and proteomic analyses, a dramatically altered biochemical landscape was revealed from adaptive cells. The resulting composite regulation we term the “membrane stress response” (MSR) confers compensation, not through restoration of lipid composition, but by remodeling the protein homeostasis network. To validate its physiological significance, we analyzed the unfolded protein response (UPR), one facet of the MSR and a key regulator of protein homeostasis. We demonstrate that the UPR maintains protein biogenesis, quality control, and membrane integrity—functions otherwise lethally compromised in lipid dysregulated cells. PMID:23000174

  19. LPS-induced serum TNF production and lethality in mice: effect of L-carnitine and some acyl-derivatives

    PubMed Central

    Ruggiero, Vito; D'Urso, Claudio M.; Albertoni, Claudio; Campo, Silvia; Martelli, Edoardo Arrigoni

    1993-01-01

    The effect of L-carnitine and some of its acyl derivatives on serum TNF production and lethality in a murine experimental endotoxin shock model was investigated. In some instances, serum IL-6 production was also evaluated. In this experimental model, C57BL/6 mice received 30 mg/kg LPS (E. cell 055:B5) injected intraperitoneally, while L-carnitine and its derivatives were administered according to different schedules. Serum levels of TNF and IL-6 were evaluated 1 h following LPS injection. The treated animals were also monitored daily for differences in body temperature, feeding, and survival for 10 days after LPS injection. Although some derivatives were able to significantly affect TNF production, the marked decrease in serum TNF levels of LPS-treated mice was not paralleled by a substantial increase in survival. PMID:18475570

  20. Glucocorticoid and antibiotic effects on hepatic microcirculation and associated host responses in lethal gram-negative bacteremia.

    PubMed

    Balis, J U; Paterson, J F; Shelley, S A; Larson, C H; Fareed, J; Gerber, L I

    1979-01-01

    Liver changes and associated host responses were evaluated in four groups of male rats, weighing 300 +/- 20 gm., which received intravenous injection of 2.2 times 10(9) live Escherichia coli. This bolus was given either without additional treatment (group A) or prior to the following regimens: intramuscular injection of gentamicin sulfate, 5 mg. per kg. (group B); intravenous injection of methylprednisolone sodium succinate, 40 mg. per kg. (group C); and intramuscular injection of gentamicin immediately after methylprednisolone sodium succinate treatment (group D). Rats given injections of saline or methylprednisolone sodium succinate served as controls. Survival rates at 10 and 20 hours were 25 per cent and 4 per cent for group A; 44 per cent and 28 per cent for group B; 94 per cent and 70 per cent for group C; 98 per cent and 98 per cent for group D, respectively. In rats of groups A and B, killed at 1, 2, 4, and 6 hours, progressive liver changes included intravascular sequestration of rapidly degranulating leukocytes, fibrinous deposits, and platelet aggregates in sinusoids as well as in spaces of Disse adjacent to subendothelial collagen, and extensive Kupffer cell disruption in association with severe midzonal necrosis. These alterations were accompanied by progressive hypoglycemia and elevations of serum enzymes, glutamic pyruvic transaminase, lactate dehydrogenase, and glutamic oxaloacetic transaminase. Hematologic studies revealed that E. coli bacteremia results in rapid leukopenia and disseminated intravascular coagulation primarily due to activation of the intrinsic coagulation pathway. All above reactions were delayed and markedly reduced in rats treated with methylprednisolone sodium succinate. The results indicate that antibiotic treatment of lethal, Gram-negative bacteremia is effective only in conjunction with early steroid treatment. The protective effects of glucocorticoids on the liver microcirculation and polymorphonuclear leukocytes appear to

  1. Sub-lethal effects induced by a mixture of three non-steroidal anti-inflammatory drugs (NSAIDs) on the freshwater bivalve Dreissena polymorpha.

    PubMed

    Parolini, Marco; Binelli, Andrea

    2012-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the sixth top-selling drugs worldwide and are commonly found in freshwater ecosystems in the high ng/l to low μg/l range. Recent studies have investigated both the acute and the chronic toxicity of single NSAIDs on different biological models, but these studies have completely neglected the fact that, in the environment, non-target organisms are exposed to mixtures of drugs that have unforeseeable toxicological behavior. This work investigated the sub-lethal effects induced by a mixture of three common NSAIDs, namely, diclofenac, ibuprofen and paracetamol, on the freshwater bivalve, the zebra mussel (Dreissena polymorpha). The mussels were exposed to three different environmental concentrations of the mixture (Low, Mid and High). A multi-biomarker approach was used to highlight cyto-genotoxic effects and the imbalance of the oxidative status of the treated specimens. The Neutral Red Retention Assay (NRRA) was used as a biomarker of cytotoxicity, whereas the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase were measured to assess the role played by the oxidative stress enzymes. In addition, the single cell gel electrophoresis assay, the DNA Diffusion assay and the micronucleus test were used to investigate possible genotoxic effects. According to our NRRA results, each treatment was able to induce a significant cellular stress in bivalves, probably due to the raise of oxidative stress, as indicated by the alteration of enzyme activities measured in treated specimens. Moreover, the mixture induced significant enhancements of DNA fragmentation, which preluded fixed genetic damage, as highlighted by the increase of both apoptotic and micronucleated cells. PMID:21971971

  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 toxicity of methyl isocyanate: a preliminary study of the dose response for eye and other effects.

    PubMed

    Salmon, A G; Kerr Muir, M; Andersson, N

    1985-12-01

    Acute toxic effects of methyl isocyanate in the rat were determined for two hour exposures to concentrations in the range 11 ppm (very slight effect) to 65 ppm (lethality: pulmonary oedema). Changes in the eye, lungs, and behaviour were noted. Eye changes were confined to erosions of the corneal epithelium and were most severe at intermediate levels of exposure. A comparison was made of the effects noted in rats with reported effects on survivors of the Bhopal disaster. Urinary thiocyanate concentrations in exposed rats were found to be reduced relative to control values. PMID:4074650

  4. [Acute tonsillopharyngitis: the effectiveness of topical therapy].

    PubMed

    Nosulya, E V; Kim, I A; Chernykh, N M; Karnoukhova, O A

    2015-01-01

    The objective of the present study was to evaluate the clinical effectiveness of a furasol sore throat gargle solution for the treatment of acute tonsillopharyngitis. Forty patients presenting with acute tonsillopharyngitis were allocated to two groups, 20 subjects in each, by means of independent sequential randomization. Prior to the onset of the treatment, all the patients were examined for determining the species composition of pharyngeal microflora with the use of an «AutoScan4 System» analyzer («Siemens», USA) and estimating the resistance to antibacterial preparations (by the disk diffusion method). All the participants of the study were prescribed antibacterial therapy. In the patients of group 1 (study group), the antibacterial treatment of acute tonsillopharyngitis was supplemented by a furasol sore throat gargle solution whereas those of group 2 (controls) were treated without topical therapy. The quantitative evaluation of the severity of manifestations of the disease before and after the treatment was based on a 5-point visual-analog scale. It was shown that systemic antibacterial therapy resulted in the consistent decrease of the frequency of occurrence of pathogenic and potentially pathogenic microflora in the patients comprising both groups. Treatment with a furasol sore throat gargle solution did not lead to the appearance of bacterial species alien to the oropharynx, nor was it accompanied by the impairment of resistance of its mucous membrane to the colonization by microorganisms. The results of the study give evidence of the well apparent regression of the subjective signs of tonsillopharyngitis and the inflammatory changes in the mucous membrane of the pharynx in the patients given the topical treatment in the form of a furasol sore throat gargle solution in addition to antibacterial therapy. It is concluded that a furasol sore throat gargle solution can be recommended for the introduction into the combined treatment of the patients

  5. Effects of salinity on short-term waterborne zinc uptake, accumulation and sub-lethal toxicity in the green shore crab (Carcinus maenas).

    PubMed

    Niyogi, Som; Blewett, Tamzin A; Gallagher, Trevor; Fehsenfeld, Sandra; Wood, Chris M

    2016-09-01

    Waterborne zinc (Zn) is known to cause toxicity to freshwater animals primarily by disrupting calcium (Ca) homeostasis during acute exposure, but its effects in marine and estuarine animals are not well characterized. The present study investigated the effects of salinity on short-term Zn accumulation and sub-lethal toxicity in the euryhaline green shore crab, Carcinus maenas. The kinetic and pharmacological properties of short-term branchial Zn uptake were also examined. Green crabs (n=10) were exposed to control (no added Zn) and 50μM (3.25mgL(-1)) of waterborne Zn (∼25% of 96h LC50 in 100 seawater) for 96h at 3 different salinity regimes (100%, 60% and 20% seawater). Exposure to waterborne Zn increased tissue-specific Zn accumulation across different salinities. However, the maximum accumulation occurred in 20% seawater and no difference was recorded between 60% and 100% seawater. Gills appeared to be the primary site of Zn accumulation, since the accumulation was significantly higher in the gills relative to the hepatopancreas, haemolymph and muscle. Waterborne Zn exposure induced a slight increase in haemolymph osmolality and chloride levels irrespective of salinity. In contrast, Zn exposure elicited marked increases in both haemolymph and gill Ca levels, and these changes were more pronounced in 20% seawater relative to that in 60% or 100% seawater. An in vitro gill perfusion technique was used to examine the characteristics of short-term (1-4h) branchial Zn uptake over an exposure concentration range of 3-12μM (200-800μgL(-1)). The rate of short-term branchial Zn uptake did not change significantly after 2h, and no difference was recorded in the rate of uptake between the anterior (respiratory) and posterior (ion transporting) gills. The in vitro branchial Zn uptake occurred in a concentration-dependent manner across different salinities. However, the rate of uptake was consistently higher in 20% seawater relative to 60% or 100% seawater - similar to

  6. Reduced Life Expectancy Model for Effects of Long Term Exposure on Lethal Toxicity with Fish

    PubMed Central

    Yu, Qiming J.; Connell, Des W.

    2013-01-01

    A model based on the concept of reduction in life expectancy (RLE model) as a result of long term exposure to toxicant has been developed which has normal life expectancy (NLT) as a fixed limiting point for a species. The model is based on the equation (LC50 = a ln(LT50) + b) where a and b are constants. It was evaluated by plotting ln LT50 against LC50 with data on organic toxicants obtained from the scientific literature. Linear relationships between LC50 and ln LT50 were obtained and a Calculated NLT was derived from the plots. The Calculated NLT obtained was in good agreement with the Reported NLT obtained from the literature. Estimation of toxicity at any exposure time and concentration is possible using the model. The use of NLT as a reference point is important since it provides a data point independent of the toxicity data set and limits the data to the range where toxicity occurs. This novel approach, which represents a departure from Haber's rule, can be used to estimate long term toxicity from limited available acute toxicity data for fish exposed to organic biocides. PMID:24455314

  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. 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

  9. Effects of cadmium at sub-lethal concentration on growth and biochemical parameters in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Heydarnejad, M Saeed; Khosravian-Hemamai, Mozhdeh; Nematollahi, Amin

    2013-01-01

    Cadmium (Cd), as one of heavy metals and an environmental stressor, may alter many physiological processes like growth and serum parameters in fish. The main objective of this study was to determine the effects of cadmium at sub-lethal concentrations (1 and 3 μg/l) on growth and serum biochemical parameters including enzymes, i.e. alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), glucose, triglyceride, cholesterol and total protein in rainbow trout (Oncorhynchus mykiss). Trout were exposed to cadmium, and, at intervals of 1, 15, and 30 days, selected parameters were evaluated. Condition Factor (K), Specific Growth Rate (SGR) and Body Weight Gain (BWG) consistently decreased, while Food Conversion Ratio (FCR) increased at the end of experiment. Glucose was elevated in trout exposed to both Cd concentrations at day 15 and then returned to levels comparable to control fish. Triglyceride and cholesterol decreased transiently at day 15 and then increased at day 30. Total protein, AST, ALT and ALP increased linearly by time and Cd concentration. This investigation suggests that growth and serum biochemical parameters could be used as important and sensitive biomarkers in ecotoxicological studies concerning the effects of metal contamination and fish health. PMID:23782857

  10. 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. PMID:26562769

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

    PubMed Central

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

    2011-01-01

    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). PMID:23407707

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

    SciTech Connect

    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 H/sub 2/O/sub 2/ may be a photoproduct of NUV; 2) some, but not all, of the effects of NUV and H/sub 2/O/sub 2/ 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. 131 references.

  13. 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.

  14. 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. PMID:3438923

  15. 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. PMID:24577726

  16. 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

  17. 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

  18. EFFECTS OF CHLORDIMEFORM ON CARDIOVASCULAR FUNCTIONAL PARAMETERS. PART 1. LETHALITY AND ARRHYTHMOGENICITY IN THE GERIATRIC RAT

    EPA Science Inventory

    Chlordimeform (CDM), a formamidine pesticide, had a profound effect on the cardiovascular function of geriatric rats. Two-year-old pentobarbital-anesthetized Sprague-Dawley rats (n=8) received sequential intravenous CDM injections of 5, 10, 30, and 60 mg/kg. A control group of ra...

  19. 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. PMID:23664473

  20. 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. PMID:26470229

  1. Antifeedant and lethal effects of the fungi Isaria fumosorosea on the Asian citrus psyllid Diaphorina citri

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An insect-infecting fungal pathogen increases mortality of Asian citrus psyllids (Diaphorina citri,Hemiptera:Psyllidae). The entomopathogenic fungi(Isaria fumosorosea [Ifr])sold as the product PFR 97™ was shown to be effective at killing and reducing feeding of the Asian citrus psyllid. The psyllid ...

  2. Inactivated pep27 mutant as an effective mucosal vaccine against a secondary lethal pneumococcal challenge in mice

    PubMed Central

    Choi, Sang-Yoon; Tran, Thao Dang-Hien; Briles, David E.

    2013-01-01

    Purpose A pep27 mutant may be able to elicit mucosal immunity against pneumococcal diseases, and could be employed as an inexpensive attenuated vaccine. However, this particular mutant contains an erythromycin-resistance marker. The purpose of the current study is to develop a markerless pep27 mutant and assess whether this inactivated mutant is able to induce mucosal immunity. Materials and Methods Mice were vaccinated intranasally with the inactivated markerless pep27 mutant every 2 weeks for a total of three times, after which time serum samples were analyzed for antibody titers. The mice were then challenged with a lethal D39 strain and their survival time was measured. The cross-reactivity of the antisera against pep27 was also compared to other mutant serotypes. Results Intranasal immunization of mice with the inactivated markerless pep27 mutant provides effective protection and rapidly cleared bacterial colonization in vivo. Moreover, antisera raised against the pep27 mutant may cross-react with several other serotype strains. Conclusion Intranasal immunization with the inactivated pep27 mutant may be able to provide mucosal immunity, and could represent an efficient mucosal vaccine. PMID:23596592

  3. 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. PMID:26361856

  4. 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

  5. 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.

  6. 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.

  7. Salinity effects on plasma ion levels, cortisol, and osmolality in Chinook salmon following lethal sampling.

    PubMed

    Stewart, Heather A; Noakes, David L G; Cogliati, Karen M; Peterson, James T; Iversen, Martin H; Schreck, Carl B

    2016-02-01

    Studies on hydromineral balance in fishes frequently employ measurements of electrolytes following euthanasia. We tested the effects of fresh- or salt-water euthanasia baths of tricaine mesylate (MS-222) on plasma magnesium (Mg(2+)) and sodium (Na(+)) ions, cortisol and osmolality in fish exposed to saltwater challenges, and the ion and steroid hormone fluctuations over time following euthanasia in juvenile spring Chinook salmon (Oncorhynchus tshawytscha). Salinity of the euthanasia bath affected plasma Mg(2+) and Na(+) concentrations as well as osmolality, with higher concentrations in fish euthanized in saltwater. Time spent in the bath positively affected plasma Mg(2+) and osmolality, negatively affected cortisol, and had no effect on Na(+) concentrations. The difference of temporal trends in plasma Mg(2+) and Na(+) suggests that Mg(2+) may be more sensitive to physiological changes and responds more rapidly than Na(+). When electrolytes and cortisol are measured as endpoints after euthanasia, care needs to be taken relative to time after death and the salinity of the euthanasia bath. PMID:26603557

  8. 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

  9. 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. PMID:25242941

  10. Lethal and sublethal effects of copper on redbreast sunfish, Lepomis auritus

    SciTech Connect

    Esman, L.A.; La Point, T.W.

    1995-12-31

    The popularity of redbreast sunfish (Lepomis auritus) as a sport fishery has been steadily increasing in South Carolina and the southeastern region of the United States. However, little is known about the toxicological sensitivity of this species. Expanding urban and suburban development threatens an increasing number of Piedmont streams with point and nonpoint source toxic discharges. As a result, redbreast sunfish face a greater influx of heavy metals, including copper, into the environment. In addition, the soft waters (10--20 mg/L as CaCO{sub 3}) characteristic of South Carolina increases the bioavailability of metals causing increased toxicity to fish. The authors determined the effect of copper, as copper sulfate (CuSO{sub 4}{center_dot}5H{sub 2}O) on redbreast sunfish using a static renewal toxicity test, monitoring mortality at frequent intervals. The overall 96hr LC50 was 0.18 mg/L Cu. A critical concentration leading to rapid time-to-death appears to fall within the range of 0.15--0.28 mg/L Cu. Normal social behavior is important for successful propagation of this species in the wild. Preliminary testing indicates that predatory behavior is unaffected at concentrations up to 50% LC50. Ultimately, such stress will lower population fitness. Therefore, the authors are determining at what concentration they see behavioral effects on feeding (e.g. handling time, capture efficiency) begin. Results of these experiments expand the behavioral and toxicological data on this species.

  11. Lethal effects of abamectin on the aquatic organisms Daphnia similis, Chironomus xanthus and Danio rerio.

    PubMed

    Novelli, Andréa; Vieira, Bruna Horvath; Cordeiro, Daniela; Cappelini, Luciana Teresa Dias; Vieira, Eny Maria; Espíndola, Evaldo Luiz Gaeta

    2012-01-01

    Abamectin is used as an acaricide and insecticide for fruits, vegetables and ornamental plants, as well as a parasiticide for animals. One of the major problems of applying pesticides to crops is the likelihood of contaminating aquatic ecosystems by drift or runoff. Therefore, toxicity tests in the laboratory are important tools to predict the effects of chemical substances in aquatic ecosystems. The aim of this study was to assess the potential hazards of abamectin to the freshwater biota and consequently the possible losses of ecological services in contaminated water bodies. For this purpose, we identified the toxicity of abamectin on daphnids, insects and fish. Abamectin was highly toxic, with an EC(50) 48 h for Daphnia similis of 5.1 ng L(-1), LC(50) 96 h for Chironomus xanthus of 2.67 μg L(-1) and LC(50) 48 h for Danio rerio of 33 μg L(-1). PMID:21955349

  12. 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.

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

    SciTech Connect

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

    2013-07-26

    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.

  14. 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.

  15. 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. PMID:19685097

  16. 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.

  17. Lethal and sublethal effects of rice polishing process on Sitophilus oryzae (Coleoptera: Curculionidae).

    PubMed

    Lucas, E; Riudavets, J

    2000-12-01

    The mechanical impact of rice polishingon the rice weevil, Sitophilus oryzae (L.), and the subsequent postpolishing effects associated with rice quality were studied. "Brown" rice (not polished), "White (infest then polish)" rice, and "White (polish then infest)" rice were used with different polishing process intensities and different initial weevil densities. Weevil progeny were more numerous in Brown than in White (infest then polish) or White (polish then infest) rice. Polishing corresponding to a weight loss of 11% in rice generated an immediate mortality of approximately 40%; the subsequent mortality caused by rice quality was also 40% (total >80%). A polishing process corresponding to 14 and 16% of rice weight loss generated a drastic mortality in the weevil population (>95%). The progeny per adult weevil was similar with high and low initial weevil densities. The development of weevil progeny was also delayed by about 1 wk in White (infest then polish) rice compared with Brown rice. Furthermore, weevil adults of the progeny were significantly heavier in Brown than in White (infest then polish) or White (polish then infest) rice. PMID:11142320

  18. Sub-lethal effects and bioconcentration of the human pharmaceutical clotrimazole in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Burkina, Viktoriia; Zamaratskaia, Galia; Oliveira, Rhaul; Fedorova, Ganna; Grabicova, Katerina; Schmidt-Posthaus, Heike; Steinbach, Christoph; Domingues, Inês; Golovko, Oksana; Sakalli, Sidika; Grabic, Roman; Randak, Tomas; Zlabek, Vladimir

    2016-09-01

    The aim of this study was to characterize biomarker responses, haematological profiles, structural changes and uptake in juvenile rainbow trout exposed to clotrimazole (CLO) at three concentrations (0.01 - [lowest environmentally relevant concentration], 1.0 [highest environmentally relevant concentration] and 10 μg L(-1)) in a semi-static system over a period of 42 days. Antioxidant defence enzymes, which responded to CLO exposure, changed the oxidative stress status of cells, but no differences were observed in lipid peroxidation. Clotrimazole triggered a biphasic response of CYP3A-like activity in liver microsomes, which may indicate a detoxification process in the liver. Histopathological alterations were most pronounced in kidneys and testes in the group exposed to 10 μg L(-1). Structural changes in the kidney included tubulonephrosis and hyaline droplet degeneration in the tubular epithelial cells. The relative proportions of germ cells in testes were changed: The number of spermatozoa was reduced, and the spermatogonia and spermatocytes were increased. The highest CLO concentration was detected in fish liver (3710 ng per gram wet tissue) and kidney (4280 ng per gram wet tissue). Depuration half-life was estimated to be 72, 159, and 682 h in liver, muscle, and kidney, respectively. Taken together, these results provide valuable toxicological data on the effects of CLO on aquatic non-target organisms, which could be useful for further understanding of the potential risks in the real aquatic environment. PMID:27268790

  19. 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. PMID:27491870

  20. 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

  1. 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.

  2. 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)

  3. Laboratory bioassays to estimate the lethal and sublethal effects of various insecticides and fungicides on Deraeocoris brevis (Hemiptera: Miridae).

    PubMed

    Amarasekare, K G; Shearer, P W

    2013-04-01

    This laboratory bioassay focused on lethal and sublethal effects of five insecticides (chlorantraniliprole, cyantraniliprole, spinetoram, novaluron, and lambda-cyhalothrin) and two fungicide treatments (sulfur and a mixture of copper hydroxide and mancozeb) on the predatory mired bug, Deraeocoris brevis (Uhler) (Hemiptera: Miridae) using second instars and adult males and females. Formulated pesticides were tested using concentrations that were equivalent to the high label rate (1x) (high rate) and 1/10th of that amount (0.1x) (low rate) dissolved in 378.5 liters of water. Lambda-cyhalothrin was highly toxic to D. brevis nymphs and adults at both rates, whereas both rates of novaluron were highly toxic to nymphs. Cyantraniliprole, chlorantraniliprole, and novaluron were less toxic to adults, and chlorantraniliprole and spinetoram were less toxic to nymphs. Both rates of spinetoram caused significant mortality to adults. Fecundity of adult females was affected negatively by the high rates of either novaluron or spinetoram, whereas the fertility was affected only by the high rate of novaluron. The high rate of spinetoram reduced survival of nymphs. Adults treated with spinetoram had reduced longevity. Cyantraniliprole caused some mortality to nymphs and affected their survival. Both rates of sulfur were toxic to nymphs and affected emergence to adults. The mixture of copper hydroxide and mancozeb was less toxic to D. brevis. Neither adult longevity nor sex ratio was affected by the fungicides. The r values for D. brecis treated with lambda-cyhalothrin, novaluron, spinetoram, and sulfur were low, indicating that these products may have negative impact on population growth. PMID:23786065

  4. REPRODUCTIVE TOXICITY AND LACK OF DOMINANT LETHAL EFFECTS OF 2,4-DINITROTOLUENE IN THE MALE RAT

    EPA Science Inventory

    Adult male Sprague Dawley rats were gavaged with 2,4-dini-trotoluene (2,4-DNT) dissolved in corn oil at 0, 60, 180, or 240 mg/kg/day for five days. A single oral dose (0.5 mg/kg) of triethylenemelamine was used as a positive control. Induction of dominant lethal events was scored...

  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. PMID:26762236

  6. 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. PMID:10940590

  7. In the Absence of Endogenous Gamma Interferon, Mice Acutely Infected with Neospora caninum Succumb to a Lethal Immune Response Characterized by Inactivation of Peritoneal Macrophages

    PubMed Central

    Nishikawa, Yoshifumi; Tragoolpua, Khajornsak; Inoue, Noboru; Makala, Levi; Nagasawa, Hideyuki; Otsuka, Haruki; Mikami, Takeshi

    2001-01-01

    Following infection with Neospora caninum, BALB/c mice were shown to be resistant to an acute infection but developed a latent chronic infection. However, BALB/c background gamma interferon (IFN-γ)-deficient mice were sensitive to the acute infection. Since the immune response in IFN-γ-deficient mice is scantly known, we examined the function of macrophages, major histocompatibility complex (MHC) class II expression, T-cell responses, and serum cytokine levels in the mice. All IFN-γ-deficient mice died within 9 days of infection with N. caninum, whereas those treated with exogenous IFN-γ lived longer. Although N. caninum invaded various organs in both types of mice at the early stage of infection, the parasite was not detected in the brains of resistant hosts until 21 days postinfection (dpi). Peritoneal macrophages from IFN-γ-deficient mice were activated by exogenous IFN-γ associated with inhibition of parasite growth and nitric oxide production as were those from BALB/c mice. IFN-γ-deficient mice failed to increase MHC class II expression on macrophages. Moreover, BALB/c mice induced T-cell proliferation while IFN-γ-deficient mice did not. However, in vivo treatment with exogenous IFN-γ induced up-regulated MHC class II expression in IFN-γ-deficient mice. BALB/c mice treated with an antibody to CD4 showed an increase in morbidity and mortality after parasite infection. In serum, significant levels of IFN-γ and interleukin-4 (IL-4) were detected in resistant hosts, whereas IL-10 was detected in IFN-γ-deficient mice. The levels of IL-12 in IFN-γ-deficient mice were higher than those in BALB/c mice at 7 dpi. The present study indicates that early IFN-γ production has a crucial role in the activation of peritoneal macrophages for the induction of protective immune responses against N. caninum. PMID:11427432

  8. Simvastatin alleviates myocardial contractile dysfunction and lethal ischemic injury in rat heart independent of cholesterol-lowering effects.

    PubMed

    ADAMEOVA, A; HARCAROVA, A; MATEJIKOVA, J; PANCZA, D; KUZELOVA, M; CARNICKA, S; SVEC, P; BARTEKOVA, M; STYK, J; Ravingerová, T

    2009-01-01

    Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are most frequently used drugs in the prevention of coronary artery disease due to their cholesterol-lowering activity. However, it is not exactly known whether these effects of statins or those independent of cholesterol decrease account for the protection against myocardial ischemia-reperfusion (I/R) injury. In this study, we investigated the effect of 5-day treatment with simvastatin (10 mg/kg) in Langendorff-perfused hearts of healthy control (C) and diabetic-hypercholesterolemic (D-H; streptozotocin + high fat-cholesterol diet, 5 days) rats subjected to 30-min global ischemia followed by 40-min reperfusion for the examination of postischemic contractile dysfunction and reperfusion-induced ventricular arrhythmias or to 30-min (left anterior descending) coronary artery occlusion and 2-h reperfusion for the infarct size determination (IS; tetrazolium staining). Postischemic recovery of left ventricular developed pressure (LVDP) in animals with D-H was improved by simvastatin therapy (62.7+/-18.2 % of preischemic values vs. 30.3+/-5.7 % in the untreated D-H; P<0.05), similar to the values in the simvastatin-treated C group, which were 2.5-fold higher than those in the untreated C group. No ventricular fibrillation occurred in the simvastatin-treated C and D-H animals during reperfusion. Likewise, simvastatin shortened the duration of ventricular tachycardia (10.2+/-8.1 s and 57.8+/-29.3 s in C and D-H vs. 143.6+/-28.6 s and 159.3+/-44.3 s in untreated C and D-H, respectively, both P<0.05). The decreased arrhythmogenesis in the simvastatin-treated groups correlated with the limitation of IS (in % of risk area) by 66 % and 62 % in C and D-H groups, respectively. However, simvastatin treatment decreased plasma cholesterol levels neither in the D-H animals nor in C. The results indicate that other effects of statins (independent of cholesterol lowering) are involved in the

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

    PubMed Central

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

    2014-01-01

    (s) involved in protecting cells against the lethal effects of radiation. PMID:24657250

  10. 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

  11. Host species vary in infection probability, sub-lethal effects, and costs of immune response when exposed to an amphibian parasite

    PubMed Central

    Bielby, Jon; Fisher, Matthew C.; Clare, Frances C.; Rosa, Gonçalo M.; Garner, Trenton W. J.

    2015-01-01

    The amphibian parasite Batrachochytrium dendrobatidis (Bd) is regarded as an extreme generalist, infecting over 500 species, but amongst these hosts there exists a great deal of variation in the susceptibility to and the costs of parasite exposure. We use two infection experiments to determine whether inter-specific variation in the sublethal and lethal effects of parasite exposure exist in two host species. We then tested the relative roles of host density and diversity on infection probability of a focal susceptible host. Our results show significant heterogeneity in host species response to parasite exposure, and that both lethal and sub-lethal costs exist in individuals that are able to resist infection, indicating that successful immune response to infection comes at a cost. Further, we show that increasing host density significantly increased the likelihood of susceptible individuals becoming infected with Bd irrespective of host diversity and variation in host susceptibility. These results suggest that populations of resistant species are likely to suffer ill-effects of exposure to Bd regardless of their infection status, and that at the stage of initial infection there was no support for the dilution of transmission events, in contrast to other studies that focus on subsequent transmission of infection. PMID:26022346

  12. Host species vary in infection probability, sub-lethal effects, and costs of immune response when exposed to an amphibian parasite.

