Lethal Nipah virus infection induces rapid overexpression of CXCL10.

Directory of Open Access Journals (Sweden)

Cyrille Mathieu

Full Text Available Nipah virus (NiV is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10, an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.

Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1

Directory of Open Access Journals (Sweden)

Sosna William A

2010-09-01

Full Text Available Abstract Background There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1 virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1 through intranasal verses inhalation routes was analyzed. Results Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1. The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 101, 102, 103, or 104 infectious virus particles per ferret. Conclusions Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1 is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.

Prion protein protects mice from lethal infection with influenza A viruses.

Directory of Open Access Journals (Sweden)

Junji Chida

2018-05-01

Full Text Available The cellular prion protein, designated PrPC, is a membrane glycoprotein expressed abundantly in brains and to a lesser extent in other tissues. Conformational conversion of PrPC into the amyloidogenic isoform is a key pathogenic event in prion diseases. However, the physiological functions of PrPC remain largely unknown, particularly in non-neuronal tissues. Here, we show that PrPC is expressed in lung epithelial cells, including alveolar type 1 and 2 cells and bronchiolar Clara cells. Compared with wild-type (WT mice, PrPC-null mice (Prnp0/0 were highly susceptible to influenza A viruses (IAVs, with higher mortality. Infected Prnp0/0 lungs were severely injured, with higher inflammation and higher apoptosis of epithelial cells, and contained higher reactive oxygen species (ROS than control WT lungs. Treatment with a ROS scavenger or an inhibitor of xanthine oxidase (XO, a major ROS-generating enzyme in IAV-infected lungs, rescued Prnp0/0 mice from the lethal infection with IAV. Moreover, Prnp0/0 mice transgenic for PrP with a deletion of the Cu-binding octapeptide repeat (OR region, Tg(PrPΔOR/Prnp0/0 mice, were also highly susceptible to IAV infection. These results indicate that PrPC has a protective role against lethal infection with IAVs through the Cu-binding OR region by reducing ROS in infected lungs. Cu content and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 and Tg(PrPΔOR/Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu content and regulate SOD1 through the OR region in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting them from lethal infection with IAVs. Our current results highlight the role of PrPC in protection against IAV infection, and suggest that PrPC might be a novel target molecule for anti-influenza therapeutics.

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

Science.gov (United States)

Gulzar, Asim; Wright, Denis J

2015-11-01

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

Lethal infection thresholds of Paenibacillus larvae for honeybee drone and worker larvae (Apis mellifera).

Science.gov (United States)

Behrens, Dieter; Forsgren, Eva; Fries, Ingemar; Moritz, Robin F A

2010-10-01

We compared the mortality of honeybee (Apis mellifera) drone and worker larvae from a single queen under controlled in vitro conditions following infection with Paenibacillus larvae, a bacterium causing the brood disease American Foulbrood (AFB). We also determined absolute P. larvae cell numbers and lethal titres in deceased individuals of both sexes up to 8 days post infection using quantitative real-time PCR (qPCR). Our results show that in drones the onset of infection induced mortality is delayed by 1 day, the cumulative mortality is reduced by 10% and P. larvae cell numbers are higher than in worker larvae. Since differences in bacterial cell titres between sexes can be explained by differences in body size, larval size appears to be a key parameter for a lethal threshold in AFB tolerance. Both means and variances for lethal thresholds are similar for drone and worker larvae suggesting that drone resistance phenotypes resemble those of related workers. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

1H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil

International Nuclear Information System (INIS)

Brown, Sarah A.E.; McKelvie, Jennifer R.; Simpson, Andre J.; Simpson, Myrna J.

2010-01-01

1 H NMR metabolomics was used to monitor earthworm responses to sub-lethal (50-1500 mg/kg) phenanthrene exposure in soil. Total phenanthrene was analyzed via soxhlet extraction, bioavailable phenanthrene was estimated by hydroxypropyl-β-cyclodextrin (HPCD) and 1-butanol extractions and sorption to soil was assessed by batch equilibration. Bioavailable phenanthrene (HPCD-extracted) comprised ∼65-97% of total phenanthrene added to the soil. Principal component analysis (PCA) showed differences in responses between exposed earthworms and controls after 48 h exposure. The metabolites that varied with exposure included amino acids (isoleucine, alanine and glutamine) and maltose. PLS models indicated that earthworm response is positively correlated to both total phenanthrene concentration and bioavailable (HPCD-extracted) phenanthrene in a freshly spiked, unaged soil. These results show that metabolomics is a powerful, direct technique that may be used to monitor contaminant bioavailability and toxicity of sub-lethal concentrations of contaminants in the environment. These initial findings warrant further metabolomic studies with aged contaminated soils. - 1 H NMR metabolomics is used to directly monitor metabolic responses of Eisenia fetida after 48 h of exposure to sub-lethal concentrations of phenanthrene in soil.

Hematological responses after inhaling {sup 238}PuO{sub 2}: An extrapolation from beagle dogs to humans

Energy Technology Data Exchange (ETDEWEB)

Scott, B.R.; Muggenburg, B.A.; Welsh, C.A.; Angerstein, D.A.

1994-11-01

The alpha emitter plutonium-238 ({sup 238}Pu), which is produced in uranium-fueled, light-water reactors, is used as a thermoelectric power source for space applications. Inhalation of a mixed oxide form of Pu is the most likely mode of exposure of workers and the general public. Occupational exposures to {sup 238}PuO{sub 2} have occurred in association with the fabrication of radioisotope thermoelectric generators. Organs and tissue at risk for deterministic and stochastic effects of {sup 238}Pu-alpha irradiation include the lung, liver, skeleton, and lymphatic tissue. Little has been reported about the effects of inhaled {sup 238}PuO{sub 2} on peripheral blood cell counts in humans. The purpose of this study was to investigate hematological responses after a single inhalation exposure of Beagle dogs to alpha-emitting {sup 238}PuO{sub 2} particles and to extrapolate results to humans.

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

Energy Technology Data Exchange (ETDEWEB)

Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G.; Xu, Fadi; Russell, Robert G.; Sopori, Mohan L., E-mail: msopori@lrri.org

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. �

Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection.

Science.gov (United States)

Percopo, Caroline M; Rice, Tyler A; Brenner, Todd A; Dyer, Kimberly D; Luo, Janice L; Kanakabandi, Kishore; Sturdevant, Daniel E; Porcella, Stephen F; Domachowske, Joseph B; Keicher, Jesse D; Rosenberg, Helene F

2015-09-01

We reported previously that priming of the respiratory tract with immunobiotic Lactobacillus prior to virus challenge protects mice against subsequent lethal infection with pneumonia virus of mice (PVM). We present here the results of gene microarray which document differential expression of proinflammatory mediators in response to PVM infection alone and those suppressed in response to Lactobacillus plantarum. We also demonstrate for the first time that intranasal inoculation with live or heat-inactivated L. plantarum or Lactobacillus reuteri promotes full survival from PVM infection when administered within 24h after virus challenge. Survival in response to L. plantarum administered after virus challenge is associated with suppression of proinflammatory cytokines, limited virus recovery, and diminished neutrophil recruitment to lung tissue and airways. Utilizing this post-virus challenge protocol, we found that protective responses elicited by L. plantarum at the respiratory tract were distinct from those at the gastrointestinal mucosa, as mice devoid of the anti-inflammatory cytokine, interleukin (IL)-10, exhibit survival and inflammatory responses that are indistinguishable from those of their wild-type counterparts. Finally, although L. plantarum interacts specifically with pattern recognition receptors TLR2 and NOD2, the respective gene-deleted mice were fully protected against lethal PVM infection by L. plantarum, as are mice devoid of type I interferon receptors. Taken together, L. plantarum is a versatile and flexible agent that is capable of averting the lethal sequelae of severe respiratory infection both prior to and post-virus challenge via complex and potentially redundant mechanisms. Published by Elsevier B.V.

Inductions of reproduction and population growth in the generalist predator Cyrtorhinus lividipennis (Hemiptera: Miridae) exposed to sub-lethal concentrations of insecticides.

Science.gov (United States)

Lu, Weiwei; Xu, Qiujing; Zhu, Jun; Liu, Chen; Ge, Linquan; Yang, Guoqing; Liu, Fang

2017-08-01

The miridbug, Cyrtorhinus lividipennis, is a significant predacious enemy of rice planthoppers. The effects of sub-lethal concentrations of triazophos, deltamethrin and imidacloprid on fecundity, egg hatchability, expression levels of genes associated with reproduction, and population growth in C. lividipennis were investigated. The fecundities for three pair combinations (♀ c × ♂ t , ♀ t × ♂ c and ♀ t × ♂ t ) treated with sub-lethal concentrations of the insecticides triazophos, deltamethrin and imidacloprid (LC 10 and LC 20 ) showed a significant increase compared to the untreated pairs (♀ c × ♂ c ). However, sub-lethal concentration treatments did not affect the egg hatchability. The ClVg expression levels of female adults exposed to triazophos, deltamethrin and imidacloprid (LC 20 ) increased by 52.6, 48.9 and 91.2%, respectively. The ClSPATA13 expression level of adult males exposed to triazophos, deltamethrim and imidacloprid (LC 20 ) increased by 80.7, 41.3 and 48.3%, respectively. Furthermore, sub-lethal concentrations of insecticides (LC 20 ) caused increased population numbers in C. lividipennis. Sub-lethal concentrations of triazophos, deltamethrin and imidacloprid stimulated reproduction and enhanced population growth of C. lividipennis. The reproductive stimulation might result from the up-regulation of ClVg or ClSPATA13. These findings may be useful in mediating populations of planthoppers. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

{sup 1}H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil

Energy Technology Data Exchange (ETDEWEB)

Brown, Sarah A.E.; McKelvie, Jennifer R.; Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, Ontario, M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.c [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, Ontario, M1C 1A4 (Canada)

2010-06-15

{sup 1}H NMR metabolomics was used to monitor earthworm responses to sub-lethal (50-1500 mg/kg) phenanthrene exposure in soil. Total phenanthrene was analyzed via soxhlet extraction, bioavailable phenanthrene was estimated by hydroxypropyl-beta-cyclodextrin (HPCD) and 1-butanol extractions and sorption to soil was assessed by batch equilibration. Bioavailable phenanthrene (HPCD-extracted) comprised approx65-97% of total phenanthrene added to the soil. Principal component analysis (PCA) showed differences in responses between exposed earthworms and controls after 48 h exposure. The metabolites that varied with exposure included amino acids (isoleucine, alanine and glutamine) and maltose. PLS models indicated that earthworm response is positively correlated to both total phenanthrene concentration and bioavailable (HPCD-extracted) phenanthrene in a freshly spiked, unaged soil. These results show that metabolomics is a powerful, direct technique that may be used to monitor contaminant bioavailability and toxicity of sub-lethal concentrations of contaminants in the environment. These initial findings warrant further metabolomic studies with aged contaminated soils. - {sup 1}H NMR metabolomics is used to directly monitor metabolic responses of Eisenia fetida after 48 h of exposure to sub-lethal concentrations of phenanthrene in soil.

Lethal Encephalitozoon cuniculi genotype III infection in Steppe lemmings (Lagurus lagurus)

Czech Academy of Sciences Publication Activity Database

Hofmannová, L.; Sak, Bohumil; Jekl, V.; Mináriková, A.; Škorič, M.; Kváč, Martin

2014-01-01

Roč. 205, 1-2 (2014), s. 357-360 ISSN 0304-4017 R&D Projects: GA ČR(CZ) GAP505/11/1163 Institutional support: RVO:60077344 Keywords : Encephalitozoon cuniculi genotype III * Steppe lemmings * Lethal infection * PCR * Histology Subject RIV: EG - Zoology Impact factor: 2.460, year: 2014

Protection from lethal infection is determined by innate immune responses in a mouse model of Ebola virus infection

International Nuclear Information System (INIS)

Mahanty, Siddhartha; Gupta, Manisha; Paragas, Jason; Bray, Mike; Ahmed, Rafi; Rollin, Pierre E.

2003-01-01

A mouse-adapted strain of Ebola Zaire virus produces a fatal infection when BALB/cj mice are infected intraperitoneally (ip) but subcutaneous (sc) infection with the same virus fails to produce illness and confers long-term protection from lethal ip rechallenge. To identify immune correlates of protection in this model, we compared viral replication and cytokine/chemokine responses to Ebola virus in mice infected ip (10 PFU/mouse), or sc (100 PFU/mouse) and sc 'immune' mice rechallenged ip (10 6 PFU/mouse) at several time points postinfection (pi). Ebola viral antigens were detected in the serum, liver, spleen, and kidneys of ip-infected mice by day 2 pi, increasing up to day 6. Sc-infected mice and immune mice rechallenged ip had no detectable viral antigens until day 6 pi, when low levels of viral antigens were detected in the livers of sc-infected mice only. TNF-α and MCP-1 were detected earlier and at significantly higher levels in the serum and tissues of ip-infected mice than in sc-infected or immune mice challenged ip. In contrast, high levels of IFN-α and IFN-γ were found in tissues within 2 days after challenge in sc-infected and immune mice but not in ip-infected mice. Mice became resistant to ip challenge within 48 h of sc infection, coinciding with the rise in tissue IFN-α levels. In this model of Ebola virus infection, the nonlethal sc route of infection is associated with an attenuated inflammatory response and early production of antiviral cytokines, particularly IFN-α, as compared with lethal ip infection

Immunotherapy with mutated onchocystatin fails to enhance the efficacy of a sub-lethal oxytetracycline regimen against Onchocerca ochengi.

Science.gov (United States)

Bah, Germanus S; Tanya, Vincent N; Makepeace, Benjamin L

2015-08-15

Human onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, has been successfully controlled by a single drug, ivermectin, for over 25 years. Ivermectin prevents the disease symptoms of severe itching and visual impairment by killing the microfilarial stage, but does not eliminate the adult parasites, necessitating repeated annual treatments. Mass drug administration with ivermectin does not always break transmission in forest zones and is contraindicated in individuals heavily co-infected with Loa loa, while reports of reduced drug efficacy in Ghana and Cameroon may signal the development of resistance. An alternative treatment for onchocerciasis involves targeting the essential Wolbachia symbiont with tetracycline or its derivatives, which are adulticidal. However, implementation of antibiotic therapy has not occurred on a wide scale due to the prolonged treatment regimen required (several weeks). In the bovine Onchocerca ochengi system, it has been shown previously that prolonged oxytetracycline therapy increases eosinophil counts in intradermal nodules, which kill the adult worms by degranulating on their surface. Here, in an "immunochemotherapeutic" approach, we sought to enhance the efficacy of a short, sub-lethal antibiotic regimen against O. ochengi by prior immunotherapy targeting onchocystatin, an immunomodulatory protein located in the adult female worm cuticle. A key asparagine residue in onchocystatin was mutated to ablate immunomodulatory activity, which has been demonstrated previously to markedly improve the protective efficacy of this vaccine candidate when used as an immunoprophylactic. The immunochemotherapeutic regimen was compared with sub-lethal oxytetracycline therapy alone; onchocystatin immunotherapy alone; a gold-standard prolonged, intermittent oxytetracycline regimen; and no treatment (negative control) in naturally infected Cameroonian cattle. Readouts were collected over one year and comprised adult

B cells are not essential for Lactobacillus-mediated protection against lethal pneumovirus infection*

Science.gov (United States)

Percopo, Caroline M.; Dyer, Kimberly D.; Garcia-Crespo, Katia E.; Gabryszewski, Stanislaw J.; Shaffer, Arthur L.; Domachowske, Joseph B.; Rosenberg, Helene F.

2014-01-01

We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice (PVM), a property known as heterologous immunity. Lactobacillus-priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. As B cells have been shown to promote heterologous immunity against respiratory virus pathogens under similar conditions, here we explore the role of B cells in Lactobacillus-mediated protection against acute pneumovirus infection. We found that Lactobacillus-primed mice feature elevated levels of airway immunoglobulins IgG, IgA and IgM and lung tissues with dense, B cell (B220+) enriched peribronchial and perivascular infiltrates with germinal centers consistent with descriptions of bronchus-associated lymphoid tissue. No B cells were detected in lung tissue of Lactobacillus-primed B-cell deficient μMT mice or Jh mice, and Lactobacillus-primed μMT mice had no characteristic infiltrates or airway immunoglobulins. Nonetheless, we observed diminished virus recovery and profound suppression of virus-induced proinflammatory cytokines CCL2, IFN-gamma, and CXCL10 in both wild-type and Lactobacillus-primed μMT mice. Furthermore, L. plantarum-primed, B-cell deficient μMT and Jh mice were fully protected from an otherwise lethal PVM infection, as were their respective wild-types. We conclude that B cells are dispensable for Lactobacillus-mediated heterologous immunity and were not crucial for promoting survival in response to an otherwise lethal pneumovirus infection. PMID:24748495

B cells are not essential for Lactobacillus-mediated protection against lethal pneumovirus infection.

Science.gov (United States)

Percopo, Caroline M; Dyer, Kimberly D; Garcia-Crespo, Katia E; Gabryszewski, Stanislaw J; Shaffer, Arthur L; Domachowske, Joseph B; Rosenberg, Helene F

2014-06-01

We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice, a property known as heterologous immunity. Lactobacillus priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. Because B cells have been shown to promote heterologous immunity against respiratory virus pathogens under similar conditions, in this study we explore the role of B cells in Lactobacillus-mediated protection against acute pneumovirus infection. We found that Lactobacillus-primed mice feature elevated levels of airway Igs IgG, IgA, and IgM and lung tissues with dense, B cell (B220(+))-enriched peribronchial and perivascular infiltrates with germinal centers consistent with descriptions of BALT. No B cells were detected in lung tissue of Lactobacillus-primed B cell deficient μMT mice or Jh mice, and Lactobacillus-primed μMT mice had no characteristic infiltrates or airway Igs. Nonetheless, we observed diminished virus recovery and profound suppression of virus-induced proinflammatory cytokines CCL2, IFN-γ, and CXCL10 in both wild-type and Lactobacillus-primed μMT mice. Furthermore, Lactobacillus plantarum-primed, B cell-deficient μMT and Jh mice were fully protected from an otherwise lethal pneumonia virus of mice infection, as were their respective wild-types. We conclude that B cells are dispensable for Lactobacillus-mediated heterologous immunity and were not crucial for promoting survival in response to an otherwise lethal pneumovirus infection.

Role of natural killer cells in innate protection against lethal ebola virus infection.