    PubMed

    Bielby, Jon; Fisher, Matthew C; Clare, Frances C; Rosa, Gonçalo M; Garner, Trenton W J

    2015-01-01

    The amphibian parasite Batrachochytrium dendrobatidis (Bd) is regarded as an extreme generalist, infecting over 500 species, but amongst these hosts there exists a great deal of variation in the susceptibility to and the costs of parasite exposure. We use two infection experiments to determine whether inter-specific variation in the sublethal and lethal effects of parasite exposure exist in two host species. We then tested the relative roles of host density and diversity on infection probability of a focal susceptible host. Our results show significant heterogeneity in host species response to parasite exposure, and that both lethal and sub-lethal costs exist in individuals that are able to resist infection, indicating that successful immune response to infection comes at a cost. Further, we show that increasing host density significantly increased the likelihood of susceptible individuals becoming infected with Bd irrespective of host diversity and variation in host susceptibility. These results suggest that populations of resistant species are likely to suffer ill-effects of exposure to Bd regardless of their infection status, and that at the stage of initial infection there was no support for the dilution of transmission events, in contrast to other studies that focus on subsequent transmission of infection. PMID:26022346

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

    PubMed

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

    2001-09-01

    Artemia salina L. (Artemiidae), the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemical and natural products. In this study the Medium Lethal Concentrations (LC50 value) of 20 plant extracts, Aloe vera (L.) Burm. F. (Aloeaceae), Artemisia absinthium L. (Asteraceae); Citrus aurantium L. (Rutaceae); Cymbopogon citratus (DC. Ex Nees) Stapf (Poaceae); Datura stramonium L. (Solanaceae); Justicia pectoralis Jacq. (Acanthaceae); Musa x paradisiaca L. (Musaceae); Ocimum basilicum L.; O. gratissimum L.; O. tenuiflorum L. (Lamiaceae); Pimenta dioica (L.) Merr. (Myrtaceae); Piper auritum Kunth (Piperaceae); Plantago major L. (Plantaginaceae); Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Ruta graveolens L. (Rutaceae); Senna alata (L.) Roxb. (Fabaceae); Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae); and Thuja occidentalis L. (Cupressaceae), were determined using Artemia salina L. (Artemiidae), with the objective of relating the results to the LD50 values reported in mice (tested at three concentrations: 10, 100, and 1000 microg/mL, for each extract). We found good correlation between the in vivo and the in vitro tests (r = 0.85 p < 0.05), and this method is a useful tool for predicting oral acute toxicity in plant extracts. PMID:11695884

  14. Effects of some hypoxic cell radiosensitizers on the decay of potentially lethal oxygen-dependent damage in fully hydrated spores.

    PubMed Central

    Tallentire, A.; Stratford, I. J.; Maughan, R. L.; Michael, B. D.

    1978-01-01

    Using a stopped-flow mixing and pulsed irradiation apparatus, a study has been made of the decay, to a harmless form, of radiation-induced species that would otherwise be lethal to spores on contact with oxygen. Aqueous suspensions of Bacillus megaterium spores were irradiated with electrons for approximately 1 s; at various times after irradiation oxygen in solution was added. As the interval between anoxic irradiation and introduction of oxygen increased, the fraction of spores surviving increased. This change in survival reflects the decay of potentially lethal species. The presence of electron-affinic radiosensitizers during irradiation enhanced the decay rate of this damage, the greatest enhancement being seen with sensitizers of the highest electron affinity. In contrast, the nitroxyl-free radical sensitizer TAN fixed the radiation-induced damage so that no increase in survival, and hence no decay, was seen. PMID:98174

  15. 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.

  16. [Acute toxicological effects of heavy metal pollution in soils on earthworms].

    PubMed

    Song, Yufang; Zhou, Qixing; Xu, Huaxia; Ren, Liping; Sun, Tieheng; Gong, Ping

    2002-02-01

    Acute and sub-acute lethal effects of single and combined Cu, Zn, Pb and Cd on earthworm was determined using meadow brown soil. Results indicated that the mortality of earthworm was significantly related with the concentrations of Cu and Zn in the soil (alpha = 0.05, RCu = 0.86, RPb = 0.87), and the inhibition rate of earthworm growth was significantly related with the concentration of Cu in the soil (alpha = 0.05, RCu = 0.84). There was no significant relation between the concentrations of other heavy metals tested and the death rate and the growth-inhibition rate. The degree of individual earthworm enduring the toxicity of heavy metals varied greatly. The threshold concentration of toxicity defined by statistical method, the level to conduce the death of individual earthworm was 300 mg.kg-1 for Cu, 1300 mg.kg-1 for Zn, 1700 mg.kg-1 for Pb, 300 mg.kg-1 for Cd. LC50 was 400-450 mg.kg-1 for Cu, 1500-1900 mg.kg-1 for Zn, 2350-2400 mg.kg-1 for Pb and 900 mg.kg-1 for Cd. Combined effects of single Cu, Zn, Pb and Cd to conduce more than 10% of the death rate of earthworm could result in 100% of the death rate of earthworm, thus showing the strong synergistic joint effect of the heavy metals. PMID:11993124

  17. 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.

  18. 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.

  19. Methylone-induced hyperthermia and lethal toxicity: role of the dopamine and serotonin transporters.

    PubMed

    Piao, Ying-Shan; Hall, Frank Scott; Moriya, Yuki; Ito, Miki; Ohara, Arihisa; Kikura-Hanajiri, Ruri; Goda, Yukihiro; Lesch, Klaus-Peter; Murphy, Dennis L; Uhl, George R; Sora, Ichiro

    2015-06-01

    Methylone (2-methylamino-1-[3,4-methylenedioxy-phenyl]propan-1-one), an amphetamine analog, has emerged as a popular drug of abuse worldwide. Methylone induces hyperthermia, which is thought to contribute toward the lethal consequences of methylone overdose. Methylone has been assumed to induce hyperthermic effects through inhibition of serotonin and/or dopamine transporters (SERT and DAT, respectively). To examine the roles of each of these proteins in methylone-induced toxic effects, we used SERT and DAT knockout (KO) mice and assessed the hyperthermic and lethal effects caused by a single administration of methylone. Methylone produced higher rates of lethal toxicity compared with other amphetamine analogs in wild-type mice. Compared with wild-type mice, lethality was significantly lower in DAT KO mice, but not in SERT KO mice. By contrast, only a slight diminution in the hyperthermic effects of methylone was observed in DAT KO mice, whereas a slight enhancement of these effects was observed in SERT KO mice. Administration of the selective D1 receptor antagonist SCH 23390 and the D2 receptor antagonist raclopride reduced methylone-induced hyperthermia, but these drugs also had hypothermic effects in saline-treated mice, albeit to a smaller extent than the effects observed in methylone-treated mice. In contradistinction to 3,4-methylenedioxymethamphetamine, which induces its toxicity through SERT and DAT, these data indicate that DAT, but not SERT, is strongly associated with the lethal toxicity produced by methylone, which did not seem to be dependent on the hyperthermic effects of methylone. DAT is therefore a strong candidate molecule for interventions aimed at preventing acute neurotoxic and lethal effects of methylone. PMID:25794333

  20. Acute toxic effects of fenpyroximate acaricide on Guppy (Poecilia reticulata Peters, 1859).

    PubMed

    Doğan, Nesli; Yazıcı, Zehra; Şişman, Turgay; Aşkin, Hakan

    2013-09-01

    Fenpyroximate (FP), an acaricide, is widely used in the prevention of acarids (mites) in fruit plant gardens. In this study, the acute toxic effects of different concentrations of FP were investigated using adult guppy (Poecilia reticulata Peters, 1859). Guppy adults were exposed to a range of FP concentrations (25, 50, 75, 100, 125, and 150 µg/L) during 48 h. Static method, which is one of the acute toxicity experiments, has been used in this study. According to probit analysis, the 48-h median lethal concentration (LC50) value of FP at 26°C was found to be 72.821 µg/L. Sublethal exposures were predetermined based on 48-h LC50 value. Guppies were exposed to low concentrations (15, 25, and 50 µg/L) of FP for 48 h. Signs of paralysis and behavior deformations were monitored every 12 h in a number of live and dead adults. Low concentrations of FP were also responsible for erratic swimming, loss of equilibrium, and being lethargic. Liver histology revealed several pathological damages including congestion, picnotic nucleus, sinusoidal dilatation, increase in melanomacrophagic centers, and endothelial degeneration. Finally, the toxicity test results provided 48-h LC50 value for FP, and low concentrations of FP can be highly detrimental to guppy adults with clear evidence of behavioral and histologic effects. PMID:22508399

  1. Agricultural adjuvants: acute mortality and effects on population growth rate of Daphnia pulex after chronic exposure.

    PubMed

    Stark, John D; Walthall, William K

    2003-12-01

    Acute and chronic toxicity of eight agricultural adjuvants (Bond, Kinetic, Plyac, R-11, Silwet L-77, Sylgard 309, X-77, and WaterMaxx) to Daphnia pulex were evaluated with 48-h acute lethal concentration estimates (LC50) and a 10-d population growth-rate measurement, the instantaneous rate of increase (r1). Based on LC50, the order of toxicity was R-11 > X-77 = Sylgard 309 = Silwet L-77 > Kinetic > Bond > Plyac > WaterMaxx; all LC50 estimates were higher than the expected environmental concentration (EEC) of 0.79 mg/L, indicating that none of these adjuvants should cause high levels of mortality in wild D. pulex populations. Extinction, defined as negative population growth rate, occurred after exposure to 0.9 mg/L R-11, 13 mg/L X-77, 25 mg/L Kinetic, 28 mg/L Silwet, 18 mg/L Sylgard, 450 mg/L Bond, 610 mg/L Plyac, and 1,600 mg/L WaterMaxx. Concentrations that caused extinction were substantially below the acute LC50 for R-11, Kinetic, Plyac, X-77, and Bond. The no-observable-effects concentration (NOEC) and lowest-observable-effects concentration (LOEC) for the number of offspring per surviving female after exposure to R-11 were 0.5 and 0.75 mg/L, respectively. The NOEC and LOEC for population size after exposure to R-11 were (1.25 and 0.5 mg/L, respectively. Both of these values were lower than the EEC, indicating that R-11 does have the potential to cause damage to D. pulex populations after application at recommended field rates. The wide range of concentrations causing extinction makes it difficult to generalize about the potential impacts that agricultural adjuvants might have on aquatic ecosystems. Therefore, additional studies that examine effects on other nontarget organisms and determine residues in aquatic ecosystems may be warranted. PMID:14713050

  2. Effect of acute airway inflammation on the pulmonary antioxidant status.

    PubMed

    Deaton, Christopher M; Marlin, David J; Smith, Nicola C; Harris, Patricia A; Dagleish, Mark P; Schroter, Robert C; Kelly, Frank J

    2005-09-01

    Effects of acute airway inflammation induced by organic dust inhalation on pulmonary antioxidant status were investigated in healthy horses and horses affected by recurrent airway obstruction. Exposure to organic dust induced acute airway neutrophilia, which was associated with increases in elastase and decreases in ascorbic acid concentrations in bronchoalveolar lavage fluid. However, markers of oxidative stress were unaffected, as was hydrogen peroxide in breath condensate. Decreases in ascorbic acid correlated with increased respiratory resistance (P = .001) when both groups were combined. In conclusion, acute neutrophilic airway inflammation does not result in significant evidence of oxidative stress in horses affected by recurrent airway obstruction. PMID:16203621

  3. Activation of budding yeast replication origins and suppression of lethal DNA damage effects on origin function by ectopic expression of the co-chaperone protein Mge1.

    PubMed

    Trabold, Peter A; Weinberger, Martin; Feng, Li; Burhans, William C

    2005-04-01

    Initiation of DNA replication in eukaryotes requires the origin recognition complex (ORC) and other proteins that interact with DNA at origins of replication. In budding yeast, the temperature-sensitive orc2-1 mutation alters these interactions in parallel with defects in initiation of DNA replication and in checkpoints that depend on DNA replication forks. Here we show that DNA-damaging drugs modify protein-DNA interactions at budding yeast replication origins in association with lethal effects that are enhanced by the orc2-1 mutation or suppressed by a different mutation in ORC. A dosage suppressor screen identified the budding yeast co-chaperone protein Mge1p as a high copy suppressor of the orc2-1-specific lethal effects of adozelesin, a DNA-alkylating drug. Ectopic expression of Mge1p also suppressed the temperature sensitivity and initiation defect conferred by the orc2-1 mutation. In wild type cells, ectopic expression of Mge1p also suppressed the lethal effects of adozelesin in parallel with the suppression of adozelesin-induced alterations in protein-DNA interactions at origins, stimulation of initiation of DNA replication, and binding of the precursor form of Mge1p to nuclear chromatin. Mge1p is the budding yeast homologue of the Escherichia coli co-chaperone protein GrpE, which stimulates initiation at bacterial origins of replication by promoting interactions of initiator proteins with origin sequences. Our results reveal a novel, proliferation-dependent cytotoxic mechanism for DNA-damaging drugs that involves alterations in the function of initiation proteins and their interactions with DNA. PMID:15647270

  4. 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. PMID:26311583

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

    PubMed Central

    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

    2016-01-01

    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. PMID:26901785

  6. 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. PMID:26901785

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

    USGS Publications Warehouse

    Clark, D.R., Jr.; 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.

  8. Dengue Virus Infection with Highly Neutralizing Levels of Cross-Reactive Antibodies Causes Acute Lethal Small Intestinal Pathology without a High Level of Viremia in Mice

    PubMed Central

    Watanabe, Satoru; Chan, Kitti Wing Ki; Wang, Jiaqi; Rivino, Laura; Lok, Shee-Mei

    2015-01-01

    ABSTRACT Severe dengue virus (DENV)-associated diseases can occur in patients who have preexisting DENV antibodies (Abs) through antibody-dependent enhancement (ADE) of infection. It is well established that during ADE, DENV-antibody immune complexes (ICs) infect Fcγ receptor-bearing cells and increase the systemic viral burden that can be measured in the blood. For protection against infection with DENV serotypes 1 to 4, strongly neutralizing Abs must be elicited to overcome the effect of ADE. Clinical observations in infants who have maternal DENV Abs or recent phase II/III clinical trials with a leading tetravalent dengue vaccine suggested a lack of correlation between Ab neutralization and in vivo disease prevention. In addressing this gap in knowledge, we found that inoculation of ICs formed with serotype cross-reactive Abs that are more than 98% neutralized in vitro promotes high mortality in AG129 mice even though peak viremia was lower than that in direct virus infection. This suggests that the serum viremia level is not always correlated with disease severity. We further demonstrated that infection with the ICs resulted in increased vascular permeability, specifically in the small intestine, accompanied with increased tissue viral load and cytokine production, which can be suppressed by anti-tumor necrosis factor alpha (anti-TNF-α) Abs. Flow cytometric analysis identified increased infection in CD11bint CD11cint/hi CD103− antigen-presenting cells by IC inoculation, suggesting that these infected cells may be responsible for the increase in TNF-α production and vascular permeability in the small intestine that lead to mortality in mice. Our findings may have important implications for the development of dengue therapeutics. IMPORTANCE We examined the relationship between the neutralizing level of Abs at the time of infection and subsequent disease progression in a mouse model in order to understand why patients who are shown to have a neutralizing

  9. 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

  10. Development of Synthetic Lethality Anticancer Therapeutics

    PubMed Central

    2015-01-01

    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. PMID:24893124

  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. PMID:24688298

  12. 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

  13. 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

  14. Acute toxicity of chemically and mechanically dispersed crude oil to juvenile sea bass (Dicentrarchus labrax): Absence of synergistic effects between oil and dispersants.

    PubMed

    Dussauze, Matthieu; Pichavant-Rafini, Karine; Le Floch, Stéphane; Lemaire, Philippe; Theron, Michaël

    2015-07-01

    The goal of the present experiment was to assess the relative acute toxicities of mechanically and chemically dispersed oil (crude Arabian Light) in controlled conditions. Juvenile sea bass (Dicentrarchus labrax) were exposed to 4 commercial formulations of dispersants (Corexit EC9500A, Dasic Slickgone NS, Finasol OSR 52, Inipol IP 90), to mechanically dispersed oil, and to the corresponding chemical dispersions. Acute toxicity was evaluated at 24 h, 48 h, 72 h, and 96 h through the determination of 10%, 50%, and 90% lethal concentrations calculated from measured total petroleum hydrocarbon (TPH) concentrations; Kaplan-Meyer mortality analyses were based on nominal concentrations. Animals were exposed to the dissolved fraction of the oil and to the oil droplets (ranging from 14.0 μm to 42.3 μm for the chemical dispersions). Kaplan-Meyer analyses demonstrated an increased mortality in the case of chemical dispersions. This difference can be attributed mainly to differences in TPH, because the chemical lethal concentrations were not reduced compared with mechanical lethal concentrations (except after 24 h of exposure). The ratios of lethal concentrations of mechanical dispersions to the different chemical dispersions were calculated to allow direct comparisons of the relative toxicities of the dispersions. The results ranged from 0.27 to 3.59, with a mean ratio close to 1 (0.92). These results demonstrate an absence of synergistic effect between oil and chemical dispersants in an operational context. PMID:25677812

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

    PubMed Central

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

    2014-01-01

    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 137Cs 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. PMID:26019540

  16. 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…

  17. 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…

  18. 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

  19. 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. PMID

  20. 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. PMID:24172303

  1. 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. PMID:24739589

  2. 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).

  3. The effects of acute and chronic stress on diabetes control.

    PubMed

    Marcovecchio, M Loredana; Chiarelli, Francesco

    2012-10-23

    Stress is an important contributor to pathological conditions in humans. Hormonal changes that occur during acute and chronic stress situations can affect glucose homeostasis in both healthy people and in those with diabetes. Several studies have reported a negative effect of acute stress on maintenance of blood glucose concentrations in patients with type 1 and type 2 diabetes. The effect of stress on glycemic control in people with diabetes may be related to a direct effect of stress hormones on blood glucose levels and an indirect effect of stress on patient behaviors related to diabetes treatment and monitoring and meal and exercise plans. In contrast, there is no clear evidence that stressful life events promote the development of diabetes in children or in adults. Stress hyperglycemia, the development of hyperglycemia during acute illness, represents another interesting connection between the stress system and glucose homeostasis. A large body of evidence supports an association between stress hyperglycemia and increased morbidity and mortality in critically ill patients. Interestingly, there is some evidence supporting a beneficial effect of insulin in reducing morbidity and mortality in patients admitted to intensive care units. Finally, stress can influence the development of type 2 diabetes indirectly by promoting obesity and metabolic syndrome. PMID:23092890

  4. Acute effects of aflatoxins on guinea pig isolated ileum.

    PubMed

    Luzi, A; Cometa, M F; Palmery, M

    2002-10-01

    Previous studies on the aflatoxins have focused mainly on their chronic toxic effects. In this study we investigated the acute gastrointestinal effects of four common aflatoxins on isolated guinea pig ileum. AFB(1) (EC(50) 4.6+/-0.4 microM) and AFB(2) (EC(50)17+/-4.4 microM) contracted isolated guinea pig ileum in a dose-dependent manner, whereas AFG(1) and AFG(2) evoked no contractions. Atropine (5.9 nM 11.8 and 23.6 nM) antagonized AFB(1)-induced contractions in a dose-dependent manner. Pretreatment with the nicotinic ganglionic blocker, hexamethonium (up to 55 microM), left AFB(1)-induced contractions unchanged. In contrast, tetrodotoxin (0.3 microM), blocked AFB(1) contractile activity. The two inhibitors of ACh release, morphine (0.3 microM) and clonidine (0.4 microM), antagonized EC(50) AFB(1)-induced contractions, and apamin, a drug that increases neuronal excitability, facilitated the EC(50) AFB(1)-induced contractile effect. The choline uptake blocker, hemicholinium (17.4 microM) markedly reduced AFB(1)-induced contractions. These results suggest that aflatoxins induce their contractile effect indirectly through the cholinergic system by stimulating acetylcholine release from the postganglionic parasympathetic nerve endings. The acute actions of aflatoxins on isolated guinea pig ileum could explain their acute gastrointestinal effects in humans and animals. PMID:12206819

  5. 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

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

    PubMed

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

    2014-01-01

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

  7. 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 PMID:27454678

  8. Norepinephrine and impulsivity: Effects of acute yohimbine

    PubMed Central

    Swann, Alan C.; Lijffijt, Marijn; Lane, Scott D.; Cox, Blake; Steinberg, Joel L.; Moeller, F. Gerard

    2013-01-01

    Rationale Rapid-response impulsivity, characterized by inability to withhold response to a stimulus until it is adequately appraised, is associated with risky behavior and may be increased in a state-dependent manner by norepinephrine. Objective We assessed effects of yohimbine, which increases norepinephrine release by blocking alpha-2 noradrenergic receptors, on plasma catecholamine metabolites, blood pressure, subjective symptoms, and laboratory-measured rapid-response impulsivity. Methods Subjects were twenty-three healthy controls recruited from the community, with normal physical examination and ECG, and negative history for hypertension, cardiovascular illness, and Axis I or II disorder. Blood pressure, pulse, and behavioral measures were obtained before and periodically after 0.4 mg/kg oral yohimbine or placebo in a randomized, counterbalanced design. Metabolites of norepinephrine (3-methoxy-4-hydroxyphenylglycol, MHPG; vanillylmandelic acid, VMA) and dopamine (homovanillic acid, HVA) were measured by high pressure liquid chromatography with electrochemical detection. Rapid-response impulsivity was measured by commission errors and reaction times on the Immediate Memory Task (IMT), a continuous performance test designed to measure impulsivity and attention. Results Yohimbine increased plasma MHPG and VMA but not HVA. Yohimbine increased systolic and diastolic blood pressure and pulse rate. On the IMT, yohimbine increased impulsive errors and impulsive response bias and accelerated reaction times. Yohimbine-associated increase in plasma MHPG correlated with increased impulsive response rates. Time courses varied; effects on blood pressure generally preceded those on metabolites and test performance. Conclusions These effects are consistent with increased rapid-response impulsivity after pharmacological noradrenergic stimulation in healthy controls. Labile noradrenergic responses, or increased sensitivity to norepinephrine, may increase risk for impulsive

  9. 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.

  10. 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.

  11. Acute effects of aerobic exercise promote learning.

    PubMed

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

    2016-01-01

    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. PMID:27146330

  12. Formaldehyde exposure and acute health effects study

    SciTech Connect

    Quackenboss, J.J.; Lebowitz, M.D.; Michaud, J.P.; Bronnimann, D. )

    1989-01-01

    To assess the effects of formaldehyde exposures on health, exposure groups were defined using baseline exposure and health questionnaires. Formaldehyde concentrations were poorly correlated with these exposure classifications, perhaps due to the time delay between classification and monitoring. The 151 households reported here had a mean HCHO concentration of 35 (S.E. 1.5 and median 30) {mu}g/m{sup 3}. Passive samplers prepared in our lab were calibrated in a chamber to derive an estimated sampling rate of 0.311 {mu}g/(mg {center dot} m{sup {minus}3} {center dot} hr). They were also compared to commercially available samplers inside of the homes, with a correlation coefficient of 0.896 and mean difference of 2.6 {mu}g/m{sup 3}. In this report of initial findings from an ongoing study, daily symptoms and peak expiratory flow measurements were compared with an HCHO exposure classification based on the median measured concentrations. None of the symptoms groups were related to HCHO exposure when controlling for age and sex. There was a significant relationship between HCHO exposure and variability in peak expiratory flows that was dependent on age group. It may be especially important to assess the variability in reactive individuals and children to determine the short-term effects of HCHO exposures and possible long-term consequences.

  13. Acute effects of aerobic exercise promote learning

    PubMed Central

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

    2016-01-01

    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. PMID:27146330

  14. Lethal Injection for Execution: Chemical Asphyxiation?

    PubMed Central

    Zimmers, Teresa A; Sheldon, Jonathan; Lubarsky, David A; López-Muñoz, Francisco; Waterman, Linda; Weisman, Richard; Koniaris, Leonidas G

    2007-01-01

    Background Lethal injection for execution was conceived as a comparatively humane alternative to electrocution or cyanide gas. The current protocols are based on one improvised by a medical examiner and an anesthesiologist in Oklahoma and are practiced on an ad hoc basis at the discretion of prison personnel. Each drug used, the ultrashort-acting barbiturate thiopental, the neuromuscular blocker pancuronium bromide, and the electrolyte potassium chloride, was expected to be lethal alone, while the combination was intended to produce anesthesia then death due to respiratory and cardiac arrest. We sought to determine whether the current drug regimen results in death in the manner intended. Methods and Findings We analyzed data from two US states that release information on executions, North Carolina and California, as well as the published clinical, laboratory, and veterinary animal experience. Execution outcomes from North Carolina and California together with interspecies dosage scaling of thiopental effects suggest that in the current practice of lethal injection, thiopental might not be fatal and might be insufficient to induce surgical anesthesia for the duration of the execution. Furthermore, evidence from North Carolina, California, and Virginia indicates that potassium chloride in lethal injection does not reliably induce cardiac arrest. Conclusions We were able to analyze only a limited number of executions. However, our findings suggest that current lethal injection protocols may not reliably effect death through the mechanisms intended, indicating a failure of design and implementation. If thiopental and potassium chloride fail to cause anesthesia and cardiac arrest, potentially aware inmates could die through pancuronium-induced asphyxiation. Thus the conventional view of lethal injection leading to an invariably peaceful and painless death is questionable. PMID:17455994

  15. 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

  16. 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.

  17. 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

  18. Acute hemodialysis effects on doppler echocardiographic indices.

    PubMed

    Abid, Leila; Rekik, Hajer; Jarraya, Fayçal; Kharrat, Ilyes; Hachicha, Jamil; Kammoun, Samir

    2014-07-01

    Conventional echocardiographic (ECHO) parameters of systolic and diastolic function of the left ventricular (LV) have been shown to be load dependent. However, the impact of pre-load reduction on tissue Doppler (TD) parameters of LV function is incompletely understood. To evaluate the effect of a single hemodialysis (HD) session on LV systolic and diastolic function using pulsed Doppler echocardiography and pulsed tissue Doppler imaging (TDI), we studied 81 chronic HD patients (40 males; mean age 52.4 ± 16.4 years) with these tools. ECHO parameters were obtained 30 min before and 30 min after HD. Fluid volume removed by HD was 1640 ± 730 cm³. HD led to reduction in LV end-diastolic volume (P <0.001), end-systolic volume (P <0.001), left atrium area (P <0.001), peak early (E-wave) trans-mitral flow velocity (P <0.001), the ratio of early to late Doppler velocities of diastolic mitral inflow (P <0.001) and aortic time velocity integral (P <0.001). No significant change in peak S velocity of pulmonary vein flow after HD was noted. Early and late diastolic (E') TDI velocities and the ratio of early to late TDI diastolic velocities (E'/A') on the lateral side of the mitral annulus decreased significantly after HD (P = 0.013; P = 0.007 and P = 0.008, respectively). Velocity of flow progression (Vp) during diastole was not affected by pre-load reduction. Pulmonary artery systolic pressure and the diameter of the inferior vena cava decreased significantly (P <0.001 and P <0.001, respectively) after HD. We conclude that most of the Doppler-derived indices of diastolic function are pre-load-dependent and velocity of flow progression was minimally affected by pre-load reduction in HD patients. PMID:24969184

  19. 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. PMID:23629662

  20. REINFORCEMENT ENHANCING EFFECTS OF ACUTE NICOTINE VIA ELECTRONIC CIGARETTES

    PubMed Central

    Perkins, Kenneth A.; Karelitz, Joshua L.; Michael, Valerie C.

    2015-01-01

    Background Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. Methods We assessed acute effects of nicotine via electronic cigarettes (“e-cigarettes”) on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10 ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled “36 mg/ml”) or placebo (“0”) e-cigarette, or no e-cigarette use. A fourth session involved smoking one’s own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Results Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Conclusions Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. PMID:26070455

  1. Specific effects of acute moderate exercise on cognitive control.

    PubMed

    Davranche, Karen; McMorris, Terry

    2009-04-01

    The main issue of this study was to determine whether cognitive control is affected by acute moderate exercise. Twelve participants [4 females (VO(2 max)=42 ml/kg/min) and 8 males (VO(2 max) = 48 ml/kg/min)] performed a Simon task while cycling at a carefully controlled workload intensity corresponding to their individual ventilatory threshold. The distribution-analytical technique and the delta plot analysis [Ridderinkhof, K. R. (2002). Activation and suppression in conflict tasks: Empirical clarification through distributional analyses. In W. Prinz & B. Hommel (Eds.), Common mechanisms in perception and action. Attention and performance (Vol. 19, pp. 494-519). Oxford: Oxford University Press.] were used to assess the role of selective response inhibition in resolving response conflict. Results showed that cognitive processes appeared to be differently affected by acute moderate exercise. Reaction time results confirmed that performance is better (faster without change in accuracy) when the cognitive task is performed simultaneously with exercise. Between-trial adjustments (post-conflict and post-error) highlighted that cognitive control adjustments are also fully efficient during exercise. However, the effect of congruency (Simon effect) appeared to be more pronounced during exercise compared to rest which suggests that the response inhibition is deteriorated during exercise. The present findings suggest that acute moderate exercise differently affects some specific aspects of cognitive functions. PMID:19138814

  2. 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)

  3. EFFECTS OF WASTEWATER TREATMENT AND SEAWATER DILUTION IN REDUCING LETHAL TOXICITY OF MUNICIPAL WASTEWATER TO SHEEPSHEAD MINNOW AND PINK SHRIMP

    EPA Science Inventory

    The study was conducted to determine the effects of treatment and seawater dilution of municipal wastewater on marine organisms. n experimental facility was built in southeast Florida that provided both unchlorinated and chlorinated effluent from three standard treatments: primar...

  4. Effect and Safety of Rosuvastatin in Acute Ischemic Stroke

    PubMed Central

    Heo, Ji Hoe; Song, Dongbeom; Nam, Hyo Suk; Kim, Eung Yeop; Kim, Young Dae; Lee, Kyung-Yul; Lee, Ki-Jeong; Yoo, Joonsang; Kim, Youn Nam; Lee, Byung Chul; Yoon, Byung-Woo; Kim, Jong S.

    2016-01-01

    Background and Purpose The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. Methods This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naïve stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. Results This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53–1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2±1.0 mm3 vs. placebo: 0.3±1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. Conclusions The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation. PMID:26846760

  5. Effects of acute oligohydramnios on respiratory system of fetal sheep.

    PubMed

    Savich, R D; Guerra, F A; Lee, C C; Padbury, J F; Kitterman, J A

    1992-08-01

    Prolonged oligohydramnios, or a lack of amniotic fluid, is associated with pulmonary hypoplasia and subsequent perinatal morbidity, but it is unclear whether short-term or acute oligohydramnios has any effect on the fetal respiratory system. To investigate the acute effects of removal of amniotic fluid, we studied nine chronically catheterized fetal sheep at 122-127 days gestation. During a control period, we measured the volume of fluid in the fetal potential airways and air spaces (VL), production rate of that fluid, incidence and amplitude of fetal breathing movements, tracheal pressures, and fetal plasma concentrations of cortisol, epinephrine, and norepinephrine. We then drained the amniotic fluid for a short period of time [24-48 h, 30.0 +/- 4.0 (SE) h] and repeated the above measurements. The volume of fluid drained for the initial studies was 1,004 +/- 236 ml. Acute oligohydramnios decreased VL from 35.4 +/- 2.9 ml/kg during control to 22.0 +/- 1.6 after oligohydramnios (P less than 0.004). Acute oligohydramnios did not affect the fetal lung fluid production rate, fetal breathing movements, or any of the other measured variables. Seven repeat studies were performed in six of the fetuses after reaccumulation of the amniotic fluid at 130-138 days, and in four of these studies the lung volume also decreased, although the overall mean for the repeat studies was not significantly different (27.0 +/- 5.2 ml/kg for control vs. 25.5 +/- 5.5 ml/kg for oligohydramnios). Again, none of the other measured variables were altered by oligohydramnios in the repeat studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1399988

  6. 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

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

    PubMed

    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

  8. Acute effect of ascorbic acid on fibrinolytic activity.

    PubMed

    Bordia, A; Paliwal, D K; Jain, K; Kothari, L K

    1978-08-01

    The acute effect of 1 g oral ascorbic acid on serum fibrinolytic activity was studied in 40 adult males. In Group I (healthy adults) administration of ascorbic acid raised the serum level by about 71%, while the fibrinolytic activity increased to a peak of 137% at 6 h. In patients with CAD (Group II) an essentially similar increase in FA was observed. In Group III, simultaneous administration of ascorbic acid with 100 g fat effectively prevented a fall in fibrinolytic activity and actually raised it by 64% above the fasting level. PMID:568476

  9. [SURGICAL TREATMENT OF AN ACUTE MESENTERIAL ISCHEMIA].

    PubMed

    Shepehtko, E N; Garmash, D A; Kurbanov, A K; Marchenko, V O; Kozak, Yu S

    2016-04-01

    Experience of surgical treatment of 143 patients, suffering an acute mesenterial ischemia, was summarized. Isolated intestinal resection was performed in 41 patients (lethality 65.9%), intestinal resection with the mesenterial vessels thrombembolectomy--in 9 (lethality 33.3%). After performance of the combined intervention postoperative lethality was in two times lower, than after isolated intestinal resection. PMID:27434952

  10. 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

  11. 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 ...

  12. 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

  13. 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

  14. Sub-lethal effects of cadmium and copper on RNA/DNA ratio and energy reserves in the green-lipped mussel Perna viridis.

    PubMed

    Yeung, Jamius W Y; Zhou, Guang-Jie; Leung, Kenneth M Y

    2016-10-01

    This study aims to test if RNA/DNA ratio and various energy reserve parameters (i.e., glycogen, lipid, protein content and total energy reserves) are sensitive biomarkers for indicating stresses induced by metal contaminants in the green-lipped mussel Perna viridis, a common organism for biomonitoring in Southeast Asia. This study was, therefore, designed to examine the effects of cadmium (Cd) and copper (Cu) on these potential biomarkers in two major energy storage tissues, adductor muscle (AM) and hepatopancreas (HP), of P. viridis after sub-lethal exposure to either metal for 10 days. The results showed that neither Cd nor Cu treatments affected the RNA/DNA ratio, glycogen and protein contents in AM and HP. As the most sensitive biomarker in P. viridis, the total lipid content in both AM and HP was significantly decreased in the treatment of 5μg Cu/L and 0.01-0.1μgCd/L, respectively. However, soft-tissue body burdens of Cu or Cd did not significantly correlate with each of the four biomarkers regardless of the tissue type. In addition, AM generally stored more glycogen than HP, whereas HP stored more lipids than AM. We proposed that multiple biomarkers may be employed as an integrated diagnostic tool for monitoring the health condition of the mussels. PMID:27262215

  15. 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.

  16. The triterpenoid CDDO-Me delays murine acute graft-versus-host disease with the preservation of graft-versus-tumor effects after allogeneic bone marrow transplantation

    PubMed Central

    Li, Minghui; Sun, Kai; Redelman, Doug; Welniak, Lisbeth A.; Murphy, William J.

    2010-01-01

    The occurrence of acute graft-versus-host disease (GVHD) and tumor relapse represent the two major obstacles impeding the efficacy of allogeneic bone marrow transplantation (BMT) in cancer. We have previously shown that the synthetic triterpenoid CDDO can inhibit murine early acute GVHD but anti-tumor effects were not assessed. In the current study, we found that a new derivative of CDDO, CDDO-Me, had an increased ability to inhibit allogeneic T cell responses and induce cell death of alloreactive T cells in vitro. Administration of CDDO-Me to mice following allogeneic BMT resulted in significant and increased protection from acute lethal GVHD compared to CDDO. This correlated with reduced TNF-α production, reduced donor T cell proliferation and decreased adhesion molecule (α4β7 integrin) expression on the donor T cells. CDDO-Me was also superior to CDDO in inhibiting leukemia growth in vitro. When CDDO-Me was administered following an allogeneic BMT to leukemia-bearing mice, significant increases in survival were observed. These findings suggest that CDDO-Me is superior to CDDO in delaying acute GVHD while preserving or possibly even augmenting GVT effects. PMID:20338256

  17. Space microbiology--lethality, mutagenicity and cytological effects of terrestrial microorganisms by irradiation of cosmic proton under simulated space condition.

    PubMed

    Koike, J; Taguchi, H

    1993-04-01

    We have been discussing in connection with a space quarantine. The subject is not merely an academic problem, but it contains a fundamental problem which avoid the contamination of other planets by terrestrial microflora. The space environments in the solar system were simulated by using an apparatus of cryostat (low temperature of 110-310K, high vacuum of 1 x 10(-8) torr) and proton irradiation from the Van de Graaff generator. After exposure to a barrage of protons corresponding to about 250 years in solar space, Tobacco mosaic virus, Bacillus subtilis spore, Staphylococcus aureus. Micrococcusflavus, Clostridium mangenoti spore and Aspergillus niger spore showed considerably high survival rates. Furthermore, it was found firstly that an irradiation of proton induced considerable mutation frequency compared to that of spontaneous and caused also the cytological effects based on a damage of chromosome. PMID:7967372

  18. 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

  19. Lethal and sublethal effects of pesticides on Chrysoperla carnea larvae (Neuroptera: Chrysopidae) and the influence of rainfastness in their degradation pattern over time.

    PubMed

    Maia, Jader Braga; Carvalho, Geraldo Andrade; Medina, Pilar; Garzón, Agustín; Gontijo, Pablo da Costa; Viñuela, Elisa

    2016-07-01

    The predator Chrysoperla carnea is a model species for the study of non-target effects of pesticides under different scenarios: registration of plant protection products under the European Union and effects of the Bt toxin. Laboratory and persistence studies were carried out with six pesticides currently used in corn crops in Spain that were applied at their maximum field recommended concentrations. The assessed end-points were larval mortality, survivorship until adult stage, duration of the larval and pupal periods, fecundity, fertility and sex ratio of the emerged adults. Based on the total effect (lethal and sublethal) caused to L3 larvae in contact with fresh residues in the laboratory, pendimethalin was harmless (IOBC 1), lambda-cyhalothrin, abamectin, and hexythiazox were slightly harmful (IOBC 2), deltamethrin was moderately harmful (IOBC 3) and chlorpyrifos was harmful (IOBC 4). Afterwards, the residues of the two most toxic pesticides in the lab (deltamethrin and chlorpyrifos) were aged under greenhouse conditions (22 ± 2 °C, 40 ± 10 % R.H., 16.9 μmol m(-2) s(-1) UV radiation) in the presence and absence of artificial rainfall (10 l m(-2) h(-1), applied 24 h after pesticide application). Deltamethrin was classified as short lived (IOBC A) in both cases. However, degradation of chlorpyrifos residues was accelerated in the presence of rainfall, leading to the classification as slightly persistent (IOBC B), while in absence of rainfall it behaved as persistent (IOBC D). Every pesticide can be recommended for inclusion in corn IPM programs where the predator is present except chlorpyrifos that exhibited high direct toxicity in the lab and prolonged residual action even in the presence of rainfall. PMID:26975320

  20. Sub-lethal effects of a copper sulfate fungicide on development and reproduction in three coccinellid species.

    PubMed Central

    Michaud, J.P.; Angela K., Grant

    2003-01-01

    Copper-based fungicides reliably control various foliar diseases in citrus production, although they are suspected to exacerbate mite problems through various mechanisms. Studies have shown negative effects of various copper formulations on entomopathogenic fungi, nematodes, and parasitoids, but few have sought to measure its impact on the biology of predatory insects. We exposed the larvae of three species of ladybeetle (Coleoptera: Coccinellidae) to field rates of copper sulfate in combination with petroleum oil, a formulation commonly applied in Florida citrus. First instar larvae of Curinus coeruleus Mulsant, Harmonia axyridis Pallas, and Olla v-nigrum Mulsant received a 24 h exposure to residues on Petri dishes, and another 24 h exposure in the third instar. Treated larvae of all three species survived to adulthood at the same rate as control larvae, but larvae of O. v-nigrum experienced a significant increase in developmental time. Female adults of C. coeruleus and H. axyridis receiving copper sulfate exposures as larvae did not differ from control adults in pre-reproductive period, fecundity or fertility over ten days of reproduction. Treated O. v-nigrum females had significantly longer pre-reproductive periods than control females and laid significantly fewer eggs, although egg fertility was equivalent. We conclude that copper-sulfate fungicides are unlikely to disrupt biological control processes in citrus groves that are mediated by these coccinellid beetles. PMID:15841232

  1. 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. PMID:26470221

  2. Acute effects of cigarette smoking on microcirculation of the thumb.

    PubMed

    van Adrichem, L N; Hovius, S E; van Strik, R; van der Meulen, J C

    1992-01-01

    The acute effect of smoking on the microcirculation of the skin of the thumb was investigated in healthy volunteers. Twenty-two were smokers and 10 were non-smokers. The flow was assessed by means of laser Doppler flowmetry. The smokers inhaled 2 cigarettes. During smoking of their first and second cigarette respectively, a mean decrease in laser Doppler flow of 23.8% and 29.0% was seen (p = 0.03; p = 0.01). Ten minutes after smoking this decrease was recovered by half. This experiment confirms that one should prohibit smoking of cigarettes pre- and postoperatively for optimal wound healing conditions. PMID:1737221

  3. Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment

    PubMed Central

    2011-01-01

    Cancer cells show a broad spectrum of bioenergetic states, with some cells using aerobic glycolysis while others rely on oxidative phosphorylation as their main source of energy. In addition, there is mounting evidence that metabolic coupling occurs in aggressive tumors, between epithelial cancer cells and the stromal compartment, and between well-oxygenated and hypoxic compartments. We recently showed that oxidative stress in the tumor stroma, due to aerobic glycolysis and mitochondrial dysfunction, is important for cancer cell mutagenesis and tumor progression. More specifically , increased autophagy/mitophagy in the tumor stroma drives a form of parasitic epithelial-stromal metabolic coupling. These findings explain why it is effective to treat tumors with either inducers or inhibitors of autophagy, as both would disrupt this energetic coupling. We also discuss evidence that glutamine addiction in cancer cells produces ammonia via oxidative mitochondrial metabolism. Ammonia production in cancer cells, in turn, could then help maintain autophagy in the tumor stromal compartment. In this vicious cycle, the initial glutamine provided to cancer cells would be produced by autophagy in the tumor stroma. Thus, we believe that parasitic epithelial-stromal metabolic coupling has important implications for cancer diagnosis and therapy, for example, in designing novel metabolic imaging techniques and establishing new targeted therapies. In direct support of this notion, we identified a loss of stromal caveolin-1 as a marker of oxidative stress, hypoxia, and autophagy in the tumor microenvironment, explaining its powerful predictive value. Loss of stromal caveolin-1 in breast cancers is associated with early tumor recurrence, metastasis, and drug resistance, leading to poor clinical outcome. PMID:21867571

  4. 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. PMID:23140535

  5. Acute interactive motoric effects of permethrin and xylene

    SciTech Connect

    Durnam, M.R.

    1992-01-01

    The potential interactive motoric effects of permethrin (a type I pyrethroid pesticide) and xylene (an aromatic hydrocarbon solvent) were assessed in male CD-I mice following acute exposure. The hypothesis was that these two compounds would interact (the effects would be more than additive) to disrupt motor performance on inverted screen tent performance and/or locomotor activity. The data obtained from this experiment do not support this hypothesis. The results failed to show a significant interaction between the permethrin and xylene on either task, however, the combination of these compounds altered the time course of motoric effects. The peak effect on the inverted screen test occurred earlier for xylene and permethrin than for permethrin alone. The xylene probably increased the rate of absorption of xylene. On locomotor activity, permethrin and xylene when given separately increased activity, however, the highest dose combination of permethrin and xylene produced a strong decrease in activity at all time points.

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

    SciTech Connect

    Philip, Binu K.; Anand, Sathanandam S.; Palkar, Prajakta S.; Mumtaz, Moiz M.; Latendresse, John R.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-10-01

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

  7. 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

  8. 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. PMID:20825811

  9. Acute effects of bright light exposure on cortisol levels.

    PubMed

    Jung, Christopher M; Khalsa, Sat Bir S; Scheer, Frank A J L; Cajochen, Christian; Lockley, Steven W; Czeisler, Charles A; Wright, Kenneth P

    2010-06-01

    Multisynaptic neural and endocrine pathways from the suprachiasmatic nucleus of the hypothalamus have been hypothesized to communicate circadian and photic information to the adrenal glands. In humans, light exposure has been reported to have no effect, increase, or decrease cortisol levels. These inconsistent findings in humans may be related to differences among studies including the intensity (approximately 500 to 5500 lux), duration (15 min to 4 h), and circadian phase of light exposure. The authors assessed the influence of exposure to bright light on cortisol levels in humans during the rising and descending phases of the circadian rhythm of cortisol, that is, when cortisol levels are high. Twenty healthy men and women were studied using a within-subject research design. Subjects were studied in an environment free of time cues for 9 to 10 days. Subjects received a 6.7-h exposure of bright light (approximately 10,000 lux; equivalent to ambient light intensity just after sunrise or just before sunset) or dim light (approximately 3 lux; equivalent to candle light) during the biological night and morning. Bright light exposure significantly reduced plasma cortisol levels at both circadian phases studied, whereas dim light exposure had little effect on cortisol levels. The finding of an acute suppressive effect of bright light exposure on cortisol levels supports the existence of a mechanism by which photic information can acutely influence the human adrenal glands. PMID:20484692

  10. 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. PMID:25271215

  11. Evaluating the Stress Response as a Bioindicator of Sub-Lethal Effects of Crude Oil Exposure in Wild House Sparrows (Passer domesticus)

    PubMed Central

    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. PMID:25029334

  12. Making sense of nickel accumulation and sub-lethal toxic effects in saline waters: Fate and effects of nickel in the green crab, Carcinus maenas.

    PubMed

    Blewett, Tamzin A; Glover, Chris N; Fehsenfeld, Sandra; Lawrence, Michael J; Niyogi, Som; Goss, Greg G; Wood, Chris M

    2015-07-01

    In freshwater, invertebrates nickel (Ni) is considered an ionoregulatory toxicant, but its mechanism of toxicity in marine settings, and how this varies with salinity, is poorly understood. This study investigated Ni accumulation and physiological mechanisms of sub-lethal Ni toxicity in the euryhaline green crab Carcinus maenas. Male crabs were exposed to 8.2μg/L (the US EPA chronic criterion concentration for salt waters) of waterborne Ni (radiolabelled with (63)Ni) at three different salinities, 20%, 60% and 100% SW for 24h. Whole body Ni accumulation in 20% SW was 3-5 fold greater than in 60% or 100% SW, and >80% of accumulated Ni was in the carapace at all salinities. Ni also accumulated in posterior gill 8, which showed a higher accumulation in 20% SW than in other salinities, a pattern also seen at higher exposure concentrations of Ni (500 and 3000μg/L). Gill perfusion experiments revealed that Ni was taken up by both anterior and posterior gills, but in 20% SW the posterior gill 8, which performs ionoregulatory functions, accumulated more Ni than the anterior gill 5, which primarily has a respiratory function. The sub-lethal consequences of Ni exposure were investigated by placing crabs in Ni concentrations of 8.2, 500, and 3000μg/L at 20, 60 or 100% SW for 24h. In 20% SW, haemolymph Ca levels were significantly decreased by exposure to Ni concentrations of 8.2μg/L or higher, whereas Na concentrations were depressed only at 3000μg/L. Na(+)/K(+)-ATPase activity was inhibited at both 500 and 3000μg/L in gill 8, but only in 20% SW. Haemolymph K, Mg, and osmolality were unaffected throughout, though all varied with salinity in the expected fashion. These data suggest that Ni impacts ionoregulatory function in the green crab, in a gill- and salinity-dependent manner. PMID:25914092

  13. Acute and chronic effects of sodium and potassium on the tropical freshwater cladoceran Pseudosida ramosa.

    PubMed

    Freitas, Emanuela Cristina; Rocha, Odete

    2011-01-01

    In this study, the toxicities of sodium and potassium to the tropical freshwater cladoceran Pseudosida ramosa were assessed. Acute toxicity tests on this species showed that the 48-h LC(50) of Na(+) was 556 mg l(-1), while that of K(+) was 17.7 mg l(-1). Long-term exposure of female P. ramosa to sodium reduced the total number of survivors from 10 to 6 at a concentration of 249 mg l(-1), 21-day fecundity from 20.4 to 14.3 eggs female(-1) at concentrations ranging from 72 to 249 mg l(-1), 21-day fertility from 20.1 to 6.5 neonates female(-1) at concentrations ranging from 25 to 249 mg l(-1). Furthermore, fecundity of each brood from the second to the fifth was significantly lower at 249 mg l(-1) and fertility of each brood from the first to the fifth at concentrations ranging from 25 to 249 mg l(-1). A significant decrease in fertility was associated with an increase in the number of aborted eggs. Long-term exposure to potassium decreased the 21-day fecundity of P. ramosa from 14.2 to 10.8 eggs female(-1) at a concentration of 11 mg l(-1) and fertility (fourth brood only) at 6.2 and 11 mg l(-1). Tropical reservoirs located near areas where the soil is overloaded with fertilizers and ferti-irrigation with vinasse already show concentrations of Na(+) and K(+) very close to those producing sub-lethal long-term effects on P. ramosa. A possible consequence is that organisms of the aquatic biota cannot adapt and freshwater taxa may become locally extinct, transferring dominance to salt-tolerant taxa. PMID:20978846

  14. 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.

  15. Acute effects of carbon monoxide on cardiac electrical stability

    SciTech Connect

    Verrier, R.L.; Mills, A.K.; Skornik, W.A. )

    1990-10-01

    The objective of this project was to determine the effects of acute carbon monoxide exposure on cardiac electrical stability. To obtain a comprehensive assessment, diverse biological models were employed. These involved cardiac electrical testing in the normal and ischemic heart in anesthetized and conscious dogs. The experimental plan was designed both to examine the direct effects of carbon monoxide exposure on the myocardium and to evaluate possible indirect influences through alterations in platelet aggregability or changes in central nervous system activity in the conscious animal. Our results indicate that exposure to relatively high levels of carbon monoxide, leading to carboxyhemoglobin concentrations of up to 20 percent, is without significant effect on ventricular electrical stability. This appears to be the case in the acutely ischemic heart as well as in the normal heart. It is important to note that the total exposure period was in the range of 90 to 124 minutes. The possibility that longer periods of exposure or exacerbation from nicotine in cigarette smoke could have a deleterious effect cannot be excluded. We also examined whether or not alterations in platelet aggregability due to carbon monoxide exposure could be a predisposing factor for cardiac arrhythmias. A model involving partial coronary artery stenosis was used to simulate the conditions under which platelet plugs could lead to myocardial ischemia and life-threatening arrhythmias. We found no changes either in the cycle frequency of coronary blood flow oscillations or in platelet aggregability during carbon monoxide exposure. Thus, carbon monoxide exposure does not appear to alter platelet aggregability or its effect on coronary blood flow during stenosis. In the final series of experiments, we examined the effects of carbon monoxide exposure in the conscious state.

  16. Neurobehavioral effects of acute styrene exposure in fiberglass boatbuilders

    SciTech Connect

    Letz, R.; Mahoney, F.C.; Hershman, D.L.; Woskie, S.; Smith, T.J. )

    1990-11-01

    A field investigation of the effects of acute exposure to styrene among fiberglass boatbuilders was performed. Personal samples of styrene in breathing zone air and postshift urinary mandelic acid were collected for 105 workers exposed and not exposed to styrene in 6 fiberglass boatbuilding companies in New England. Three tests from the computerized Neurobehavioral Evaluation System (NES) were performed by the subjects in the morning before exposure to styrene, near midday, and at the end of the work day. Duration of exposure averaged 2.9 years (SD = 4.6), 8-hour TWA styrene exposure averaged 29.9 ppm (SD = 36.2), and urinary mandelic acid averaged 347 mg/g creatinine (SD = 465). Regression analyses indicated a statistically significant relationship between postshift performance on the Symbol-Digit test and both acute styrene exposure and mandelic acid. Other analyses comparing workers exposed to less than 50 ppm and greater than 50 ppm styrene also showed a significant effect on Symbol-Digit performance. All three NES tests showed test-retest correlation coefficients above .80, and ease of use for collection of neurobehavioral data under field conditions was demonstrated.

  17. Effects of age on hemorheological responses to acute endurance exercise.

    PubMed

    Ahmadizad, Sajad; Moradi, Akram; Nikookheslat, Saeed; Ebrahimi, Hadi; Rahbaran, Adel; Connes, Philippe

    2011-01-01

    The purpose of this investigation was to examine the effects of age on the acute responses of hemorheological variables and biochemical parameters to a single bout of sub-maximal endurance exercise. Fifteen young (20-30 years), 15 middle-aged (40-50 years) and 12 old (60-70 years) male subjects participated in the study. All subjects performed one single bout of endurance exercise encompassed 30-min cycling at 70-75% of maximal heart rate which was followed by 30-min recovery. Three blood samples were taken before, immediately after exercise and after 30-min recovery. Resting levels of hematocrit, red blood cells count, plasma albumin and fibrinogen concentrations, plasma viscosity and whole blood viscosity were significantly different among the three groups (P < 0.01). Thirty minutes of cycling resulted in significant increases (P < 0.05) in all parameters; while these changes were temporary and returned to pre-exercise level at the end of recovery. Responses of all parameters to exercise and recovery were not significantly different among the three groups (P > 0.05). Fibrinogen changes during exercise and recovery were corrected for exercise- and recovery-induced changes in plasma volume. Data analysis showed effects of exercise and recovery only for raw data (P > 0.05). In addition, raw and corrected fibrinogen data in response to exercise and recovery were not age-related. Our results demonstrate that age does not affect the hemorheological responses to an acute endurance exercise in healthy men. PMID:22214687

  18. Effectiveness of chelation therapy with time after acute uranium intoxication

    SciTech Connect

    Domingo, J.L.; Ortega, A.; Llobet, J.M.; Corbella, J. )

    1990-01-01

    The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-1,3- benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) were administered ip at 0, 0.25, 1, 4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0, 0.25, or 1 hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy.

  19. 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; Da Costa Mattos, Rita De Cássia Oliveira

    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. PMID:27054706

  20. 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

  1. Interaction of sub-lethal concentrations of mercury(II) with DNA in eukaryotic cells

    SciTech Connect

    Williams, M.; Holliday, J. )

    1991-03-11

    Mercury compounds are used in a variety of industrial and manufacturing processes and it is the major component in certain types of dental amalgams. Thus a large percentage of the populations is a risk to acute and/or chronic exposure to sub-lethal concentrations of mercury. While questions have been raised concerning the possible health risks associated with such exposure, there is virtually nothing known particularly at the molecular level concerning the biological effects of such exposure. The authors studies have demonstrated that while the majority of mercury(II) that is incorporated into cells (human and Chinese hamster ovary) following exposure to sub-lethal concentrations of mercury(II) is bound to cytoplasmic proteins, there is also binding of mercury to the DNA and this occurs in a dose-dependent manner. Furthermore they have demonstrated, using the Chinese hamster ovary cell line AS52 which contains a stably integrated single functional copy of the Escherichia coli xanthine-guanine phosphoribosyl-transferase gene (gpt), that relatively non-lethal concentrations of mercury(II) induced a higher frequency of mutation in the gpt gene when compared to the spontaneous mutation frequency observed in non-treated cells.

  2. Brine shrimp lethality assay of Bacopa monnieri.

    PubMed

    D'Souza, Prashanth; Deepak, Mundkinajeddu; Rani, Padmaja; Kadamboor, Sandhya; Mathew, Anjana; Chandrashekar, Arun P; Agarwal, Amit

    2002-03-01

    Successive petroleum ether, chloroform, ethanol and water extracts, a saponin rich fraction (SRF) and bacoside A isolated from Bacopa monnieri were tested for brine shrimp lethality. Successive ethanol extracts and SRF showed potent activity. Bacoside A showed the maximum activity with a LC(50) of 38.3 microg/mL. The results confirmed the previous reports of an anticancer effect of Bacopa monnieri and suggest bacoside A as the active constituent. PMID:11933129

  3. 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. PMID:26649821

  4. Mutation induced extinction in finite populations: lethal mutagenesis and lethal isolation.

    PubMed

    Wylie, C Scott; Shakhnovich, Eugene I

    2012-01-01

    Reproduction is inherently risky, in part because genomic replication can introduce new mutations that are usually deleterious toward fitness. This risk is especially severe for organisms whose genomes replicate "semi-conservatively," e.g. viruses and bacteria, where no master copy of the genome is preserved. Lethal mutagenesis refers to extinction of populations due to an unbearably high mutation rate (U), and is important both theoretically and clinically, where drugs can extinguish pathogens by increasing their mutation rate. Previous theoretical models of lethal mutagenesis assume infinite population size (N). However, in addition to high U, small N can accelerate extinction by strengthening genetic drift and relaxing selection. Here, we examine how the time until extinction depends jointly on N and U. We first analytically compute the mean time until extinction (τ) in a simplistic model where all mutations are either lethal or neutral. The solution motivates the definition of two distinct regimes: a survival phase and an extinction phase, which differ dramatically in both how τ scales with N and in the coefficient of variation in time until extinction. Next, we perform stochastic population-genetics simulations on a realistic fitness landscape that both (i) features an epistatic distribution of fitness effects that agrees with experimental data on viruses and (ii) is based on the biophysics of protein folding. More specifically, we assume that mutations inflict fitness penalties proportional to the extent that they unfold proteins. We find that decreasing N can cause phase transition-like behavior from survival to extinction, which motivates the concept of "lethal isolation." Furthermore, we find that lethal mutagenesis and lethal isolation interact synergistically, which may have clinical implications for treating infections. Broadly, we conclude that stably folded proteins are only possible in ecological settings that support sufficiently large populations

  5. Definition of lethality thresholds for KE less-lethal projectiles

    NASA Astrophysics Data System (ADS)

    Cuadros, Jaime H.

    1997-01-01

    The interest in the definition and application of the lethality threshold for KE less-lethal projectiles has increased in the last few years, as the demand for proper use of these weapons has increased from the public at large and the law enforcement community. Experiments have been performed and reported utilizing commercially available projectiles in 12 ga., 37 mm against an anthropomorphic dummy and damage criteria developed by the automobile industry. The utility of the method is discussed and future trends are presented.

  6. 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

  7. Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans

    PubMed Central

    Hart, Carl L; Gunderson, Erik W; Perez, Audrey; Kirkpatrick, Matthew G; Thurmond, Andrew; Comer, Sandra D; Foltin, Richard W

    2016-01-01

    Intranasal methamphetamine abuse has increased dramatically in the past decade, yet only one published study has investigated its acute effects under controlled laboratory conditions. Thus, the current study examined the effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Eleven nontreatment-seeking methamphetamine abusers (two females, nine males) completed this four-session, in-patient, within-participant, double-blind study. During each session, one of four intranasal methamphetamine doses (0, 12, 25, and 50 mg/70 kg) was administered and methamphetamine plasma concentrations, cardiovascular, subjective, and psychomotor/cognitive performance effects were assessed before drug administration and repeatedly thereafter. Following drug administration, methamphetamine plasma concentrations systematically increased for 4 h postdrug administration then declined. Methamphetamine dose dependently increased cardiovascular measures and ‘positive’ subjective effects, with peaks occurring approximately 5–15 min after drug administration, when plasma levels were still ascending. In addition, cognitive performance on less complicated tasks was improved by all active methamphetamine doses, whereas performance on more complicated tasks was improved only by the intermediate doses (12 and 25 mg). These results show that intranasal methamphetamine produced predictable effects on multiple behavioral and physiological measures before peak plasma levels were observed. Of interest is the dissociation between methamphetamine plasma concentrations with cardiovascular measures and positive subjective effects, which might have important implications for potential toxicity after repeated doses. PMID:17851535

  8. Synthetic lethal approaches to breast cancer therapy.

    PubMed

    Rehman, Farah L; Lord, Christopher J; Ashworth, Alan

    2010-12-01

    The promise of personalized therapy for breast cancer is that therapeutic efficacy will be increased while toxic effects are reduced to a minimum. To achieve this goal, there is now an emphasis on the design of therapies that are based not only on the clinical manifestations of the disease, but also on the underlying molecular and cellular biology of cancer. However, identifying targets for personalized therapies in breast cancer is challenging. Here, we describe how biological concepts such as synthetic lethality and oncogene addiction can be used to identify new therapeutic targets and approaches. We discuss the current clinical developments in implementing synthetic lethality therapies, and highlight new ways in which this approach could be used to target specific subsets of breast cancer. PMID:20956981

  9. 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

  10. The population genetics of synthetic lethals.

    PubMed

    Phillips, P C; Johnson, N A

    1998-09-01

    Synthetic lethals are variants at different loci that have little or no effect on viability singly but cause lethality in combination. The importance of synthetic lethals and, more generally, of synthetic deleterious loci (SDL) has been controversial. Here, we derive the expected frequencies for SDL under a mutation-selection balance for the complete haploid model and selected cases of the diploid model. We have also obtained simple approximations that demonstrate good fit to exact solutions based on numerical iterations. In the haploid case, equilibrium frequencies of carrier haplotypes (individuals with only a single mutation) are comparable to analogous single-locus results, after allowing for the effects of linkage. Frequencies in the diploid case, however, are much higher and more comparable to the square root of the single-locus results. In particular, when selection operates only on the double-mutant homozygote and linkage is not too tight, the expected frequency of the carriers is approximately the quartic root of the ratio between the mutation rate and the selection coefficient of the synthetics. For a reasonably wide set of models, the frequencies of carriers can be on the order of a few percent. The equilibrium frequencies of these deleterious alleles can be relatively high because, with SDL, both dominance and epistasis act to shield carriers from exposure to selection. We also discuss the possible role of SDL in maintaining genetic variation and in hybrid breakdown. PMID:9725860

  11. 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

  12. The effects of an acute psychosocial stressor on episodic memory

    PubMed Central

    Stawski, Robert S.; Sliwinski, Martin J.; Smyth, Joshua M.