Science.gov (United States)

Warfield, Kelly L; Perkins, Jeremy G; Swenson, Dana L; Deal, Emily M; Bosio, Catharine M; Aman, M Javad; Yokoyama, Wayne M; Young, Howard A; Bavari, Sina

2004-07-19

Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1-3 d before Ebola virus infection rapidly induced protective immunity. VLP injection enhanced the numbers of natural killer (NK) cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets. Unlike wild-type mice, treatment of NK-deficient or -depleted mice with VLPs had no protective effect against Ebola virus infection and NK cells treated with VLPs protected against Ebola virus infection when adoptively transferred to naive mice. The mechanism of NK cell-mediated protection clearly depended on perforin, but not interferon-gamma secretion. Particles containing only VP40 were sufficient to induce NK cell responses and provide protection from infection in the absence of the viral GP. These findings revealed a decisive role for NK cells during lethal Ebola virus infection. This work should open new doors for better understanding of Ebola virus pathogenesis and direct the development of immunotherapeutics, which target the innate immune system, for treatment of Ebola virus infection.

Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model.

Science.gov (United States)

Cheresiz, S V; Semenova, E A; Chepurnov, A A

2016-01-01

Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups.

Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model

Directory of Open Access Journals (Sweden)

S. V. Cheresiz

2016-01-01

Full Text Available Establishment of small animal models of Ebola virus (EBOV infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups.

Role of Natural Killer Cells in Innate Protection against Lethal Ebola Virus Infection

OpenAIRE

Warfield, Kelly L.; Perkins, Jeremy G.; Swenson, Dana L.; Deal, Emily M.; Bosio, Catharine M.; Aman, M. Javad; Yokoyama, Wayne M.; Young, Howard A.; Bavari, Sina

2004-01-01

Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1–3 d before Ebola virus infection rapidly induced protective immunity. VLP injectio...

Sub-Lethal Dose of Shiga toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cythoarquitecture.

Directory of Open Access Journals (Sweden)

Luciana eD’Alessio

2016-02-01

Full Text Available Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test, and ultrastructural analysis (transmission electron microscope. Intravenous administration of vehicle (control group, sub-lethal dose of 0.5 ηg and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n=6. Blood–Brain Barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance.

The effects of oil sands wastewater on fish resulting from exposure to sub-lethal concentrations

International Nuclear Information System (INIS)

Birkholz, D.A.; Goudey, J.S.; Balch, G.C.; Nelson, L.R.; MacKinnon, M.

1995-01-01

Rainbow trout, Oncorhynchus mykiss, were exposed to sub-lethal concentrations of oil sands wastewater in flow through laboratory experiments as well as to artificial ponds containing sub-lethal concentrations of tailings pond water and fine tails in order to study the viability of the wet landscape remediation option. Large (200--300 g) fish were used for all the exposures in this preliminary study and the following data were collected: blood cell counts, sex hormone concentrations, sexual maturation, stress protein concentrations, PAH-metabolites in bile, condition factors, liver somatic indices, mixed function oxygenase induction, PAHs in muscle, external condition and the condition of internal organs. The data obtained from this study revealed no adverse effects upon fish during extended field exposures. Given similar exposure conditions in the release waters of a wet landscape reclamation, the data suggest that there may be no adverse effects upon fish, however, longer term studies, other indicator organisms and additional chronic tests should be conducted

Experimental Salmonella typhimurium infections in rats. II. Active and passive immunization as protection against a lethal bacterial dose

DEFF Research Database (Denmark)

Hougen, H P; Jensen, E T; Klausen, B

1990-01-01

Immunization against a lethal dose of Salmonella typhimurium was studied in athymic and thymus-bearing LEW rats. Active immunization was performed with formalin-killed whole cell vaccine or sublethal infection prior to the lethal infection. After vaccination with killed bacteria the euthymic...... from immunized thymus grafted animals provided only limited protective effect, and treatment with cells from athymic animals had no effect. The study shows that although isogeneic thymus-grafted nude rats become resistent to reinfection with S. typhimurium, only large doses of spleen cells from...

An orally available, small-molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model.

Science.gov (United States)

Krumm, Stefanie A; Yan, Dan; Hovingh, Elise S; Evers, Taylor J; Enkirch, Theresa; Reddy, G Prabhakar; Sun, Aiming; Saindane, Manohar T; Arrendale, Richard F; Painter, George; Liotta, Dennis C; Natchus, Michael G; von Messling, Veronika; Plemper, Richard K

2014-04-16

Measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral RNA polymerase. Prophylactic oral treatment of ferrets infected intranasally with a lethal CDV dose reduced viremia and prolonged survival. Ferrets infected with the same dose of virus that received post-infection treatment at the onset of viremia showed low-grade viral loads, remained asymptomatic, and recovered from infection, whereas control animals succumbed to the disease. Animals that recovered also mounted a robust immune response and were protected against rechallenge with a lethal CDV dose. Drug-resistant viral recombinants were generated and found to be attenuated and transmission-impaired compared to the genetic parent virus. These findings may pioneer a path toward an effective morbillivirus therapy that could aid measles eradication by synergizing with vaccination to close gaps in herd immunity due to vaccine refusal.

One-pot synthesis of strongly fluorescent DNA-CuInS{sub 2} quantum dots for label-free and ultrasensitive detection of anthrax lethal factor DNA

Energy Technology Data Exchange (ETDEWEB)

Liu, Ziping; Su, Xingguang, E-mail: suxg@jlu.edu.cn

2016-10-26

Herein, high quality DNA-CuInS{sub 2} QDs are facilely synthesized through a one-pot hydrothermal method with fluorescence quantum yield as high as 23.4%, and the strongly fluorescent DNA-CuInS{sub 2} QDs have been utilized as a novel fluorescent biosensor for label-free and ultrasensitive detection of anthrax lethal factor DNA. L-Cysteine (L-Cys) and a specific-sequence DNA are used as co-ligands to stabilize the CuInS{sub 2} QDs. The specific-sequence DNA consists of two domains: phosphorothiolates domain (sulfur-containing variants of the usual phosphodiester backbone) controls the nanocrystal passivation and serves as a ligand, and the functional domain (non-phosphorothioates) controls the biorecognition. The as-prepared DNA-CuInS{sub 2} QDs have high stability, good water-solubility and low toxicity. Under the optimized conditions, a linear correlation was established between the fluorescence intensity ratio I/I{sub 0} (I{sub 0} is the original fluorescence intensity of DNA-CuInS{sub 2} QDs, and I is the fluorescence intensity of DNA-CuInS{sub 2} QDs/GO with the addition of various concentrations of anthrax lethal factor DNA) and the concentration of anthrax lethal factor DNA in the range of 0.029–0.733 nmol L{sup −1} with a detection limit of 0.013 nmol L{sup −1}. The proposed method has been successfully applied to the determination of anthrax lethal factor DNA sequence in human serum samples with satisfactory results. Because of low toxicity and fine biocompatibility, DNA-CuInS{sub 2} QDs also hold potential applications in bioimaging. - Highlights: • Strongly fluorescent DNA-QDs were successfully prepared by a one-pot hydrothermal method with quantum yield up to 23.4%. • A biosensor for label-free detection of anthrax lethal factor DNA was established based on the as-prepared DNA-QDs. • The DNA sensor took advantage of the feature that ssDNA binds to GO with significantly higher affinity than dsDNA. • Good sensitivity and selectivity were

Maize lethal necrosis (MLN), an emerging threat to maize-based food security in sub-Saharan Africa

Science.gov (United States)

In sub-Saharan Africa, maize is a staple food and key determinant of food security for smallholder farming communities. Pest and disease outbreaks are key constraints to maize productivity. In September 2011, a serious disease outbreak, later diagnosed as maize lethal necrosis (MLN), was reported on...

Measurement of oxygen enhancement ratio for sub-lethal region using saccharomyces cerevisiae

International Nuclear Information System (INIS)

Nairy, Rajesha K.; Anjaria, K.B.; Bhat, Nagesh N.; Chaurasia, Rajesh K.; Balakrishnan, Sreedevi; Yerol, Narayana

2013-01-01

Oxygen is one of the best known modifiers of radiation sensitivity and the biological effects is greater in the presence of oxygen, and significant modifying effect will be observed only for low LET radiations. The reduced oxygen availability is sensed which trigger homeostatic responses, which impact on virtually all areas of biology and medicine. Failure to achieve complete response following radiotherapy of large tumors is attributed to the presence of radio-resistant hypoxic cells, therefore clarifying the mechanism of the oxygen effect is important. In the present study, a mutant type diploid yeast strain, Saccharomyces cerevisiae D7 was used to study Oxygen Enhancement Ratio (OER) using 60 Co gamma radiation. Cells were washed thrice by centrifugation (2000 g for 5 min) and re-suspended to a cell concentration of 1x108 cells mL-1 in a sterile polypropylene vial for irradiation (sub-lethal dose range, 0-100 Gy). Hypoxic conditions were achieved by incubating the cells in airtight vials at 30℃ for 30 min prior to irradiation. The gene conversion and back mutation analysis were carried out according to the standard protocol. Gene conversion is the radio-sensitive biological endpoint, that can be studied in Saccharomyces cerevisiae D7 yeast cells at trp locus in tryptophan (Trp- medium) deficient medium. The dose response relation at euoxic and hypoxic condition in sub-lethal doses are found to be linear and is represented by Y (Euoxic) = (6.54±0.102) D with R2=0.999 and for hypoxic condition Y(Hypoxic) = (3.346±0.033) D with R2=0.996. The OER can be calculated by dividing the euoxic slope with hypoxic slope, and is 1.95. Back mutation, which is a result of reversion of Isoleucine auxotrophs to prototrophs gives very good information at sub-lethal doses. The dose response relation between back mutated cells and radiation doses at Euoxic and hypoxic condition can be represented as Y(Euoxic) = (2.85±0.126) D with R2= 0.976 and for hypoxic condition Y

Commentary on inhaled {sup 239}PuO{sub 2} in dogs - a prophylaxis against lung cancer?

Energy Technology Data Exchange (ETDEWEB)

Cuttler, J.M., E-mail: jerrycuttler@rogers.com [Cuttler and Associates, Vaughan, ON (Canada); Feinendegen, L. [Brookhaven National Laboratories, Upton, NY (United States)

2015-07-01

Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the Linear No-Threshold (LNT) hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from {sup 239}PuO{sub 2} inhalation, as a prophylaxis against lung cancer. (author)

Commentary on inhaled {sup 239}PuO{sub 2} in dogs - a prophylaxis against lung cancer?

Energy Technology Data Exchange (ETDEWEB)

Cuttler, J.M. [Cuttler and Assoc., Vaughan, Ontario (Canada); Feinendegen, L. [Brookhaven National Laboratories, Upton, New York (United States)

2015-06-15

Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the Linear No-Threshold (LNT) hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from {sup 239}PuO {sub 2} inhalation, as a prophylaxis against lung cancer. (author)

Toxicological perspectives of inhaled therapeutics and nanoparticles.

Science.gov (United States)

Hayes, Amanda J; Bakand, Shahnaz

2014-07-01

The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

Directory of Open Access Journals (Sweden)

Marit Kramski

Full Text Available The intentional re-introduction of Variola virus (VARV, the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV and Monkeypox virus (MPXV cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus.A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2 pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50 (minimal monkey infectious dose 50% of 8.3x10(2 pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

Chloride and sulphate toxicity to Hydropsyche exocellata (Trichoptera, Hydropsychidae): Exploring intraspecific variation and sub-lethal endpoints

Energy Technology Data Exchange (ETDEWEB)

Sala, Miquel [Centre Tecnològic Forestal de Catalunya - CTFC, Solsona, Catalunya (Spain); Faria, Melissa [CESAM, Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro (Portugal); Sarasúa, Ignacio [Technische Universität München, Munich, Bayern (Germany); Barata, Carlos [Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Barcelona (Spain); Bonada, Núria [Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Universitat de Barcelona (UB), Diagonal 643, 08028 Barcelona, Catalonia (Spain); Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Institut de Recerca de la Biodiversitat (IRBio), Universitat de Barcelona - UB, Diagonal 643, 08028 Barcelona, Catalonia (Spain); Brucet, Sandra [Aquatic Ecology Group, BETA Tecnio Centre, University of Vic - Central University of Catalonia, Vic, Catalonia (Spain); Catalan Institution for Research and Advanced Studies, ICREA, Barcelona 08010 (Spain); Llenas, Laia; Ponsá, Sergio [Aquatic Ecology Group, BETA Tecnio Centre, University of Vic - Central University of Catalonia, Vic, Catalonia (Spain); Prat, Narcís [Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Universitat de Barcelona (UB), Diagonal 643, 08028 Barcelona, Catalonia (Spain); Soares, Amadeu M.V.M. [CESAM, Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro (Portugal); and others

2016-10-01

The rivers and streams of the world are becoming saltier due to human activities. In spite of the potential damage that salt pollution can cause on freshwater ecosystems, this is an issue that is currently poorly managed. Here we explored intraspecific differences in the sensitivity of freshwater fauna to two major ions (Cl{sup −} and SO{sub 4}{sup 2−}) using the net-spinning caddisfly Hydropsyche exocellata Dufour 1841 (Trichoptera, Hydropsychidae) as a model organism. We exposed H. exocellata to saline solutions (reaching a conductivity of 2.5 mS cm{sup −1}) with Cl{sup −}:SO{sub 4}{sup 2−} ratios similar to those occurring in effluents coming from the meat, mining and paper industries, which release dissolved salts to rivers and streams in Spain. We used two different populations, coming from low and high conductivity streams. To assess toxicity, we measured sub-lethal endpoints: locomotion, symmetry of the food-capturing nets and oxidative stress biomarkers. According to biomarkers and net building, the population historically exposed to lower conductivities (B10) showed higher levels of stress than the population historically exposed to higher conductivities (L102). However, the differences between populations were not strong. For example, net symmetry was lower in the B10 than in the L102 only 48 h after treatment was applied, and biomarkers showed a variety of responses, with no discernable pattern. Also, treatment effects were rather weak, i.e. only some endpoints, and in most cases only in the B10 population, showed a significant response to treatment. The lack of consistent differences between populations and treatments could be related to the high salt tolerance of H. exocellata, since both populations were collected from streams with relatively high conductivities. The sub-lethal effects tested in this study can offer an interesting and promising tool to monitor freshwater salinization by combining physiological and behavioural bioindicators

Experimental chronic Pseudomonas aeruginosa lung infection in rats. Non-specific stimulation with LPS reduces lethality as efficiently as specific immunization

DEFF Research Database (Denmark)

Lange, K H; Hougen, H P; Høiby, N

1995-01-01

In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis, we investigated the possibility of preventing chronic lung inflammation or decreasing the progression of the infection. We compared the lethality, pathology, bacterial clearance, and immunogenicity after...... with either E. coli LPS or P. aeruginosa sonicate. Four and two weeks prior to challenge other rats were vaccinated with either E. coli LPS or P. aeruginosa sonicate. Controls did not receive any stimulation or vaccination. The lethality after challenge was lower in rats stimulated with E. coli LPS (p = 0...... but not to prevent the chronic P. aeruginosa lung infection and inflammation caused by alginate-embedded bacteria....

Sub-lethal toxicity of chlorpyrifos on Common carp, Cyprinus carpio (Linnaeus, 1758: Biochemical response

Directory of Open Access Journals (Sweden)

Mahdi Banaee

2014-01-01

Full Text Available Chlorpyrifos, an organophosphate pesticide, is widely used to control pests in agriculture farms and orchards of fruit trees. In this study, the fish were exposed to sub-lethal concentrations of chlorpyrifos which were determined based on numerical value of 96 h LC50. Blood was sampled after 10, 20 and 30 days and biochemical parameters including glucose, total protein, albumin, globulin, triglyceride and cholesterol levels, and aspartate aminotransferase (AST, alanine aminotransferase (ALT, lactate dehydrogenase (LDH, creatine kinase (CK, alkaline phosphatase (ALP and acetylcholinsetrase (AChE activities were measured. Behavioral changes in the fish were also recorded during the experiment. Unbalanced swimming, swimming in the surface water and hyperglycemia, increased blood triglyceride, and increased levels of AST, LDH and CK activities as well as decreased levels of AChE activity were important changes that were observed in the specimens exposed to chlorpyrifos during experimental periods. The most important alterations in the blood biochemical parameters were measured in the specimens exposed to 40 µg/L chlorpyrifos on the 20th and 30th day of the trial. In conclusion, results of the present study indicated that exposure to sub-lethal concentrations of chlorpyrifos as low as 40 µg/L may cause biochemical and behavioral changes in Cyprinus carpio.

Assessing Sub-Lethal Impacts of Petroleum Compounds on Marine Benthic Systems

Energy Technology Data Exchange (ETDEWEB)

Lindgren, J. Fredrik

2012-07-01

Petroleum and its different distillates commonly end up in the marine environment. One source of these additions is discharges originating from shipping activities; accidents, ship wrecks, operational spills etc. Depending on several different factors that govern the fate of petroleum released into the marine environment the effects of the discharge will differ, from acute toxic to long term sub-lethal effects. While effects on biota from large spills have thoroughly been investigated in the past long term sub-lethal effects are somewhat less examined. Therefore the objective of this thesis has been to develop and apply a method to analyze what effects low concentrations of petroleum, which often ends up in marine sediments, have on benthic sediment biota. Ecotoxicological endpoints that were evaluated were density changes of meiofauna and variations in the microbial community function, measured as inorganic nutrient fluxes over the sediment-water interface the potential to perform a metabolic process. These types of organisms are two important key players in marine benthic sedimentary habitats, performing ecosystem services such as degradation of organic matter, recycling of nutrients and various pollutants and they constitute a carbon link to higher trophic levels. As manual classification of meiofauna is very time-consuming process including an extended learning process for the taxonomist, this thesis is in its first part focused at the field of automatic classification. To classify meiofaunal communities a novel technique was developed where the image analysis software ZooImage was adapted to automatically classify higher taxonomic taxa of meiofauna, with successful results. The technique was evaluated by classifying meiofaunal communities from five different depths in the Gullmar Fjord, Sweden. The accuracy of the analyses was tested using ZooImage's internal 10-fold cross-validation method, and by comparing digitalized samples from the different sites

Deposition, distribution and retention of inhaled /sup 239/PuO/sub 2/ in the lungs of rats with pulmonary emphysema

Energy Technology Data Exchange (ETDEWEB)

Lundgren, D L; Damon, E G; Diel, J H; Hahn, F F [Lovelace Foundation for Medical Education and Research, Albuquerque, NM (USA). Inhalation Toxicology Research Inst.