    2009-01-01

    Although stressors are believed to impair memory, experimental studies with humans have provided inconsistent support for this conclusion. The current study was designed to examine the effect of an acute psychosocial stressor, and subsequent reactivity, on episodic memory. One hundred participants completed a list-recall task before and after random assignment into a stressor or nonstressor condition. Participants assigned to the stressor condition exhibited both impaired delayed and immediate recall, and also exhibited increasesin the commission of intrusions and perseverations. The experience of off-task thoughts and intentional suppression of such thoughts, were associated with greater impairment of immediate recall. Changes in state anxiety, negative mood, and heart rate were unrelated to changes in memory. These data indicate that exposure to a stressor impaired the recall of previously learned information, and compromised the recall of newly acquired information. Furthermore, cognitive interference is an important factor regarding stress-related impairments of episodic memory. memory. PMID:19727439

  13. Acute Effects of Marijuana Smoking on Negative and Positive Affect

    PubMed Central

    Metrik, Jane; Kahler, Christopher W.; McGeary, John E.; Monti, Peter M.; Rohsenow, Damaris J.

    2013-01-01

    Human studies and animal experiments present a complex and often contradictory picture of the acute impact of marijuana on emotions. The few human studies specifically examining changes in negative affect find either increases or reductions following delta-9-tetrahydrocannabinol (THC) administration. In a 2 × 2, instructional set (told THC vs. told no THC) by drug administration (smoked marijuana with 2.8% THC vs. placebo) between-subjects design, we examined the pharmacologic effect of marijuana on physiological and subjective stimulation, subjective intoxication, and self-reported negative and positive affect with 114 weekly marijuana smokers. Individuals were first tested under a baseline/no smoking condition and again under experimental condition. Relative to placebo, THC significantly increased arousal and confusion/bewilderment. However, the direction of effect on anxiety varied depending on instructional set: Anxiety increased after THC for those told placebo but decreased among other participants. Furthermore, marijuana users who expected more impairment from marijuana displayed more anxiety after smoking active marijuana, whereas those who did not expect the impairment became less anxious after marijuana. Both pharmacologic and stimulus expectancy main effects significantly increased positive affect. Frequent marijuana users were less anxious after smoking as compared to less frequent smokers. These findings show that expectancy instructions and pharmacology play independent roles in effects of marijuana on negative affect. Further studies examining how other individual difference factors impact marijuana's effects on mood are needed. PMID:24319318

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

    PubMed

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

    2015-07-01

    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 game

  15. 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

  16. 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. PMID:26682949

  17. From neurotoxic to chemosensory effects: new insights on acute solvent neurotoxicity exemplified by acute effects of 2-ethylhexanol.

    PubMed

    van Thriel, Christoph; Kiesswetter, Ernst; Schäper, Michael; Blaszkewicz, Meinolf; Golka, Klaus; Juran, Stephanie; Kleinbeck, Stefan; Seeber, Andreas

    2007-03-01

    Historically, acute solvent neurotoxicity was strongly related to reversible narcotic states that could be detected by neurobehavioral tests (e.g., simple reaction time). Nowadays, the occupational exposure to chemicals is markedly reduced and the avoidance of chemosensory effects is more important for the regulation of solvents. Exemplarily, this study examines if the chemosensory perception of 2-ethylhexanol is capable to distract performance in demanding neurobehavioral tasks. In two experiments three time-weighted average concentrations of 2-ethylhexanol (C(TWA): 1.5, 10, and 20 ppm) were investigated. In experiment A (n=24) variable concentrations over time (4h) were used, experiment B (n=22) investigated constant concentrations. The experiments were conducted in a 29 m3 exposure laboratory. Cross-over designs with randomized sequences of exposures were used. Among the 46 male participants 19 subjects reported enhanced chemical sensitivity; the other 27 subjects did not show this personality feature. During the exposure periods neurobehavioral tests were presented twice (beginning; end), the intensity of chemosensory perceptions were rated thrice. The intensity of chemosensory perceptions showed a clear dose-dependency. Subjects' performance in the vigilance test was not affected by the different exposures. Moreover, the results of neurobehavioral tests measuring executive function were neither affected by the C(TWA) concentration nor by the exposure peaks. With increasing C(TWA), a subgroup of the chemically sensitive subjects showed deteriorated accuracy in a divided attention task. Especially the 20 ppm conditions were very annoying. Only during the constant 10 ppm condition the time courses of the annoyance and nasal irritation ratings indicated some adaptation. In general, with the applied neurobehavioral tests distractive effects of acute 2-ethylhexanol exposures up to 20 ppm could not be confirmed. In sensitive groups such distractive effects of

  18. 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.

  19. 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.

  20. Acute side effects of homologous interleukin-3 in rhesus monkeys.

    PubMed Central

    van Gils, F. C.; Mulder, A. H.; van den Bos, C.; Burger, H.; van Leen, R. W.; Wagemaker, G.

    1993-01-01

    Interleukin-3 treatment of juvenile rhesus monkeys elicits a dose- and time-dependent syndrome that includes urticaria, palpable lymph nodes, splenomegaly, thrombocytopenia, anemia, vomiting, diarrhea, intestinal bleeding, edema, and arthritis, apart from a strong stimulation of hemopoiesis. Arthritis was found to occur significantly more often in animals expressing the major histocompatibility complex alleles B9 and Dr5. Histological analysis revealed an abundance of mast cells in urticaria and, to a lesser extent, in lungs and synovia of arthritic joints. Active osteoclasts were abundant in ribs and arthritic joints. Extramedullary hemopoiesis was encountered in liver, spleen, and kidneys. The spleen showed deposits of hemosiderin, and in the liver, Kupffer cells were loaded with iron, indicating enhanced turnover of hemoglobin. Lymph nodes and bone marrow showed macrophages involved in hemophagocytosis, which probably contributed to the development of anemia and thrombopenia. Biochemical parameters in sera were indicative of parenchymal liver damage, with cholestasis and increased erythrocyte destruction. The side effects were strongly reduced in monkeys subjected to total body irradiation just before interleukin-3 treatment. Histamine antagonists were not significantly effective in preventing side effects, which is explained by the perpetual stimulation of basophilic granulocytes by exogenous interleukin-3. The nature of the side effects indicates that interleukin-3 may be involved in the pathogenesis of acute type hypersensitivity reactions and arthritis. Images Figure 1 Figure 2 Figure 3 PMID:8256852

  1. Toxicity and critical body residues of Cd, Cu and Cr in the aquatic oligochaete Tubifex tubifex (Müller) based on lethal and sublethal effects.

    PubMed

    Méndez-Fernández, Leire; Martínez-Madrid, Maite; Rodriguez, Pilar

    2013-12-01

    The aim of the present study was to estimate critical body residues (CBRs) of three metals [cadmium (Cd), copper (Cu), chromium (Cr)] in the aquatic oligochaete Tubifex tubifex based on lethal (LBR) and sublethal effects (CBR), and to discuss the relevance of the exposure to sediment for deriving CBR. Toxicity parameters (LC50, EC50, LBR50 and CBR50) were estimated for each metal by means of data on survival and on several sublethal variables measured in short-term (4 days), water-only exposures and in long-term, chronic (14 and 28 days) exposures using metal-spiked sediment. Sublethal endpoints included autotomy in short-term exposure, as well as reproduction and growth in chronic bioassays. LBR50 and CBR50 were 3-6 times higher in sediment than in water-only exposure to Cd and about 2-11 times higher for Cu, depending on the measured endpoint; however, for Cr these parameters varied only by a factor of 1.2. Cu and Cr LBR50 and CBR50 values in 96 h water-only exposure were very similar (survival 2.39 μmol Cu g(-1) dw, 2.73 μmol Cr g(-1) dw; autotomy 0.53 μmol Cu g(-1) dw, 0.78 μmol Cr g(-1) dw). However, in metal-spiked sediments, 28 d CBR50 values for autotomy, reproduction and growth ranged 6.76-29.54 μmol g(-1) dw for Cd, 3.88-6.23 μmol g(-1) dw for Cu, 0.65 μmol g(-1) dw for Cr (calculated only on total number of young). Exposure conditions (time and presence/absence of sediment) seem to be influential in deriving metal CBR values of Cd and Cu, while appear to be irrelevant for Cr. Thus, CBR approach for metals is complex and tissue residue-toxicity relationship is not directly applicable so far. PMID:24085604

  2. Late-acting dominant lethal genetic systems and mosquito control

    PubMed Central

    Phuc, Hoang Kim; Andreasen, Morten H; Burton, Rosemary S; Vass, Céline; Epton, Matthew J; Pape, Gavin; Fu, Guoliang; Condon, Kirsty C; Scaife, Sarah; Donnelly, Christl A; Coleman, Paul G; White-Cooper, Helen; Alphey, Luke

    2007-01-01

    Background Reduction or elimination of vector populations will tend to reduce or eliminate transmission of vector-borne diseases. One potential method for environmentally-friendly, species-specific population control is the Sterile Insect Technique (SIT). SIT has not been widely used against insect disease vectors such as mosquitoes, in part because of various practical difficulties in rearing, sterilization and distribution. Additionally, vector populations with strong density-dependent effects will tend to be resistant to SIT-based control as the population-reducing effect of induced sterility will tend to be offset by reduced density-dependent mortality. Results We investigated by mathematical modeling the effect of manipulating the stage of development at which death occurs (lethal phase) in an SIT program against a density-dependence-limited insect population. We found late-acting lethality to be considerably more effective than early-acting lethality. No such strains of a vector insect have been described, so as a proof-of-principle we constructed a strain of the principal vector of the dengue and yellow fever viruses, Aedes (Stegomyia) aegypti, with the necessary properties of dominant, repressible, highly penetrant, late-acting lethality. Conclusion Conventional SIT induces early-acting (embryonic) lethality, but genetic methods potentially allow the lethal phase to be tailored to the program. For insects with strong density-dependence, we show that lethality after the density-dependent phase would be a considerable improvement over conventional methods. For density-dependent parameters estimated from field data for Aedes aegypti, the critical release ratio for population elimination is modeled to be 27% to 540% greater for early-acting rather than late-acting lethality. Our success in developing a mosquito strain with the key features that the modeling indicated were desirable demonstrates the feasibility of this approach for improved SIT for disease

  3. 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…

  4. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of...

  5. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of...

  6. Effects of acute cooling on fish electroretinogram: a comparative study.

    PubMed

    Gačić, Zoran; Milošević, Milena; Mićković, Branislav; Nikčević, Miroslav; Damjanović, Ilija

    2015-06-01

    Temperature dependence of electroretinogram (ERG) was investigated in 3 fish species occupying different habitats--dogfish shark (Scyliorhinus canicula), Prussian carp (Carassius gibelio) and European eel (Anguilla anguilla). Acute cooling of the shark isolated eyecup from 23°C down to 6°C induced suppression of the electroretinographic b-wave--a complete degradation of this component was observed at 6°C. On the other hand, photoreceptor component of the ERG, the negative late receptor potential was not affected by cooling. The fact that the suppression of the dogfish shark b-wave at low temperatures was as a rule irreversible testifies about breakdown of neural retinal function at cold temperature extremes. Although in vivo experiments on immobilized Prussian carps have never resulted in complete deterioration of the b-wave at low temperatures, significant suppression of this ERG component by cooling was detected. Suppressing the effect of low temperatures on Prussian carp ERG might be due to the fact that C. gibelio, as well as other cyprinids, can be characterized as a warmwater species preferring temperatures well above cold extremes. The ERG of the eel, the third examined species, exhibited the strongest resistance to extremely low temperatures. During acute cooling of in situ eyecup preparations of migrating silver eels from 30°C down to 2°C the form of ERG became wider, but the amplitude of the b-wave only slightly decreased. High tolerance of eel b-wave to cold extremes shown in our study complies with ecological data confirming eurythermia in migrating silver eels remarkably adapted to cold-water environment as well. PMID:25759261

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

    PubMed Central

    Thai, Chester A.; Zhang, Ying

    2015-01-01

    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. PMID:23055093

  8. Antitumoral effect of Ocoxin on acute myeloid leukemia

    PubMed Central

    Díaz-Rodríguez, Elena; Hernández-García, Susana; Sanz, Eduardo; Pandiella, Atanasio

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy whose incidence is growing in developed countries. In the relapse setting, very limited therapeutic options are available and in most cases only palliative care can be offered to patients. The effect of a composite formulation that contains several antioxidants, Ocoxin Oral solution (OOS), was tested in this condition. When analyzed in vitro, OOS exhibited anti-AML action that was both time and dose dependent. In vivo OOS induced a ralentization of tumor growth that was due to a decrease in cell proliferation. Such effect could, at least partially, be due to an increase in the cell cycle inhibitor p27, although other cell cycle proteins seemed to be altered. Besides, OOS induced an immunomodulatory effect through the induction of IL6. When tested in combination with other therapeutic agents normally used in the treatment of AML patients, OOS demonstrated a higher antiproliferative action, suggesting that it may be used in combination with those standard of care treatments to potentiate their antiproliferative action in the AML clinic. PMID:26756220

  9. [Acute Toxic Effects of Bromate on Aquatic Organisms].

    PubMed

    Wang, Zhi-wei; Liu, Dong-mei; Zhang, Wen-juan; Cui, Fu-yi

    2016-02-15

    Acute toxic effects of potassium bromate, sodium bromate and potassium bromide on luminescent bacteria, water flea, green alga and zebrafish were studied using standard toxic testing methods. The results showed that the pollutants had no effect on the luminous intensity of luminescent bacteria. The 96 h EC5. of potassium bromate on Scenedesmus obliquus was 738.18 mg x L(-1), 48 h EC50 on Daphnia magna and Moina was 154.01 mg x L(-1) was 161.80 mg x L(-1), while 48 h LC50 was 198 52 mg x L(-1), 175.68 mg x L(-1), and 96 h LC50 on zebrafish was 931.4 mg x L(-1). The 96 h EC50 of sodium bromate on Scenedesmus obliquus was 540.26 mg x L(-1), 48 h EC50 Daphnia magna and Moina was 127.90 mg x L(-1), 111.07 mg x L(-1), while 48 h LC50 was 161.80 mg x L(-1), 123.47 mg x L(-1), and 96 h LC50 on zebrafish was 1065.6 mg x L(-1). But the effects of potassium bromide on the above several kinds of aquatic organisms were far smaller than those of potassium bromate and sodium bromate. The toxic effects on test organisms were due to the impacts of bromate after the comparison of different pollutants, and the effects were more obvious with the increase of exposure time. The order of sensitivity to the toxic effects of bromate was Daphnia magna, Moina > Scenedesmus obliquus > zebrafish > Chlorella vulgaris, luminescent bacteria. PMID:27363170

  10. [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. PMID:25536784

  11. 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

  12. Aflatrem: a tremorgenic mycotoxin with acute neurotoxic effects.

    PubMed Central

    Valdes, J J; Cameron, J E; Cole, R J

    1985-01-01

    Tremorgenic mycotoxins induce neurologic symptoms ranging from mental confusion to tremors, seizures and death, and are apparently the only class of mycotoxins with significant central nervous system activity. Tremorgens have been implicated in a number of neurologic diseases of cattle collectively known as staggers syndromes, and pose significant agricultural and health problems for both cattle and humans. Although the effects of tremorgens are thought to result from transient perturbations of amino acid neurotransmitter release mechanisms, there is reason to believe that acute exposures to toxins with such synaptic effects may result in degeneration of neuronal fiber processes. To test this hypothesis, rats were given a single tremorgenic (3 mg/kg, IP) dose of aflatrem, and kinetics of amino acid neurotransmitter uptake was assessed in isolated hippocampal nerve terminals at 1 day, 1 week, and 2 weeks after injection. Results indicate a decrease in the capacity of the GABA and glutamate uptake systems, which was interpreted as a loss of nerve terminals. The affinity constants suggest a decrease in release of these transmitters as well. In addition to its transient influence on transmitter release, a single low dose of aflatrem is able to induce degeneration of neuronal processes in hippocampal neurotransmitter systems and therefore represents a long-term health threat. PMID:2867895

  13. Effects of melatonin implants in pony mares. 1. Acute effects.

    PubMed

    Peltier, M R; Robinson, G; Sharp, D C

    1998-04-15

    The effects of melatonin implant treatment over a four week period on LH, estradiol (E2) and progesterone (P4) secretion during the breeding season were studied in ovary-intact and ovariectomized pony mares. Mares with melatonin implants had significantly higher daytime melatonin concentrations than mares with sharm implants (P = 0.0065). In ovariectomized mares, LH secretion did not differ between mares with melatonin and sham implants. In ovary-intact mares, melatonin implants altered the pattern of LH secretion (P = 0.0023) in such a way that an increase in LH secretion was observed during the periovulatory period. Estradiol and P4 secretion were unaffected by melatonin implants. These results suggest that constant administration of melatonin may enhance the secretion of LH during the periovulatory surge but does not adversely affect E2, P4 or basal LH secretion in mares during the breeding season. PMID:10732050

  14. 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. PMID:24269878

  15. Acute toxic effects in mice of an extract from the marine algae Gonyaulax monilata.

    PubMed

    Erker, E F; Slaughter, L J; Bass, E L; Pinion, J; Wutoh, J

    1985-01-01

    Unialgal cultures of Gonyaulax monilata were cultured and harvested. A modified Westphall procedure was used to prepare an extract which did not contain saxitoxin, the gonyautoxins and structurally related toxins. The extract was administered i.p. to young adult, male CD-1 mice and produced: sedation, abdominal constriction, fecal clumping in the perianal area, ataxia, tremors, cyanosis, loss of reflexes, convulsions and death (LD50 = 2.28 mg/kg). Gross and microscopic pathology in the treated mice included: acute active hyperemia of the viscera, multifocal areas of necrosis of the musculature of the intestinal wall and diaphragm and the presence of cytoplasmic vacuoles in the peripheral margins of the acinar portion of the pancreas. Clinical pathology of the mice which survived 24 hr included significant elevation in the levels of serum lactic dehydrogenase, glutamic pyruvic and glutamic oxaloacetic transaminases. Some of these mice also had significantly decreased white blood cell counts. The extract administered orally produced similar signs without the abdominal constriction and convulsions (median lethal oral dose = 6.73 mg/kg). Gross pathology findings included extensive and severe congestion of the abdominal visceral organs. Vehicle control mice were normal. In conclusion, G. monilata, previously reported as nontoxic in homeotherms, yields an extract which contains a water soluble glycosidic substance(s) which is lethal to mice. PMID:4089872

  16. 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. PMID:27067622

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

    PubMed

    Moraga, Felipe; Ahumada, Vanessa; Crovari, Fernando

    2016-01-01

    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. PMID:26817927

  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. Acute effects of acrolein in human volunteers during controlled exposure

    PubMed Central

    Dwivedi, Aishwarya M.; Johanson, Gunnar; Lorentzen, Johnny C.; Palmberg, Lena; Sjögren, Bengt; Ernstgård, Lena

    2015-01-01

    Abstract Context: Acrolein is a reactive aldehyde mainly formed by combustion. The critical effect is considered to be irritation of the eyes and airways; however, the scarce data available make it difficult to assess effect levels. Objective: The aim of the study was to determine thresholds for acute irritation for acrolein. Methods: Nine healthy volunteers of each sex were exposed at six occasions for 2 h at rest to: clean air, 15 ppm ethyl acetate (EA), and 0.05 ppm and 0.1 ppm acrolein with and without EA (15 ppm) to mask the potential influence of odor. Symptoms related to irritation and central nervous system effects were rated on 100-mm Visual Analogue Scales. Results: The ratings of eye irritation were slightly but significantly increased during exposure to acrolein in a dose-dependent manner (p < 0.001, Friedman test) with a median rating of 8 mm (corresponding to “hardly at all”) at the 0.1 ppm condition and with no influence from EA. No significant exposure-related effects were found for pulmonary function, or nasal swelling, nor for markers of inflammation and coagulation in blood (IL-6, C-reactive protein, serum amyloid A, fibrinogen, factor VIII, von Willebrand factor, and Clara cell protein) or induced sputum (cell count, differential cell count, IL-6 and IL-8). Blink frequency recorded by electromyography was increased during exposure to 0.1 ppm acrolein alone but not during any of the other five exposure conditions. Conclusion: Based on subjective ratings, the present study showed minor eye irritation by exposure to 0.1 ppm acrolein. PMID:26635308

  20. Activated mouse eosinophils protect against lethal respiratory virus infection

    PubMed Central

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

    2014-01-01

    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. PMID:24297871

  1. Protective effects of protostemonine on LPS/GalN-induced acute liver failure: Roles of increased hepatic expression of heme oxygenase-1.

    PubMed

    Cheng, Zhuo; Yue, Ling; Zhao, Wenhao; Yang, Xinzhou; Shu, Guangwen

    2015-12-01

    Here, we explored protective effects of protostemonine (PSN), on mouse acute liver failure induced by lipopolysaccharide/d-galactosamine (LPS/GalN). PSN dose-dependently declined LPS/GalN-induced lethality of mice as well as increase of ALT/AST activities in their serum. Hepatoprotective effects of PSN were also supported by liver histopathological examinations. After LPS/GalN treatment, severe oxidative stresses in the liver could be detected by boosted MDA and ROS as well as decreased GSH. Moreover, hepatic expression of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, were sharply elevated. These symptoms were dose-dependently ameliorated by PSN. Mechanistically, PSN promoted the transcription and translation of heme oxygenase-1 (HO-1) in hepatocytes and liver Kupffer cells. Nrf2 is a master transcription factor contributing to the expression of HO-1. PSN elevated Nrf2 nuclear accumulation and enhanced Nrf2/HO-1 promoter interaction. Suppressing enzyme activity of HO-1 by co-treating mice with HO-1 inhibitor ZnPP abolished protective effects of PSN. ZnPP also abrogated alleviative impacts of PSN on LPS/GalN-mediated hepatic oxidative stresses and inflammatory responses. Finally, we showed that PSN exhibited undetectable toxic effects on vital organs of mice. Our findings suggested that PSN is able to attenuate LPS/GalN-induced acute liver failure and upregulating HO-1 expression is implicated in its hepatoprotective activity. PMID:26363973

  2. Method of reliable determination of minimal lethal antibiotic concentrations.

    PubMed Central

    Pearson, R D; Steigbigel, R T; Davis, H T; Chapman, S W

    1980-01-01

    The lack of a standardized, statistically reliable method for in vitro determinations of the minimal lethal or bactericidal concentrations of antibiotics has complicated analyses of isolates of Staphylococcus aureus which appear to be inhibited but not killed by the usual concentrations of cell wall-active antibiotics. We describe a method which identifies some of the covariants involved in determinations of minimal lethal concentrations. Lethality was defined as a 99.9% reduction in the initial inoculum of bacteria after 24 h of incubation. We limited the sample volume to 0.01 ml to minimize the inhibitory effect of antibiotic and corresponding rejection values, which detected lethality with a high degree of sensitivity and specificity. When the number of colonies on subculture was equal to or less than the rejection value, the antibiotic was considered lethal for the test organism. Rejection values encompassed initial inocula from 10(5) to 10(7) colony-forming units per ml for single and duplicate samples and allowed for 1 or 5% variability in pipette volumes and errors in initial inoculum determinations. This method was used to determine the minimal lethal concentrations of semi-synthetic penicillins for S. aureau isolates, one of which was tolerant to the killing action of penicillin. Images PMID:7447427

  3. Effect of Acute and Chronic Calcium Administration on Plasma Renin

    PubMed Central

    Kotchen, Theodore A.; Mauli, Kimball I.; Luke, Robert; Rees, Douglas; Flamenbaum, Walter

    1974-01-01

    To evaluate the effect of Ca++ on renin release, plasma renin activity (PRA) was measured after acute and chronic Ca++ administration. 1% CaCl2 was infused into one renal artery of 10 anesthetized dogs (0.3 mg/kg/min). The excreted fraction of filtered calcium (EFca++) and EFNa+ from the infused kidney were elevated (P < 0.04) during three successive 15-min infusion periods. Serum calcium concentration was significantly elevated (P < 0.001). Creatinine clearance, systemic arterial pressure, and renal blood flow did not change (P > 0.10). Compared to control (45 ng/ml/h±5.2 SE), renal venous PRA was suppressed (P < 0.0001) after infusion of Ca++ for 15, 30, and 45 min (20 ng/ml/h±4.6, 16 ng/ml/h±4.0, and 13 ng/ml/h±2.7, respectively). 15 and 30-min after infusion, PRA did not differ from control (P > 0.20). Chronic Ca++ loading was achieved in Sprague-Dawley rats by replacing drinking water with 1% CaCl2 for 17 days. At sacrifice, serum Ca++, Na+, and K+ of controls (n = 12) did not differ (P > 0.60) from Ca++-loaded rats (n = 12). Ca++ excretion (467 μeq/24 h±51) was elevated (P < 0.001) compared to controls (85 μeq/24 h±12). PRA (8.6 ng/ml/h±1.4) and renal renin content of Ca++-loaded rats did not differ from controls (P > 0.80). However, after 8 days of sodium deprivation, both PRA and renal renin content of calcium-loaded animals were significantly lower than the respective values in pair-fed controls (P < 0.005). During the period of sodium deprivation, calcium-drinking animals were in greater negative sodium balance than controls (P < 0.005). The data are consistent with the hypothesis that acute and chronic calcium administration inhibit renin secretion. PMID:4436432

  4. 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

  5. The effects of acute hyperinsulinemia on bone metabolism

    PubMed Central

    Ivaska, Kaisa K; Heliövaara, Maikki K; Ebeling, Pertti; Bucci, Marco; Huovinen, Ville; Väänänen, H Kalervo; Nuutila, Pirjo; Koistinen, Heikki A

    2015-01-01

    Insulin signaling in bone-forming osteoblasts stimulates bone formation and promotes the release of osteocalcin (OC) in mice. Only a few studies have assessed the direct effect of insulin on bone metabolism in humans. Here, we studied markers of bone metabolism in response to acute hyperinsulinemia in men and women. Thirty-three subjects from three separate cohorts (n=8, n=12 and n=13) participated in a euglycaemic hyperinsulinemic clamp study. Blood samples were collected before and at the end of infusions to determine the markers of bone formation (PINP, total OC, uncarboxylated form of OC (ucOC)) and resorption (CTX, TRAcP5b). During 4 h insulin infusion (40 mU/m2 per min, low insulin), CTX level decreased by 11% (P<0.05). High insulin infusion rate (72 mU/m2 per min) for 4 h resulted in more pronounced decrease (−32%, P<0.01) whereas shorter insulin exposure (40 mU/m2 per min for 2 h) had no effect (P=0.61). Markers of osteoblast activity remained unchanged during 4 h insulin, but the ratio of uncarboxylated-to-total OC decreased in response to insulin (P<0.05 and P<0.01 for low and high insulin for 4 h respectively). During 2 h low insulin infusion, both total OC and ucOC decreased significantly (P<0.01 for both). In conclusion, insulin decreases bone resorption and circulating levels of total OC and ucOC. Insulin has direct effects on bone metabolism in humans and changes in the circulating levels of bone markers can be seen within a few hours after administration of insulin. PMID:26047829

  6. 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.

  7. Mechanisms of interleukin-22's beneficial effects in acute pancreatitis.

    PubMed

    Huan, Chongmin; Kim, Daniel; Ou, Peiqi; Alfonso, Antonio; Stanek, Albert

    2016-02-15

    Acute pancreatitis (AP) is a disorder characterized by parenchymal injury of the pancreas controlled by immune cell-mediated inflammation. AP remains a significant challenge in the clinic due to a lack of specific and effective treatment. Knowledge of the complex mechanisms that regulate the inflammatory response in AP is needed for the development of new approaches to treatment, since immune cell-derived inflammatory cytokines have been recognized to play critical roles in the pathogenesis of the disease. Recent studies have shown that interleukin (IL)-22, a cytokine secreted by leukocytes, when applied in the severe animal models of AP, protects against the inflammation-mediated acinar injury. In contrast, in a mild AP model, endogenous IL-22 has been found to be a predominantly anti-inflammatory mediator that inhibits inflammatory cell infiltration via the induction of Reg3 proteins in acinar cells, but does not protect against acinar injury in the early stage of AP. However, constitutively over-expressed IL-22 can prevent the initial acinar injury caused by excessive autophagy through the induction of the anti-autophagic proteins Bcl-2 and Bcl-XL. Thus IL-22 plays different roles in AP depending on the severity of the AP model. This review focuses on these recently reported findings for the purpose of better understanding IL-22's regulatory roles in AP which could help to develop a novel therapeutic strategy. PMID:26909233

  8. 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

  9. Antinatriuretic effect of acute morphine administration in conscious rats.

    PubMed

    Walker, L A; Murphy, J C

    1984-05-01

    The renal response to the acute administration of morphine was examined in conscious, chronically catheterized, nonhydrated rats. After control clearance periods, morphine sulfate was injected i.v. at 4 mg/kg followed by an infusion of 2 mg/kg X hr. Morphine caused an increase in urine flow which was variable in magnitude and duration. The initial diuresis was not maintained despite continued morphine administration and replacement of lost fluid. Compared to vehicle treatment morphine also induced marked sodium and chloride retention which was sustained throughout the 2-hr infusion period. There were no changes in blood pressure or heart during the clearance periods, although an initial transient hypotension and bradycardia were observed with morphine injection. There were no changes in glomerular filtration rate which could account for the antinatriuresis. Naloxone pretreatment blocked all of the observed renal responses. The results indicate that morphine exerts its effects on electrolyte excretion by enhancing renal tubular sodium or chloride reabsorption rather than changes in systemic hemodynamics or glomerular filtration rate. In a separate series of experiments, urine osmolality, osmolar clearance and free water clearance were estimated. All rats receiving morphine transiently excreted a hypotonic urine (minimum 183 +/- 23 mOsmol/kg of H2O) with a reduction in osmolar clearance and a sharp increase in free water clearance. These findings are consistent with a temporary inhibition of vasopressin release by morphine. PMID:6716265

  10. Plasmapheresis in Acute Fatty Liver of Pregnancy: An Effective Treatment

    PubMed Central

    Seyyed Majidi, Mohammad Reza

    2013-01-01

    Acute fatty liver of pregnancy (AFLP) is an idiopathic disorder with an unknown cause occurring in late pregnancy. The treatment in these patients is often immediate termination of pregnancy, and plasmapheresis provides an effective treatment option. In this paper, we introduce three pregnant women treated with plasmapheresis. The first case was a 22-year-old primigravida woman treated with 22 sessions of plasmapheresis due to AFLP, hepatic and renal failure, coagulopathy, and ventilator-dependent respiratory failure. The second case was a 23-year-old woman in her second pregnancy treated with 4 plasmapheresis sessions due to AFLP, hepatic and renal failure, coagulopathy, and hypoglycemia. The third patient was a 23-year-old primigravida woman treated with 3 plasmapheresis sessions due to AFLP, renal failure, and coagulopathy. Plasmapheresis can be a life-saving treatment in patients with AFLP and is strongly recommended for patients with severity of their disease accompanied by other organ disorders. In addition, shortening the time interval between the termination of pregnancy and initializing plasmapheresis improves the outcome and reduces the duration of hospital stay and sessions of plasmapheresis. PMID:23424692

  11. Effects of acute spinalization on neurons of postural networks.

    PubMed

    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

  12. Acute effects of copper and mercury on the estuarine fish Pomatoschistus microps: linking biomarkers to behaviour.

    PubMed

    Vieira, L R; Gravato, C; Soares, A M V M; Morgado, F; Guilhermino, L

    2009-09-01

    The main objective of the present study was to investigate possible links between biomarkers and swimming performance in the estuarine fish Pomatoschistus microps acutely exposed to metals (copper and mercury). In independent bioassays, P. microps juveniles were individually exposed for 96 h to sub-lethal concentrations of copper or mercury. At the end of the assays, swimming performance of fish was measured using a device specially developed for epibenthic fish (SPEDE). Furthermore, the following biomarkers were measured: lipid peroxidation (LPO) and the activity of the enzymes acetylcholinesterase (AChE), lactate dehydrogenase (LDH), glutathione S-transferases (GST), 7-ethoxyresorufin-O-deethylase (EROD), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx). LC(50)s of copper and mercury (dissolved throughout metal concentrations) at 96h were 568 microg L(-1), and 62 microg L(-1), respectively. Significant and concentration-dependent effects of both metals on swimming resistance and covered distance against water flow were found at concentrations equal or higher than 50 microg L(-1) for copper and 3 microg L(-1) for mercury (dissolved throughout metal concentrations). These results indicate that SPEDE was efficacious to quantify behavioural alterations in the epibenthic fish P. microps at ecologically relevant concentrations. Significant alterations by both metals on biomarkers were found including: inhibition of AChE and EROD activities, induction of LDH, GST and anti-oxidant enzymes, and increased LPO levels, with LOEC values ranging from 25 to 200 microg L(-1), for copper and from 3 to 25 microg L(-1) for mercury (dissolved throughout metal concentrations). Furthermore, significant and positive correlations were found between some biomarkers (AChE and EROD) and behavioural parameters, while negative correlations were found for others (LPO, anti-oxidant enzymes and LDH) suggesting that disruption of cholinergic

  13. 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. PMID:19777152

  14. 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.

  15. Effects of oral montelukast on airway function in acute asthma.

    PubMed

    Cýllý, A; Kara, A; Ozdemir, T; Oğüş, C; Gülkesen, K H

    2003-05-01

    Montelukast, a specific cysteinyl leukotriene receptor antagonist, has been shown to improve pulmonary function within 1 h of ingestion. This study was undertaken to compare the effects on peak expiratory flow rate (PEFR) of oral montelukast added to intravenous steroid, intravenous steroid alone and placebo during the 24 h period following administration. Seventy asthmatic patients (FEV1 40-80% predicted and > or = 15% improvement after inhaled beta agonist) were enrolled in a single blind study to receive oral montelukast (10 mg) plus intravenous prednisolone (1 mg/kg), intravenous prednisolone (1 mg/kg) or placebo in a randomised fashion. The patients received one ofthe above three groups of medication before any other treatments. This was immediately followed by the aerosol treatments of 100 mcg of terbutaline sulphate divided into three doses during 1 h as described in the consensus statement. Thereafter, patients were observed for 24 h to document the effects on PEFR, Borg dyspnoea score and need for rescue medication. The primary end point was percentage change at different time points. Secondary end points were Borg dyspnoea score and use of rescue medication. Compared with placebo, montelukast added to the prednisolone group and the prednisolone alone group had significant percentage change from baseline in PEFR in the entire 24 h period (P<0.05). The difference in PEFR between montelukast plus prednisolone group and prednisolone group favoured the montelukast plus prednisolone group but did not reach statistical significance. Furthermore, montelukast plus prednisolone group required less inhaled short-acting beta agonistthan other two groups. The results of this study indicate that adding montelukast to steroid in acute asthma may have some additive improvement in lung functions. PMID:12735671

  16. 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.

  17. Acute Toxicity Investigation and Anti-diarrhoeal Effect of the Chloroform-Methanol Extract of the Leaves of Persea americana

    PubMed Central

    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. PMID:25237361

  18. 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. PMID:25237361

  19. Acute Effects of Ecstasy on Memory Are more Extensive than Chronic Effects

    PubMed Central

    Shariati, Mohamad Bakhtiar Hesam; Sohrabi, Maryam; Shahidi, Siamak; Nikkhah, Ali; Mirzaei, Fatemeh; Medizadeh, Mehdi; Asl, Sara Soleimani

    2014-01-01

    Introduction Exposure to 3, 4- methylenedioxymethamphetamine (MDMA) could lead to serotonergic system toxicity in the brain. This system is responsible for learning and memory functions. Studies show that MDMA causes memory impairment dose-dependently and acutely. The present study was designed to evaluate the chronic and acute effects of MDMD on spatial memory and acquisition of passive avoidance. Methods Adult male Wistar rats (200-250 g) were given single or multiple injections of MDMA (10 mg/kg, IP). Using passive avoidance and Morris Water Maze (MWM) tasks, learning and spatial memory functions were assessed. The data were analyzed by SPSS 16 software and one- way analysis of variance (ANOVA) test. Results Our results showed that there were significant differences in latency to enter the dark compartment (STL) between sham and MDMA- treated groups. Acute group significantly showed more STL in comparison with chronic group. Furthermore, MDMA groups spent more time in dark compartment (TDS) than the sham group. Administration of single dose of MDMA significantly caused an increase in TDS compared with the chronic group. In the MWM, MDMA treatment significantly increased the traveled distance and escaped latency compared to the sham group. Like to passive avoidance task, percentage of time spent in the target quadrant in MDMA- treated animals impaired in MWM compared with sham group. Discussion These data suggest that MDMA treatment impairs learning and memory functions that are more extensive in acute- treated rats. PMID:25337384

  20. Testing mutagenic properties with the dominant lethal test on the male mouse.

    PubMed

    Lorke, D; Machemer, L

    1975-01-01

    Mytagecity studies were carried out with fluorescent whitening agents (FWAs) using the dominant lethal test on male mice. Own tests with five FWAs, and those of KEPLINGER, et al. (Toxicol. Appl. Pharmacol.27: 494-506, 1974), with four FWAs, are described. In our tests, acute oral administration of five FWAs at a dose of 5000 mg/kg body weight gave no evidence of a mutagenic effect during 8 weeks' mating. The FWAs used were three bis(triazinylamino)stilbenedisulfonic acid derivatives and a 1,3-diphenyl-2-pyrazoline derivative. The results of the tests carried out by KEPLINGER, et al. showed that intraperitoneal injection of the four FWAs produced no mutagenic effect during six weeks' mating; the whiteners used were a triazolylstilbenemonosulfonic acid derivative (50 mg/kg), two bis(triazinylamino)stilbenedisulfonic acid derivatives (50 mg/kg) and a bis(sulfostyryl)biphenyl derivative (10 mg/kg). PMID:1064544

  1. Atropine sulfate and 2-pyridine aldoxime methylchloride elicit stress-induced convulsions and lethality in mice and guinea pigs.

    PubMed

    Donzanti, B A; Green, M D; Shores, E I

    1985-01-01

    The present study demonstrates that dose combinations of atropine sulfate and 2-pyridine aldoxime methylchloride (2-PAM), which do not produce any overt toxic effects on the behavior of mice or guinea pigs in a stable environment, elicit clonic-tonic convulsions and death when the animals are physically stressed by cold water swimming. Phenoxybenzamine (1-6 mg/kg), diazepam (0.625 and 1.25 mg/kg) and pilocarpine (2.5 and 5 mg/kg) significantly decreased (or abolished) the occurrence of atropine and 2-PAM stressed-induced convulsions and/or lethality. In contrast, propranolol (20 mg/kg), was ineffective in preventing either convulsions or lethality. Changes in plasma glucose levels and internal body temperature did not appear to explain the precipitation of convulsions or ensuing death. These results suggest that during acute physical stress, relatively low doses of atropine and 2-PAM produce toxic and lethal effects due to the activation of alpha-adrenergic mechanisms along with a concomitant inactivation of cholinergic mechanisms. PMID:4092617

  2. 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.

  3. Effective anaesthesia of the acutely inflamed pulp: part 1. The acutely inflamed pulp.

    PubMed

    Virdee, S S; Seymour, D; Bhakta, S

    2015-10-23

    Achieving profound pulpal anaesthesia in a mandibular molar diagnosed with irreversible pulpitis can be argued to be the most testing of dental anaesthetic challenges. This can be attributed to the technical complexities of conventional techniques and the presence of pulp pathosis. Reasons for why the latter influences the ability to attain pulpal anaesthesia is not yet fully understood, but its frequent occurrence is well documented. In light of overcoming this it has become common practice to prescribe antibiotics, refer onto secondary care or to even commence treatment without appropriately anaesthetising the tooth. Therefore, this two part series aims to help practitioners attain clinically acceptable pulpal anaesthesia in the most testing of scenarios; the acutely inflamed mandibular molar. They should then be able to apply these same principles to other teeth presenting with similar symptoms. This section outlines the clinical presentation and pathophysiology associated with an acutely inflamed pulp, defines what it is to attain pulpal anaesthesia and critically analyses theories as to why these teeth are up to eight times more difficult to anaesthetise than their healthy counterparts. PMID:26494344

  4. 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. PMID:22120696

  5. Effect of Obstructive Sleep Apnea in Acute Coronary Syndrome.

    PubMed

    Leão, Sílvia; Conde, Bebiana; Fontes, Paulo; Calvo, Teresa; Afonso, Abel; Moreira, Ilídio

    2016-04-01

    The effect of obstructive sleep apnea (OSA) on clinical outcomes after acute coronary syndrome (ACS) is incompletely defined. We sought to determine the prevalence of OSA in patients with ACS and evaluate prognostic impact of OSA and continuous positive airway pressure (CPAP) therapy in these patients. This was a prospective longitudinal cohort study of 73 patients admitted on cardiac intensive care unit for ACS. Cardiorespiratory sleep study and/or polysomnography were performed in all patients. CPAP was recommended if Apnea-Hypopnea Index ≥5. The main study outcome was a composite of death for any cause, myocardial infarction, and myocardial revascularization. OSA was diagnosed in 46 patients (63%). Age and cardiovascular risk factors were not significantly different between groups. OSA was classified as mild (m-OSA) in 14 patients (30%) and as moderate-to-severe (s-OSA) in 32 patients (70%). After a median follow-up of 75 months (interquartile range 71 to 79), patients with s-OSA had lower event-free survival rate. After adjustment for gender, patients with s-OSA showed a significantly higher incidence of the composite end point (hazard ratio 3.58, 95% CI 1.09 to 17.73, p = 0.035). Adherence to CPAP occurred in 19 patients (41%), but compliance to CPAP therapy did not reduce the risk of composite end point (hazard ratio 0.87, 95% CI 0.31 to 2.46, p = 0.798). In conclusion, OSA is an underdiagnosed disease with high prevalence in patients with ACS. It is urgent to establish screening protocols because those have high diagnostic yield and allow identifying a group of patients with manifestly unfavorable prognosis. PMID:26857162

  6. 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).

  7. 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

  8. Effects of Montelukast in an Experimental Model of Acute Pancreatitis.

    PubMed

    Angı, Serkan; Eken, Hüseyin; Kılıc, 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. MATERIAL AND 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

  9. 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.

  10. RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice

    PubMed Central

    Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D.; New, Maria I.; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J.

    2014-01-01

    The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias. PMID:24821812

  11. 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...

  12. COMPARISONS OF THE ACUTE EFFECTS OF CHOLINESTERASE INHIBITORS USING A NEUROBEHAVIORAL SCREENING BATTERY IN RATS

    EPA Science Inventory

    The clinical signs of intoxication produced by cholinesterase inhibitors, many of which are used as pesticides, are considered important information for regulatory purposes. e conducted acute studies of cholinesterase inhibitors in order to compare their effects as determined by ...

  13. Lethal mobilization of DDT by cowbirds

    USGS Publications Warehouse

    Van Velzen, A.C.; Stiles, W.B.; Stickel, L.F.

    1972-01-01

    This study is an experimental demonstration of lethal mobilization of DDT by brown-headed cowbirds (Molothrus ater) and the effects of food deprivation on the distribution and loss of DDT, DDD, and DDE. The principal experimental group consisted of 20 birds fed a dietary dosage of 100 ppm of DDT for 13 days. After 2 days of full rations of untreated food, they were subjected to food restriction. Food was reduced to 43 percent of normal. Seven of the 20 birds died within 4 days. No birds died in the three control groups, treated as follows: ( 1 ) 20 birds fed 100 ppm DDT for 13 days and full rations of untreated food thereafter, (2) 20 birds fed only untreated food but subjected to food restriction, and (3) 20 birds fed full rations of untreated food throughout. In a pilot study, birds were fed 100, 200, or 300 ppm of DDT and subjected to two periods of food restriction, the first of these immediately after dosage ceased and the second 4 months later. DDT-dosed birds from all dosage levels died in each period of food restriction. Before the weight loss that accompanied food restriction, the brains of DDT-dosed birds had concentrations of DDT and DDD that were far below the lethal range. Concentrations increased rapidly to lethal levels. In these birds, DDT in carcasses decreased while DDD increased. DDT-dosed birds that died during food restriction lost 16 percent of their total body burden of DDT + DDD + DDE, 21 percent of their weight, and 81 percent of their fat. The DDT-dosed birds that were subjected to food restriction but survived lost a significantly greater proportion of their body burden of residues than similarly dosed birds not subjected to weight loss. Brain levels of DDT and DDD in birds that died during food restriction soon after dosage did not differ significantly from brain levels of birds that died in a period of food restriction 4 months after dosage. Concentrations of DDE were significantly higher in the latter group, although they were lower

  14. Tasers--less than lethal!

    PubMed

    Sharma, Abiram; Theivacumar, Nada S; Souka, Hesham M

    2009-05-01

    We report a case of potentially lethal injury associated with the use of Taser. A 42-year-old man was stopped by police for potential detention. He held a large carving knife over his epigasrium threatening to stab himself. With a view to achieving immobilisation, a Taser gun was used. On activation of the Taser, the subject suffered a 7-cm wide and 10-cm deep stab injury to the upper abdomen. In this case, activation of the Taser resulted in the contraction of skeletal muscles, flexors more intensely than extensors, resulting in the stab injury. PMID:19416583

  15. Tasers – Less than Lethal!

    PubMed Central

    Sharma, Abiram; Theivacumar, Nada S; Souka, Hesham M

    2009-01-01

    We report a case of potentially lethal injury associated with the use of Taser. A 42-year-old man was stopped by police for potential detention. He held a large carving knife over his epigasrium threatening to stab himself.With a view to achieving immobilisation, a Taser gun was used. On activation of the Taser, the subject suffered a 7-cm wide and 10-cm deep stab injury to the upper abdomen. In this case, activation of the Taser resulted in the contraction of skeletal muscles, flexors more intensely than extensors, resulting in the stab injury. PMID:19416583

  16. 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…

  17. EFFECTS OF ACUTE PYRETHROID EXPOSURE ON THERMOREGULATION IN RATS.

    EPA Science Inventory

    Pyrethroid insecticides produce acute neurotoxicity in mammals. According to the FQPA mandate, the USEPA is required to consider the risk of cumulative toxicity posed to humans through exposure to pyrethroid mixtures. Thermoregulatory response (TR) is being used to determine if t...

  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. PMID:10763112

  19. 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. PMID:17553606

  20. The acute effects of vibration training on balance and stability amongst soccer players.

    PubMed

    Cloak, Ross; Nevill, Alan; Wyon, Matthew

    2016-01-01

    Acute whole body vibration training (WBVT) is a tool used amongst coaches to improve performance prior to activity. Its effects on other fitness components, such as balance and stability, along with how different populations respond are less well understood. The aim of the current research is to determine the effect of acute WBVT on balance and stability amongst elite and amateur soccer players. Forty-four healthy male soccer players (22 elite and 22 amateur) were assigned to a treatment or control group. The intervention group then performed 3 × 60 seconds static squat on vibration platform at 40 Hz (±4 mm) with Y balance test (YBT) scores and dynamic postural stability index (DPSI) measured pre and post. DPSI was significantly lower in the elite players in the acute WBVT compared to amateur players (F1, 40= 6.80; P = 0.013). YBT anterior reach distance showed a significant improvement in both amateur and elite players in the acute WBVT group (F1, 40= 32.36; P < 0.001). The improvement in DPSI amongst the elite players indicates a difference in responses to acute high frequency vibration between elite and amateur players during a landing stability task. The results indicate that acute WBVT improves anterior YBT reach distances through a possible improvement in flexibility amongst both elite and amateur players. In conclusion, acute WBVT training appears to improve stability amongst elite soccer players in comparison to amateur players, the exact reasoning behind this difference requires further investigation. PMID:25357208

  1. 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

  2. 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. PMID:24671550

  3. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. PMID:27299279

  4. Acute and non-acute effects of cannabis on human memory function: a critical review of neuroimaging studies.

    PubMed

    Bossong, Matthijs G; Jager, Gerry; Bhattacharyya, Sagnik; Allen, Paul

    2014-01-01

    Smoking cannabis produces a diverse range of effects, including impairments in learning and memory. These effects are exerted through action on the endocannabinoid system, which suggests involvement of this system in human cognition. Learning and memory deficits are core symptoms of psychiatric and neurological disorders such as schizophrenia and Alzheimer's disease, and may also be related to endocannabinoid dysfunction in these disorders. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of psychiatric disorders. Here we review neuroimaging studies that investigated acute and non-acute effects of cannabis on human learning and memory function, both in adults and in adolescents. Overall, results of these studies show that cannabis use is associated with a pattern of increased activity and a higher level of deactivation in different memory-related areas. This could reflect either increased neural effort ('neurophysiological inefficiency') or a change in strategy to maintain good task performance. However, the interpretation of these findings is significantly hampered by large differences between study populations in cannabis use in terms of frequency, age of onset, and time that subjects were abstinent from cannabis. Future neuroimaging studies should take these limitations into account, and should focus on the potential of cannabinoid compounds for treatment of cognitive symptoms in psychiatric disorders. PMID:23829369

  5. The effect of solar-geomagnetic activity during and after admission on survival in patients with acute coronary syndromes

    NASA Astrophysics Data System (ADS)

    Vencloviene, Jone; Babarskiene, Ruta; Milvidaite, Irena; Kubilius, Raimondas; Stasionyte, Jolanta

    2014-08-01

    A number of studies have established the effects of solar-geomagnetic activity on the human cardio-vascular system. It is plausible that the heliophysical conditions existing during and after hospital admission may affect survival in patients with acute coronary syndromes (ACS). We analyzed data from 1,413 ACS patients who were admitted to the Hospital of Kaunas University of Medicine, Lithuania, and who survived for more than 4 days. We evaluated the associations between active-stormy geomagnetic activity (GMA), solar proton events (SPE), and solar flares (SF) that occurred 0-3 days before and after admission, and 2-year survival, based on Cox's proportional-hazards model, controlling for clinical data. After adjustment for clinical variables, active-stormy GMA on the 2nd day after admission was associated with an increased (by 1.58 times) hazard ratio (HR) of cardiovascular death (HR = 1.58, 95 % CI 1.07-2.32). For women, geomagnetic storm (GS) 2 days after SPE occurred 1 day after admission increased the HR by 3.91 times (HR = 3.91, 95 % CI 1.31-11.7); active-stormy GMA during the 2nd-3rd day after admission increased the HR by over 2.5 times (HR = 2.66, 95 % CI 1.40-5.03). In patients aged over 70 years, GS occurring 1 day before or 2 days after admission, increased the HR by 2.5 times, compared to quiet days; GS in conjunction with SF on the previous day, nearly tripled the HR (HR = 3.08, 95 % CI 1.32-7.20). These findings suggest that the heliophysical conditions before or after the admission affect the hazard ratio of lethal outcome; adjusting for clinical variables, these effects were stronger for women and older patients.

  6. The effect of solar-geomagnetic activity during and after admission on survival in patients with acute coronary syndromes.

    PubMed

    Vencloviene, Jone; Babarskiene, Ruta; Milvidaite, Irena; Kubilius, Raimondas; Stasionyte, Jolanta

    2014-08-01

    A number of studies have established the effects of solar-geomagnetic activity on the human cardio-vascular system. It is plausible that the heliophysical conditions existing during and after hospital admission may affect survival in patients with acute coronary syndromes (ACS). We analyzed data from 1,413 ACS patients who were admitted to the Hospital of Kaunas University of Medicine, Lithuania, and who survived for more than 4 days. We evaluated the associations between active-stormy geomagnetic activity (GMA), solar proton events (SPE), and solar flares (SF) that occurred 0-3 days before and after admission, and 2-year survival, based on Cox's proportional-hazards model, controlling for clinical data. After adjustment for clinical variables, active-stormy GMA on the 2nd day after admission was associated with an increased (by 1.58 times) hazard ratio (HR) of cardiovascular death (HR=1.58, 95 % CI 1.07-2.32). For women, geomagnetic storm (GS) 2 days after SPE occurred 1 day after admission increased the HR by 3.91 times (HR=3.91, 95 % CI 1.31-11.7); active-stormy GMA during the 2nd-3rd day after admission increased the HR by over 2.5 times (HR=2.66, 95 % CI 1.40-5.03). In patients aged over 70 years, GS occurring 1 day before or 2 days after admission, increased the HR by 2.5 times, compared to quiet days; GS in conjunction with SF on the previous day, nearly tripled the HR (HR=3.08, 95 % CI 1.32-7.20). These findings suggest that the heliophysical conditions before or after the admission affect the hazard ratio of lethal outcome; adjusting for clinical variables, these effects were stronger for women and older patients. PMID:24018849

  7. Acute cardiorespiratory effects of intracisternal injections of mercuric chloride.

    PubMed

    Azevedo, Bruna Fernandes; Futuro Neto, Henrique de Azevedo; Stefanon, Ivanita; Vassallo, Dalton Valentin

    2011-06-01

    The present studies were conducted to changes arising from mercury poisoning in the central nervous system (CNS), with a focus on determining the receptors and neurotransmitters involved. Currently, little is known regarding the neurological basis of the cardiopulmonary effects of mercury poisoning. We evaluated changes in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), respiratory rate (RR) and heart rate (HR) following a 5 μl intracisternal (i.c) injection of mercuric chloride (HgCl(2)) and the participation of the autonomic nervous system in these responses. 58 animals were utilized and distributed randomly into 10 groups and administered a 5 μL intracisternal injection of 0.68 μg/kg HgCl(2) (n=7), 1.2 μg/kg HgCl(2) (n=7), 2.4 μg/kg HgCl(2) (n=7), 60 μg/kg HgCl(2) (n=7), 120 μg/kg HgCl(2) (n=3), saline (control) (n=7), 60 μg/kg HgCl(2) plus prazosin (n=6), saline plus prazosin (n=6), 60 μg/kg HgCl(2) plus metilatropina (n=4) or saline plus metilatropina (n=4)HgCl(2). Anesthesia was induced with halothane and maintained as needed with urethane (1.2 g/kg) administered intravenously (i.v.) through a cannula placed in the left femoral vein. The left femoral artery was also cannulated to record systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR). A tracheotomy was performed to record respiratory rate. Animals were placed in a stereotaxic frame, and the cisterna magna was exposed. After a stabilization period, solutions (saline or HgCl(2)) were injected i.c., and cardiopulmonary responses were recorded for 50 min. Involvement of the autonomic nervous system was assessed through the i.v. injection of hexamethonium (20 mg/kg), prazosin (1 mg/kg) and methylatropine (1 mg/kg) 10 min before the i.c. injection of HgCl(2) or saline. Treatment with 0.68, 1.2, 2.4 μg/kg HgCl(2) or saline did not modify basal cardiorespiratory parameters, whereas the 120 μg/kg dose induced acute toxicity, provoking respiratory

  8. Synergistic inhibition of the lethal fungal pathogen Batrachochytrium dendrobatidis: the combined effect of symbiotic bacterial metabolites and antimicrobial peptides of the frog Rana muscosa.

    PubMed

    Myers, Jillian M; Ramsey, Jeremy P; Blackman, Alison L; Nichols, A Elizabeth; Minbiole, Kevin P C; Harris, Reid N

    2012-08-01

    A powerful mechanism for protection against disease in animals is synergy between metabolites present in the natural microbiota of the host and antimicrobial peptides (AMPs) produced by the host. We studied this method of protection in amphibians in regard to the lethal disease chytridiomycosis, which is caused by Batrachochytrium dendrobatidis (Bd). In this study, we show that the AMPs of Rana muscosa, as well as the metabolite 2,4-diacetylphloroglucinol (2,4-DAPG) from Pseudomonas fluorescens, a bacterial species normally found on the skin of R. muscosa, were inhibitory to the growth of Bd in vitro. When both AMPs and 2,4-DAPG were used in growth inhibition assays, they worked synergistically to inhibit the growth of Bd. This synergy resulted in reduced minimum concentrations necessary for inhibition by either 2,4-DAPG or AMPs. This inhibitory concentration of AMPs did not inhibit the growth of a P. fluorescens strain that produced 2,4-DAPG in vitro, although its growth was inhibited at higher peptide concentrations. These data suggest that the AMPs secreted onto frog skin and the metabolites secreted by the resident beneficial bacteria may work synergistically to enhance protection against Bd infection on amphibian skin. These results may aid conservation efforts to augment amphibian skins' resistance to chytridiomycosis by introducing anti-Bd bacterial species that work synergistically with amphibian AMPs. PMID:22914957

  9. The Effects of Inhaled Steroids on Recurrent Wheeze After Acute Bronchiolitis

    PubMed Central

    Green, Patricia; Aronoff, Stephen C.

    2015-01-01

    Background. Acute bronchiolitis infection during infancy is associated with an increased risk of asthma later in life. The objective of this study was to determine if inhaled steroids are effective in preventing the development of recurrent wheeze or asthma following acute bronchiolitis. Methods. Multiple databases and bibliographies of selected references were searched. Inclusion required (a) a randomized controlled trial of inhaled steroids and control group, (b) at least 2 weeks duration of therapy started during the acute phase of disease, and (c) identification of the rate of recurrent wheeze or asthma at least 6 months after therapy. Results. Of 1410 studies reviewed, 8 reports were included in this meta-analysis (748 patients). The overall odds ratio for developing recurrent wheeze or asthma with treatment versus without treatment was 1.02 (95% confidence interval = 0.58-1.81). Conclusions. A course of inhaled steroids after acute bronchiolitis is not effective in preventing recurrent wheeze or asthma. PMID:27335972

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

    PubMed

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

    2014-09-01

    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 (4mg/kg, ice-cold PBS, s.c.) produced a rapid cholinergic crisis that evolved into status epilepticus (SE) and death within 6-8min. The EEG profile for POX induced SE was characterized and showed clinical and electrographic seizures with 7-10Hz spike activity. Treatment of 100% lethal POX intoxication with an optimized three drug regimen (atropine, 2mg/kg, i.p., 2-PAM, 25mg/kg, i.m. and diazepam, 5mg/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 [Ca(2+)]i (Ca(2+) plateau) and significant multifocal neuronal injury. POX SE induced Ca(2+) plateau had its origin in Ca(2+) release from intracellular Ca(2+) stores since inhibition of ryanodine/IP3 receptor lowered elevated Ca(2+) levels post SE. POX SE induced neuronal injury and alterations in Ca(2+) dynamics may underlie some of the long term morbidity associated with OP toxicity. PMID:24785379

  11. Central nervous system effects in acute thallium poisoning.

    PubMed

    Tsai, Yu-Tai; Huang, Chin-Chang; Kuo, Hung-Chou; Wang, Hsuan-Min; Shen, Wu-Shiun; Shih, Tung-Sheng; Chu, Nai-Shin

    2006-03-01

    We report the central nervous system manifestations, neuropsychological studies and brain magnetic resonance image (MRI) findings of two patients with acute thallium intoxication. Neurologically the patients suffered from confusion, disorientation, and hallucination in the acute stage, followed by anxiety, depression, lack of attention, and memory impairment, in addition to peripheral neuropathy. Neuropsychological tests revealed an impairment of memory function, including reversed digital span, memory registration, memory recall, memory recognition, similarity, proverb reasoning, and verbal fluency. High concentrations of thallium were found in the urine, blood, and drinking water of these two patients. Brain MRI showed lesions in the corpus striatum in one patient. During the follow-up periods, the clinical manifestations and neuropsychological studies showed a slowly progressive improvement, and a follow-up brain MRI 1.5 months later demonstrated a resolution of the lesions. We conclude that thallium intoxication might induce encephalopathy, and brain MRI studies demonstrated the acute-stage brain lesions in a severe intoxicated patient. In addition, neuropsychological tests also confirmed memory deficits, although the brain lesions in the corpus striatum might resolve. PMID:16337004

  12. Effect of Yi Gong San Decoction on Iron Homeostasis in a Mouse Model of Acute Inflammation

    PubMed Central

    Zheng, Qin; Guan, Yu; Xia, Lemin; Wang, Zhicheng; Jiang, Yiling; Zhang, Xiaofeng; Wang, Jianying; Wang, Guohua; Pu, Yiqiong; Xia, Jing; Luo, Meihong

    2016-01-01

    We investigated the effect of Yi Gong San (YGS) decoction on iron homeostasis and the possible underlying mechanisms in a mouse model of acute inflammation in this study. Our findings suggest that YGS regulates iron homeostasis by downregulating the level of HAMP mRNA, which may depend on regulation of the IL-6/STAT3 or BMP/HJV/SMAD pathway during acute inflammation. PMID:27143982

  13. Minimal Effects of Acute Liver Injury/Acute Liver Failure on Hemostasis as Assessed by Thromboelastography

    PubMed Central

    Stravitz, R. Todd; Lisman, Ton; Luketic, Velimir A.; Sterling, Richard K.; Puri, Puneet; Fuchs, Michael; Ibrahim, Ashraf; Lee, William M.; Sanyal, Arun J.