1981-02-01

Individuals with chronic obstructive lung disease, such as emphysema, may be more susceptible to injury from other inhaled pollutants. However, dose-response studies of inhaled radionuclides conducted to aid in estimating the biological effects of inhaled radionuclides in man have typically used healthy laboratory animals. Changes in radionuclide deposition, distribution and retention in the lungs as the result of pre-existing lung diseases could alter the radiation dose or the resulting biological effects. An experimental animal model for human emphysema, in which emphysema is induced by the intratracheal instillation of either elastase or papain, has been reviewed. This model was used to study the effects of pulmonary emphysema on the deposition, distribution and retention of inhaled /sup 239/PuO/sub 2/ in rats.

Sub-lethal cadmium exposure increases phytochelatin concentrations in the aquatic snail Lymnaea stagnalis

Energy Technology Data Exchange (ETDEWEB)

SF, Gonçalves [Department of Biology & CESAM, Centre for Environmental and Marine Studies, University of Aveiro, 3810-193 Aveiro (Portugal); SK, Davies [Department of Surgery and Cancer, Imperial College London, Sir Alexander Fleming Building, London SW7 2AZ (United Kingdom); Bennett, M. [Department of Life Sciences, Imperial College London, Sir Alexander Fleming Building, London SW7 2AZ (United Kingdom); Raab, A.; Feldmann, J. [TESLA, Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, Scotland (United Kingdom); Kille, P. [Cardiff School of Biosciences, Cardiff University, Park Place, Cardiff CF10 3US (United Kingdom); Loureiro, S. [Department of Biology & CESAM, Centre for Environmental and Marine Studies, University of Aveiro, 3810-193 Aveiro (Portugal); DJ, Spurgeon [Centre for Ecology and Hydrology, Maclean Building, Benson Lane, Wallingford OX10 8BB (United Kingdom); JG, Bundy, E-mail: j.bundy@imperial.ac.uk [Department of Surgery and Cancer, Imperial College London, Sir Alexander Fleming Building, London SW7 2AZ (United Kingdom)

2016-10-15

Phytochelatins are metal-binding metabolites found in almost all plant species and some animal groups, including nematodes and annelids, where they can play an important role in detoxifying metals such as cadmium. Species from several other taxa contain a phytochelatin synthase (PCS) gene orthologue, including molluscs, indicating they may have the potential to synthesize phytochelatins. However, the presence of a gene alone does not demonstrate that it plays a functional role in metal detoxification. In the present study, we show that the aquatic snail Lymnaea stagnalis produced both penta- and heptapeptide phytochelatins (i.e. phytochelatin-2 and phytochelatin-3), and their levels increased in response to sub-lethal levels of cadmium. - Highlights: • Little is known about the role of phytochelatins in metal detoxification in animals. • We detected phytochelatins (PC{sub 2} and PC{sub 3}) in a mollusc species, Lymnaea stagnalis. • Phytochelatins increased in Lymnaea stagnalis when exposed to cadmium. • Future research on phytochelatin responses in molluscs would be valuable.

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

Science.gov (United States)

Lilly, Elizabeth A.; Ikeh, Melanie; Nash, Evelyn E.; Fidel, Paul L.

2018-01-01

ABSTRACT Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections

Directory of Open Access Journals (Sweden)

Elizabeth A. Lilly

2018-01-01

Full Text Available Polymicrobial intra-abdominal infections (IAIs are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis. Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge. Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO] survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of

/sup 239/PuO/sub 2/ aerosol inhalation with emphasis on pulmonary connective tissue modifications

Energy Technology Data Exchange (ETDEWEB)

Metivier, H; Masse, R; Nobil' e, D; Lafuma, J

1975-09-01

Inhalation studies were undertaken in which plutonium dioxide (/sup 239/PuO/sub 2/) was administered to either unanesthetized Wistar rats or anaesthetized baboons. In both groups of animals some deaths occurred from acute lung damage resulting from cell necrosis particularly to vascular tissue followed by alveolar oedema. At later stages, marked interstitial pneumonitis and interstitial fibrosis occurred and deaths resulted from respiratory insufficiency preceded by high arterial blood pCO/sub 2/ and low pO/sub 2/. In rats as many as 50% of the animals finally developed lung neoplasms but only two such tumors were found in baboons. Attempts were made to correlate biochemical parameters with observed tissue damage and animal mortality.

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

Science.gov (United States)

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

2016-04-01

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

B cells are not essential for Lactobacillus-mediated protection against lethal pneumovirus infection*

OpenAIRE

Percopo, Caroline M.; Dyer, Kimberly D.; Garcia-Crespo, Katia E.; Gabryszewski, Stanislaw J.; Shaffer, Arthur L.; Domachowske, Joseph B.; Rosenberg, Helene F.

2014-01-01

We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice (PVM), a property known as heterologous immunity. Lactobacillus-priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. As B cells have been shown ...

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

International Nuclear Information System (INIS)

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

1995-01-01

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

Critical analysis of the maximum non inhibitory concentration (MNIC) method in quantifying sub-lethal injury in Saccharomyces cerevisiae cells exposed to either thermal or pulsed electric field treatments.

Science.gov (United States)

Kethireddy, V; Oey, I; Jowett, Tim; Bremer, P

2016-09-16

Sub-lethal injury within a microbial population, due to processing treatments or environmental stress, is often assessed as the difference in the number of cells recovered on non-selective media compared to numbers recovered on a "selective media" containing a predetermined maximum non-inhibitory concentration (MNIC) of a selective agent. However, as knowledge of cell metabolic response to injury, population diversity and dynamics increased, the rationale behind the conventional approach of quantifying sub-lethal injury must be scrutinized further. This study reassessed the methodology used to quantify sub-lethal injury for Saccharomyces cerevisiae cells (≈ 4.75 Log CFU/mL) exposed to either a mild thermal (45°C for 0, 10 and 20min) or a mild pulsed electric field treatment (field strengths of 8.0-9.0kV/cm and energy levels of 8, 14 and 21kJ/kg). Treated cells were plated onto either Yeast Malt agar (YM) or YM containing NaCl, as a selective agent at 5-15% in 1% increments. The impact of sub-lethal stress due to initial processing, the stress due to selective agents in the plating media, and the subsequent variation of inhibition following the treatments was assessed based on the CFU count (cell numbers). ANOVA and a generalised least squares model indicated significant effects of media, treatments, and their interaction effects (P<0.05) on cell numbers. It was shown that the concentration of the selective agent used dictated the extent of sub-lethal injury recorded owing to the interaction effects of the selective component (NaCl) in the recovery media. Our findings highlight a potential common misunderstanding on how culture conditions impact on sub-lethal injury. Interestingly for S. cerevisiae cells the number of cells recovered at different NaCl concentrations in the media appears to provide valuable information about the mode of injury, the comparative efficacy of different processing regimes and the inherent degree of resistance within a population. This

Transporting Patients with Lethal Contagious Infections

National Research Council Canada - National Science Library

Swartz, Colleen

2002-01-01

.... The AIT is a unique military medical team capable of worldwide air evacuation and management of a limited number of patients who are potentially exposed to known and unknown lethal communicable...

Inhaled Antibiotics for Ventilator-Associated Infections.

Science.gov (United States)

Palmer, Lucy B

2017-09-01

Multidrug-resistant organisms are creating a challenge for physicians treating the critically ill. As new antibiotics lag behind the emergence of worsening resistance, intensivists in countries with high rates of extensively drug-resistant bacteria are turning to inhaled antibiotics as adjunctive therapy. These drugs can provide high concentrations of drug in the lung that could not be achieved with intravenous antibiotics without significant systemic toxicity. This article summarizes current evidence describing the use of inhaled antibiotics for the treatment of bacterial ventilator-associated pneumonia and ventilator-associated tracheobronchitis. Preliminary data suggest aerosolized antimicrobials may effectively treat resistant pathogens with high minimum inhibitory concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig.

Science.gov (United States)

Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn

2015-05-01

The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species. © 2014 Society for Risk Analysis.

Inhaled antibiotics for lower respiratory tract infections: focus on ciprofloxacin.

Science.gov (United States)

Serisier, D J

2012-05-01

The administration of antibiotics by the inhaled route offers an appealing and logical approach to treating infectious respiratory conditions. Studies in the cystic fibrosis (CF) population have established the efficacy of this therapeutic concept and inhaled antibiotic therapy is now one of the pillars of management in CF. There are now a number of new inhaled antibiotic formulations that have shown impressive preliminary evidence for efficacy in CF and are commencing phase III efficacy studies. Translation of this paradigm into the non-CF bronchiectasis population has proven difficult thus far, apparently due to problems with tolerability of inhaled formulations. Inhaled versions of ciprofloxacin have shown good tolerability and microbiological efficacy in preliminary studies, suggesting that effective inhaled antibiotics are finally on the horizon for this previously neglected patient population. The increased use of long-term inhaled antibiotics for a wider range of non-CF indications presents risks to the broader community of greater antimicrobial resistance development that must be carefully weighed against any demonstrated benefits. Copyright 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

Tuning of the Lethal Response to Multiple Stressors with a Single-Site Mutation during Clinical Infection by Staphylococcus aureus

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Krishan Kumar

2017-10-01

Full Text Available The agr system of Staphylococcus aureus promotes invasion of host tissues, and as expected, agents that block agr quorum sensing have anti-infective properties. Paradoxically, agr-defective mutants are frequently recovered from patients, especially those persistently infected with S. aureus. We found that an agr deficiency increased survival of cultured bacteria during severe stress, such as treatment with gentamicin, ciprofloxacin, heat, or low pH. With daptomycin, deletion of agr decreased survival. Therefore, agr activity can be either detrimental or protective, depending on the type of lethal stress. Deletion of agr had no effect on the ability of the antimicrobials to block bacterial growth, indicating that agr effects are limited to lethal action. Thus, the effect of an agr deletion is on bacterial tolerance, not resistance. For gentamicin and daptomycin, activity can be altered by agr-regulated secreted factors. For ciprofloxacin, a detrimental function was downregulation of glutathione peroxidase (bsaA, an enzyme responsible for defense against oxidative stress. Deficiencies in agr and bsaA were epistatic for survival, consistent with agr having a destructive role mediated by reactive oxygen species. Enhanced susceptibility to lethal stress by wild-type agr, particularly antimicrobial stress, helps explain why inactivating mutations in S. aureus agr commonly occur in hospitalized patients during infection. Moreover, the agr quorum-sensing system of S. aureus provides a clinically relevant example in which a single-step change in the response to severe stress alters the evolutionary path of a pathogen during infection.

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

Energy Technology Data Exchange (ETDEWEB)

Flaskos, J., E-mail: flaskos@vet.auth.gr [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Nikolaidis, E. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Harris, W. [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); Sachana, M. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Hargreaves, A.J., E-mail: alan.hargreaves@ntu.ac.uk [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Chloride and sulphate toxicity to Hydropsyche exocellata (Trichoptera, Hydropsychidae): Exploring intraspecific variation and sub-lethal endpoints

International Nuclear Information System (INIS)

Sala, Miquel; Faria, Melissa; Sarasúa, Ignacio; Barata, Carlos; Bonada, Núria; Brucet, Sandra; Llenas, Laia; Ponsá, Sergio; Prat, Narcís; Soares, Amadeu M.V.M.

2016-01-01

The rivers and streams of the world are becoming saltier due to human activities. In spite of the potential damage that salt pollution can cause on freshwater ecosystems, this is an issue that is currently poorly managed. Here we explored intraspecific differences in the sensitivity of freshwater fauna to two major ions (Cl"− and SO_4"2"−) using the net-spinning caddisfly Hydropsyche exocellata Dufour 1841 (Trichoptera, Hydropsychidae) as a model organism. We exposed H. exocellata to saline solutions (reaching a conductivity of 2.5 mS cm"−"1) with Cl"−:SO_4"2"− ratios similar to those occurring in effluents coming from the meat, mining and paper industries, which release dissolved salts to rivers and streams in Spain. We used two different populations, coming from low and high conductivity streams. To assess toxicity, we measured sub-lethal endpoints: locomotion, symmetry of the food-capturing nets and oxidative stress biomarkers. According to biomarkers and net building, the population historically exposed to lower conductivities (B10) showed higher levels of stress than the population historically exposed to higher conductivities (L102). However, the differences between populations were not strong. For example, net symmetry was lower in the B10 than in the L102 only 48 h after treatment was applied, and biomarkers showed a variety of responses, with no discernable pattern. Also, treatment effects were rather weak, i.e. only some endpoints, and in most cases only in the B10 population, showed a significant response to treatment. The lack of consistent differences between populations and treatments could be related to the high salt tolerance of H. exocellata, since both populations were collected from streams with relatively high conductivities. The sub-lethal effects tested in this study can offer an interesting and promising tool to monitor freshwater salinization by combining physiological and behavioural bioindicators. - Highlights: • We assessed Cl

Inhaled phage therapy: a promising and challenging approach to treat bacterial respiratory infections.

Science.gov (United States)

Bodier-Montagutelli, Elsa; Morello, Eric; L'Hostis, Guillaume; Guillon, Antoine; Dalloneau, Emilie; Respaud, Renaud; Pallaoro, Nikita; Blois, Hélène; Vecellio, Laurent; Gabard, Jérôme; Heuzé-Vourc'h, Nathalie

2017-08-01

Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site. Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context. Recent phage formulation and aerosolization attempts are also reviewed, raising technical challenges to achieve efficient pulmonary deposition via inhalation. Expert opinion: Overall, the inhalation of phages as antibacterial treatment seems both clinically relevant and technically feasible. Several crucial points still need to be investigated, such as phage product pharmacokinetics and immunogenicity. Furthermore, given phage-specific features, appropriate regulatory and manufacturing guidelines will need to be defined. Finally, randomized controlled clinical trials should be carried out to establish phage therapy's clinical positioning in the antimicrobial arsenal against RTIs.

Sub-lethal irradiation of human colorectal tumor cells imparts enhanced and sustained susceptibility to multiple death receptor signaling pathways.

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Victoria Ifeadi

Full Text Available BACKGROUND: Death receptors (DR of the TNF family function as anti-tumor immune effector molecules. Tumor cells, however, often exhibit DR-signaling resistance. Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack. The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The ability of radiation to modulate the expression of multiple death receptors (Fas/CD95, TRAILR1/DR4, TRAILR2/DR5, TNF-R1 and LTβR was examined in colorectal tumor cells. The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays. The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined. We found that radiation increased surface expression of Fas, DR4 and DR5 but not LTβR or TNF-R1 in these cells. Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation. Sub-lethal tumor cell irradiation alone exhibited minimal cell death, but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis, but not LTβR-induced death. Furthermore, radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation. Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation did reduce Bcl-X(L and c-FLIP protein expression, this reduction did not correlate with the radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the three cell types. CONCLUSIONS/SIGNIFICANCE: Irradiation of tumor cells can overcome Fas and TRAIL

Estimation of the acute inhalation hazards of chemicals based on route-to-route and local endpoint extrapolation: Experience from Bulk Maritime Transport

NARCIS (Netherlands)

Höfer, T.; James, D.; Syversen, T.; Bowmer, T.

2011-01-01

Data on acute lethal inhalation toxicity from animal studies are commonly required for assessing the hazards to human health of volatile, gaseous and dusty chemicals or their mixtures. The International Maritime Organisation (IMO) made the provision of acute inhalation toxicity data a mandatory

Depressed Hypoxic and Hypercapnic Ventilatory Responses at Early Stage of Lethal Avian Influenza A Virus Infection in Mice.

Directory of Open Access Journals (Sweden)

Jianguo Zhuang

Full Text Available H5N1 virus infection results in ~60% mortality in patients primarily due to respiratory failure, but the underlying causes of mortality are unclear. The goal of this study is to reveal respiratory disorders occurring at the early stage of infection that may be responsible for subsequent respiratory failure and death. BALB/c mice were intranasally infected with one of two H5N1 virus strains: HK483 (lethal or HK486 (non-lethal virus. Pulmonary ventilation and the responses to hypoxia (HVR; 7% O2 for 3 min and hypercapnia (HCVR; 7% CO2 for 5 min were measured daily at 2 days prior and 1, 2, and 3 days postinfection (dpi and compared to mortality typically by 8 dpi. At 1, 2, and 3 dpi, immunoreactivities (IR of substance P (SP-IR in the nodose ganglion or tyrosine hydroxylase (TH-IR in the carotid body coupled with the nucleoprotein of influenza A (NP-IR was examined in some mice, while arterial blood was collected in others. Our results showed that at 2 and 3 dpi: 1 both viral infections failed to alter body temperature and weight, [Formula: see text], or induce viremia while producing similarly high lung viral titers; 2 HK483, but not HK486, virus induced tachypnea and depressed HVR and HCVR without changes in arterial blood pH and gases; and 3 only HK483 virus led to NP-IR in vagal SP-IR neurons, but not in the carotid body, and increased density of vagal SP-IR neurons. In addition, all HK483, rather than HK486, mice died at 6 to 8 dpi and the earlier death was correlated with more severe depression of HVR and HCVR. Our data suggest that tachypnea and depressed HVR/HCVR occur at the early stage of lethal H5N1 viral infection associated with viral replication and increased SP-IR density in vagal neurons, which may contribute to the respiratory failure and death.

Inhaled /sup 239/PuO/sub 2/ and/or total-body gamma radiation: Early mortality and morbidity in rats and dogs

Energy Technology Data Exchange (ETDEWEB)

Filipy, R.E.; Decker, J.R.; Lai, Y.L.; Lauhala, K.E.; Buschbom, R.L.; Hiastala, M.P.; McGee, D.R.; Park, J.F.; Kuffel, E.G.; Ragan, H.A.; Cannon, W.C.; Yaniv, S.S.; Scott, B.R.

1988-08-01

Rats and beagle dogs were given doses of /sup 60/Co gamma radiation and/or body burdens of /sup 239/PuO/sub 2/ within lethal ranges in an experiment to determine and compare morbidity and mortality responses of both species within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell concentrations and by long-term loss of body weight and diminished pulmonary function in animals of both species that survived the acute gamma radiation syndrome. Inhaled plutonium caused a loss of body weight and diminished pulmonary function in both species, but its only effect on blood cell concentrations was lymphocytopenia in dogs. Combined gamma irradiation and plutonium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Plutonium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the long-term effect of plutonium lung burdens in both species. Rats were less sensitive to both kinds of radiation, whether administered alone or in combination. 71 refs., 105 figs., 48 tabs.

Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

Energy Technology Data Exchange (ETDEWEB)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

2011-12-15

Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

sigE facilitates the adaptation of Bordetella bronchiseptica to stress conditions and lethal infection in immunocompromised mice

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Barchinger Sarah E

2012-08-01

Full Text Available Abstract Background The cell envelope of a bacterial pathogen can be damaged by harsh conditions in the environment outside a host and by immune factors during infection. Cell envelope stress responses preserve the integrity of this essential compartment and are often required for virulence. Bordetella species are important respiratory pathogens that possess a large number of putative transcription factors. However, no cell envelope stress responses have been described in these species. Among the putative Bordetella transcription factors are a number of genes belonging to the extracytoplasmic function (ECF group of alternative sigma factors, some of which are known to mediate cell envelope stress responses in other bacteria. Here we investigate the role of one such gene, sigE, in stress survival and pathogenesis of Bordetella bronchiseptica. Results We demonstrate that sigE encodes a functional sigma factor that mediates a cell envelope stress response. Mutants of B. bronchiseptica strain RB50 lacking sigE are more sensitive to high temperature, ethanol, and perturbation of the envelope by SDS-EDTA and certain β-lactam antibiotics. Using a series of immunocompromised mice deficient in different components of the innate and adaptive immune responses, we show that SigE plays an important role in evading the innate immune response during lethal infections of mice lacking B cells and T cells. SigE is not required, however, for colonization of the respiratory tract of immunocompetent mice. The sigE mutant is more efficiently phagocytosed and killed by peripheral blood polymorphonuclear leukocytes (PMNs than RB50, and exhibits decreased cytotoxicity toward macrophages. These altered interactions with phagocytes could contribute to the defects observed during lethal infection. Conclusions Much of the work on transcriptional regulation during infection in B. bronchiseptica has focused on the BvgAS two-component system. This study reveals that the Sig

Protection against lethal Marburg virus infection mediated by lipid encapsulated small interfering RNA.

Science.gov (United States)

Ursic-Bedoya, Raul; Mire, Chad E; Robbins, Marjorie; Geisbert, Joan B; Judge, Adam; MacLachlan, Ian; Geisbert, Thomas W

2014-02-15

Marburg virus (MARV) infection causes severe morbidity and mortality in humans and nonhuman primates. Currently, there are no licensed therapeutics available for treating MARV infection. Here, we present the in vitro development and in vivo evaluation of lipid-encapsulated small interfering RNA (siRNA) as a potential therapeutic for the treatment of MARV infection. The activity of anti-MARV siRNAs was assessed using dual luciferase reporter assays followed by in vitro testing against live virus. Lead candidates were tested in lethal guinea pig models of 3 different MARV strains (Angola, Ci67, Ravn). Treatment resulted in 60%-100% survival of guinea pigs infected with MARV. Although treatment with siRNA targeting other MARV messenger RNA (mRNA) had a beneficial effect, targeting the MARV NP mRNA resulted in the highest survival rates. NP-718m siRNA in lipid nanoparticles provided 100% protection against MARV strains Angola and Ci67, and 60% against Ravn. A cocktail containing NP-718m and NP-143m provided 100% protection against MARV Ravn. These data show protective efficacy against the most pathogenic Angola strain of MARV. Further development of the lipid nanoparticle technology has the potential to yield effective treatments for MARV infection.

INHALATION ANTIBIOTICS ARE ESSENTIAL FOR THE CONTROL OF INFECTION IN CHILDREN WITH CYSTIC FIBROSIS

Directory of Open Access Journals (Sweden)

O.I. Simonova

2011-01-01

Full Text Available The article discusses the problem of basis therapy in patients with chronic Pseudomonas aeruginosa infection and cystic fibrosis. Authors showed the safety, good tolerance and high efficacy of constant treatment with special tobramycin solution delivered by nebulizer (Tobi in children including ones under 6 years old. Even first inhalations of tobramycin result in decrease of Pseudomonas aeruginosa rate in bacterial inoculation or to it complete removal. The drug helps stabilization of clinical and functional state of patients, improvement of airflow and common state, and to clinical remission.Key words: children, cystic fibrosis, chronic Pseudomonas aeruginosa infection, tobramycin, nebulizer therapy.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 119–123

Radioprotective effect of chitosan in sub-lethally X-ray irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Nishimura, Yoshikazu; Ikota, Nobuo; Arima, Hiromi; Watanabe, Yoshito; Yukawa, Masae; Ozawa, Toshihiko [National Inst. of Radiological Sciences, Chiba (Japan); Kim, Hee-Sun [Korea Hydro and Nuclear Power Corp., Seoul (Korea, Republic of). Radiation Health Research Inst.; Bom, Hee-Seung; Kim, Young-Ho [Chonnam Univ., Kwangju (Korea, Republic of). Hospital

2003-03-01

The radioprotective effect of chitosan was studied in mice following whole-body X-ray irradiation. C3H/He mice were exposed to 7 Gy, and their survival rates were examined. The survival rates of chitosan-diet mice were about 20% higher than those of mice on a standard diet, and the rates dropped sharply to a plateau at day 10 after X-ray irradiation. The chitosan-diet mice had an increased weight ratio of spleen to body within the experimental period. The leukocyte, thrombocyte, and erythrocyte counts as well as the hematocrit and hemoglobin levels were recovered significantly and more rapidly in the chitosan-diet mice than the standard-diet mice at day 14 after irradiation. The scavenging abilities of chitosan were evaluated by the electron spin resonance (ESR) spin-trapping method. These observations suggested that chitosan led to hematopoetic activation and leuko-cytogenesis in mice after sub-lethal dose irradiation, and that the biological response might be caused by radical trapping or scavenging. (author)

Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer-Deficient Neonates

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Eleonore Ostermann

2015-05-01

Full Text Available Among Herpesviruses, Human Cytomegalovirus (HCMV or HHV-5 represents a major threat during congenital or neonatal infections, which may lead to encephalitis with serious neurological consequences. However, as opposed to other less prevalent pathogens, the mechanisms and genetic susceptibility factors for CMV encephalitis are poorly understood. This lack of information considerably reduces the prognostic and/or therapeutic possibilities. To easily monitor the effects of genetic defects on brain dissemination following CMV infection we used a recently developed in vivo mouse model based on the neonatal inoculation of a MCMV genetically engineered to express Luciferase. Here, we further validate this protocol for live imaging, and demonstrate increased lethality associated with viral infection and encephalitis in mutant mice lacking Dicer activity. Our data indicate that miRNAs are important players in the control of MCMV pathogenesis and suggest that miRNA-based endothelial functions and integrity are crucial for CMV encephalitis.

Healthcare-associated infections in sub-Saharan Africa.

Science.gov (United States)

Rothe, C; Schlaich, C; Thompson, S

2013-12-01

Healthcare-associated infections (HCAIs) are the most frequent adverse consequences of healthcare worldwide, threatening the health of both patients and healthcare workers (HCWs). The impact of HCAI is particularly felt in resource-poor countries, with an already overstretched health workforce and a high burden of community-acquired infection. To provide an overview of the current situation in sub-Saharan Africa with regards to the spectrum of HCAI, antimicrobial resistance, occupational exposure and infection prevention. We reviewed the literature published between 1995 and 2013 and from other sources such as national and international agencies. Sparse data suggest that HCAIs are widespread in sub-Saharan Africa, with surgical site being the dominant focus of infection. Nosocomial transmission of multidrug-resistant tuberculosis is a considerable concern, as is the prevalence of meticillin-resistant S. aureus and resistant Enterobacteriaceae. In HCWs, vaccination rates against vaccine-preventable occupational hazards are low, as is reporting and subsequent human immunodeficiency virus-testing after occupational exposure. HCWs have an increased risk of tuberculosis relative to the general population. Compliance with hand hygiene is highly variable within the region. Injection safety in immunization programmes has improved over the past decade, mainly due to the introduction of autodestruct syringes. Despite the scarcity of data, the burden of HCAI in sub-Saharan Africa appears to be high. There is evidence of some improvement in infection prevention and control, though widespread surveillance data are lacking. Overall, measures of infection prevention and occupational safety are scarce. Copyright © 2013 The Healthcare Infection Society. All rights reserved.

Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

International Nuclear Information System (INIS)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A.; Alaee, Mehran; Simpson, Andre J.; Simpson, Myrna J.

2011-01-01

Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: → NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. → Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. → NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - 1 H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

Effects of Helicobacter pylori infection on common lethal factors for hepatitis B virus-related cirrhosis

Directory of Open Access Journals (Sweden)

LI Yuling

2015-09-01

Full Text Available ObjectiveTo study the relationship between Helicobacter pylori (H. pylori infection and common lethal factors for hepatitis B virus-related cirrhosis (HBC. MethodsA total of 235 patients with HBC who were admitted to our hospitals from October 2008 to October 2014 were retrospectively analyzed. The infection rate of H. pylori in those patients was calculated. In the 155 patients with esophagogastric varices and 97 patients with portal hypertensive gastropathy (PHG, the infection rate of H. pylori was compared between those with different degrees of esophagogastric varices or PHG. In the 32 patients whose blood ammonia was determined, the level of blood ammonia was compared between H. pylori-positive and -negative groups. Between-group comparison of continuous data was performed by t test and analysis of variance, and between-group comparison of categorical data was performed by χ2 test. ResultsThe infection rate of H. pylori in the 235 patients with HBC was 80.85% (190/235. In the 155 patients with esophagogastric varices, who had tortuous serpentine uplift or bead-like changes of esophageal varices and tumor-like changes (with or without gastric erosion of gastric varices visible under endoscopy, there was significant difference in infection rate of H. pylori between patients with mild, moderate, and severe varices (50.55% (46/91 vs 43.59% (17/39 vs 76% (19/25, χ2=6.913, P＜0.05. In the 97 patients with PHG, who had snake skin-like changes, cherry red spots, scarlet rash, and erosion bleeding of gastric mucosa visible under endoscopy, there was significant difference in infection rate of H. pylori between patients with mild and severe PHG (43.33% (26/60 vs 67.57% (25/37, χ2=5.391, P＜005.In patients whose blood ammonia was determined, patients in H. pylori-positive group had a significantly higher average concentration of blood ammonia than those in H. pylori-negative group (62.76±13.43 vs 47.20±12.51 μmol/L, t= 3.39, P＜0

Lethal Zika Virus Disease Models in Young and Older Interferon α/β Receptor Knock Out Mice

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Andrea Marzi

2018-04-01

Full Text Available The common small animal disease models for Zika virus (ZIKV are mice lacking the interferon responses, but infection of interferon receptor α/β knock out (IFNAR−/− mice is not uniformly lethal particularly in older animals. Here we sought to advance this model in regard to lethality for future countermeasure efficacy testing against more recent ZIKV strains from the Asian lineage, preferably the American sublineage. We first infected IFNAR−/− mice subcutaneously with the contemporary ZIKV-Paraiba strain resulting in predominantly neurological disease with ~50% lethality. Infection with ZIKV-Paraiba by different routes established a uniformly lethal model only in young mice (4-week old upon intraperitoneal infection. However, intraperitoneal inoculation of ZIKV-French Polynesia resulted in uniform lethality in older IFNAR−/− mice (10–12-weeks old. In conclusion, we have established uniformly lethal mouse disease models for efficacy testing of antivirals and vaccines against recent ZIKV strains representing the Asian lineage.

Back to the future: revisiting HIV-1 lethal mutagenesis

Science.gov (United States)

Dapp, Michael J.; Patterson, Steven E.; Mansky, Louis M.

2012-01-01

The concept of eliminating HIV-1 infectivity by elevating the viral mutation rate was first proposed over a decade ago, even though the general concept had been conceived earlier for RNA viruses. Lethal mutagenesis was originally viewed as a novel chemotherapeutic approach for treating HIV-1 infection in which use of a viral mutagen would over multiple rounds of replication lead to the lethal accumulation of mutations, rendering the virus population non infectious – known as the slow mutation accumulation model. There have been limitations in obtaining good efficacy data with drug leads, leaving some doubt into clinical translation. More recent studies of the APOBEC3 proteins as well as new progress in the use of nucleoside analogs for inducing lethal mutagenesis have helped to refocus attention on rapid induction of HIV-1 lethal mutagenesis in a single or limited number of replication cycles leading to a rapid mutation accumulation model. PMID:23195922

In Vitro Evaluation of Sub-Lethal Concentrations of Plant-Derived Antifungal Compounds on FUSARIA Growth and Mycotoxin Production

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Caterina Morcia

2017-07-01

Full Text Available Phytopathogenic fungi can lead to significant cereal yield losses, also producing mycotoxins dangerous for human and animal health. The fungal control based on the use of synthetic fungicides can be complemented by "green" methods for crop protection, based on the use of natural products. In this frame, the antifungal activities of bergamot and lemon essential oils and of five natural compounds recurrent in essential oils (citronellal, citral, cinnamaldehyde, cuminaldehyde and limonene have been evaluated against three species of mycotoxigenic fungi (Fusarium sporotrichioides, F. graminearum and F. langsethiae responsible for Fusarium Head Blight in small-grain cereals. The natural products concentrations effective for reducing or inhibiting the in vitro fungal growth were determined for each fungal species and the following scale of potency was found: cinnamaldehyde > cuminaldehyde > citral > citronellal > bergamot oil > limonene > lemon oil. Moreover, the in vitro mycotoxin productions of the three Fusaria strains exposed to sub-lethal concentrations of the seven products was evaluated. The three fungal species showed variability in response to the treatments, both in terms of inhibition of mycelial growth and in terms of modulation of mycotoxin production that can be enhanced by sub-lethal concentrations of some natural products. This last finding must be taken into account in the frame of an open field application of some plant-derived fungicides.

1H NMR-Based Metabolomic Analysis of Sub-Lethal Perfluorooctane Sulfonate Exposure to the Earthworm, Eisenia fetida, in Soil

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Myrna J. Simpson

2013-08-01

Full Text Available 1H NMR-based metabolomics was used to measure the response of Eisenia fetida earthworms after exposure to sub-lethal concentrations of perfluorooctane sulfonate (PFOS in soil. Earthworms were exposed to a range of PFOS concentrations (five, 10, 25, 50, 100 or 150 mg/kg for two, seven and fourteen days. Earthworm tissues were extracted and analyzed by 1H NMR. Multivariate statistical analysis of the metabolic response of E. fetida to PFOS exposure identified time-dependent responses that were comprised of two separate modes of action: a non-polar narcosis type mechanism after two days of exposure and increased fatty acid oxidation after seven and fourteen days of exposure. Univariate statistical analysis revealed that 2-hexyl-5-ethyl-3-furansulfonate (HEFS, betaine, leucine, arginine, glutamate, maltose and ATP are potential indicators of PFOS exposure, as the concentrations of these metabolites fluctuated significantly. Overall, NMR-based metabolomic analysis suggests elevated fatty acid oxidation, disruption in energy metabolism and biological membrane structure and a possible interruption of ATP synthesis. These conclusions obtained from analysis of the metabolic profile in response to sub-lethal PFOS exposure indicates that NMR-based metabolomics is an excellent discovery tool when the mode of action (MOA of contaminants is not clearly defined.

Perioperative respiratory adverse events in children with active upper respiratory tract infection who received general anesthesia through an orotracheal tube and inhalation agents

OpenAIRE

Kim, So Yeon; Kim, Jeong Min; Lee, Jae Hoon; Kang, Young Ran; Jeong, Seung Ho; Koo, Bon-Nyeo

2013-01-01

Background Active upper respiratory tract infection (URI), orotracheal intubation and use of inhalation anesthetics are known risk factors for perioperative respiratory adverse events (RAE). This study investigated the risk factors of perioperative RAE in children with these risk factors. Methods The records of 159 children who underwent general anesthesia with an orotracheal tube and inhalation were reviewed. These patients also had at least one of the following URI symptoms on the day of su...

{sup 1}H NMR-based metabolomics of time-dependent responses of Eisenia fetida to sub-lethal phenanthrene exposure

Energy Technology Data Exchange (ETDEWEB)

Lankadurai, Brian P.; Wolfe, David M.; Simpson, Andre J. [Department of Chemistry, University of Toronto, 1265 Military Trail, Toronto, Ontario M1C 1A4 Canada (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Chemistry, University of Toronto, 1265 Military Trail, Toronto, Ontario M1C 1A4 Canada (Canada)

2011-10-15

{sup 1}H NMR-based metabolomics was used to examine the response of the earthworm Eisenia fetida after exposure to sub-lethal concentrations of phenanthrene over time. Earthworms were exposed to 0.025 mg/cm{sup 2} of phenanthrene (1/64th of the LC{sub 50}) via contact tests over four days. Earthworm tissues were extracted using a mixture of chloroform, methanol and water, resulting in polar and non-polar fractions that were analyzed by {sup 1}H NMR after one, two, three and four days. NMR-based metabolomic analyses revealed heightened E. fetida responses with longer phenanthrene exposure times. Amino acids alanine and glutamate, the sugar maltose, the lipids cholesterol and phosphatidylcholine emerged as potential indicators of phenanthrene exposure. The conversion of succinate to fumarate in the Krebs cycle was also interrupted by phenanthrene. Therefore, this study shows that NMR-based metabolomics is a powerful tool for elucidating time-dependent relationships in addition to the mode of toxicity of phenanthrene in earthworm exposure studies. - Highlights: > NMR-based earthworm metabolomic analysis of the mode of action of phenanthrene is presented. > The earthworm species E. fetida were exposed to sub-lethal phenanthrene concentrations. > Both polar and non-polar metabolites of E. fetida tissue extracts were analyzed by {sup 1}H NMR. > Longer phenanthrene exposure times resulted in heightened earthworm responses. > An interruption of the Krebs cycle was also observed due to phenanthrene exposure. - {sup 1}H NMR metabolomics is used to determine the relationship between phenanthrene exposure and the metabolic response of the earthworm E. fetida over time and also to elucidate the phenanthrene mode of toxicity.

Protection from genital herpes disease, seroconversion and latent infection in a non-lethal murine genital infection model by immunization with an HSV-2 replication-defective mutant virus.