    2016-01-01

    Background & Aims Patients with acute liver injury/failure (ALI/ALF) are assumed to have a bleeding diathesis on the basis of elevated INR; however, clinically significant bleeding is rare. We hypothesized that patients with ALI/ALF have normal hemostasis despite elevated INR Methods Fifty-one patients with ALI/ALF were studied prospectively using thromboelastography (TEG), which measures the dynamics and physical properties of clot formation in whole blood. ALI was defined as an INR ≥1.5 in a patient with no previous liver disease, and ALF as ALI with hepatic encephalopathy. Results Thirty-seven of 51 patients (73%) had ALF and 22 patients (43%) underwent liver transplantation or died. Despite a mean INR of 3.4±1.7 (range 1.5–9.6), mean TEG parameters were normal, and 5 individual TEG parameters were normal in 32 (63%). Low maximum amplitude, the measure of ultimate clot strength, was confined to patients with platelet counts <126 × 109/L. Maximum amplitude was higher in patients with ALF than ALI and correlated directly with venous ammonia concentrations and with increasing severity of liver injury assessed by elements of the systemic inflammatory response syndrome. All patients had markedly decreased procoagulant factor V and VII levels, which were proportional to decreases in anticoagulant proteins and inversely proportional to elevated factor VIII levels. Conclusions Despite elevated INR, most patients with ALI/ALF maintain normal hemostasis by TEG, the mechanisms of which include an increase in clot strength with increasing severity of liver injury, increased factor VIII levels, and a commensurate decline in pro- and anticoagulant proteins. PMID:21703173

  14. The effects of acute stress on Pavlovian-instrumental transfer in rats.

    PubMed

    Pielock, Steffi M; Braun, Stephanie; Hauber, Wolfgang

    2013-03-01

    Pavlovian stimuli invigorate ongoing instrumental action, a phenomenon termed the Pavlovian-instrumental transfer (PIT) effect. Acute stressors can markedly enhance the release of corticotropin-releasing factor (CRF), and CRF injection into the nucleus accumbens increases the PIT effect. However, it is unknown whether acute stressors by themselves would amplify the PIT effect. Here, we examined the effects of acute stressors on PIT. Rats first received Pavlovian and instrumental training, and then the impact of the Pavlovian stimuli on instrumental responding was analyzed in the subsequent PIT test. Acute stressors were applied prior to the PIT test. Because the effects of acute stressors critically depend on stressor type and time of day, we used two acute stressors that involved one or several distinct stressors (denoted here as "single" vs. "multiple" stressors) applied either in the light or the dark period of the light:dark cycle. The results revealed that single and multiple stressors applied in the light period did not alter the PIT effect--that is, the ability of an appetitive Pavlovian stimulus to enhance leverpressing--or the basal leverpress rate. When applied in the dark period, single and multiple stressors also did not alter the PIT effect, but they did markedly reduce the basal leverpress rate. Diazepam pretreatment did not counteract the declines in basal instrumental responding in the PIT test that were induced by either a single or multiple stressors. Our findings suggest that acute stressors were unable to amplify the incentive salience of reward-predictive Pavlovian stimuli to activate instrumental responding, but, depending on the time of day of stressor exposure, they did reduce basal instrumental responding. PMID:23065681

  15. 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.

  16. 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

    2012-08-01

    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. PMID:22698813

  17. Development of short, acute exposure hazard estimates: a tool for assessing the effects of chemical spills in aquatic environments.

    PubMed

    Bejarano, Adriana C; Farr, James K

    2013-08-01

    Management decisions aimed at protecting aquatic resources following accidental chemical spills into rivers and coastal estuaries require estimates of toxic thresholds derived from realistic spill conditions: acute pulse exposures of short duration (h), information which often is unavailable. Most existing toxicity data (median lethal concentration or median effective concentration) come from tests performed under constant exposure concentrations and exposure durations in the 24-h to 96-h range, conditions not typical of most chemical spills. Short-exposure hazard concentration estimates were derived for selected chemicals using empirical toxicity data. Chemical-specific 5th percentile hazard concentrations (HC5) of species sensitivity distributions (SSD) from individual exposure durations (6-96 h) were derived via bootstrap resampling and were plotted against their original exposure durations to estimate HC5s and 95% confidence intervals (CIs) at shorter exposures (1, 2, and 4 h). This approach allowed the development of short-exposure HC5s for 12 chemicals. Model verification showed agreement between observed and estimated short-exposure HC5s (r(2) adjusted = 0.95, p < 0.0001), and comparison of estimated short-exposure HC5s with empirical toxicity data indicated generally conservative hazard estimates. This approach, applied to 2 real spill incidents, indicated hazard estimates above expected environmental concentrations (acrylonitrile), and suggested that environmental concentrations likely exceeded short-exposure hazard estimates (furfural). Although estimates generated through this approach were likely overprotective, these were derived from environmentally realistic exposure durations, providing risk-assessors with a tool to manage field decisions. Environ Toxicol Chem 2013;32:1918-1927. © 2013 SETAC. PMID:23625642

  18. [Cardioprotective effect of GABA derivatives in acute alcohol intoxication].

    PubMed

    Perfilova, V N; Tiurenkov, I N; Berestovitskaia, V M; Vasil'eva, O S

    2006-01-01

    Cardioprotective properties of GABA analogs under conditions of acute alcoholic intoxication have been studied using the following functional tests: volume loads, tests for adrenoreactivity, and maximum isometric load. The experiments showed that a 32% aqueous ethanol solution intraperitoneally injected in a dose of 8 g/kg produces a cardiotoxic action, which is manifested by a decrease in the inotropic reserve in load tests. Citrocard (50 mg/kg), phenibut (50 mg/kg), and piracetam (200 mg/kg) prevent the alcohol-induced myocardium injury, as shown by the heart contractility retained on a higher level in the test group than in the control group. PMID:16995433

  19. Effects of acute hypercapnia with and without acidosis on lung inflammation and apoptosis in experimental acute lung injury.

    PubMed

    Nardelli, L M; Rzezinski, A; Silva, J D; Maron-Gutierrez, T; Ornellas, D S; Henriques, I; Capelozzi, V L; Teodoro, W; Morales, M M; Silva, P L; Pelosi, P; Garcia, C S N B; Rocco, P R M

    2015-01-01

    We investigated the effects of acute hypercapnic acidosis and buffered hypercapnia on lung inflammation and apoptosis in experimental acute lung injury (ALI). Twenty-four hours after paraquat injection, 28 Wistar rats were randomized into four groups (n=7/group): (1) normocapnia (NC, PaCO2=35-45 mmHg), ventilated with 0.03%CO2+21%O2+balancedN2; (2) hypercapnic acidosis (HC, PaCO2=60-70 mmHg), ventilated with 5%CO2+21%O2+balancedN2; and (3) buffered hypercapnic acidosis (BHC), ventilated with 5%CO2+21%O2+balancedN2 and treated with sodium bicarbonate (8.4%). The remaining seven animals were not mechanically ventilated (NV). The mRNA expression of interleukin (IL)-6 (p=0.003), IL-1β (p<0.001), and type III procollagen (PCIII) (p=0.001) in lung tissue was more reduced in the HC group in comparison with NC, with no significant differences between HC and BHC. Lung and kidney cell apoptosis was reduced in HC and BHC in comparison with NC and NV. In conclusion, in this experimental ALI model, hypercapnia, regardless of acidosis, reduced lung inflammation and lung and kidney cell apoptosis. PMID:25246186

  20. Human Motor Cortex Functional Changes in Acute Stroke: Gender Effects

    PubMed Central

    Di Lazzaro, Vincenzo; Pellegrino, Giovanni; Di Pino, Giovanni; Ranieri, Federico; Lotti, Fiorenza; Florio, Lucia; Capone, Fioravante

    2016-01-01

    The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization. We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH) and unaffected hemisphere (UH) by measuring resting and active motor threshold (AMT) and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS) of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI), to evidence hemispheric asymmetry. AMT differed significantly between AH and UH only in the male group (p = 0.004), not in females (p > 0.200), and both LIAMT and LIRMT were significantly higher in males than in females (respectively p = 0.033 and p = 0.042). LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non-invasive stimulation strategy designed to foster stroke recovery. PMID:26858590

  1. Effects of COX-2 inhibitor in temporomandibular joint acute inflammation.

    PubMed

    Schütz, T C B; Andersen, M L; Tufik, S

    2007-05-01

    Since it is recognized that cyclo-oxygenase-2 mediates nociception and the sleep-wake cycle as well, and that acute inflammation of the temporomandibular joint (TMJ) results in sleep disturbances, we hypothesized that cyclo-oxygenase-2 inhibitor would restore the sleep pattern in this inflammatory rat model. First, sleep was monitored after the injection of Freund's adjuvant (FA group) or saline (SHAM group) into the rats' temporomandibular joint. Second, etoricoxib was co-administered in these groups. The Freund's adjuvant group showed a reduction in sleep efficiency, in rapid eye movement (REM), and in non-REM sleep, and an increase in sleep and REM sleep latency when compared with the SHAM group, while etoricoxib substantially increased sleep quality in the Freund's adjuvant group. These parameters returned progressively to those found in the SHAM group. Etoricoxib improved the sleep parameters, suggesting the involvement of the cyclo-oxygenase-2 enzyme in acute inflammation of the TMJ, specifically in REM sleep. PMID:17452571

  2. Effect of Thoracentesis on Intubated Patients with Acute Lung Injury.

    PubMed

    Bloom, Matthew B; Serna-Gallegos, Derek; Ault, Mark; Khan, Ahsan; Chung, Rex; Ley, Eric J; Melo, Nicolas; Margulies, Daniel R

    2016-03-01

    Pleural effusions occur frequently in mechanically ventilated patients, but no consensus exists regarding the clinical benefit of effusion drainage. We sought to determine the impact of thoracentesis on gas exchange in patients with differing severities of acute lung injury (ALI). A retrospective analysis was conducted on therapeutic thoracenteses performed on intubated patients in an adult surgical intensive care unit of a tertiary center. Effusions judged by ultrasound to be 400 mL or larger were drained. Subjects were divided into groups based on their initial P:F ratios: normal >300, ALI 200 to 300, and acute respiratory distress syndrome (ARDS) <200. Baseline characteristics, physiologic variables, arterial blood gases, and ventilator settings before and after the intervention were analyzed. The primary end point was the change in measures of oxygenation. Significant improvements in P:F ratios (mean ± SD) were seen only in patients with ARDS (50.4 ± 38.5, P = 0.001) and ALI (90.6 ± 161.7, P = 0.022). Statistically significant improvement was observed in the pO2 (31.1, P = 0.005) and O2 saturation (4.1, P < 0.001) of the ARDS group. The volume of effusion removed did not correlate with changes in individual patient's oxygenation. These data support the role of therapeutic thoracentesis for intubated patients with abnormal P:F ratios. PMID:27099064

  3. Alcohol Consumption and Nearly Lethal Suicide Attempts.

    ERIC Educational Resources Information Center

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

    2002-01-01

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

  4. Lethality of Suicide Attempt Rating Scale.

    ERIC Educational Resources Information Center

    Smith, K.; And Others

    1984-01-01

    Presents an 11-point scale for measuring the degree of lethality of suicide attempts. The scale has nine example "anchors" and uses the relative lethality of an extensive table of drugs. The scale can be used reliably by nonmedical personnel with no prior training. (Author/BL)

  5. Meloxicam-induced rhabdomyolysis in the context of an acute ross river viral infection.

    PubMed

    Al Kindi, Mahmood; Limaye, Vidya; Hissaria, Pravin

    2012-01-01

    Acute rhabdomyolysis is a clinical and laboratory syndrome resulting from the breakdown of skeletal muscle, with the release of intracellular contents into the circulatory system, which can cause potentially lethal complications. Here, we present the case of a patient who developed acute rhabdomyolysis after consumption of meloxicam for jaw pain and experienced generalized myalgias in the context of an acute febrile illness with generalized urticaria. Further investigation indicated elevated muscle enzymes and acute renal failure. Serological analysis revealed that the patient was positive for Ross River virus (RRV) IgM. Genetic studies to detect CYP2C9 polymorphisms were negative. Meloxicam was discontinued. He responded to conservative measures within 2 weeks. Oral aspirin challenge was negative, suggesting a drug-specific effect of meloxicam rather than a class effect. Our case indicates a causative role for meloxicam and/or acute RRV in rhabdomyolysis. PMID:22211172

  6. The contribution of electrophysiology to knowledge of the acute and chronic effects of ethanol.

    PubMed

    Little, H J

    1999-12-01

    This review describes the effects of ethanol on the components of neuronal transmission and the relationship of such effects to the behavioural actions of ethanol. The concentrations of ethanol with acute actions on voltage-sensitive ion channels are first described, then the actions of ethanol on ligand-gated ion channels, including those controlled by cholinergic receptors, 5-hydroxytryptamine receptors, the various excitatory amino acid receptors, and gamma-aminobutyric acid receptors. Acute effects of ethanol are then described on brain areas thought to be involved in arousal and attention, the reinforcing effects of ethanol, the production of euphoria, the actions of ethanol on motor control, and the amnesic effects of ethanol; the acute effects of ethanol demonstrated by EEG studies are also discussed. Chronic effects of alcohol on neuronal transmission are described in the context of the various components of the ethanol withdrawal syndrome, withdrawal hyperexcitability, dysphoria and anhedonia, withdrawal anxiety, craving, and relapse drinking. Electrophysiological studies on the genetic influences on the effects of ethanol are discussed, particularly the acute actions of ethanol and electrophysiological differences reported in individuals predisposed to alcoholism. The conclusion notes the concentration of studies on the classical transmitters, with relative neglect of the effects of ethanol on peptides and on neuronal interactions between brain areas and integrated patterns of neuronal activity. PMID:10665833

  7. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  8. Effects of acute and chronic inhalation of paint thinner in mice: behavioral and immunohistochemical study.

    PubMed

    Fifel, Karim; Bennis, Mohamed; Ba-M'hamed, Saâdia

    2014-06-01

    Abuse of volatile inhalants has become a worldwide issue mainly among adolescents of low income social class. Acute and chronic exposure to these substances results in serious neurological and behavioral impairments. Although real exposure consists largely of simultaneous inhalation of multiple solvents, the vast majority of basic research studies have evaluated the actions of a single volatile component leaving the behavioral and neuronal effects of chemical mixture not fully understood. In this study, we investigated the acute behavioral effects of 300, 450 and 600 ppm of paint thinner inhalation on anxiety, locomotor activity and spatial memory. Additionally, the cognitive impairments related to chronic exposure of the same concentrations of thinner for 45 days were assessed. To understand the neuronal correlates of acute exposure to thinner, we used c-Fos immunohistochemistry as an endogenous marker of neuronal activation following 600 ppm of thinner. The results reveal that (i) chronically thinner exposed mice showed cognitive deficits in Morris water maze and object recognition tasks; (ii) acute inhalation of thinner induces a wide range of behavioral changes. These changes include an anxiolytic effect toward the aversive environmental bright light and a dose dependent effect on explorative locomotion. The wide range of behavioral alterations induced by acute thinner inhalation is consistent with the widespread distribution of thinner-induced c-Fos expression in multiple brain structures. PMID:24218105

  9. Acute Effects of Exposure to (56)Fe and (16)O Particles on Learning and Memory.

    PubMed

    Rabin, Bernard M; Poulose, Shibu M; Carrihill-Knoll, Kirsty L; Ramirez, Francisco; Bielinski, Donna F; Heroux, Nicholas; Shukitt-Hale, Barbara

    2015-08-01

    Although it has been shown that exposure to HZE particles disrupts cognitive performance when tested 2-4 weeks after irradiation, it has not been determined whether exposure to HZE particles acutely affects cognitive performance, i.e., within 4-48 h after exposure. The current experiments were designed to determine the acute effects of exposure to HZE particles ((16)O and (56)Fe) on cognitive performance and whether exposure to HZE particles affected learning or memory, as well as to understand the relationship between acute changes in the levels of NOX2 (a measure of oxidative stress) and COX2 (a measure of neuroinflammation) in specific brain regions and cognitive performance. The results of these studies indicate that the acute effects of radiation exposure on cognitive performance are on memory, not learning. Further, the acute effects of exposure to HZE particles on oxidative stress and neuroinflammation and their relationship to cognitive performance indicate that, although the effects of exposure to both (56)Fe and (16)O are widespread, only changes in specific regions of the brain may be related to changes in cognitive function. PMID:26207687

  10. Recognizing acute health effects of substitute fungicides: are first-aid reports effective?

    PubMed

    Teschke, K; Hertzman, C; Wiens, M; Dimich-Ward, H; Hershler, R; Ostry, A; Kelly, S J

    1992-01-01

    Recently, many British Columbia sawmills stopped using traditional chlorophenate anti-sapstain fungicides and substituted 2-(thiocyanomethylthio) benzothiazole (TCMTB) and copper-8-quinolinolate (Copper 8). We conducted a cross-sectional study with two aims: to ascertain which acute health effects, if any, were associated with the use of the substitute fungicides; and to determine the effectiveness of first-aid records as a means of detecting acute health outcomes. Workers in five coastal sawmills were asked to complete a self-administered questionnaire about symptoms considered potentially related and unrelated to fungicide exposure, and about injuries commonly reported in sawmills. In addition, we collected first-aid records from the mills, and asked senior workers to estimate the duration of exposure to fungicides for each job. Symptoms found to be consistently elevated in TCMTB mills included dry skin around the eyes, blood-stained mucus from the nose, nose bleed, peeling skin, burning or itching skin, and skin redness or rash. No symptoms were consistently elevated in the Copper 8 mills. Symptoms related to TCMTB exposure were recorded only 12 times in first-aid logs during the study period (versus 335 questionnaire self-reports). This low symptom-recording frequency may be a function of established patterns of first-aid use in which illness symptoms are reported less frequently than injuries. PMID:1585948

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

    SciTech Connect

    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 LD{sub 50} 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 24 h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD{sub 50} 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 LD{sub 50} sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin. - Highlights: • Inhalation exposure of rats to LD{sub 50} sarin causes death through respiratory failure. • Severe bronchoconstriction is the major cause of sarin-induced respiratory failure. • Transfer of sarin exposed rats to 60% oxygen improves the mortality temporarily.

  12. Modelling the effects of ionizing radiation on survival of animal population: acute versus chronic exposure.

    PubMed

    Kryshev, A I; Sazykina, T G

    2015-03-01

    The objective of the present paper was application of a model, which was originally developed to simulate chronic ionizing radiation effects in a generic isolated population, to the case of acute exposure, and comparison of the dynamic features of radiation effects on the population survival in cases of acute and chronic exposure. Two modes of exposure were considered: acute exposure (2-35 Gy) and chronic lifetime exposure with the same integrated dose. Calculations were made for a generic mice population; however, the model can be applied for other animals with proper selection of parameter values. In case of acute exposure, in the range 2-11 Gy, the population response was in two phases. During a first phase, there was a depletion in population survival; the second phase was a recovery period due to reparation of damage and biosynthesis of new biomass. Model predictions indicate that a generic mice population, living in ideal conditions, has the potential for recovery (within a mouse lifetime period) from acute exposure with dose up to 10-11 Gy, i.e., the population may recover from doses above an LD50 (6.2 Gy). Following acute doses above 14 Gy, however, the mice population went to extinction without recovery. In contrast, under chronic lifetime exposures (500 days), radiation had little effect on population survival up to integrated doses of 14-15 Gy, so the survival of a population subjected to chronic exposure was much better compared with that after an acute exposure with the same dose. Due to the effect of "wasted radiation", the integrated dose of chronic exposure could be about two times higher than acute dose, producing the same effect on survival. It is concluded that the developed generic population model including the repair of radiation damage can be applied both to acute and chronic modes of exposure; results of calculations for generic mice population are in qualitative agreement with published data on radiation effects in mice. PMID

  13. Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema.

    PubMed

    Desai, Ketaki V; Laine, Glen A; Stewart, Randolph H; Cox, Charles S; Quick, Christopher M; Allen, Steven J; Fischer, Uwe M

    2008-06-01

    Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures. PMID:18375722

  14. Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs* **

    PubMed Central

    Torres, Ronaldo Lopes; Torres, Iraci Lucena da Silva; Laste, Gabriela; Ferreira, Maria Beatriz Cardoso; Cardoso, Paulo Francisco Guerreiro; Belló-Klein, Adriane

    2014-01-01

    Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels. PMID:25029646

  15. Effect of HIV infection on time to recovery from an acute manic episode

    PubMed Central

    Nakimuli-Mpungu, E; Mutamba, B; Nshemerirwe, S; Kiwuwa, MS; Musisi, S

    2010-01-01

    Introduction Understanding factors affecting the time to recovery from acute mania is critical in the management of manic syndromes. The aim of this study was to determine the effect of HIV infection on time to recovery from acute mania. Methods We performed a retrospective study in which medical charts of individuals who were treated for acute mania were reviewed. Survival analysis with Cox regression models were used to compare time to recovery from an acute manic episode between human immunodeficiency virus (HIV)-positive individuals and HIV-negative individuals. Results Median survival time was one week for HIV-positive individuals and more than four weeks for HIV-negative individuals (χ2 = 18.4, P value = 0.000). HIV infection was the only marginally significant independent predictor of survival probability on the acute admission ward (hazards ratio 2.87, P = 0.06). Conclusion Acute mania in HIV-infected persons responds faster to psychotropic drugs compared with that in HIV-negative persons. PMID:22096397

  16. COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE.

    EPA Science Inventory

    The utility of laboratory animal data in toxicology depends upon the ability to generalize the results quantitatively to humans. To compare the acute behavioral effects of inhaled toluene in humans to those in animals, dose-effect curves were fitted by meta-analysis of published...

  17. Acute effects of exposure to 56Fe and 16O particles on learning and memory

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although it has been shown that exposure to HZE particles disrupts cognitive performance when tested 2-4 weeks after irradiation, it has not been determined whether exposure to HZE particles can exert acute effects on cognitive performance; i.e., effects within 4-48 hrs after exposure. The present ...

  18. A QUANTITATIVE COMPARISON OF THE EFFECTS OF ACUTE INHALED TOLUENE IN HUMAN RATS

    EPA Science Inventory

    The effects of acute exposure to toluene have been explored more thoroughly than other hydrocarbon solvents. These effects have been experimentally studied in humans and other species, e.g., rats, as well as in a number of in vitro preparations. The existence ofdosimetric and eff...

  19. Acute Effect of Decaffeinated Coffee on Heart Rate, Blood Pressure, and Exercise Performance in Healthy Subjects

    PubMed Central

    Prakash, Ravi; Kaushik, Vidya S.

    1988-01-01

    The effect of decaffeinated coffee on the cardiovascular exercise performance in nine healthy volunteers was evaluated in a double-blind randomized fashion. The heart rate, blood pressure, and duration of exercise were unchanged, and no arrhythmias or ischemic changes were seen on the electrocardiogram after drinking decaffeinated coffee. It was concluded that decaffeinated coffee has no discernible, acute, adverse cardiovascular effects. PMID:3339645

  20. ASSESSING THE IMPORTANCE OF THE BEHAVIORAL EFFECT OF ACUTE EXPOSURE TO TOLUENE IN HUMANS.

    EPA Science Inventory

    There is increasing interest in being able to evaluate potential benefit-cost relationships of controlling exposure to toxic substances. Behavioral effects of acute toluene exposure could be subjected to benefit-cost analysis if it's effects were quantitatively compared to tho...

  1. Acute effects of cigarette smoke exposure on experimental skin flaps

    SciTech Connect

    Nolan, J.; Jenkins, R.A.; Kurihara, K.; Schultz, R.C.

    1985-04-01

    Random vascular patterned caudally based McFarlane-type skin flaps were elevated in groups of Fischer 344 rats. Groups of rats were then acutely exposed on an intermittent basis to smoke generated from well-characterized research filter cigarettes. Previously developed smoke inhalation exposure protocols were employed using a Maddox-ORNL inhalation exposure system. Rats that continued smoke exposure following surgery showed a significantly greater mean percent area of flap necrosis compared with sham-exposed groups or control groups not exposed. The possible pathogenesis of this observation as well as considerations and correlations with chronic human smokers are discussed. Increased risks of flap necrosis by smoking in the perioperative period are suggested by this study.

  2. Acute health effects of accidental chlorine gas exposure

    PubMed Central

    2014-01-01

    Objectives This study was conducted to report the course of an accidental release of chlorine gas that occurred in a factory in Gumi-si, South Korea, on March 5, 2013. We describe the analysis results of 2 patients hospitalized because of chlorine-induced acute health problems, as well as the clinical features of 209 non-hospitalized patients. Methods We analyzed the medical records of the 2 hospitalized patients admitted to the hospital, as well as the medical records and self-report questionnaires of 209 non-hospitalized patients completed during outpatient treatment. Results Immediately after the exposure, the 2 hospitalized patients developed acute asthma-like symptoms such as cough and dyspnea, and showed restrictive and combined pattern ventilatory defects on the pulmonary function test. The case 1 showed asthma-like symptoms over six months and diurnal variability in peak expiratory flow rate was 56.7%. In case 2, his FEV1 after treatment (93%) increased by 25% compared to initial FEV1 (68%). Both cases were diagnosed as chlorine-induced reactive airways dysfunction syndrome (RADS) on the basis of these clinical features. The most frequent chief complaints of the 209 non-hospitalized patients were headache (22.7%), followed by eye irritation (18.2%), nausea (11.2%), and sore throat (10.8%), with asymptomatic patients accounting for 36.5%. The multiple-response analysis of individual symptom revealed headache (42.4%) to be the most frequent symptom, followed by eye irritation (30.5%), sore throat (30.0%), cough (29.6%), nausea (27.6%), and dizziness (27.3%). Conclusions The 2 patients hospitalized after exposure to chlorine gas at the leakage site showed a clinical course corresponding to RADS. All of the 209 non-hospitalized patients only complained of symptoms of the upper airways and mucous membrane irritation. PMID:25852940

  3. Acute and medium term effects of a 10-week running intervention on mood state in apprentices

    PubMed Central

    Walter, Katrin; von Haaren, Birte; Löffler, Simone; Härtel, Sascha; Jansen, Carl-Philipp; Werner, Christian; Stumpp, Jürgen; Bös, Klaus; Hey, Stefan

    2013-01-01

    Exercise and physical activity have proven benefits for physical and psychological well-being. However, it is not clear if healthy young adults can enhance mood in everyday life through regular exercise. Earlier studies mainly showed positive effects of acute exercise and exercise programs on psychological well-being in children, older people and in clinical populations. Few studies controlled participants' physical activity in daily life, performed besides the exercise program, which can impact results. In addition the transition from mood enhancement induced by acute exercise to medium or long-term effects due to regular exercise is not yet determined. The purpose of this pilot study was to examine the acute effects of an aerobic running training on mood and trends in medium term changes of mood in everyday life of young adults. We conducted a 10-week aerobic endurance training with frequent mood assessments and continuous activity monitoring. 23 apprentices, separated into experimental and control group, were monitored over 12 weeks. To control the effectiveness of the aerobic exercise program, participants completed a progressive treadmill test pre and post the intervention period. The three basic mood dimensions energetic arousal, valence and calmness were assessed via electronic diaries. Participants had to rate their mood state frequently on 3 days a week at five times of measurement within 12 weeks. Participants' physical activity was assessed with accelerometers. All mood dimensions increased immediately after acute endurance exercise but results were not significant. The highest acute mood change could be observed in valence (p = 0.07; η2 = 0.27). However, no medium term effects in mood states could be observed after a few weeks of endurance training. Future studies should focus on the interaction between acute and medium term effects of exercise training on mood. The decreasing compliance over the course of the study requires the development of

  4. Acute toxicity and synergistic and antagonistic effects of the aromatic compounds of some essential oils against Culex quinquefasciatus Say larvae.

    PubMed

    Pavela, Roman

    2015-10-01

    The efficacy of 30 aromatic compounds and their mutual binary combinations was assessed for acute toxicity against the larvae Culex quinquefasciatus. Based on comparison of the lethal doses, thymol and p-cymene were selected as the most effective (LD50 = 18 and 21 mg L(-1), respectively, and LD90 = 25 and 30 mg L(-1), respectively). Although the LD50 for terpinolene and trans-anethole was also estimated at 21 mg L(-1), their LD90 was significantly higher compared to the substances above (245 and 34 mg L(-1), respectively). In total, 435 binary combinations were tested, of which 249 combinations showed a significant synergistic effect, while 74 combinations showed a significant antagonistic effect on mortality. Only nine substances were identified as being able to create a synergistic effect with more than 20 substances: limonene, trans-anethole, 4-allylanisole, carvacrol, isoeugenol, menthone, carvone, borneol, and camphor. The highest synergistic effect on larval mortality was achieved for the combinations: eugenol and isoeugenol, carvone and carvacrol, carvone and 4-allylanisole, carvone and α-terpineol, carvone and menthone, limonene and trans-anethole, limonene and menthone, α-pinene and menthone, β-citronellol and menthone, carvacrol and 4-allylanisole, carvacrol and terpineol, α-terpinene and trans-anethole, camphor and menthone, camphene and menthone, and 4-allylanisole and menthone. Significant differences between achieved mortality and the mutual mixing ratio were found for the five selected binary mixtures that had shown the most significant synergistic effect in the previous tests. The mixture of limonene and trans-anethole showed the highest mortality, with the mixing ratio 1:1; the mixture of eugenol and isoeugenol caused 90.2% mortality, with the mixing ratio 1:3. One hundred percent mortality was achieved if carvacrol was contained in a mixture with carvone in a ratio >2. After a comparison of all our results, based on our experiments, we

  5. Acute and training effects of resistance exercise on heart rate variability.

    PubMed

    Kingsley, J Derek; Figueroa, Arturo

    2016-05-01

    Heart rate variability (HRV) has been used as a non-invasive method to evaluate heart rate (HR) regulation by the parasympathetic and sympathetic divisions of the autonomic nervous system. In this review, we discuss the effect of resistance exercise both acutely and after training on HRV in healthy individuals and in those with diseases characterized by autonomic dysfunction, such as hypertension and fibromyalgia. HR recovery after exercise is influenced by parasympathetic reactivation and sympathetic recovery to resting levels. Therefore, examination of HRV in response to acute exercise yields valuable insight into autonomic cardiovascular modulation and possible underlying risk for disease. Acute resistance exercise has shown to decrease cardiac parasympathetic modulation more than aerobic exercise in young healthy adults suggesting an increased risk for cardiovascular dysfunction after resistance exercise. Resistance exercise training appears to have no effect on resting HRV in healthy young adults, while it may improve parasympathetic modulation in middle-aged adults with autonomic dysfunction. Acute resistance exercise appears to decrease parasympathetic activity regardless of age. This review examines the acute and chronic effects of resistance exercise on HRV in young and older adults. PMID:25524332

  6. Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic Review.