Science.gov (United States)

Diaz, Fernando M; Knipe, David M

2016-01-15

Viral vaccines have traditionally protected against disease, but for viruses that establish latent infection, it is desirable for the vaccine to reduce infection to reduce latent infection and reactivation. While seroconversion has been used in clinical trials of herpes simplex virus (HSV) vaccines to measure protection from infection, this has not been modeled in animal infection systems. To measure the ability of a genital herpes vaccine candidate to protect against various aspects of infection, we established a non-lethal murine model of genital HSV-2 infection, an ELISA assay to measure antibodies specific for infected cell protein 8 (ICP8), and a very sensitive qPCR assay. Using these assays, we observed that immunization with HSV-2 dl5-29 virus reduced disease, viral shedding, seroconversion, and latent infection by the HSV-2 challenge virus. Therefore, it may be feasible to obtain protection against genital disease, seroconversion and latent infection by immunization, even if sterilizing immunity is not achieved. Copyright © 2015 Elsevier Inc. All rights reserved.

Lethal Epistaxis.

Science.gov (United States)

Byard, Roger W

2016-09-01

Epistaxis or nosebleed refers to bleeding from the nostrils, nasal cavity, or nasopharynx. Occasional cases may present with torrential lethal hemorrhage. Three cases are reported to demonstrate particular features: Case 1: A 51-year-old woman with lethal epistaxis with no obvious bleeding source; Case 2: A 77-year-old man with treated nasopharyngeal carcinoma who died from epistaxis arising from a markedly neovascularized tumor bed; Case 3: A 2-year-old boy with hemophilia B who died from epistaxis with airway obstruction in addition to gastrointestinal bleeding. Epistaxis may be associated with trauma, tumors, vascular malformations, bleeding diatheses, infections, pregnancy, endometriosis, and a variety of different drugs. Careful dissection of the nasal cavity is required to locate the site of hemorrhage and to identify any predisposing conditions. This may be guided by postmortem computerized tomographic angiography (PCTA). Despite careful dissection, however, a source of bleeding may never be identified. © 2016 American Academy of Forensic Sciences.

Effects of sub-lethal dose of γ-irradiation on lysosomal enzymes in tissue of pigeon

International Nuclear Information System (INIS)

Shah, V.C.; Gadhia, P.K.

1979-01-01

Effects of total body γ-irradiation with sub-lethal dose (300 rad) on three lysosomal enzymes namely acid phosphatase, ribonuclease-II and deoxyribonuclease-II have been studied in pigeons. Liver, kidney and spleen were the tissues studied at different intervals like 1-h, 24-h, 48-h, and 72-h of irradiation. The specific activities ('crude' fraction) of acid phosphatase and ribonuclease-II increased significantly in spleen and liver at 48-h of irradiation. The activity of deoxyribonuclease-II in liver and spleen was increased only at 72-h post-irradiation. On the other hand, the total activities of three lysosomal enzymes did not show remarkable change throughout 72-h of irradiation. (author)

A lethal model of disseminated dengue virus type 1 infection in AG129 mice.

Science.gov (United States)

Milligan, Gregg N; Sarathy, Vanessa V; White, Mellodee M; Greenberg, M Banks; Campbell, Gerald A; Pyles, Richard B; Barrett, Alan D T; Bourne, Nigel

2017-10-01

The mosquito-borne disease dengue is caused by four serologically and genetically related flaviviruses termed DENV-1 to DENV-4. Dengue is a global public health concern, with both the geographical range and burden of disease increasing rapidly. Clinically, dengue ranges from a relatively mild self-limiting illness to a severe life-threatening and sometimes fatal disease. Infection with one DENV serotype produces life-long homotypic immunity, but incomplete and short-term heterotypic protection. The development of small-animal models that recapitulate the characteristics of the disseminated disease seen clinically has been difficult, slowing the development of vaccines and therapeutics. The AG129 mouse (deficient in interferon alpha/beta and gamma receptor signalling) has proven to be valuable for this purpose, with the development of models of disseminated DENV-2,-3 and -4 disease. Recently, a DENV-1 AG129 model was described, but it requires antibody-dependent enhancement (ADE) to produce lethality. Here we describe a new AG129 model utilizing a non-mouse-adapted DENV-1 strain, West Pacific 74, that does not require ADE to induce lethal disease. Following high-titre intraperitoneal challenge, animals experience a virus infection with dissemination to multiple visceral tissues, including the liver, spleen and intestine. The animals also become thrombocytopenic, but vascular leakage is less prominent than in AG129 models with other DENV serotypes. Taken together, our studies demonstrate that this model is an important addition to dengue research, particularly for understanding the pathological basis of the disease between DENV serotypes and allowing the full spectrum of activity to test comparisons for putative vaccines and antivirals.

Induction of high tolerance to artemisinin by sub-lethal administration: A new in vitro model of P. falciparum.

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Serena De Lucia

Full Text Available Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1, by treating P. falciparum Palo Alto (PA cultures with sub-lethal concentrations of dihydroartemisinin (DHA. The resistance phenotype was maintained for over 1 year through monthly maintenance treatments with low doses of 2.5 nM DHA. There was a moderate increase in the DHA IC50 in ARS1 when compared with parental strain PA after 72 h of drug exposure (from 0.68 nM to 2 nM DHA. In addition, ARS1 survived treatment physiologically relevant DHA concentrations (700 nM observed in patients. Furthermore, we confirmed a lack of cross-resistance against a panel of antimalarials commonly used as partner drugs in ACTs. Finally, ARS1 did not contain Pfk13 propeller domain mutations associated with ART resistance in the Greater Mekong Region. With a stable growth rate, ARS1 represents a valuable tool for the development of new antimalarial compounds and studies to further elucidate the mechanisms of ART resistance.

Exposure to Sub-lethal 2,4-Dichlorophenoxyacetic Acid Arrests Cell Division and Alters Cell Surface Properties in Escherichia coli

Science.gov (United States)

Bhat, Supriya V.; Kamencic, Belma; Körnig, André; Shahina, Zinnat; Dahms, Tanya E. S.

2018-01-01

Escherichia coli is a robust, easily adaptable and culturable bacterium in vitro, and a model bacterium for studying the impact of xenobiotics in the environment. We have used correlative atomic force – laser scanning confocal microscopy (AFM-LSCM) to characterize the mechanisms of cellular response to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). One of the most extensively used herbicides world-wide, 2,4-D is known to cause hazardous effects in diverse non-target organisms. Sub-lethal concentrations of 2,4-D caused DNA damage in E. coli WM1074 during short exposure periods which increased significantly over time. In response to 2,4-D, FtsZ and FtsA relocalized within seconds, coinciding with the complete inhibition of cell septation and cell elongation. Exposure to 2,4-D also resulted in increased activation of the SOS response. Changes to cell division were accompanied by concomitant changes to surface roughness, elasticity and adhesion in a time-dependent manner. This is the first study describing the mechanistic details of 2,4-D at sub-lethal levels in bacteria. Our study suggests that 2,4-D arrests E. coli cell division within seconds after exposure by disrupting the divisome complex, facilitated by dissipation of membrane potential. Over longer exposures, 2,4-D causes filamentation as a result of an SOS response to oxidative stress induced DNA damage. PMID:29472899

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

Science.gov (United States)

Terryn, Sanne; Francart, Aurélie; Rommelaere, Heidi; Stortelers, Catelijne; Van Gucht, Steven

2016-01-01

Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP. PMID:27483431

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection.

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Sanne Terryn

2016-08-01

Full Text Available Post-exposure prophylaxis (PEP against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days and decreased mortality (60% versus 19% survival rate, when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

Sub-lethal effects of the neurotoxic pyrethroid insecticide Fastac 50EC on the general motor and locomotor activities of the non-targeted beneficial carabid beetle Platynus assimilis (Coleoptera: Carabidae).

Science.gov (United States)

Tooming, Ene; Merivee, Enno; Must, Anne; Sibul, Ivar; Williams, Ingrid

2014-06-01

Sub-lethal effects of pesticides on behavioural endpoints are poorly studied in carabids (Coleoptera: Carabidae) though changes in behaviour caused by chemical stress may affect populations of these non-targeted beneficial insects. General motor activity and locomotion are inherent in many behavioural patterns, and changes in these activities that result from xenobiotic influence mirror an integrated response of the insect to pesticides. Influence of pyrethroid insecticides over a wide range of sub-lethal doses on the motor activities of carabids still remains unclear. Video tracking of Platynus assimilis showed that brief exposure to alpha-cypermethrin at sub-lethal concentrations ranged from 0.01 to 100 mg L(-1) caused initial short-term (24 h) locomotor hypo-activity. In addition, significant short- and long-term concentration and time-dependent changes occurred in general motor activity patterns and rates. Conspicuous changes in motor activity of Platynus assimilis beetles treated at alpha-cypermethrin concentrations up to 75,000-fold lower than maximum field recommended concentration (MFRC) suggest that many, basic fitness-related behaviours might be severely injured as well. These changes may negatively affect carabid populations in agro-ecosystems. Long-term hypo-activity could directly contribute to decreased trap captures of carabids frequently observed after insecticide application in the field. © 2013 Society of Chemical Industry.

Papaya Lethal Yellowing Virus (PLYV) Infects Vasconcellea cauliflora

NARCIS (Netherlands)

Amaral, P.P.R.; Resende, de R.O.; Souza, M.T.

2006-01-01

Papaya lethal yellowing virus (PLYV) é um dos três vírus descritos infectando mamoeiros (Carica papaya L.) no Brasil. Vasconcellea cauliflora (Jacq.) A. DC., antes denominada de Carica cauliflora (Jacq.), é uma reconhecida fonte de resistência natural ao Papaya ringspot virus (PRSV), causador da

An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus.

Science.gov (United States)

Leung, Ho-Chuen; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Zhao, Han-Jun; Cheung, Chung-Yan; Ng, Fai; Huang, Jian-Dong; Zheng, Bo-Jian

2015-04-01

In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.

1H NMR-based metabolomics of time-dependent responses of Eisenia fetida to sub-lethal phenanthrene exposure

International Nuclear Information System (INIS)

Lankadurai, Brian P.; Wolfe, David M.; Simpson, Andre J.; Simpson, Myrna J.

2011-01-01

1 H NMR-based metabolomics was used to examine the response of the earthworm Eisenia fetida after exposure to sub-lethal concentrations of phenanthrene over time. Earthworms were exposed to 0.025 mg/cm 2 of phenanthrene (1/64th of the LC 50 ) via contact tests over four days. Earthworm tissues were extracted using a mixture of chloroform, methanol and water, resulting in polar and non-polar fractions that were analyzed by 1 H NMR after one, two, three and four days. NMR-based metabolomic analyses revealed heightened E. fetida responses with longer phenanthrene exposure times. Amino acids alanine and glutamate, the sugar maltose, the lipids cholesterol and phosphatidylcholine emerged as potential indicators of phenanthrene exposure. The conversion of succinate to fumarate in the Krebs cycle was also interrupted by phenanthrene. Therefore, this study shows that NMR-based metabolomics is a powerful tool for elucidating time-dependent relationships in addition to the mode of toxicity of phenanthrene in earthworm exposure studies. - Highlights: → NMR-based earthworm metabolomic analysis of the mode of action of phenanthrene is presented. → The earthworm species E. fetida were exposed to sub-lethal phenanthrene concentrations. → Both polar and non-polar metabolites of E. fetida tissue extracts were analyzed by 1 H NMR. → Longer phenanthrene exposure times resulted in heightened earthworm responses. → An interruption of the Krebs cycle was also observed due to phenanthrene exposure. - 1 H NMR metabolomics is used to determine the relationship between phenanthrene exposure and the metabolic response of the earthworm E. fetida over time and also to elucidate the phenanthrene mode of toxicity.

Mucor irregularis infection and lethal midline granuloma: a case report and review of published literature.

Science.gov (United States)

Li, Dong Ming; Lun, Li De

2012-12-01

Mucor irregularis (Rhizomucor variabilis) infection and lethal midline granuloma (LMG) are characterized by progressive swelling, ulceration, and destruction of the central face that is usually fatal. Pathological features are inflammation, necrosis, and granulation. LMG has been called by various names, and in recent years, it has been known as NK/T cell lymphoma. However, diagnosis still relies on the progressive necrosis course rather than malignancy in histology. The disease has long challenged physicians, particularly when it worsens with radiotherapy or chemotherapy but sometimes achieves total remission without anti-malignancy therapies. We describe a 35-year-old man who had typical clinical-pathological symptoms of LMG, which turned out to be primary M. irregularis infection; that was diagnosed by positive tissue culture and fungal elements in histology. The patient was successfully treated with antifungal therapy (liposomal amphotericin B, total 4,600 mg and amphotericin B total 277 mg, over a duration of 70 days). We hereby review current knowledge about the epidemiology, clinical manifestations, radiographic characteristics, and pathologic features of LMG with those of M. irregularis infection and their associations. We conclude that primary M. irregulars infection can mimic the clinico-pathological symptoms of LMG and the condition responds favorably to aggressive antifungal therapy.

Presence of virus neutralizing antibodies in cerebral spinal fluid correlates with non-lethal rabies in dogs.

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Clement W Gnanadurai

Full Text Available Rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.Non-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico correlates with the presence of high level of virus neutralizing antibodies (VNA in the cerebral spinal fluid (CSF and mild immune cell accumulation in the central nervous system (CNS. By contrast, dogs that succumbed to rabies showed only little or no VNA in the serum or in the CSF and severe inflammation in the CNS. Dogs vaccinated with a rabies vaccine showed no clinical signs of rabies and survived challenge with a lethal dose of wild-type DRV. VNA was detected in the serum, but not in the CSF of immunized dogs. Thus the presence of VNA is critical for inhibiting virus spread within the CNS and eventually clearing the virus from the CNS.Non-lethal infection with wt RABV correlates with the presence of VNA in the CNS. Therefore production of VNA within the CNS or invasion of VNA from the periphery into the CNS via compromised blood-brain barrier is important for clearing the virus infection from CNS, thereby preventing an otherwise lethal rabies virus infection.

Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.

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Cristian Cillóniz

2009-10-01

Full Text Available The enormous toll on human life during the 1918-1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5N1 avian influenza virus infection, a better understanding of the host response to highly pathogenic influenza viruses is essential. To this end, we compared pathology and global gene expression profiles in bronchial tissue from macaques infected with either the reconstructed 1918 pandemic virus or the highly pathogenic avian H5N1 virus A/Vietnam/1203/04. Severe pathology was observed in respiratory tissues from 1918 virus-infected animals as early as 12 hours after infection, and pathology steadily increased at later time points. Although tissues from animals infected with A/Vietnam/1203/04 also showed clear signs of pathology early on, less pathology was observed at later time points, and there was evidence of tissue repair. Global transcriptional profiles revealed that specific groups of genes associated with inflammation and cell death were up-regulated in bronchial tissues from animals infected with the 1918 virus but down-regulated in animals infected with A/Vietnam/1203/04. Importantly, the 1918 virus up-regulated key components of the inflammasome, NLRP3 and IL-1beta, whereas these genes were down-regulated by A/Vietnam/1203/04 early after infection. TUNEL assays revealed that both viruses elicited an apoptotic response in lungs and bronchi, although the response occurred earlier during 1918 virus infection. Our findings suggest that the severity of disease in 1918 virus-infected macaques is a consequence of the early up-regulation of cell death and inflammatory related genes, in which additive or synergistic effects likely dictate the severity of tissue damage.

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

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Diego J. Maselli

2017-05-01

Full Text Available The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM. These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

Late effects following inhalation of mixed oxide (U,PuO{sub 2}) mox aerosol in the rat; Effets tardifs de l'inhalation d'aerosols de Mox 2,5% ou 7,1% Pu chez le rat

Energy Technology Data Exchange (ETDEWEB)

Griffiths, N.; Van Der Meeren, A.; Fritsch, P.; Maximilien, R

2008-07-01

Exposure to alpha-emitting particles is a potential long-term health risk to workers in nuclear fuel fabrication plants. Mixed Oxide (MOX: U,PuO{sub 2}) fuels containing low percentages of plutonium obtained from spent nuclear fuels are increasingly employed and in the case of accidental contamination by inhalation or wounds may result in the development of late-occurring pathologies such as lung cancer. However the long term risks particularly with regard to lung cancer are to date unclear. In the case of MOX the risk may indeed be different from that assigned to the individual components, plutonium and uranium. Several factors are influential (i) the dissolution of Pu depends on the physico-chemical properties, for example risk of lung cancer is increased 10 fold after Pu(NO{sub 3}){sub 2} as compared with PuO{sub 2}. (ii) The solubility of Pu is variable whether delivered as PuO{sub 2} or contained within MOX. (iii) The risk of cancer appears to increase with spatial homogeneity of the lung alpha dose. The objective of this study was to investigate the long term effects in rat lungs following MOX aerosol inhalation of similar particle size containing 2.5 or 7.1% Pu. Conscious rats were exposed to MOX aerosols using a 'nose-only' system and kept for their entire life (2-3 years). Different Initial Lung Deposits (ILDs) were obtained using different concentrations of the MOX suspension. Lung total alpha activity was determined in vivo at intervals over the study period by external counting as well as at autopsy in order to estimate the total lung dose. Anatomo-pathological and immunohistochemical analyses were performed on fixed lung tissue after euthanasia. The frequencies of lung pathologies and tumours were determined on lung sections at several different levels. In addition, autoradiography of lung sections was performed in order to assess the spatial localisation of a activity. Inhalation of MOX at ILD ranging from 1-20 kBq resulted in lung

Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax

National Research Council Canada - National Science Library

Heine, H. S; Bassett, J; Miller, L; Bassett, A; Ivins, B. E; Lehous, D; Arhin, F. F; Parr, Jr., T. R; Moeck, G

2008-01-01

The inhaled form of Bacillus anthracis infection may be fatal to humans. The current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days...

Anthrax lethal toxin disrupts intestinal barrier function and causes systemic infections with enteric bacteria.

Directory of Open Access Journals (Sweden)

Chen Sun

Full Text Available A variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (MAPK signaling pathways, including Bacillus anthracis. Anthrax lethal toxin (LT has specific proteolytic activity against the upstream regulators of MAPKs, the MAPK kinases (MKKs. Using a murine model of intoxication, we show that LT causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. This pathology correlates with an LT-dependent blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. C57BL/6J mice treated with intravenous LT nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. LT-dependent intestinal pathology depends upon its proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics, indicating that it is both a cause and an effect of infection. These findings indicate that targeting of MAPK signaling pathways by anthrax LT compromises the structural integrity of the mucosal layer, serving to undermine the effectiveness of the intestinal barrier. Combined with the well-described immunosuppressive effects of LT, this disruption of the intestinal barrier provides a potential mechanism for host invasion via the enteric route, a common portal of entry during the natural infection cycle of Bacillus anthracis.