    PubMed

    Broyd, Samantha J; van Hell, Hendrika H; Beale, Camilla; Yücel, Murat; Solowij, Nadia

    2016-04-01

    Cannabis use has been associated with impaired cognition during acute intoxication as well as in the unintoxicated state in long-term users. However, the evidence has been mixed and contested, and no systematic reviews of the literature on neuropsychological task-based measures of cognition have been conducted in an attempt to synthesize the findings. We systematically review the empirical research published in the past decade (from January 2004 to February 2015) on acute and chronic effects of cannabis and cannabinoids and on persistence or recovery after abstinence. We summarize the findings into the major categories of the cognitive domains investigated, considering sample characteristics and associations with various cannabis use parameters. Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis. Psychomotor function is most affected during acute intoxication, with some evidence for persistence in chronic users and after cessation of use. Impaired verbal memory, attention, and some executive functions may persist after prolonged abstinence, but persistence or recovery across all cognitive domains remains underresearched. Associations between poorer performance and a range of cannabis use parameters, including a younger age of onset, are frequently reported. Little further evidence has emerged for the development of tolerance to the acutely impairing effects of cannabis. Evidence for potential protection from harmful effects by cannabidiol continues to increase but is not definitive. In light of increasing trends toward legalization of cannabis, the knowledge gained from this body of research needs to be incorporated into strategies to minimize harm. PMID:26858214

  7. Lethal outcome in xanthogranulomatous endometritis.

    PubMed

    Noack, Frank; Briese, Juliane; Stellmacher, Florian; Hornung, Daniela; Horny, Hans-Peter

    2006-05-01

    Xanthogranulomatous inflammation is rare, mainly involving the kidneys, while primary xanthogranulomatous endometritis (XE) is a very unusual finding, histologically characterized by partial or complete replacement of the mucosa by granulation tissue with an abundance of foamy histiocytes, siderophages and multinucleated giant cells. We present the case of a 69-year-old woman with a short history of abdominal pain and a palpable mass in the pouch of Douglas. Dilatation of the cervix drained a pyometra. Histological examination of the curettage rendered the diagnosis of XE. Microbiological studies revealed enterococcus spp. and Peptostreptococcus magnus. Despite antibiotic treatment the patient died of heart failure due to systemic inflammation. Autopsy confirmed the diagnosis of XE with transmural extension into the peritoneal cavity. Such a lethal course of XE is extraordinary. Proposed causes of XE include obstruction, infection and hemorrhage. Demonstration of enterococcus spp. and P. magnus supports the probable significance of bacteria in the development of XE. Because this condition may mimic malignant disease macroscopically and histologically, knowledge of XE is of major importance for both pathologists and gynecologists. PMID:16725016

  8. Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

    PubMed

    Tracey, K J; Morgello, S; Koplin, B; Fahey, T J; Fox, J; Aledo, A; Manogue, K R; Cerami, A

    1990-12-01

    We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects. PMID:2254457

  9. A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka

    PubMed Central

    2012-01-01

    Background Acute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka. Methods Economic analysis was applied using public healthcare system payer perspective. Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008. Results An affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes. Conclusions Post ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated

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

    PubMed

    Chen, Ya-nan; Yuan, Ling

    2015-10-01

    Coptis chinensis rhizome and preparations were widely used for the treatment of fish diseases in aquaculture. the acute toxicological effect of CRE on lethal, movement and phototaxis was studied on Daphnia carinata monoclone as a test animal in the present experiment. The results showed that CRE was acute toxic to this animal and alkaloids berberine concentrations in CRE changed in the following sequence: half lethal > half inhibitory > limitable, which led to a significant change in phototaxis index of Daphnia carinata. The concentration of CRE for the significant change in phototaxis index was 4.27 mg x L(-1), which was lower than the concentration in water to cure the fish diseases and this conclusion indicated an ecological risk of this antibiotic to Daphnia carinata in aquaculture. In addition, the concentration of CRE in phototaxis index was changed from 30.62 times at 48th hour to 36.51 times at 24th hour that were lower than half lethal concentration. Detecting phototaxis index was easy and only 3 hours was required, so utilizing the quickly change of Daphnia carinata phototaxis can be an effective method to monitor the toxicity effect of CRE on Daphnia carinata. The abuse of rhizome or preparations in aquaculture might destroy the aquatic food chain, resulting in an imbalance of aquatic ecosystems. PMID:26841628

  11. The effects of acute alcohol administration on the human brain: Insights from neuroimaging

    PubMed Central

    Bjork, James M.; Gilman, Jodi M.

    2014-01-01

    Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. PMID:23978384

  12. Outpatient parenteral antimicrobial therapy with ceftriaxone for acute tonsillopharyngitis: efficacy, patient satisfaction, cost effectiveness, and safety

    PubMed Central

    Al Alawi, Samah; Abdulkarim, Somaya; Elhennawy, Hazem; Al-Mansoor, Anwar; Al Ansari, Ahmed

    2015-01-01

    Background Outpatient parenteral antimicrobial therapy (OPAT) is the administration of intravenous antimicrobial therapy to patients in an outpatient setting. It may be used for patients who have infections that require parenteral treatment but who are otherwise stable enough to not require admission as inpatients. Objective We aimed to review the treatment of patients with acute tonsillopharyngitis at the OPAT health care clinic in the Bahrain Defense Force Royal Medical Services (BDF-RMS), with regard to efficacy, patient satisfaction, cost effectiveness, and safety. Methods A retrospective case notes review was conducted for all patients admitted to the OPAT clinic in the BDF-RMS with acute tonsillopharyngitis treated with ceftriaxone, between March 2012 and March 2014. Results In the period between March 2012 and March 2014, 97 patients with acute tonsillopharyngitis were treated with ceftriaxone for a minimum of 3 days at the OPAT clinic. In total, 94.8% of patients completed the prescribed course of ceftriaxone. Total cure was achieved in 89.7% of patients. Usage of the OPAT clinic led to cost savings of 10,693 BD, while total bed days saved were 301 over the 2-year period examined by this study. Participants in the program expressed high satisfaction rates, and the average (± standard deviation) score on a patient satisfaction survey was 4.41 (± 0.31) out of a total of 5. This study highlights the efficacy, patient satisfaction, cost effectiveness, and safety of the OPAT clinic service for the treatment of acute tonsillopharyngitis with ceftriaxone. We found a 45.5% drop in admission rate for acute tonsillopharyngitis after starting the OPAT service clinic and that 301 bed days were saved through this treatment. Conclusion This study showed that the management of acute tonsillopharyngitis with ceftriaxone in the OPAT clinic is safe, clinically effective, and cost effective, with low rates of complications/readmissions and high levels of patient

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

    SciTech Connect

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

    1994-09-01

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

  14. The acute and chronic effects of "NO LOAD" resistance training.

    PubMed

    Counts, Brittany R; Buckner, Samuel L; Dankel, Scott J; Jessee, Matthew B; Mattocks, Kevin T; Mouser, J Grant; Laurentino, Gilberto C; Loenneke, Jeremy P

    2016-10-01

    The purpose of the study was to remove the influence of an external load and determine if muscle growth can be elicited by maximally contracting through a full range of motion. In addition, the acute physiologic and perceptual responses to each stimulus were also investigated. Thirteen participants completed 18 sessions of unilateral elbow flexion exercise. Each arm was designated to either NO LOAD or HIGH LOAD condition (70% one repetition maximum). For the NO LOAD condition, participants repeatedly contracted as hard as they could through a full range of motion without the use of an external load. Our results show that anterior muscle thickness increased similarly from Pre to Post, with no differences between conditions for the 50% [Pre: 2.7 (0.8) vs. Post: 2.9 (0.7)], 60% [Pre: 2.9 (0.7) vs. Post: 3.1 (0.7)] or 70% [Pre: 3.2 (0.7) vs. Post: 3.5 (0.7)] sites. There was a significant condition×time interaction for one repetition maximum (p=0.017), with HIGH LOAD (+2.3kg) increasing more than the NO LOAD condition (+1kg). These results extend previous studies that have observed muscle growth across a range of external loads and muscle actions and suggest that muscle growth can occur independent of an external load provided there are enough muscle fibers undergoing mechanotransduction. PMID:27329807

  15. Effect of acute cytomegalovirus infection on drug-induced SLE.

    PubMed Central

    Schattner, A.; Sthoeger, Z.; Geltner, D.

    1994-01-01

    A 58 year old woman developed systemic symptoms, interstitial lung disease, splenomegaly, leukopenia and anti-histone and anti-nuclear antibodies (ANA), while treated with hydralazine for hypertension. Five months after presentation she was admitted with high fever, skin rash and atypical lymphocytosis due to acute cytomegalovirus (CMV) infection. Worsening leukopenia and increased ANA were found, and high titres of anti-DNA antibodies, anti-cardiolipin antibodies and rheumatoid factors appeared. Hydralazine was stopped and the patient gradually became asymptomatic. All autoantibodies spontaneously disappeared (over 16 weeks), and the white cell count and spleen size became normal. The patient was found to be a slow acetylator and to have both HLA-DR4 and selective IgA deficiency. Thus, a multifactorial genetic susceptibility to develop drug-induced lupus was brought out in stages first by hydralazine and then by CMV, yet all manifestations and autoantibodies resolved spontaneously, demonstrating the complex interplay of varied environmental factors with a genetic predisposition in the pathogenesis of autoimmunity. PMID:7831173

  16. Lethal head entrapment--a problem characteristic of early childhood.

    PubMed

    Byard, Roger W; Charlwood, Cheryl

    2009-08-01

    Accidental deaths in infancy and early childhood often result from young childrens' lack of understanding of the dangers of certain situations and their physical inability to extricate themselves from potentially lethal circumstances. Two cases are reported to demonstrate an age-related susceptibility in the young to lethal head entrapment. Case 1: a 5-month-old girl smothered when she slipped down in her stroller, trapping her head beneath the frame and forcing her face into the soft material of the base. Case 2: a 14-month-old boy was hanged while exploring a filing cabinet when his head became caught between two lower drawers. Additional mental and physical characteristics that predispose young children and infants to lethal head entrapment include an inability to effectively problem solve once confronted with a hazardous situation, and relatively large heads and weak neck musculature. Because of these features lethal head entrapment represents a particular circumstance that may predispose to accidental asphyxial deaths in the very young. A combination of careful death scene and autopsy evaluations will be required to confirm the alleged circumstances of death in these cases, including mortuary re-enactments and assessment of the deceased infant's level of physical maturity and mobility. PMID:19573845

  17. Dominant-lethal mutations and heritable translocations in mice

    SciTech Connect

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

  18. Subcutaneous wounding postirradiation reduces radiation lethality in mice.

    PubMed

    Garrett, Joy; Orschell, Christie M; Mendonca, Marc S; Bigsby, Robert M; Dynlacht, Joseph R

    2014-06-01

    The detonation of an improvised nuclear device during a radiological terrorist attack could result in the exposure of thousands of civilians and first responders to lethal or potentially lethal doses of ionizing radiation (IR). There is a major effort in the United States to develop phamacological mitigators of radiation lethality that would be effective particularly if administered after irradiation. We show here that giving female C57BL/6 mice a subcutaneous surgical incision after whole body exposure to an LD50/30 X-ray dose protects against radiation lethality and increases survival from 50% to over 90% (P = 0.0001). The increase in survival, at least in part, appears to be due to enhanced recovery of hematopoiesis, notably red blood cells, neutrophils and platelets. While a definitive mechanism has yet to be elucidated, we propose that this approach may be used to identify potentially novel mechanisms and pathways that could aid in the development of novel pharmacological radiation countermeasures. PMID:24811864

  19. Cognitive and physiological effects of an acute physical activity intervention in elementary school children

    PubMed Central

    Jäger, Katja; Schmidt, Mirko; Conzelmann, Achim; Roebers, Claudia M.

    2014-01-01

    The aim of the present study was to investigate the effects of an acute physical activity intervention that included cognitive engagement on executive functions and on cortisol level in young elementary school children. Half of the 104 participating children (6–8 years old) attended a 20-min sport sequence, which included cognitively engaging and playful forms of physical activity. The other half was assigned to a resting control condition. Individual differences in children's updating, inhibition, and shifting performance as well as salivary cortisol were assessed before (pre-test), immediately after (post-test), and 40 min after (follow-up) the intervention or control condition, respectively. Results revealed a significantly stronger improvement in inhibition in the experimental group compared to the control group, while it appeared that acute physical activity had no specific effect on updating and shifting. The intervention effect on inhibition leveled out 40 min after physical activity. Salivary cortisol increased significantly more in the experimental compared to the control group between post-test and follow-up and results support partly the assumed inverted U-shaped relationship between cortisol level and cognitive performance. In conclusion, results indicate that acute physical activity that includes cognitive engagement may have immediate positive effects on inhibition, but not necessarily on updating and shifting in elementary school children. This positive effect may partly be explained through cortisol elevation after acute physical activity. PMID:25566148

  20. A Multivariate Model of Stakeholder Preference for Lethal Cat Management

    PubMed Central

    Wald, Dara M.; Jacobson, Susan K.

    2014-01-01

    Identifying stakeholder beliefs and attitudes is critical for resolving management conflicts. Debate over outdoor cat management is often described as a conflict between two groups, environmental advocates and animal welfare advocates, but little is known about the variables predicting differences among these critical stakeholder groups. We administered a mail survey to randomly selected stakeholders representing both of these groups (n = 1,596) in Florida, where contention over the management of outdoor cats has been widespread. We used a structural equation model to evaluate stakeholder intention to support non-lethal management. The cognitive hierarchy model predicted that values influenced beliefs, which predicted general and specific attitudes, which in turn, influenced behavioral intentions. We posited that specific attitudes would mediate the effect of general attitudes, beliefs, and values on management support. Model fit statistics suggested that the final model fit the data well (CFI = 0.94, RMSEA = 0.062). The final model explained 74% of the variance in management support, and positive attitudes toward lethal management (humaneness) had the largest direct effect on management support. Specific attitudes toward lethal management and general attitudes toward outdoor cats mediated the relationship between positive (p<0.05) and negative cat-related impact beliefs (p<0.05) and support for management. These results supported the specificity hypothesis and the use of the cognitive hierarchy to assess stakeholder intention to support non-lethal cat management. Our findings suggest that stakeholders can simultaneously perceive both positive and negative beliefs about outdoor cats, which influence attitudes toward and support for non-lethal management. PMID:24736744

  1. Effects of acute and chronic psychological stress on isolated islets' insulin release

    PubMed Central

    Zardooz, Homeira; Zahediasl, Saleh; Rostamkhani, Fatemeh; Farrokhi, Babak; Nasiraei, Shiva; Kazeminezhad, Behrang; Gholampour, Roohollah

    2012-01-01

    This study investigated the effects of acute and chronic psychological stress on glucose-stimulated insulin secretion from isolated pancreatic islets. Male Wistar rats were divided into two control and stressed groups; each further was allocated into fed and fasted groups. Stress was induced by communication box for one (acute), fifteen and thirty (chronic) days. After islet isolation, their number, size and insulin output were assessed. Plasma corticosterone level was determined. In fasted animals, acute stress increased basal and post stress plasma corticosterone level, while 30 days stress decreased it compared to day 1. In fed rats, acute stress increased only post stress plasma corticosterone concentration, however, after 15 days stress, it was decreased compared to day 1. Acute stress did not change insulin output; however, the insulin output was higher in the fed acutely stressed rats at 8.3 and 16.7 mM glucose than fasted ones. Chronic stress increased insulin output on day 15 in the fasted animals but decreased it on day 30 in the fed animals at 8.3 and 16.7 mM glucose. In the fasted control rats insulin output was lower than fed ones. In the chronic stressed rats insulin output at 8.3 and 16.7 mM glucose was higher in the fasted than fed rats. The number of islets increased in the fasted rats following 15 days stress. This study indicated that the response of the isolated islets from acute and chronically stressed rats are different and depends on the feeding status.

  2. Acclimation and acute temperature effects on population differences in oxidative phosphorylation.

    PubMed

    Baris, Tara Z; Crawford, Douglas L; Oleksiak, Marjorie F

    2016-01-15

    Temperature changes affect metabolism on acute, acclamatory, and evolutionary time scales. To better understand temperature's affect on metabolism at these different time scales, we quantified cardiac oxidative phosphorylation (OxPhos) in three Fundulus taxa acclimated to 12 and 28°C and measured at three acute temperatures (12, 20, and 28°C). The Fundulus taxa (northern Maine and southern Georgia F. heteroclitus, and a sister taxa, F. grandis) were used to identify evolved changes in OxPhos. Cardiac OxPhos metabolism was quantified by measuring six traits: state 3 (ADP and substrate-dependent mitochondrial respiration); E state (uncoupled mitochondrial activity); complex I, II, and IV activities; and LEAK ratio. Acute temperature affected all OxPhos traits. Acclimation only significantly affected state 3 and LEAK ratio. Populations were significantly different for state 3. In addition to direct effects, there were significant interactions between acclimation and population for complex I and between population and acute temperature for state 3. Further analyses suggest that acclimation alters the acute temperature response for state 3, E state, and complexes I and II: at the low acclimation temperature, the acute response was dampened at low assay temperatures, and at the high acclimation temperature, the acute response was dampened at high assay temperatures. Closer examination of the data also suggests that differences in state 3 respiration and complex I activity between populations were greatest between fish acclimated to low temperatures when assayed at high temperatures, suggesting that differences between the populations become more apparent at the edges of their thermal range. PMID:26582639

  3. Chronic hyperleptinemia induces resistance to acute natriuretic and NO-mimetic effects of leptin.

    PubMed

    Bełtowski, Jerzy; Wójcicka, Grazyna; Jamroz-Wiśniewska, Anna; Wojtak, Andrzej

    2010-01-01

    Apart from controlling energy balance, leptin, secreted by adipose tissue, is also involved in the regulation of cardiovascular function. Previous studies have demonstrated that acutely administered leptin stimulates natriuresis and vascular nitric oxide (NO) production and that these effects are impaired in obese animals. However, the mechanism of resistance to leptin is not clear. Because obesity is associated with chronically elevated leptin, we examined if long-term hyperleptinemia impairs acute effects of leptin on sodium excretion and NO production in the absence of obesity. Hyperleptinemia was induced in lean rats by administration of exogenous leptin at a dose of 0.5mg/kg/day for 7 days, and then acute effect of leptin (1mg/kg i.v.) was studied under general anesthesia. Leptin increased fractional sodium excretion and decreased Na(+),K(+)-ATPase activity in the renal medulla. In addition, leptin increased the level of NO metabolites and cyclic GMP in plasma and aortic wall. These acute effects of leptin were impaired in hyperleptinemic animals. In both control and hyperleptinemic groups the effect of leptin on Na(+) excretion and renal Na(+),K(+)-ATPase was abolished by phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, but not by protein kinase B/Akt inhibitor, triciribine,. In contrast, acute effect of leptin on NO metabolites and cGMP was abolished by triciribine but not by wortmannin. Leptin stimulated Akt phosphorylation at Ser(473) in aortic tissue but not in the kidney, and this effect was comparable in control and hyperleptinemic groups. These results suggest that hyperleptinemia may mediate "renal" and "vascular" leptin resistance observed in obesity. PMID:19854228

  4. Cholescintigraphy in acute acalculous cholecystitis

    SciTech Connect

    Ramanna, L.; Brachman, M.B.; Tanasescu, D.E.; Berman, D.S.; Waxman, A.D.

    1984-08-01

    Acute acalculous cholecystitis is a relatively rare but potentially lethal condition if not treated promptly. Since stones are not present, diagnostic procedures such as ultrasound or other radiological procedures are frequently not helpful. Tc-99m iminodiacetic acid scan results were analyzed in 11 proven cases of acute acalculous cholecystitis. All had positive tests with nonvisualization of the gallbladder giving a sensitivity of 100%. Tc-99m iminodiacetic acid cholescintigraphy is a highly reliable test and is easily performed even in acutely ill patients and should be the test of choice in all patients predisposed to and suspected of acute acalculous cholecystitis.

  5. Comparative Effectiveness Research: Alternatives to "Traditional" Computed Tomography Use in the Acute Care Setting.

    PubMed

    Moore, Christopher L; Broder, Joshua; Gunn, Martin L; Bhargavan-Chatfield, Mythreyi; Cody, Dianna; Cullison, Kevin; Daniels, Brock; Gans, Bradley; Kennedy Hall, M; Gaines, Barbara A; Goldman, Sarah; Heil, John; Liu, Rachel; Marin, Jennifer R; Melnick, Edward R; Novelline, Robert A; Pare, Joseph; Repplinger, Michael D; Taylor, Richard A; Sodickson, Aaron D

    2015-12-01

    Computed tomography (CT) scanning is an essential diagnostic tool and has revolutionized care of patients in the acute care setting. However, there is widespread agreement that overutilization of CT, where benefits do not exceed possible costs or harms, is occurring. The goal was to seek consensus in identifying and prioritizing research questions and themes that involve the comparative effectiveness of "traditional" CT use versus alternative diagnostic strategies in the acute care setting. A modified Delphi technique was used that included input from emergency physicians, emergency radiologists, medical physicists, and an industry expert to achieve this. PMID:26576033

  6. Self-regulation strategies may enhance the acute effect of exercise on smoking delay.

    PubMed

    Hatzigeorgiadis, Antonis; Pappa, Vassiliki; Tsiami, Anastasia; Tzatzaki, Theodora; Georgakouli, Kalliopi; Zourbanos, Nikos; Goudas, Marios; Chatzisarantis, Nikos; Theodorakis, Yannis

    2016-06-01

    The present study examined the acute effect of a moderate intensity aerobic exercise session combined with self-regulation on smoking delay in physically inactive smokers. Participants were 11 adults (5 males and 6 females) that completed three experimental conditions: control, exercise, and exercise using self-regulation strategies (SR). Following the experimental treatment smoking for the two exercise conditions delayed significantly more than for the control condition; in addition exercise SR delayed smoking marginally more that the plain exercise condition. Findings supported previous research that acute exercise reduces cravings to smoke, and suggests that the use of self-regulation strategies may strengthen exercise for smoking cessation interventions. PMID:26851493

  7. ACUTE BEHAVORIAL EFFECTS FROM EXPOSURE TO TWO-STROKE ENGINE EXHAUST

    EPA Science Inventory

    Benefits of changing from two-stroke to four-stroke engines (and other remedial requirements) can be evaluated (monetized) from the standpoint of acute behavioral effects of human exposure to exhaust from these engines. The monetization process depends upon estimates of the magn...

  8. Antinociceptive, antiinflammatory and acute toxicity effects of Salvia leriifolia Benth seed extract in mice and rats.

    PubMed

    Hosseinzadeh, Hossein; Haddadkhodaparast, Mohammad H; Arash, Ali R

    2003-04-01

    The antinociceptive and antiinflammatory effects as well as the acute toxicity of Salvia leriifolia aqueous seed extract were studied in mice and rats. Antinociceptive activity was assessed using the hot-plate and tail flick tests. The effect on acute inflammation was studied using vascular permeability increased by acetic acid and xylene-induced ear oedema in mice. The activity against chronic inflammation was assessed using the cotton pellet test in rats. The LD(50) of the extract was found to be 19.5 g/kg (i.p.) in mice. The aqueous seed extract showed significant and dose-dependent (1.25-10 g/kg) antinociceptive activity over 7 h, and was inhibited by naloxone pretreatment. Significant and dose-dependent (2.5-10 g/kg) activity was observed against acute inflammation induced by acetic acid and in the xylene ear oedema test. In the chronic inflammation test the extract (2.5-5 g/kg) showed significant and dose-dependent antiinflammatory activity. The aqueous seed extract of S. leriifolia may therefore have supraspinal antinociceptive effects which may be mediated by opioid receptors, and showed considerable effects against acute and chronic inflammation. PMID:12722156

  9. The effect of acute haemorrhage in the dog and man on plasma-renin concentration

    PubMed Central

    Brown, J. J.; Davies, D. L.; Lever, A. F.; Robertson, J. I. S.; Verniory, A.

    1966-01-01

    1. The effect of acute haemorrhage on the plasma renin concentration was studied in the dog and man. 2. Plasma-renin concentration was regularly increased after the larger bleeds; after the smaller haemorrhages plasma-renin concentration remained unchanged. 3. The results are discussed in relation to current hypotheses concerning the control of renin and aldosterone secretion. PMID:4287431

  10. Acute bilateral glaucoma and panuveitis as a side effect of topiramate for weight loss treatment.

    PubMed

    Pikkel, Yoav Yechezkel

    2014-01-01

    A 54-year-old male patient presented to our clinic with acute angle-closure glaucoma and panuveitis in both eyes after being treated with topiramate for binge eating and obesity. This case report emphasises the hazardous side effects of treatment with topiramate with unusual indication and the precaution a caretaker must take when treating a patient. PMID:24744070

  11. Time Scale Effects in Acute Association between Air-Pollution and Mortality

    EPA Science Inventory

    We used wavelet analysis and generalized additive models (GAM) to study timescale effects in the acute association between mortality and air-pollution. Daily averages of measured NO2 concentrations in the metropolitan Paris area are used as indicators of human exposure...

  12. The Chronic and Acute Effects of Exercise Upon Selected Blood Measures.

    ERIC Educational Resources Information Center

    Roitman, J. L.; Brewer, J. P.

    This study investigated the effects of chronic and acute exercise upon selected blood measures and indices. Nine male cross-country runners were studied. Red blood count, hemoglobin, and hematocrit were measured using standard laboratory techniques; mean corpuscular volume (MCV), mean corpuscular hemoglobin, and mean corpuscular hemoglobin…

  13. State/Trait Anxiety and Anxiolytic Effects of Acute Physical Exercises

    ERIC Educational Resources Information Center

    Guszkowska, Monika

    2009-01-01

    Study aim: To determine anxiolytic effects of acute physical exertions in relation to the initial anxiety state and trait in women. Material and methods: A group of 163 women aged 16-56 years, attending fitness clubs in Warsaw, participated in the study. They selected a single exercise to perform--strength, aerobic or mixed, lasting 30 to over 60…

  14. NEUROCHEMICAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL ACUTE EXPOSURE TO CHLORPYRIFOS IN RATS.

    EPA Science Inventory

    Lots of information is available surrounding the acute toxicity of anticholinesterase pesticides, but these have been very few detailed studies on the chronic effects of these pesticides. Humans are exposed on a chronic basis and some humans believe that have been affected advers...

  15. EFFECT OF ACUTE MATERNAL TOXICITY ON FETAL DEVELOPMENT IN THE MOUSE

    EPA Science Inventory

    The effects of acute alterations in maternal health status upon fetal development were assessed following exposure of pregnant CD-1 mice on day 8 of gestation to one of ten chemicals at a dose calculated to be the maternal LD10 or LD40. The dams were killed on day 18 of gestation...

  16. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats

    EPA Science Inventory

    Acute ozone exposure increases circulating stress hormones and induces peripheral metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for ozone-induced systemic metabolic effects and lung injury. Male Wis...

  17. Neurobehavorial effects of acute exposure to four solvents: meta-abalyses

    EPA Science Inventory

    Meta-and re-analyses of the available data for the neurobehavioral effects of acute inhalation exposure to toluene were reported by Benignus et al. (2007). The present study was designed to test the generality of the toluene results in as many other solvents as possible by furthe...

  18. COMPARISON OF ACUTE NEUROBEHAVIORAL EFFECTS OF N-METHYL CARBAMATE INSECTICIDES.

    EPA Science Inventory

    The acute neurobehavioral and cholinesterase (ChE)-inhibiting effects of N-methyl carbamate insecticides have not been systematically compared. We evaluated five carbamates - carbaryl (CB), propoxur (PP), oxamyl (OM), methomyl (MM), and methiocarb (MC). Adult male Long-Evans ra...

  19. Acute Alcohol Effects on Repetition Priming and Word Recognition Memory with Equivalent Memory Cues

    ERIC Educational Resources Information Center

    Ray, Suchismita; Bates, Marsha E.

    2006-01-01

    Acute alcohol intoxication effects on memory were examined using a recollection-based word recognition memory task and a repetition priming task of memory for the same information without explicit reference to the study context. Memory cues were equivalent across tasks; encoding was manipulated by varying the frequency of occurrence (FOC) of words…

  20. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats#

    EPA Science Inventory

    Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats ...

  1. TOWARD COST-BENEFIT ANALYSIS OF ACUTE BEHAVIORAL EFFECTS OF TOLUENE IN HUMANS

    EPA Science Inventory

    There is increasing interest in being able to express the consequences of exposure to potentially toxic compounds in monetary terms in order to evaluate potential cost-benefit relationships of controlling exposure. Behavioral effects of acute toluene exposure could be subjected ...

  2. Acute effects of all-trans-retinoic acid in ischemic injury

    Technology Transfer Automated Retrieval System (TEKTRAN)

    All-trans-retinoic acid (ATRA) is a vitamin A derivative that is important in neuronal patterning, survival, and neurite outgrowth. We investigated the relatively acute effects of ATRA (100 nM and 1 µM) on cell swelling in ischemic injury and on key features hypothesized to contribute to cell swelli...

  3. Chinese Head Trauma Data Bank: Effect of Hyperthermia on the Outcome of Acute Head Trauma Patients

    PubMed Central

    Li, Jin

    2012-01-01

    Abstract Hyperthermia may accentuate the detrimental consequences of brain injury and worsen the outcome of patients with acute head trauma, especially severe traumatic brain injury (TBI). We explored the effect of different magnitudes and durations of hyperthermia in the first 3 days after injury on the outcome of 7145 patients with acute head trauma, including 1626 with severe TBI. The differences in mortality and unfavorable outcome between the normothermia group, mild fever group, moderate fever group, and high fever group were statistically significant (p<0.001). The mortality and unfavorable outcome of severe TBI patients in the groups also differed significantly (p<0.001). The mortality and unfavorable outcome of patients with 1 day, 2 days, and 3 days of high fever were significantly increased (p<0.01). Our data strongly indicate that both degree and duration of early post-trauma hyperthermia are closely correlated with the outcome of acute TBI patients, especially severely injured ones, which indicates that hyperthermia may play a detrimental role in the delayed mechanisms of damage after acute TBI. Prevention of early hyperthermia after acute head trauma is therefore essential to the management of TBI patients. PMID:22026424

  4. Effect of Early Statin Treatment in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction

    PubMed Central

    Sim, Doo Sun; Cho, Kyung Hoon; Ahn, Youngkeun; Kim, Young Jo; Chae, Shung Chull; Hong, Taek Jong; Seong, In Whan; Chae, Jei Keon; Kim, Chong Jin; Cho, Myeong Chan; Rha, Seung-Woon; Bae, Jang Ho; Seung, Ki Bae; Park, Seung Jung

    2013-01-01

    Background and Objectives The benefit of early statin treatment following acute myocardial infarction (MI) complicated with cardiogenic shock (CS) has not been well studied. We sought to assess the effect of early statin therapy in patients with CS complicating acute MI. Subjects and Methods We studied 553 statin-naive patients with acute MI and CS (Killip class IV) who underwent revascularization therapy between November 2005 and January 2008 at 51 hospitals in the Korea Acute Myocardial Infarction Registry. Patients were divided into 2 groups: those who received statins during hospitalization (n=280) and those who did not (n=273). The influence of statin treatment on a 12-month clinical outcome was examined using a matched-pairs analysis (n=200 in each group) based on the propensity for receiving statin therapy during hospitalization. Results Before adjustment, patients receiving statin, compared to those not receiving statin, had a more favorable clinical profile, were less likely to suffer procedural complications, and more likely to receive adequate medical therapy. Patients receiving statin had lower unadjusted in-hospital mortality and composite rate of mortality, MI, and repeat revascularization at 12 months, which remained significantly lower after adjustment for patient risk, procedural characteristics, and treatment propensity. Conclusion In CS patients with acute MI undergoing revascularization therapy, early statin treatment initiated during hospitalization was associated with lower rates of in-hospital death and 12-month adverse cardiac events. PMID:23508129

  5. The effect of obesity on inflammatory cytokine and leptin production following acute mental stress.

    PubMed

    Caslin, H L; Franco, R L; Crabb, E B; Huang, C J; Bowen, M K; Acevedo, E O

    2016-02-01

    Obesity may contribute to cardiovascular disease (CVD) risk by eliciting chronic systemic inflammation and impairing the immune response to additional stressors. There has been little assessment of the effect of obesity on psychological stress, an independent risk factor for CVD. Therefore, it was of interest to examine interleukin-6, tumor necrosis factor-α, interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1Ra), and leptin following an acute mental stress task in nonobese and obese males. Twenty college-aged males (21.3 ± 0.56 years) volunteered to participate in a 20-min Stroop color-word and mirror-tracing task. Subjects were recruited for obese (body mass index: BMI > 30) and nonobese (BMI < 25) groups, and blood samples were collected for enzyme-linked immunosorbent assay analysis. The acute mental stress task elicited an increase in heart rate, catecholamines, and IL-1β in all subjects. Additionally, acute mental stress increased cortisol concentrations in the nonobese group. There was a significant reduction in leptin in obese subjects 30 min posttask compared with a decrease in nonobese subjects 120 min posttask. Interestingly, the relationship between the percent change in leptin and IL-1Ra at 120 min posttask in response to an acute mental stress task was only observed in nonobese individuals. This is the first study to suggest that adiposity in males may impact leptin and inflammatory signaling mechanisms following acute mental stress. PMID:26511907

  6. Antibodies against recombinant catalytic domain of lethal toxin of Clostridium sordellii neutralize lethal toxin toxicity in HeLa cells.

    PubMed

    Arya, Preetika; Ponmariappan, S; Singh, Lokendra; Prasad, G B K S

    2013-02-01

    Lethal toxin of Clostridium sordellii (MLD 150 ng/kg) is one of the most potent Clostridial toxins and is responsible for most of the diseases including sudden death syndrome in cattle, sheep and toxic shock syndrome, necrotizing faciitis, neonatal omphalitis and gangrene in humans. Lethal toxin (TcsL) is a single chain protein of about 270 kDa. In the present study, 1.6 kb DNA fragment encoding for the catalytic domain of TcsL was PCR amplified, cloned in pQE30 UA vector and expressed in E. coli SG 13009. The expression of recombinant lethal toxin protein (rTcsL) was optimized and it was purified under native conditions using a single step Ni-NTA affinity chromatography. The purified recombinant protein was used for the production of polyclonal antibodies in mice and rabbit. The raised antibodies reacted specifically with the purified rTcsL and intact native lethal toxin on Western blot. The biological activity of the recombinant protein was tested in HeLa cells where it showed the cytotoxicity. Further, the polyclonal antibodies were used for in-vitro neutralization of purified rTcsL, acid precipitated C. sordellii and C. difficile native toxins in HeLa cells. Mice and rabbit anti-rTcsL sera effectively neutralized the cytotoxicity of rTcsL and C. sordellii native toxin but it did not neutralize the cytotoxicity of C. difficile toxin in HeLa cells. PMID:22894159

  7. The effect of chronic vs. acute injection of vasopressin on animal learning and memory.

    PubMed

    Hamburger-Bar, R; Klein, A; Belmaker, R H

    1985-01-01

    The effect of chronic and acute treatment with DDAVP, a vasopressin analog, was studied in 2 month old male rats, using an active avoidance test in a shuttle box. The experiment lasted 6 weeks: an acquisition period of 4 weeks and an extinction period of 2 weeks. Rats were treated one hour before behavioral testing 3 times a week for 6 weeks with either DDAVP 20 micrograms/rat/day for the whole period (chronic group) or with DDAVP for the first week and again once only on the first day of the extinction period (acute group) or with saline. Chronic treatment with DDAVP resulted in better acquisition and in a marked retardation of extinction compared with the acute treatment group. These results were obtained both in normal rats and in rats pretreated at age 5 days of life with intracisternal 6-OH dopamine. PMID:3991361

  8. Effect of acute exercise and cardiovascular fitness on cognitive function: an event-related cortical desynchronization study.

    PubMed

    Chang, Yu-Kai; Chu, Chien-Heng; Wang, Chun-Chih; Song, Tai-Fen; Wei, Gao-Xia

    2015-03-01

    This study aimed to clarify the effects of acute exercise and cardiovascular fitness on cognitive function using the Stroop test and event-related desynchronization (ERD) in an aged population. Old adults (63.10 ± 2.89 years) were first assigned to either a high-fitness or a low-fitness group, and they were then subjected to an acute exercise treatment and a reading control treatment in a counterbalanced order. Alpha ERD was recorded during the Stroop test, which was administered after both treatments. Acute exercise improved cognitive performance regardless of the level of cognition, and old adults with higher fitness levels received greater benefits from acute exercise. Additionally, acute exercise, rather than overall fitness, elicited greater lower and upper alpha ERDs relative to the control condition. These findings indirectly suggest that the beneficial effects of acute exercise on cognitive performance may result from exercise-induced attentional control observed during frontal neural excitation. PMID:25308605

  9. Lethal and teratogenic effects of long-term low-intensity radio frequency radiation at 428 MHz on developing chick embryo

    SciTech Connect

    Saito, K.; Suzuki, K.; Motoyoshi, S. )

    1991-06-01

    Exposure of developing chick embryos to 428 MHz radio frequency (RF) radiation at a power density of 5.5 mW/cm2 for more than 20 days resulted in embryolethal and/or teratogenic effects and delayed hatching. These adverse biological effects were not due to any thermal effect of the RF radiation. The authors have demonstrated teratogenicity in the chick embryo as a result of protracted low-dose RF irradiation.

  10. The effect of sodium tetraborate and alum in the management of acute childhood diarrhoea.

    PubMed

    Aung, M M; U, P P

    1986-03-01

    The effect of oral rehydration (OR) has been well established in the management of dehydration in acute childhood diarrhoea. Many authors have been trying to find additives of all types which would be effective in retaining oral fluids and promoting their active absorption into the circulation. Any agent which will effectively reduce oral rehydration requirements should be considered for prospective studies. Amongst the traditional medicines, it was noticed that sodium tetraborate (borax) and alum reduced appreciably the fluid requirement in many cases of acute childhood diarrhoea. This traditional usage of these chemicals without any noticeable side effects has been described for centuries. During preliminary observations on 26 of our children given these salts no side effects were detected. PMID:2428288

  11. The effect of an acute increase in central blood volume on the response of cerebral blood flow to acute hypotension.

    PubMed

    Ogoh, Shigehiko; Hirasawa, Ai; Sugawara, Jun; Nakahara, Hidehiro; Ueda, Shinya; Shoemaker, J Kevin; Miyamoto, Tadayoshi

    2015-09-01

    The purpose of the present study was to examine whether the response of cerebral blood flow to an acute change in perfusion pressure is modified by an acute increase in central blood volume. Nine young, healthy subjects voluntarily participated in this study. To measure dynamic cerebral autoregulation during normocapnic and hypercapnic (5%) conditions, the change in middle cerebral artery mean blood flow velocity was analyzed during acute hypotension caused by two methods: 1) thigh-cuff occlusion release (without change in central blood volume); and 2) during the recovery phase immediately following release of lower body negative pressure (LBNP; -50 mmHg) that initiated an acute increase in central blood volume. In the thigh-cuff occlusion release protocol, as expected, hypercapnia decreased the rate of regulation, as an index of dynamic cerebral autoregulation (0.236 ± 0.018 and 0.167 ± 0.025 s(-1), P = 0.024). Compared with the cuff-occlusion release, the acute increase in central blood volume (relative to the LBNP condition) with LBNP release attenuated dynamic cerebral autoregulation (P = 0.009). Therefore, the hypercapnia-induced attenuation of dynamic cerebral autoregulation was not observed in the LBNP release protocol (P = 0.574). These findings suggest that an acute change in systemic blood distribution modifies dynamic cerebral autoregulation during acute hypotension. PMID:26159757

  12. [Effect of shengmaisan on serum lipid peroxidation in acute viral myocarditis].

    PubMed

    Zhao, M H; Rong, Y Z; Lu, B J

    1996-03-01

    The effect of Shengmaisan (SMS) on 62 acute viral myocarditis patients and its peroxidation damage was studied. The results revealed that the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in blood were decreased and the content of malondialdehyde (MDA) in plasma was increased in acute viral myocarditis patients in comparison with the healthy controls (P < 0.001). 62 acute viral myocarditis patients were divided into two groups: SMS group and placebo group. After treatment, both SOD and GSH-Px activities were increased and the level of MDA decreased (P < 0.001) in SMS group, while those in placebo group were not changed (P < 0.05). The results suggested that the myocardial damage of viral myocarditis is closely related with lipid peroxidation SMS acts as an effective free radical scavenger and anti-lipid peroxidation drug. SMS could prevent the damage of myocardia and might be taken as one of the effective therapeutic methods in treatment of acute viral myocarditis. PMID:9208534

  13. Acute effects of mercuric chloride on glycogen and protein content of zebra fish, Danio rerio.

    PubMed

    Vutukuru, S S; Basani, Kalpana

    2013-03-01

    Presence of mercury and other heavy metals above permissible levels in water bodies across the globe is posing a serious threat to aquatic biota and public health. Occurrence of mercury above the permissible limits in the aquatic ecosystem of Hyderabad city is well established. In this context, we carried out static- renewal bioassays on the zebra fish, Danio rerio exposed to different concentrations of mercuric chloride, and the 96-h median lethal concentration (LC50) was found to be 0.077 mgl(-1). Behavioral manifestations like loss of scales, hyper secretion of mucus, surfacing and darting movements, loss of balance, irregular swimming patterns were noticed in the fish exposed to 0.077 mgl(-1). The present study also examined the toxic effects of mercuric chloride on vital biochemical constituent's total glycogen and total protein. Significant decrease (p < 0.001) in glycogen and protein content of fish exposed to 0.077 mgl(-1). PMID:24620592

  14. Effect of acute heat stress on plant nutrient metabolism proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Abrupt heating decreased the levels (per unit total root protein) of all but one of the nutrient metabolism proteins examined, and for most of the proteins, effects were greater for severe vs. moderate heat stress. For many of the nutrient metabolism proteins, initial effects of heat (1 d) were r...

  15. The Effect of Vigorous Intensity Acute Exercise on Executive Function

    ERIC Educational Resources Information Center

    Phillips, David Spencer

    2012-01-01

    The effect of physical activity (PA) and consequent influence on cognition within adult seniors has been widely published. However, there is a paucity of causal research relating PA and cognition to schoolchildren within an authentic setting. Also, little is known about the required intensity and dosage of PA to effect executive function (EF)…

  16. Lethally Innocuous Visual Display Units.

    ERIC Educational Resources Information Center

    Cawkell, A. E.

    1991-01-01

    Examines conflicting studies which report on the effects of Visual Display Units (VDU) on health. Five aspects of alleged VDU effects are discussed: (1) radiation or emission effects; (2) visual effects; (3) postural effects; (4) effects on the arms and fingers; and (5) ultrasonic noise from scanning components. (36 references) (MAB)

  17. The Effects of Acute Exercise and Exercise Training on Plasma Homocysteine: A Meta-Analysis

    PubMed Central

    Deminice, Rafael; Ribeiro, Diogo Farias; Frajacomo, Fernando Tadeu Trevisan

    2016-01-01

    Background Although studies have demonstrated that physical exercise alters homocysteine levels in the blood, meta-analyses of the effects of acute exercise and exercise training on homocysteine blood concentration have not been performed, especially regarding the duration and intensity of exercise, which could affect homocysteine levels differently. Objective The aim of this meta-analysis was to ascertain the effects of acute exercise and exercise training on homocysteine levels in the blood. Method A review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses using the online databases PubMed, SPORTDiscus, and SciELO to identify relevant studies published through June 2015. Review Manager was used to calculate the effect size of acute exercise and exercise training using the change in Hcy plasmaserum concentration from baseline to post-acute exercise and trained vs. sedentary control groups, respectively. Weighted mean differences were calculated using random effect models. Results Given the abundance of studies, acute exercise trials were divided into two subgroups according to exercise volume and intensity, whereas the effects of exercise training were analyzed together. Overall, 22 studies with a total of 520 participants indicated increased plasma homocysteine concentration after acute exercise (1.18 μmol/L, 95% CI: 0.71 to 1.65, p < .01). Results of a subgroup analysis indicated that either long-term exercise of low-to-moderate intensity (1.39 μmol/L, 95% CI: 0.9 to 1.89, p < .01) or short-term exercise of high intensity (0.83 μmol/L, 95% CI: 0.19 to 1.40, p < .01) elevated homocysteine levels in the blood. Increased homocysteine induced by exercise was significantly associated with volume of exercise, but not intensity. By contrast, resistance training reduced plasma homocysteine concentration (-1.53 μmol/L, 95% CI: -2.77 to -0.28, p = .02), though aerobic training did not. The cumulative

  18. Photoinduced lethal and sublethal toxicity of retene, a polycyclic aromatic hydrocarbon derived from resin acid, to coregonid larvae.

    PubMed

    Vehniäinen, Eeva-Riikka; Häkkinen, Jani; Oikari, Aimo

    2003-12-01

    A comparative investigation on the acute phototoxicity of retene to vendace (Coregonus albula) and whitefish (C. lavaretus), both having pelagial larvae in spring, was conducted. To test the concept of early warning of sublethal biomarkers in relation to lethality to posthatch stages, we examined the effects of ultraviolet-B (UV-B) and retene on the levels of cytochrome P4501A (CYP1A) and heat shock protein 70 (HSP70) by exposing the animals to elevated levels of these factors for 48 and 72 h, respectively. Whereas UV-B and retene on their own were not lethal, simultaneous retene and UV-B exposure caused very high mortality to both species. The median lethal concentration (LC50; i.e., the concentration at which half of the larvae died) of retene as a precursor was 41 g/L for vendace and 15 to 16 microg/L, depending on the UV-B dose, for whitefish. Retene evoked substantial induction of CYP1A in larvae of both species, and UV-B induced CYP1A in whitefish. In vendace, no effect on HSP70 levels by any factor was observed. In whitefish, however, UV-B radiation and water retene alone upregulated HSP70, but no additive response was detected. The CYPIA is a biomarker of exposure to retene in both species. The HSP70 is an early warning signal of UV-B exposure in whitefish. As a species, vendace appears to be more resistant than whitefish to the phototoxicity of retene, as indicated by the higher tolerance. PMID:14713041

  19. Protective effects of intravenous immunoglobulin and antimicrobial agents on acute pneumonia in leukopenic mice.

    PubMed

    Shimizu, Masaru; Katoh, Hideya; Hamaoka, Saeko; Kinoshita, Mao; Akiyama, Koichi; Naito, Yoshifumi; Sawa, Teiji

    2016-04-01

    Multi-drug resistant Pseudomonas aeruginosa causes the type of acute lung injury that is strongly associated with bacteremia, sepsis, and mortality, especially under immunocompromised conditions. Although administration of immunoglobulin solution is an applicable immunotherapy in immunocompromised patients, efficacy of immunoglobulin administration against multi-drug resistant P. aeruginosa pneumonia has not been well evaluated. In this study, we investigated the effectiveness of prophylactic administration of immunoglobulin solution (IVIG) in comparison with that of other types of antimicrobial agents, such as anti-PcrV IgG, piperacillin/tazobactam, or colistin in an immunocompromised mouse model of P. aeruginosa pneumonia. Colistin was the most effective agent for preventing acute lung injury, bacteremia, cytokinemia, and sepsis. Among the four tested antimicrobial agents, after colistin, anti-PcrV IgG and IVIG were the most effective at protecting mice from mortality. Piperacillin/tazobactam did not prevent acute lung injury or bacteremia; rather, it worsened lung histology. The data suggest that using an agent for which a positive result in an in vitro susceptibility test has been obtained may not always prevent acute lung injury in a leukopenic host infected with P. aeruginosa. Clinicians should consider the possibility of discrepancies between in vitro and in vivo tests because the absence of in vitro bactericidal activity in an antimicrobial agent is not always a reliable predictor of its lack of ability to eradicate bacteria in vivo, even in immunocompromised hosts. Based on our findings, the potential protective effects of IVIG against the acute lung injury induced by P. aeruginosa should be reevaluated. PMID:26867796

  20. Effects of copper on the acute cortisol response and associated physiology in rainbow trout.

    PubMed

    Tellis, Margaret S; Alsop, Derek; Wood, Chris M

    2012-03-01

    The aim of this study was to determine the effects of chronic waterborne copper (Cu) exposure on the acute stress-induced cortisol response and associated physiological consequences in rainbow trout (Oncorhynchus mykiss). Trout were exposed to 30 μg Cu/L in moderately hard water (120 mg/L as CaCO(3)) for 40 days, following which time the acute cortisol response was examined with a series of stressors. At 40 days, a 65% increase in Cu was observed in the gill, but no accumulation was observed in the liver, brain or head kidney. Stressors such as air exposure or confinement did not elicit an increase in circulating cortisol levels for Cu-exposed fish, in contrast to controls. However, this inhibitory effect on the acute cortisol response appeared to have few implications on the ability of Cu-exposed fish to maintain ion and carbohydrate homeostasis. For example, plasma Na(+), Ca(2+) and glucose levels as well as hepatic glycogen levels were the same post-stress in control and Cu-exposed fish. Trout were also challenged with exposure to 50% seawater for 48 h, where Cu-exposed trout maintained plasma Na(+), glucose and hepatic glycogen levels. However, Cu-exposed fish experienced decreased plasma K(+) levels throughout the Cu exposure and stress tests. In conclusion, chronic Cu exposure resulted in the abolition of an acute cortisol response post-stress. There was no Cu accumulation in the hypothalamus-pituitary-interrenal axis (HPI axis) suggesting this was not a direct toxic effect of Cu on the cortisol regulatory pathway. However, the lack of an acute cortisol response in Cu-exposed fish did not impair the ability of the fish to maintain ion and carbohydrate homeostasis. This effect on cortisol may be a strategy to reduce costs during the chronic stress of Cu exposure, and not endocrine disruption as a result of toxic injury. PMID:21964321

  1. Effect of Acute and Chronic Electroconvulsive Shock on 5-Hydroxytrypamine 6 Receptor Immunoreactivity in Rat Hippocampus

    PubMed Central

    Kim, Hyun Jung; Kang, Seungwoo; Kim, Hyun Ju; Choi, Sun-Hye; Shin, Seungkeun; Lee, Hyung Ha

    2014-01-01

    Electroconvulsive shock (ECS) induces not only an antidepressant effect but also adverse effects such as amnesia. One potential mechanism underlying both the antidepressant and amnesia effect of ECS may involve the regulation of serotonin (5-hydroxytryptamine) 6 (5-HT6) receptor, but less is known about the effects of acute ECS on the changes in 5-HT6 receptor expression in the hippocampus. In addition, as regulation of 5-HT receptor expression is influenced by the number of ECS treatment and by interval between ECS treatment and sacrifice, it is probable that magnitude and time-dependent changes in 5-HT6 receptor expression could be influenced by repeated ECS exposure. To explore this possibility, we observed and compared the changes of 5-HT6 receptor immunoreactivity (5-HT6 IR) in rat hippocampus at 1, 8, 24, or 72 h after the treatment with either a single ECS (acute ECS) or daily ECS for 10 days (chronic ECS). We found that acute ECS increased 5-HT6 IR in the CA1, CA3, and granule cell layer of hippocampus, reaching peak levels at 8 h and returning to basal levels 72 h later. The magnitude and time-dependent changes in 5-HT6 IR observed after acute ECS were not affected by chronic ECS. These results demonstrate that both acute and chronic ECS transiently increase the 5-HT6 IR in rat hippocampus, and suggest that the magnitude and time-dependent changes in 5-HT6 IR in the hippocampus appear not to be influenced by repeated ECS treatment. PMID:25258570

  2. Lethal infection by Bordetella pertussis mutants in the infant mouse model.

    PubMed Central

    Weiss, A A; Goodwin, M S

    1989-01-01

    Different aspects of lethal infection of infant mice with Bordetella pertussis were examined. Mutants deficient in vir-regulated genes were tested for the ability to cause a lethal infection in the infant mouse model. Adenylate cyclase toxin-hemolysin and pertussis toxin were required to cause a lethal infection at low doses. Mixed infection caused by challenging the mice with an equal number of pertussis toxin and adenylate cyclase toxin-hemolysin mutants at a dose at which neither alone was lethal was also unable to cause a lethal infection. Production of the filamentous hemagglutinin and the dermonecrotic toxin was not required to cause a lethal infection. Nine other mutants in vir-regulated genes whose phenotypes have yet to be determined were also tested. Only two of these mutants were impaired in the ability to cause a lethal infection. Expression of fimbriae does not appear to affect the dose required to cause a lethal infection; however, fimbrial expression was correlated with the later stages of a nonlethal, persistent infection. Growth of the bacteria in MgSO4, a condition which reversibly suppresses expression of the genes required for virulence, did not alter the ability of the bacteria to cause a lethal infection. Auxotrophic mutants deficient in leucine biosynthesis were as virulent as the parental strain; however, mutants deficient in methionine biosynthesis were less virulent. A B. parapertussis strain was much less effective in promoting a lethal infection than any of the wild-type B. pertussis strains examined. A persistent infection in the lungs was observed for weeks after challenge for mice given a sublethal dose of B. pertussis, and transmission from infected infants to the mother was never observed. PMID:2572561

  3. Acute effects of carbon monoxide on cardiac electrical stability. Research report, Sep 85-Jul 88

    SciTech Connect

    Verrier, R.L.; Mills, A.K.; Skornik, W.A.

    1990-01-01

    The objective of the project was to determine the effects of acute carbon monoxide exposure on cardiac electrical stability in the normal and ischemic heart of anesthetized and conscious dogs. Exposure (90 to 120 minutes) to relatively high levels of carbon monoxide, leading to carboxyhemoglobin concentrations of up to 20 percent, was without significant effect on ventricular electrical stability in laboratory dogs. This appears to be the case in the acutely ischemic heart as well as in the normal heart. Using a model involving partial coronary artery stenosis, no changes were found in either the cycle frequency of coronary blood flow oscillations or in platelet aggregability during carbon monoxide exposure. Also examined were the effects of carbon monoxide exposure in the conscious state in order to take into consideration possible adverse consequences mediated by the central nervous system. The study found no adverse effects on the cardiac-excitable properties in response to either a 2-hour- or 24-hour-exposure paradigm.

  4. Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

    SciTech Connect

    McGuire, S.A.

    1991-02-01

    The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m{sup 3} for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m{sup 3} (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs.

  5. Acute Toxic Effects of the Herbicide Formulation Focus(®) Ultra on Embryos and Larvae of the Moroccan Painted Frog, Discoglossus scovazzi.

    PubMed

    Wagner, Norman; Lötters, Stefan; Veith, Michael; Viertel, Bruno

    2015-11-01

    For regulatory and scientific purposes, there is a need to understand the sensitivity of a wider variety of wild species of amphibians and the sensitivities within their life stages to chemicals of widespread use such as herbicides. We investigated the acute toxic effects of the herbicide formulation Focus Ultra [with the active ingredient (a.i.) cycloxydim plus solvent naphtha and sodium dioctylsulphosuccinate as added substances] on embryos and early stage larvae of the Moroccan painted frog (Discoglossus scovazzi). Different clinical signs (twitching, convulsion, and narcosis) occurred at 40 and 80 mg/L in embryos (4 and 8 mg a.i./L) and narcotic effects (total immobilization or irregular escape responses) at 10, 15, and 20 mg/L in larvae (1, 1.5, and 2 mg a.i./L). Growth inhibition (total length), starting at 20 mg/L in embryos and 2.5 mg/L in larvae (2 and 0.25 mg a.i./L, respectively) was understood as sign of toxicity (retardation) and not as sign of teratogenicity. However, the connection to teratogenesis remained unclear though total length reduction occurred at concentrations <20 % of the 96-h LC50 value and at a minimum concentration that inhibits growth of only 17 % of the 96-h LC50 value. Starting at 20 mg/L, mortality in embryos significantly increased and at 15 mg/L in early larvae (2 and 1.5 mg a.i./L, respectively). Mortality of larvae was enhanced during the first 24 h of exposure to 15 and 20 mg/L (1.5 and 2 mg a.i./L). Morphology of the embryos remained unobtrusive. In contrary, axial malformations significantly increased in the early larvae starting at 10 mg/L (1 mg a.i./L), a concentration free of lethal effects. In all considered end points, larvae were significantly more sensitive than embryos, probably because of developmental and physiological properties or different exposure and bioavailability of the compound. Focus Ultra induced comparable lethal and immobilization effects in D. scovazzi as it does to standard test

  6. Acute and subacute effects of the ultrasonic blade and electrosurgery on nerve physiology

    PubMed Central

    Chen, Chaoyang; Kallakuri, Srinivasu; Cavanaugh, John M.; Broughton, Duan; Clymer, Jeffrey W.

    2015-01-01

    Abstract Ultrasonic blades have been shown to cause less acute electrophysiological damage when applied near nerves than monopolar electrosurgery (ES). This study was performed to determine whether the acute nerve damage observed for ES, as well as the relative lack of damage observed for ultrasonic dissection, extends through a subacute timeframe. Muscle incisions were made in rat with the Harmonic® Blade (HB) and ES at a distance of 2 mm from the sciatic nerve. Sham surgery was also performed which consisted of similar exposure of the sciatic nerve without use of an energized device. Electrophysiological function was assessed acutely over a 3-h period, and subacutely after a 7-day survival, by monitoring the sciatic nerve compound action potential (CAP), conduction velocity (CV), von Frey hair (VFH) stimulation force, leukocyte infiltration, and impaired axonal transport via β-amyloid precursor protein (β-APP) immunocytochemistry. During the acute period, ES produced significantly lower CAP and CV, and higher levels of leukocytes and β-APP than sham, whereas the ultrasonic blade was not significantly different from sham, and had significantly lower VFH force than ES. After the subacute survival, ES continued to display significantly lower CAP and CV, and higher levels of leukocytes and β-APP than sham, whereas ultrasonic blade had higher CAP and CV than sham, and lower VFH than ES. This study confirms that incisions made with an ultrasonic blade cause less acute nerve damage than monopolar ES, and are comparable to sham surgery at a distance of 2 mm from the sciatic nerve. The negative effects of electrosurgery extend through at least a 7-day survival period, whereas subacute recovery after application of the ultrasonic blade was comparable to that of sham surgery. For surgical procedures in the vicinity of vital nerves, use of the ultrasonic blade represents a lower risk than ES for both acute and subacute neural trauma. PMID:25812024

  7. Effects of central opiate and serotoninergic structures on heart rhythm during acute myocardial ischemia.

    PubMed

    Prokop'eva, E V; Pivovarov, Y I

    2001-12-01

    Electrostimulation of the central gray matter in the sylvian aqueduct and nucleus raphe magnus produced an antiarrhythmic effect during acute myocardial ischemia. Stimulation and blockade of opiate receptors in the central amygdaloid nucleus and lateral hypothalamus with dalargin and naloxone induced the same effect. Destruction of the central gray matter in the sylvian aqueduct and nucleus raphe magnus decreased electrical stability of ischemic myocardium. PMID:12152875

  8. The Acute Abdominal Aorta.

    PubMed

    Mellnick, Vincent M; Heiken, Jay P

    2015-11-01

    Acute disorders of the abdominal aorta are potentially lethal conditions that require prompt evaluation and treatment. Computed tomography (CT) is the primary imaging method for evaluating these conditions because of its availability and speed. Volumetric CT acquisition with multiplanar reconstruction and three-dimensional analysis is now the standard technique for evaluating the aorta. MR imaging may be useful for select applications in stable patients in whom rupture has been excluded. Imaging is indispensable for diagnosis and treatment planning, because management has shifted toward endoluminal repair. Acute abdominal aortic conditions most commonly are complications of aneurysms and atherosclerosis. PMID:26526434

  9. Toluene inducing acute respiratory failure in a spray paint sniffer

    PubMed Central

    Peralta, Diego P.; Chang, Aymara Y.

    2012-01-01

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

  10. Cross-shift study of acute respiratory effects in cement production workers.

    PubMed

    Aminian, Omid; Aslani, Maryam; Sadeghniiat Haghighi, Khosro

    2014-01-01

    Cement dust exposure is associated with increased respiratory impairment. As the major occupational hazard in the cement production industry is cement particles, our aim was to more thoroughly examine the acute effects of occupational exposure to cement dust on the respiratory system. A cross-shift study was conducted in a cement factory in Iran. 100 high exposed workers from production and packing sections and 100 low exposed from office workers were included. Environmental total dust was measured in each section. Assessment of lung function was done by pre and post shift spirometry. At the end of the day shift, acute respiratory symptoms were recorded. The means of total dust among high and low exposed workers were 16.55 mg/m3 and 0.9 mg/m3, respectively. The most common acute respiratory symptoms in high exposed workers were stuffy nose (52%) and shortness of breath (49%). A statistically significant post shift reduction in PEF, FEV1, FEF 25-75, FVC and FEV1/ FVC was demonstrated in high exposed group. Multivariate linear regression showed a significant relationship between the percentage of the cross-shift decrease in spirometric indices and exposure to cement dust. We detected significant relationship between exposure to cement dust and acute respiratory symptoms and pulmonary function indices. Effective dust-control measures and preparing a suitable strategy for respiratory protection are highly recommended. PMID:24659073

  11. Gliding Arc Discharge in the Potato Pathogen Erwinia carotovora subsp. atroseptica: Mechanism of Lethal Action and Effect on Membrane-Associated Molecules▿

    PubMed Central

    Moreau, M.; Feuilloley, M. G. J.; Veron, W.; Meylheuc, T.; Chevalier, S.; Brisset, J.-L.; Orange, N.

    2007-01-01

    Gliding arc (glidarc) discharge is a physicochemical technique for decontamination at atmospheric pressure and ambient temperature. It leads to the destruction of bacterial phytopathogens responsible for important losses in industrial agriculture, namely, Erwinia spp., without the formation of resistant forms. We investigated the effect of a novel optimized prototype allowing bacterial killing without lag time. This prototype also decreases the required duration of treatment by 50%. The study of the time course effect of the process on bacterial morphology suggests that glidarc induces major alterations of the bacterial membrane. We showed that glidarc causes the release of bacterial genomic DNA. By contrast, an apparent decrease in the level of extractible lipopolysaccharide was observed; however, no changes in the electrophoretic pattern and cytotoxic activity of the macromolecule were noted. Analysis of extractible proteins from the outer membrane of the ba