Biodiversity of soil bacteria exposed to sub-lethal concentrations of phosphonium-based ionic liquids: Effects of toxicity and biodegradation

DEFF Research Database (Denmark)

Sydow, Mateusz; Owsianiak, Mikołaj; Framski, Grzegorz

2018-01-01

on the structure of microbial community present in an urban park soil in 100-day microcosm experiments. The biodiversity decreased in all samples (Shannon's index decreased from 1.75 down to 0.74 and OTU's number decreased from 1399 down to 965) with the largest decrease observed in the microcosms spiked with ILs...... ILs or their metabolites. Thus, the introduction of phosphonium-based ILs into soils at sub-lethal concentrations may result not only in a decrease in biodiversity due to toxic effects, but also in enrichment with ILs-degrading bacteria....

Characterization of Toxoplasma DegP, a rhoptry serine protease crucial for lethal infection in mice.

Directory of Open Access Journals (Sweden)

Gaelle Lentini

Full Text Available During the infection process, Apicomplexa discharge their secretory organelles called micronemes, rhoptries and dense granules to sustain host cell invasion, intracellular replication and to modulate host cell pathways and immune responses. Herein, we describe the Toxoplasma gondii Deg-like serine protein (TgDegP, a rhoptry protein homologous to High temperature requirement A (HtrA or Deg-like family of serine proteases. TgDegP undergoes processing in both types I and II strains as most of the rhoptries proteins. We show that genetic disruption of the degP gene does not impact the parasite lytic cycle in vitro but affects virulence in mice. While in a type I strain DegPI appears dispensable for the establishment of an infection, removal of DegPII in a type II strain dramatically impairs the virulence. Finally, we show that KO-DegPII parasites kill immunodeficient mice as efficiently as the wild-type strain indicating that the protease might be involved in the complex crosstalk that the parasite engaged with the host immune response. Thus, this study unravels a novel rhoptry protein in T. gondii important for the establishment of lethal infection.

Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Psuedomonas aeruginosa infection

DEFF Research Database (Denmark)

Bisgaard, H; Pedersen, S S; Nielsen, K G

1997-01-01

The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis (CF) and complicating chronic Pseudomonas aeruginosa (P.a.) lung infection was studied in a placebo-controlled, parallel, double-blind single center trial. Active treatment...... consisted of budesonide dry powder, 800 microg twice daily, delivered from a Turbuhaler. The study period covered two successive 3-mo intervals between elective courses of intravenous anti-Pseudomonas antibiotics. Fifty-five patients entered the study, with a mean age of 20 yr and a mean FEV1 of 63...

[INHALED ANTIBIOTICS IN TREATMENT OF NOSOCOMIAL PNEUMONIA].

Science.gov (United States)

Kuzovlev, A N; Moroz, V V; Golubev, A M

2015-01-01

Nosocomial pneumonia is the most common infection in intensive care units. Currently the problem of resistance of noso-comial pathogens to miost of antibiotics is crucial. Using of inhaled antibiotics in combination with intravenous drugs is eff ective and safe method for treatment of nosocomial pneumonia. The literature review describes current opportunities of ihhaled antibiotic therapy of nosocomial pneumonia, descriptions of drugs, the advantages and disadvantages of this treatment. Special attention is paid for using inhaled aminoglycosides for nosocomial pneumonia.

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

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Michael H. Norris

2018-01-01

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

Inhaled Antibiotics in Reanimatology: Problem State and Development Prospects (Review

Directory of Open Access Journals (Sweden)

A. N. Kuzovlev

2017-01-01

Full Text Available Nosocomial pneumonia is the second most common nosocomial infection in critical care units and most common in ALV patients (9—27%. The purpose of this literature review is to discuss the latest domestic and foreign body of evidence concerning the use of inhaled antibiotics в critical care. Search for domestic publications (literature reviews, observation studies, double blind randomized studies was carried out in elibrary.ru database, for foreign — in PubMed. Database for the period of yrs. 2005—2017. The following search enquiries were used: «inhaled antibiotics», «nosocomial pneumonia», «inhaled tobramycin», «inhaled colistin». The analysis includes 67 publications of yrs. 2007—2017 and 1 publication of yr. 2000. The literature review includes drug descriptions, contemporary capabilities of inhaled antibiotic therapy for nosocomial pneumonia, the advantages and drawbacks of this method of treatment. Special attention is focused on the use of inhaled aminoglycosides and inhaled colistin during nosocomial pneumonia in critical care units.

Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity.

Directory of Open Access Journals (Sweden)

Caline G Matar

2015-05-01

Full Text Available Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primary Plasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68 infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodium transmission.

The effect of sub-lethal damage repair and exchange on the final slope of cell survival curves

International Nuclear Information System (INIS)

Carlone, M.C.; Wilkins, D.E.; Raaphorst, G.P.

2003-01-01

Full text: The Lea-Catcheside dose rate protraction factor, G, is the most widely used model to describe the effects of dose rate on cell survival. In the linear quadratic formalism, this factor modifies the beta component of cell killing; G is greatest for acute irradiations while vanishing at low dose rates. We have found a simple compartmental model that can derive the Lea-Catcheside function. This compartmental model clearly shows that the G function can only be derived using a little known assumption: the diminution of sub-lethal damage due to exchange of repairable lesions is negligible compared to that due to repair. This assumption was explicitly stated by Lea, but it does not appear to have been restated or verified since very early work on cell survival. The implication of this assumption is that sub-lethal damage can be modeled without considering exchange, which is evidenced by the fact that the G function does not contain parameters relating to exchange. By using a new model that fully accounts for repair and exchange of sublethal lesions, a cell survival expression that has a modified G function, but that retains the linear quadratic formalism, can be obtained. At low doses, this new model predicts linear-quadratic behavior, but the behavior gradually changes to mono-exponential at high doses, which is consistent with experimental observations. Modeling cell survival of well-known survival curves using the modified linear quadratic model shows statistically significant improvement in the fits to the cell survival data as compared to best fits obtained with the linear quadratic model. It is shown that these improvements in fits are due to a superior representation of the high dose region of the survival curve

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.

Science.gov (United States)

Mbare, Oscar; Lindsay, Steven W; Fillinger, Ulrike

2013-03-14

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. 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. 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% of eggs laid by females exposed to 0

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

Science.gov (United States)

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

Determination of gamma radiation lethal dose (LD{sub 50}) and resveratrol cytotoxicity level in tumor cells line

Energy Technology Data Exchange (ETDEWEB)

Magalhaes, Vanessa D.; Rogero, Sizue O.; Rogero, Jose R. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Cruz, Aurea S. [Instituto Adolfo Lutz (IAL-SP) Secao de Culturas Celulares, SP (Brazil)

2011-07-01

Cancer is a disease with high incidence and it is considered a worldwide public health problem. Resveratrol is a polyphenol occurring naturally in a wide variety of plants according to response of ultraviolet radiation (UV) exposition or according to mechanical stress resulting of pathogens or chemical and physical agents. This polyphenol possesses a pharmacological activity of carcinogenesis inhibition in multiple levels. It also protects cells by scavenging the free radicals which are considered toxic products. These free radicals are formed of natural process of cell aging and also by incidence of ionizing radiation in the organism. Thus, resveratrol is considered as a cell radioprotector. On the other hand, in some elevated concentrations resveratrol may be considered as a radiosensitizing. The aim of this work was the determination of radiation lethal dose (LD{sub 50}) and also verifies the cytotoxicity level of resveratrol in tumor cells line: muco epidermoid pulmonary carcinoma cells (NCI-H292) and rhabdomyosarcoma cells (RD). The cytotoxicity test was performed by neutral red uptake assay. The results of resveratrol IC{sub 50%} in NCI-H292 cells was 192{mu}M and in RD cells was 128{mu}M; and RD cells gamma radiation LD{sub 50} was 435Gy. (author)

Inhalation of antibiotics in cystic fibrosis

NARCIS (Netherlands)

Touw, D J; Brimicombe, R W; Hodson, M E; Heijerman, H G; Bakker, W

Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of

Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

Energy Technology Data Exchange (ETDEWEB)

Morimoto, Yasuo, E-mail: yasuom@med.uoeh-u.ac.jp; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro [University of Occupational and Environmental Health (Japan); Shimada, Manabu; Kubo, Masaru [Hiroshima University (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Kawaguchi, Kenji; Sasaki, Takeshi [National Institute of Advanced Industrial Science and Technology (AIST) (Japan)

2015-11-15

We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO{sub 2}) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO{sub 2} nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO{sub 2} nanoparticles (2, 10 mg/m{sup 3}, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO{sub 2} nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO{sub 2} nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO{sub 2} nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO{sub 2} nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

Chloride and sulphate toxicity to Hydropsyche exocellata (Trichoptera, Hydropsychidae): Exploring intraspecific variation and sub-lethal endpoints.

Science.gov (United States)

Sala, Miquel; Faria, Melissa; Sarasúa, Ignacio; Barata, Carlos; Bonada, Núria; Brucet, Sandra; Llenas, Laia; Ponsá, Sergio; Prat, Narcís; Soares, Amadeu M V M; Cañedo-Arguelles, Miguel

2016-10-01

The rivers and streams of the world are becoming saltier due to human activities. In spite of the potential damage that salt pollution can cause on freshwater ecosystems, this is an issue that is currently poorly managed. Here we explored intraspecific differences in the sensitivity of freshwater fauna to two major ions (Cl(-) and SO4(2-)) using the net-spinning caddisfly Hydropsyche exocellata Dufour 1841 (Trichoptera, Hydropsychidae) as a model organism. We exposed H. exocellata to saline solutions (reaching a conductivity of 2.5mScm(-1)) with Cl(-):SO4(2-) ratios similar to those occurring in effluents coming from the meat, mining and paper industries, which release dissolved salts to rivers and streams in Spain. We used two different populations, coming from low and high conductivity streams. To assess toxicity, we measured sub-lethal endpoints: locomotion, symmetry of the food-capturing nets and oxidative stress biomarkers. According to biomarkers and net building, the population historically exposed to lower conductivities (B10) showed higher levels of stress than the population historically exposed to higher conductivities (L102). However, the differences between populations were not strong. For example, net symmetry was lower in the B10 than in the L102 only 48h after treatment was applied, and biomarkers showed a variety of responses, with no discernable pattern. Also, treatment effects were rather weak, i.e. only some endpoints, and in most cases only in the B10 population, showed a significant response to treatment. The lack of consistent differences between populations and treatments could be related to the high salt tolerance of H. exocellata, since both populations were collected from streams with relatively high conductivities. The sub-lethal effects tested in this study can offer an interesting and promising tool to monitor freshwater salinization by combining physiological and behavioural bioindicators. Copyright © 2016 Elsevier B.V. All rights

Integrated microfluidic technology for sub-lethal and behavioral marine ecotoxicity biotests

Science.gov (United States)

Huang, Yushi; Reyes Aldasoro, Constantino Carlos; Persoone, Guido; Wlodkowic, Donald

2015-06-01

Changes in behavioral traits exhibited by small aquatic invertebrates are increasingly postulated as ethically acceptable and more sensitive endpoints for detection of water-born ecotoxicity than conventional mortality assays. Despite importance of such behavioral biotests, their implementation is profoundly limited by the lack of appropriate biocompatible automation, integrated optoelectronic sensors, and the associated electronics and analysis algorithms. This work outlines development of a proof-of-concept miniaturized Lab-on-a-Chip (LOC) platform for rapid water toxicity tests based on changes in swimming patterns exhibited by Artemia franciscana (Artoxkit M™) nauplii. In contrast to conventionally performed end-point analysis based on counting numbers of dead/immobile specimens we performed a time-resolved video data analysis to dynamically assess impact of a reference toxicant on swimming pattern of A. franciscana. Our system design combined: (i) innovative microfluidic device keeping free swimming Artemia sp. nauplii under continuous microperfusion as a mean of toxin delivery; (ii) mechatronic interface for user-friendly fluidic actuation of the chip; and (iii) miniaturized video acquisition for movement analysis of test specimens. The system was capable of performing fully programmable time-lapse and video-microscopy of multiple samples for rapid ecotoxicity analysis. It enabled development of a user-friendly and inexpensive test protocol to dynamically detect sub-lethal behavioral end-points such as changes in speed of movement or distance traveled by each animal.

Perioperative respiratory adverse events in children with active upper respiratory tract infection who received general anesthesia through an orotracheal tube and inhalation agents.

Science.gov (United States)

Kim, So Yeon; Kim, Jeong Min; Lee, Jae Hoon; Kang, Young Ran; Jeong, Seung Ho; Koo, Bon-Nyeo

2013-08-01

Active upper respiratory tract infection (URI), orotracheal intubation and use of inhalation anesthetics are known risk factors for perioperative respiratory adverse events (RAE). This study investigated the risk factors of perioperative RAE in children with these risk factors. The records of 159 children who underwent general anesthesia with an orotracheal tube and inhalation were reviewed. These patients also had at least one of the following URI symptoms on the day of surgery: clear or green nasal secretion, dry or moist cough, nasal congestion, or fever. RAE such as laryngospasm, bronchospasm, oxygen desaturation and sustained cough were collected before induction, during intubation, during extubation, after extubation and in the postanesthesia care unit. Forty-five patients had RAE. The patients with RAE were younger than those without RAE. There were more passive smokers and a greater number of intubation attempts in patients with RAE than in those without RAE. The type of surgery and type of inhalation agents were not different between patients with and without RAE. Passive smoking was the only independent risk factor for RAE. In children with an active URI using orotracheal tube and inhalation anesthetics, passive smoking is an important risk factor for RAE.

Myxoma virus M130R is a novel virulence factor required for lethal myxomatosis in rabbits.

Science.gov (United States)

Barrett, John W; Werden, Steven J; Wang, Fuan; McKillop, William M; Jimenez, June; Villeneuve, Danielle; McFadden, Grant; Dekaban, Gregory A

2009-09-01

Myxoma virus (MV) is a highly lethal, rabbit-specific poxvirus that induces a disease called myxomatosis in European rabbits. In an effort to understand the function of predicted immunomodulatory genes we have deleted various viral genes from MV and tested the ability of these knockout viruses to induce lethal myxomatosis. MV encodes a unique 15 kD cytoplasmic protein (M130R) that is expressed late (12h post infection) during infection. M130R is a non-essential gene for MV replication in rabbit, monkey or human cell lines. Construction of a targeted gene knockout virus (vMyx130KO) and infection of susceptible rabbits demonstrate that the M130R knockout virus is attenuated and that loss of M130R expression allows the rabbit host immune system to effectively respond to and control the lethal effects of MV. M130R expression is a bona fide poxviral virulence factor necessary for full and lethal development of myxomatosis.

Inhaled Antibiotics in the Treatment of Nosocomial Pneumonia

Directory of Open Access Journals (Sweden)

A. N. Kuzovlev

2013-01-01

Full Text Available Nosocomial pneumonia is the most common nosocomial infection in intensive care units. Rational antibiotic therapy is the basis for the treatment of nosocomial pneumonia. There is currently a challenge of the pathogens of nosocomial pneumonia being resistant to most of the antibiotics recommended for its treatment. Inhaled antibiotics used in combination with systemic drugs are an effective and safe treatment for nosocomial pneumonia. This review of literature characterizes the current possibilities of inhaled antibiotic therapy for nosocomial pneumonia in detail and describes medicaments and the advantages and disadvantages of this treatment option. Despite insufficient evidence in circumstances where the microorganisms are polyresistant and where the design of novel antibiotics shows no promise, the use of inhaled antibiotics is an important alternative in the treatment of severe nosocomial pneumonia caused by polyresistant gram-negative bacteria. Key words: nosocomial pneumonia, antibiotic therapy, inhaled antibiotics, resistance.

Evidence for the efficacy of aztreonam for inhalation solution in the management of Pseudomonas aeruginosa in patients with cystic fibrosis

DEFF Research Database (Denmark)

Hansen, Christine; Skov, Marianne

2015-01-01

and the clinical outcome of this infection; this article focuses on the use of inhaled antibiotics in chronic P. aeruginosa infection in CF, and specifically on studies including the use of inhaled aztreonam lysine in P. aeruginosa infection. Studies were identified using PubMed and ClinicalTrials.gov, searching...

Developing a Comprehensive Risk Assessment Framework for Geological Storage CO<sub>2sub>

Energy Technology Data Exchange (ETDEWEB)

Duncan, Ian [Univ. of Texas, Austin, TX (United States)

2014-08-31

The operational risks for CCS projects include: risks of capturing, compressing, transporting and injecting CO₂; risks of well blowouts; risk that CO<sub>2sub> will leak into shallow aquifers and contaminate potable water; and risk that sequestered CO<sub>2sub> will leak into the atmosphere. This report examines these risks by using information on the risks associated with analogue activities such as CO<sub>2sub> based enhanced oil recovery (CO<sub>2sub>-EOR), natural gas storage and acid gas disposal. We have developed a new analysis of pipeline risk based on Bayesian statistical analysis. Bayesian theory probabilities may describe states of partial knowledge, even perhaps those related to non-repeatable events. The Bayesian approach enables both utilizing existing data and at the same time having the capability to adsorb new information thus to lower uncertainty in our understanding of complex systems. Incident rates for both natural gas and CO<sub>2sub> pipelines have been widely used in papers and reports on risk of CO<sub>2sub> pipelines as proxies for the individual risk created by such pipelines. Published risk studies of CO<sub>2sub> pipelines suggest that the individual risk associated with CO2 pipelines is between 10^-3 and 10^-4, which reflects risk levels approaching those of mountain climbing, which many would find unacceptably high. This report concludes, based on a careful analysis of natural gas pipeline failures, suggests that the individual risk of CO<sub>2sub> pipelines is likely in the range of 10-6 to 10-7, a risk range considered in the acceptable to negligible range in most countries. If, as is commonly thought, pipelines represent the highest risk component of CCS outside of the capture plant, then this conclusion suggests that most (if not all) previous quantitative- risk assessments of components of CCS may be orders of magnitude to high. The potential lethality of unexpected CO<sub>2sub> releases

Sub-lethal effects of pesticide residues in brood comb on worker honey bee (Apis mellifera development and longevity.

Directory of Open Access Journals (Sweden)

Judy Y Wu

Full Text Available 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

RpoS plays a central role in the SOS induction by sub-lethal aminoglycoside concentrations in Vibrio cholerae.

Science.gov (United States)

Baharoglu, Zeynep; Krin, Evelyne; Mazel, Didier

2013-01-01

Bacteria encounter sub-inhibitory concentrations of antibiotics in various niches, where these low doses play a key role for antibiotic resistance selection. However, the physiological effects of these sub-lethal concentrations and their observed connection to the cellular mechanisms generating genetic diversification are still poorly understood. It is known that, unlike for the model bacterium Escherichia coli, sub-minimal inhibitory concentrations (sub-MIC) of aminoglycosides (AGs) induce the SOS response in Vibrio cholerae. SOS is induced upon DNA damage, and since AGs do not directly target DNA, we addressed two issues in this study: how sub-MIC AGs induce SOS in V. cholerae and why they do not do so in E. coli. We found that when bacteria are grown with tobramycin at a concentration 100-fold below the MIC, intracellular reactive oxygen species strongly increase in V. cholerae but not in E. coli. Using flow cytometry and gfp fusions with the SOS regulated promoter of intIA, we followed AG-dependent SOS induction. Testing the different mutation repair pathways, we found that over-expression of the base excision repair (BER) pathway protein MutY relieved this SOS induction in V. cholerae, suggesting a role for oxidized guanine in AG-mediated indirect DNA damage. As a corollary, we established that a BER pathway deficient E. coli strain induces SOS in response to sub-MIC AGs. We finally demonstrate that the RpoS general stress regulator prevents oxidative stress-mediated DNA damage formation in E. coli. We further show that AG-mediated SOS induction is conserved among the distantly related Gram negative pathogens Klebsiella pneumoniae and Photorhabdus luminescens, suggesting that E. coli is more of an exception than a paradigm for the physiological response to antibiotics sub-MIC.

Quantity and Quality of Inhaled Dose Predicts Immunopathology in Tuberculosis

Directory of Open Access Journals (Sweden)

Kevin Patrick Fennelly

2015-06-01

Full Text Available Experimental animal models of tuberculosis (TB have convincingly demonstrated that inhaled dose predicts immunopathology and survival. In contrast, the importance of inhaled dose has generally not been appreciated in TB epidemiology, clinical science, or the practice of TB control. Infectiousness of TB patients has traditionally been assessed using microscopy for acid-fast bacilli in the sputum, which should be considered only a risk factor. We have recently demonstrated that cough aerosol cultures from index cases with pulmonary TB are the best predictors of new infection among household contacts. We suggest that cough aerosols of M. tuberculosis are the best surrogates of inhaled dose, and we hypothesize that the quantity of cough aerosols is associated with TB infection versus disease. Although several factors affect the quality of infectious aerosols, we propose that the particle size distribution of cough aerosols is an important predictor of primary upper airway disease and cervical lymphadenitis and of immune responses in exposed hosts. We hypothesize that large droplet aerosols (> 5 microns containing M. tuberculosis deposit in the upper airway and can induce immune responses without establishing infection. We suggest that this may partially explain the large proportion of humans who never develop TB disease in spite of having immunological evidence of M. tuberculosis infection (e.g. positive TST or IGRA. If these hypotheses are proven true, they would alter the current paradigm of latent TB infection and reactivation, further demonstrating the need for better biomarkers or methods of assessing TB infection and the risk of developing disease.

Objective measurement of inhaler inhalation flow profile using acoustic methods

Energy Technology Data Exchange (ETDEWEB)

Lacalle, H.; Taylor, T.E.; Marco, S.; Reilly, R.B.

2016-07-01

Patients with asthma and chronic obstructive pulmonary diseases (COPD) are mostly treated with inhalers that deliver medication directly to their airways. Drug delivery from dry powder inhalers (DPIs) is very much reliant on the inhalation manoeuvre, specifically the peak inspiratory flow rate (PIFR), inspiratory capacity (IC) and inhalation rise time (IRT) of the inhalation. It has been widely reported that patients may not follow correct inhalation technique while using their inhaler. In this study, a novel acoustic method is proposed to accurately estimate inhalation flow profile using only one inhalation recording for calibration. An Ellipta DPI was placed inside an airtight container with a spirometer connected in order to measure inhalation flow parameters. An acoustic recording device (Inhaler Compliance Assessment (INCA)) was also attached to the DPI. Inhalation audio and flow signals were recorded simultaneously. The data were collected from 20 healthy subjects while performing inhaler inhalations at a range of inspiratory flow rates. A power law regression model was computed to obtain the relationship between the acoustic envelope of the inhalation and flow profile of each recording. Each model was tested on the remaining audio signals to estimate flow profile. The average estimation error was found to be 10.5±0.3% for estimating flow profile from audio signals. Inhalation flow profile parameters (PIFR, IC and IRT) could then be measured from the estimated flow profile with high accuracy giving information on user inhalation technique. This method may assist in improving patient inhaler adherence and overall disease control. (Author)

Oral versus inhaled antibiotics for bronchiectasis.

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Spencer, Sally; Felix, Lambert M; Milan, Stephen J; Normansell, Rebecca; Goeminne, Pieter C; Chalmers, James D; Donovan, Tim

2018-03-27

Bronchiectasis is a chronic inflammatory disease characterised by a recurrent cycle of respiratory bacterial infections associated with cough, sputum production and impaired quality of life. Antibiotics are the main therapeutic option for managing bronchiectasis exacerbations. Evidence suggests that inhaled antibiotics may be associated with more effective eradication of infective organisms and a lower risk of developing antibiotic resistance when compared with orally administered antibiotics. However, it is currently unclear whether antibiotics are more effective when administered orally or by inhalation. To determine the comparative efficacy and safety of oral versus inhaled antibiotics in the treatment of adults and children with bronchiectasis. We identified studies through searches of the Cochrane Airways Group's Specialised Register (CAGR), which is maintained by the Information Specialist for the group. The Register contains trial reports identified through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched ClinicalTrials.gov and the WHO trials portal. We searched all databases in March 2018 and imposed no restrictions on language of publication. We planned to include studies which compared oral antibiotics with inhaled antibiotics. We would have considered short-term use (less than four weeks) for treating acute exacerbations separately from longer-term use as a prophylactic (4 weeks or more). We would have considered both intraclass and interclass comparisons. We planned to exclude studies if the participants received continuous or high-dose antibiotics immediately before the start of the trial, or if they have received a diagnosis of cystic fibrosis (CF), sarcoidosis, active allergic bronchopulmonary aspergillosis or active non-tuberculous Mycobacterial infection

Inhaled medicinal cannabis and the immunocompromised patient.

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Ruchlemer, Rosa; Amit-Kohn, Michal; Raveh, David; Hanuš, Lumír

2015-03-01

Medicinal cannabis is an invaluable adjunct therapy for pain relief, nausea, anorexia, and mood modification in cancer patients and is available as cookies or cakes, as sublingual drops, as a vaporized mist, or for smoking. However, as with every herb, various microorganisms are carried on its leaves and flowers which when inhaled could expose the user, in particular immunocompromised patients, to the risk of opportunistic lung infections, primarily from inhaled molds. The objective of this study was to identify the safest way of using medicinal cannabis in immunosuppressed patients by finding the optimal method of sterilization with minimal loss of activity of cannabis. We describe the results of culturing the cannabis herb, three methods of sterilization, and the measured loss of a main cannabinoid compound activity. Systematic sterilization of medicinal cannabis can eliminate the risk of fatal opportunistic infections associated with cannabis among patients at risk.

Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

Energy Technology Data Exchange (ETDEWEB)

Finch, G.L.; Nikula, K.J.; Barr, E.B. [and others

1995-12-01

Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.

A novel challenge test incorporating irradiation (60Co) of compost sub-samples to validate thermal lethality towards pathogenic bacteria.

Science.gov (United States)

Moore, John E; Watabe, Miyuki; Stewart, Andrew; Cherie Millar, B; Rao, Juluri R

2009-01-01

Maturing compost heaps normally attaining temperatures ranging from 55 to 65 degrees C is generally regarded to conform to recommended biological risks and sanitation standards for composts stipulated by either EU or US-EPA. Composted products derived from animal sources are further required by EU biohazard safety regulatory legislation that such composts either attain 70 degrees C for over 3h during maturation or via treatment at 70 degrees C for 1h before being considered for dispensation on land. The setting of the upper limit of thermal lethality at 70 degrees C/1h for achieving biosecurity of the animal waste composted products (e.g. pelleted fertilizer formulations) is not properly substantiated by specific validation tests, comprising a 'wipe-out' step (usually via autoclaving) followed by inoculation of a prescribed bacterium, exposure to 70 degrees C/1h and the lethality determined. Pelleted formulations of composts are not amenable for wet methods (autoclaving) for wipe-out sterilization step as this is detrimental to the pellet and compromises sample integrity. This study describes a laboratory method involving the employment of ((60)Co) irradiation 'wipe-out' step to: (a) compost sub-samples drawn from compost formulation heaps and (b) pelleted products derived from composted animal products while determining the thermal lethality of a given time/temperature (70 degrees C/1h) treatment process and by challenging the irradiated sample (not just with one bacterium but), out with 10 potential food-poisoning organisms from the bacterial genera (Campylobacter, Escherichia, Listeria, Salmonella, Yersinia) frequently detected in pig and poultry farm wastes. This challenge test on compost sub-samples can be a useful intervention ploy for 'inspection and validation' technique for composters during the compost maturity process, whose attainment of temperatures of 55-65 degrees C is presumed sufficient for attainment of sanitation. Stringent measures are further

Inhalable Antimicrobials for Treatment of Bacterial Biofilm-Associated Sinusitis in Cystic Fibrosis Patients

DEFF Research Database (Denmark)

Klodzinska, Sylvia Natalie; Priemel, Petra Alexandra; Rades, Thomas

2016-01-01

Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa infec...... and management of biofilm infections caused by P. aeruginosa and discusses critical issues related to novel antimicrobial drug formulation design approaches.......Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa....... aeruginosa from the respiratory tract after a first infection has been shown to delay chronic pulmonary infection with the bacteria for up to two years. The challenges with providing a suitable treatment for bacterial sinusitis include: (i) identifying a suitable antimicrobial compound; (ii) selecting...

Therapeutic efficacy of antibodies lacking Fcγ receptor binding against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies [corrected].

Directory of Open Access Journals (Sweden)

Katherine L Williams

2013-02-01

Full Text Available Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV. At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal DENV infection. We found that neutralizing modified MAbs that recognize the fusion loop or the A strand epitopes on domains II and III of the envelope protein, respectively, act therapeutically by competing with and/or displacing enhancing antibodies. By analyzing these relationships, we developed a novel in vitro suppression-of-enhancement assay that predicts the ability of modified MAbs to act therapeutically against antibody-enhanced disease in vivo. These studies provide new insight into the biology of DENV pathogenesis and the requirements for antibodies to treat lethal DENV disease.

A LigA three-domain region protects hamsters from lethal infection by Leptospira interrogans.

Directory of Open Access Journals (Sweden)

Mariana L Coutinho

2011-12-01

Full Text Available The leptospiral LigA protein consists of 13 bacterial immunoglobulin-like (Big domains and is the only purified recombinant subunit vaccine that has been demonstrated to protect against lethal challenge by a clinical isolate of Leptospira interrogans in the hamster model of leptospirosis. We determined the minimum number and location of LigA domains required for immunoprotection. Immunization with domains 11 and 12 was found to be required but insufficient for protection. Inclusion of a third domain, either 10 or 13, was required for 100% survival after intraperitoneal challenge with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. As in previous studies, survivors had renal colonization; here, we quantitated the leptospiral burden by qPCR to be 1.2×10(3 to 8×10(5 copies of leptospiral DNA per microgram of kidney DNA. Although renal histopathology in survivors revealed tubulointerstitial changes indicating an inflammatory response to the infection, blood chemistry analysis indicated that renal function was normal. These studies define the Big domains of LigA that account for its vaccine efficacy and highlight the need for additional strategies to achieve sterilizing immunity to protect the mammalian host from leptospiral infection and its consequences.

Saharan dust levels in Greece and received inhalation doses

Directory of Open Access Journals (Sweden)

C. Mitsakou

2008-12-01

Full Text Available The desert of Sahara is one of the major sources of mineral dust on Earth, producing around 2×10⁸ tons/yr. Under certain weather conditions, dust particles from Saharan desert get transported over the Mediterranean Sea and most of Europe. The limiting values set by the directive EC/30/1999 of European Union can easily be exceeded by the transport of desert dust particles in the south European Region and especially in urban areas, where there is also significant contribution from anthropogenic sources. In this study, the effects of dust transport on air quality in several Greek urban areas are quantified. PM<sub>10sub> concentration values from stationary monitoring stations are compared to dust concentrations for the 4-year period 2003–2006. The dust concentration values in the Greek areas were estimated by the SKIRON modelling system coupled with embedded algorithms describing the dust cycle. The mean annual dust contribution to daily-averaged PM<sub>10sub> concentration values was found to be around or even greater than 10% in the urban areas throughout the years examined. Natural dust transport may contribute by more than 20% to the annual number of exceedances – PM<sub>10sub> values greater than EU limits – depending on the specific monitoring location. In a second stage of the study, the inhaled lung dose received by the residents in various Greek locations is calculated. The particle deposition efficiency of mineral dust at the different parts of the human respiratory tract is determined by applying a lung dosimetry numerical model, which incorporates inhalation dynamics and aerosol physical processes. The inhalation dose from mineral dust particles was greater in the upper respiratory system (extrathoracic region and less significant in the lungs, especially in the sensitive alveolar region. However, in cases of dust episodes, the amounts of mineral dust deposited along the human lung are comparable to those

HIV Infection and AIDS in Sub-Saharan Africa: Current Status, Challenges and Opportunities.

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Kharsany, Ayesha B M; Karim, Quarraisha A

2016-01-01

Global trends in HIV infection demonstrate an overall increase in HIV prevalence and substantial declines in AIDS related deaths largely attributable to the survival benefits of antiretroviral treatment. Sub-Saharan Africa carries a disproportionate burden of HIV, accounting for more than 70% of the global burden of infection. Success in HIV prevention in sub-Saharan Africa has the potential to impact on the global burden of HIV. Notwithstanding substantial progress in scaling up antiretroviral therapy (ART), sub-Saharan Africa accounted for 74% of the 1.5 million AIDS related deaths in 2013. Of the estimated 6000 new infections that occur globally each day, two out of three are in sub-Saharan Africa with young women continuing to bear a disproportionate burden. Adolescent girls and young women aged 15-24 years have up to eight fold higher rates of HIV infection compared to their male peers. There remains a gap in women initiated HIV prevention technologies especially for women who are unable to negotiate the current HIV prevention options of abstinence, behavior change, condoms and medical male circumcision or early treatment initiation in their relationships. The possibility of an AIDS free generation cannot be realized unless we are able to prevent HIV infection in young women. This review will focus on the epidemiology of HIV infection in sub-Saharan Africa, key drivers of the continued high incidence, mortality rates and priorities for altering current epidemic trajectory in the region. Strategies for optimizing the use of existing and increasingly limited resources are included.

HIV Infection and AIDS in Sub-Saharan Africa: Current Status, Challenges and Opportunities

Science.gov (United States)

Kharsany, Ayesha B.M.; Karim, Quarraisha A.

2016-01-01

Global trends in HIV infection demonstrate an overall increase in HIV prevalence and substantial declines in AIDS related deaths largely attributable to the survival benefits of antiretroviral treatment. Sub-Saharan Africa carries a disproportionate burden of HIV, accounting for more than 70% of the global burden of infection. Success in HIV prevention in sub-Saharan Africa has the potential to impact on the global burden of HIV. Notwithstanding substantial progress in scaling up antiretroviral therapy (ART), sub-Saharan Africa accounted for 74% of the 1.5 million AIDS related deaths in 2013. Of the estimated 6000 new infections that occur globally each day, two out of three are in sub-Saharan Africa with young women continuing to bear a disproportionate burden. Adolescent girls and young women aged 15-24 years have up to eight fold higher rates of HIV infection compared to their male peers. There remains a gap in women initiated HIV prevention technologies especially for women who are unable to negotiate the current HIV prevention options of abstinence, behavior change, condoms and medical male circumcision or early treatment initiation in their relationships. The possibility of an AIDS free generation cannot be realized unless we are able to prevent HIV infection in young women. This review will focus on the epidemiology of HIV infection in sub-Saharan Africa, key drivers of the continued high incidence, mortality rates and priorities for altering current epidemic trajectory in the region. Strategies for optimizing the use of existing and increasingly limited resources are included. PMID:27347270

Toxicity studies of inhaled beta-emitting radionuclides - Status report

Energy Technology Data Exchange (ETDEWEB)

Hahn, F F; Boeker, B B; Gillett, N A; Griffith, W C; Lundgren, D L; McClellan, R O; Muggenburg, B A; Snipes, M B

1988-12-01

The effects of beta-emitting radionuclides inhaled in either a relatively soluble form ({sup 90}SrCl{sub 2}, {sup 144}CeCl{sub 3}, {sup 91}yl{sub 3}, or {sup 137}CsCl) or in a relatively insoluble form ({sup 90}Y, {sup 91}Y, {sup 144}Ce or {sup 90}Sr in fused aluminosilicate particles [FAP]) have been studied in laboratory animals. The results showed that the total beta dose and the dose-rate pattern can modify both the neoplastic and non-neoplastic effects of inhaled beta-emitting radionuclides. In addition, the solubility and chemical characteristics of the radionuclides influence which organs are affected. Effects are seen primarily in organs where the radionuclide is ultimately accumulated, e.g., lung, bone, liver, or tracheobronchial lymph nodes. In addition, effects may be seen in organs where there is little accumulation, but where the radiation dose may still be high, e.g., nasal epithelium and heart. Studies of inhaled {sup 144}Ce-FAP in four different species showed that, compared to mice and dogs, lung tumor risk factors are very low for Syrian hamsters and high for rats. Studies of mice, Syrian hamsters, rats, and dogs repeatedly exposed to aerosols of {sup 144}Ce-FAP showed that lung tumor incidence correlates better with cumulative dose to the lung than with dose rate. Most of the studies in this program are nearing completion and full analyses are in progress. (author)

The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4.

Science.gov (United States)

Hutt, Julie A; Lovchik, Julie A; Dekonenko, Alexander; Hahn, Andrew C; Wu, Terry H

2017-02-01

The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4. Our results are consistent with initial uptake of aerosolized SCHU S4 from the nasal cavity, lungs, and possibly the gastrointestinal tract. Bacteremia with hematogenous dissemination was first detected 2 days after exposure. Shortly thereafter, the infected rats exhibited fever, tachypnea, and hypertension that persisted for 24 to 36 hours and then rapidly decreased as animals succumbed to infection between days 5 and 8 after exposure. Tachycardia was observed briefly, but only after the core body temperature and blood pressure began to decrease as the animals were near death. Initial neutrophilic and histiocytic inflammation in affected tissues became progressively more fibrinous and necrotizing over time. At death, as many as 10 10 colony-forming units were found in the lungs, spleen, and liver. Death was attributed to sepsis and disseminated intravascular coagulation. Overall, the pathogenesis of pneumonic tularemia in the female F344 rat model appears to replicate the disease in humans. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Stress response of the black coral Leiopathes glaberrima when exposed to sub-lethal amounts of crude oil and dispersant

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Dannise V. Ruiz-Ramos

2017-12-01

Full Text Available The 2010 Deep Water Horizon oil well failure released billions of gallons of crude oil into the deep Gulf of Mexico, and, combined with chemical dispersants, this oil caused significant coral mortality. However, the mechanisms by which oil and dispersed oil impact deep marine fauna are not well understood. Here, we investigate the effects of oil and dispersed oil on a black coral common in the deep Gulf of Mexico, 'Leiopathes glaberrima. 'This coral occurs in several color morphs that show ecological and genetic differences. We hypothesized that dispersed oil would be more detrimental to coral health than oil alone and that this difference would be detectable in the gene expression response of the colonies even at sub-lethal concentrations. In two experiments, four and six colonies of red and white color morphs were exposed to oil, dispersant, and dispersed oil for a minimum of 96 hours. Visual assessment indicated that indeed dispersant and dispersed oil treatments were more damaging than oil alone, for target concentrations of 25 mg L–1. Decline in health was observed for all treatments, independently of color morphotype, but the decline was faster in the white colonies exposed to dispersant. The responses to the treatments were also investigated by monitoring gene expression after 24 hours of sub-lethal chemical exposure. Coral gene expression differed by chemical stressor. Interestingly, the polycyclic aromatic hydrocarbon biomarker gene, cytochrome P450, was only up-regulated in dispersed oil but not oil alone, suggesting that the dispersant increased the availability of such hydrocarbons in the tissue. The gene expression response was apparent at 24 hours when visual impacts were not (yet detectable. The use of chemical dispersants in oil-spill remediation may cause health declines in deep-water corals and deserves further study.

Lactobacillus priming of the respiratory tract: Heterologous immunity and protection against lethal pneumovirus infection.

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Garcia-Crespo, Katia E; Chan, Calvin C; Gabryszewski, Stanislaw J; Percopo, Caroline M; Rigaux, Peter; Dyer, Kimberly D; Domachowske, Joseph B; Rosenberg, Helene F

2013-03-01

We showed previously that wild-type mice primed via intranasal inoculation with live or heat-inactivated Lactobacillus species were fully (100%) protected against the lethal sequelae of infection with the virulent pathogen, pneumonia virus of mice (PVM), a response that is associated with diminished expression of proinflammatory cytokines and diminished virus recovery. We show here that 40% of the mice primed with live Lactobacillus survived when PVM challenge was delayed for 5months. This robust and sustained resistance to PVM infection resulting from prior interaction with an otherwise unrelated microbe is a profound example of heterologous immunity. We undertook the present study in order to understand the nature and unique features of this response. We found that intranasal inoculation with L. reuteri elicited rapid, transient neutrophil recruitment in association with proinflammatory mediators (CXCL1, CCL3, CCL2, CXCL10, TNF-alpha and IL-17A) but not Th1 cytokines. IFNγ does not contribute to survival promoted by Lactobacillus-priming. Live L. reuteri detected in lung tissue underwent rapid clearance, and was undetectable at 24h after inoculation. In contrast, L. reuteri peptidoglycan (PGN) and L. reuteri genomic DNA (gDNA) were detected at 24 and 48h after inoculation, respectively. In contrast to live bacteria, intranasal inoculation with isolated L. reuteri gDNA elicited no neutrophil recruitment, had minimal impact on virus recovery and virus-associated production of CCL3, and provided no protection against the negative sequelae of virus infection. Isolated PGN elicited neutrophil recruitment and proinflammatory cytokines but did not promote sustained survival in response to subsequent PVM infection. Overall, further evaluation of the responses leading to Lactobacillus-mediated heterologous immunity may provide insight into novel antiviral preventive modalities. Published by Elsevier B.V.

Genital Chlamydia trachomatis and Neisseria gonorrhoeae infections among women in sub-Saharan Africa: A structured review.

Science.gov (United States)

Dubbink, Jan Henk; Verweij, Stephan P; Struthers, Helen E; Ouburg, Sander; McIntyre, James A; Morré, Servaas A; Peters, Remco Ph

2018-01-01

Chlamydia trachomatis and Neisseria gonorrhoeae constitute major public health problems among women, but the burden of infection in sub-Saharan Africa is poorly documented. We conducted a structured review of the prevalence and incidence of genital, oral and anal C. trachomatis and N. gonorrhoeae infection in women in sub-Saharan Africa. We searched Medline, EMBASE and Web of Science over a 10-year period for studies on epidemiology of genital, oral and anal chlamydial infection and gonorrhoea in women in all countries of sub-Saharan Africa. We assessed geographic and demographic differences in prevalence and incidence of infection; weighted mean prevalence estimates were calculated with a random-effect model. A total of 102 study results were included, with data available for 24/49 of sub-Saharan countries. The weighted prevalence of chlamydial infection was lower among women in community-based studies (3.9%; 95% CI: 2.9-5.1%) than for women recruited at primary healthcare facilities (6.0%; 95% CI: 4.2-8.4%, p sub-Saharan Africa. Better control strategies are warranted to reduce the burden of infection and to prevent long-term complications of these infections.

A rat model of smoke inhalation injury: Influence of combustion smoke on gene expression in the brain

International Nuclear Information System (INIS)

Lee, Heung M.; Greeley, George H.; Herndon, David N.; Sinha, Mala; Luxon, Bruce A.; Englander, Ella W.

2005-01-01

Acute smoke inhalation causes death and injury in victims of home and industrial fires as well as victims of combat situations. The lethal factors in combustion smoke inhalation are toxic gases and oxygen deficiency, with carbon monoxide (CO) as a primary cause of death. In survivors, inhalation of smoke can result in severe immediate and delayed neuropathologies. To gain insight into the progression of molecular events contributing to smoke inhalation sequelae in the brain, we developed a smoke inhalation rat model and conducted a genome-wide analysis of gene expression. Microarray analysis revealed a modified brain transcriptome with changes peaking at 24 h and subsiding within 7 days post-smoke. Overall, smoke inhalation downregulated genes associated with synaptic function, neurotransmission, and neurotrophic support, and upregulated genes associated with stress responses, including nitric oxide synthesis, antioxidant defenses, proteolysis, inflammatory response, and glial activation. Notably, among the affected genes, many have been previously implicated in other types of brain injury, demonstrating the usefulness of microarrays for analysis of changes in gene expression in complex insults. In accord with previously described modulations of nitric oxide homeostasis in CO poisoning, microarray analysis revealed increased brain expression of nitric oxide synthase (NOS) and NOS ligand after inhalation of smoke. Furthermore, immunostaining showed significant elevations in perivascular NOS and in protein nitration, corroborating the involvement of nitric oxide perturbations in post-smoke sequelae in the brain. Thus, the new rat model, in combination with microarray analyses, affords insight into the complex molecular pathophysiology of smoke inhalation in the brain

Subchronic inhalation of carbon tetrachloride alters the tissue retention of acutely inhaled plutonium-239 nitrate in F344 rats and syrian golden hamsters

Energy Technology Data Exchange (ETDEWEB)

Benson, J.M.; Barr, E.B.; Lundgren, D.L. [and others

1995-12-01

Carbon tetrachloride (CCl{sub 4}) has been used extensively in the nuclear weapons industry, so it is likely that nuclear plant workers have been exposed to both CCl{sub 4} and plutonium compounds. Future exposures may occur during {open_quotes}cleanup{close_quotes} operations at weapons productions sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. Inhalation of 20 and 100 ppm CCl{sub 4} by hamsters reduces uptake of {sup 239}Pu solubilized from lung, shunting the {sup 239}Pu to the skeleton.

Inhaled antibiotics for the treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients: challenges to treatment adherence and strategies to improve outcomes

Directory of Open Access Journals (Sweden)

Bodnár R

2016-02-01

Full Text Available Réka Bodnár,1,2 Ágnes Mészáros,2 Máté Oláh,2 Tamás Ágh3 1Department of Pediatric Pulmonology, Heim Pál Children’s Hospital, Budapest, Hungary; 2University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary; 3Syreon Research Institute, Budapest, Hungary Background: Inhaled antibiotics (ABs are recommended for use in the therapy of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF. The aim of this systematic literature review was to identify level of adherence to inhaled ABs and to determine predictors and consequences of nonadherence in CF. Methods: A systematic literature search of English-language articles was conducted in April 2015 using Medline and Embase. No publication date limit was applied. The literature screening was conducted by two independent reviewers. All of the included studies were assessed for quality. Results: The search yielded 193 publications, of which ten met the inclusion criteria and underwent data extraction. Seven studies focused on inhaled tobramycin, one on inhaled colistimethate, one on inhaled levofloxacin, and one on inhaled aztreonam lysine. Medication adherence to inhaled ABs was analyzed by pharmacy refill history, daily phone diary, parent and child self-reports, vials counting, or electronic monitoring. In randomized controlled trials (n=3, proportion of adherent patients (>75%–80% of required doses taken ranged from 86% to 97%; in prospective cohort studies (n=3, adherence rates ranged between 36% and 92%, and in retrospective studies (n=4 it ranged between 60% and 70%. The adherence to inhaled ABs in CF was found to be associated with the complexity of treatment, time of drug administration, age of patients, treatment burden (adverse events, taste, and patient satisfaction. Conclusion: The high diversity of adherence data was because of the different study designs (randomized controlled trials vs real-world studies and the lack

Toxicity assessment of sodium fluoride in Drosophila melanogaster after chronic sub-lethal exposure.

Science.gov (United States)

Dutta, Moumita; Rajak, Prem; Khatun, Salma; Roy, Sumedha

2017-01-01

Sodium fluoride (NaF), one of the most frequently used fluoride compound is composed of Na + and F - . Apart from its use in water fluoridation, NaF also acts as a major component for different dental products like toothpastes, gels and mouth rinses etc. The present study was carried out to explore the toxic impact of chronic NaF exposure on a non-target organism, Drosophila melanogaster. The larvae exposed to different concentrations of NaF through food showed a significant increase in HSP70 expression both qualitatively and quantitatively. The altered tail length and tail intensity in Comet assay validate the increased DNA damage in treated larvae. The activity of AChE, oxidative stress marker enzymes, phase I and phase II detoxifying enzymes were found to be significantly inhibited in the treated larvae when compared to control though there was no evidence of dose dependent change in each case. The alterations in the mentioned parameters can be due to increased body Fluoride ion (F - ) concentration since the analysis with ion electrode analyzer revealed that F - concentration increased significantly with NaF treatment. Hence, the results suggest that D. melanogaster manifest prominent toxic response when subjected to chronic exposure to sub-lethal NaF concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute, Sub-lethal Cyanide Poisoning in Mice is Ameliorated by Nitrite Alone: Complications Arising from Concomitant Administration of Nitrite and Thiosulfate as an Antidotal Combination

Science.gov (United States)

Cambal, Leah K.; Swanson, Megan R.; Yuan, Quan; Weitz, Andrew C.; Li, Hui-Hua; Pitt, Bruce R.; Pearce, Linda L.; Peterson, Jim

2011-01-01

Sodium nitrite alone is shown to ameliorate sub-lethal cyanide toxicity in mice when given from ~1 hour before until 20 minutes after the toxic dose as demonstrated by the recovery of righting ability. An optimum dose (12 mg/kg) was determined to significantly relieve cyanide toxicity (5.0 mg/kg) when administered to mice intraperitoneally. Nitrite so administered was shown to rapidly produce NO in the bloodsteam as judged by the dose dependent appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin. It is argued that antagonism of cyanide inhibition of cytochrome c oxidase by NO is the crucial antidotal activity rather than the methemoglobin-forming action of nitrite. Concomitant addition of sodium thiosulfate to nitrite-treated blood resulted in the detection of sulfidomethemoblobin by EPR spectroscopy. Sulfide is a product of thiosulfate hydrolysis and, like cyanide, is known to be a potent inhibitor of cytochrome c oxidase; the effects of the two inhibitors being essentially additive under standard assay conditions, rather than dominated by either one. The findings afford a plausible explanation for an observed detrimental effect in mice associated with the use of the standard nitrite-thiosulfate combination therapy at sub-lethal levels of cyanide intoxication. PMID:21534623

Lethal and sub-lethal evaluation of Indigo Carmine dye and byproducts after TiO2 photocatalysis in the immune system of Eisenia andrei earthworms.

Science.gov (United States)

Genázio Pereira, Patrícia Christina; Reimão, Roberta Valoura; Pavesi, Thelma; Saggioro, Enrico Mendes; Moreira, Josino Costa; Veríssimo Correia, Fábio

2017-09-01

The Indigo carmine (IC) dye has been widely used in textile industries, even though it has been considered toxic for rats, pigs and humans. Owing to its toxicity, wastes containing this compound should be treated to minimize or eliminate their toxic effects on the biota. As an alternative to wastewater treatment, advanced oxidative processes (AOPs) have been highlighted due to their high capacity to destruct organic molecules. In this context, this study aimed to evaluate Indigo Carmine toxicity to soil organisms using the earthworm Eisenia andrei as a model-organism and also verify the efficiency of AOP in reducing its toxicity to these organisms. To this end, lethal (mortality) and sub-lethal (loss or gain of biomass, reproduction, behavior, morphological changes and immune system cells) effects caused by this substance and its degradation products in these annelids were evaluated. Morphological changes were observed even in organisms exposed to low concentrations, while mortality was the major effect observed in individuals exposed to high levels of indigo carmine dye. The organisms exposed to the IC during the contact test showed mortality after 72h of exposure (LC 50 = 75.79mgcm - 2 ), while those exposed to photoproducts showed mortality after 48h (LC 50 = 243min). In the chronic study, the organisms displayed a mortality rate of 14%, while those exposed to the photoproduct reached up to 32.7%. A negative influence of the dye on the reproduction rate was observed, while by-products affected juvenile survival. A loss of viability and alterations in the cellular proportion was verified during the chronic test. However, the compounds did not alter the behavior of the annelids in the leak test (RL ranged from 20% to 30%). Although photocatalysis has been presented as an alternative technology for the treatment of waste containing the indigo carmine dye, this process produced byproducts even more toxic than the original compounds to E. andrei. Copyright © 2017

Modeling Inhalational Tularemia: Deliberate Release and Public Health Response

Science.gov (United States)

Hall, Ian M.; Leach, Steve

2011-01-01

Two epidemic modeling studies of inhalational tularemia were identified in the published literature, both demonstrating the high number of potential casualties that could result from a deliberate aerosolized release of the causative agent in an urban setting. However, neither study analyzed the natural history of inhalational tularemia nor modeled the relative merits of different mitigation strategies. We first analyzed publicly available human/primate experimental data and reports of naturally acquired inhalational tularemia cases to better understand the epidemiology of the disease. We then simulated an aerosolized release of the causative agent, using airborne dispersion modeling to demonstrate the potential number of casualties and the extent of their spatial distribution. Finally, we developed a public health intervention model that compares 2 mitigation strategies: targeting antibiotics at symptomatic individuals with or without mass distribution of antibiotics to potentially infected individuals. An antibiotic stockpile that is sufficient to capture all areas where symptomatic individuals were infected is likely to save more lives than treating symptomatic individuals alone, providing antibiotics can be distributed rapidly and their uptake is high. However, with smaller stockpiles, a strategy of treating symptomatic individuals alone is likely to save many more lives than additional mass distribution of antibiotics to potentially infected individuals. The spatial distribution of symptomatic individuals is unlikely to coincide exactly with the path of the dispersion cloud if such individuals are infected near their work locations but then seek treatment close to their homes. The optimal mitigation strategy will depend critically on the size of the release relative to the stockpile level and the effectiveness of treatment relative to the speed at which antibiotics can be distributed. PMID:22044315

Reproductive-phase and interphase lethal cell damage after irradiation and treatment with cytostatics

International Nuclear Information System (INIS)

Hagemann, G.

1979-01-01

After X-ray irradiation of manual cells, two lethal fractions occur due to reproductive and interphase death under low and high radiation doses. The damage kinetics on which this fact is based is compared with hypothetical tumour frequencies and leucemia induction caused in experiments. The reproductive-lethal damage can be manifested by means of colony size spectrometry, with the median colony size class differences (MCD) serving as measure for the damage found. The simultaneous effects of the cytostatics BLEOMYCIN or ICRF 159 and X-rays on reproductive lethal and interphase-lethal damage are measured by means of MCD and survival fraction, and the additive and intensifying effect' is judged with the help of suitably defined terms. This shows that the clinically used ICRF 159 has an additive effect on interphase-lethal and a sub-additive effect on reproductive-lethal cell damage. Thus, favourable results may be expected for the electivity factor in fractionated irradiation and with regard to delayed damage in healthy tissue. (orig.) 891 MG/orig. 892 RDG [de

Inhaled Steroids

Science.gov (United States)

... considerations when your dosage changes. What about side effects and inhaled steroids? The most common side effects with inhaled steroids ... inhaled steroid has much less potential for side effects than steroid pills or syrups. There have been concerns regarding ...

Inhalant Abuse

Science.gov (United States)

... is when you pour the product into a bag, hold it over your mouth and nose, and inhale. How is inhalant abuse diagnosed? If you think your child is abusing inhalants, talk to them. Be honest and open. Tell them ...

Hypertension in Pregnancy among HIV-Infected Women in Sub ...

African Journals Online (AJOL)

Hypertension in Pregnancy among HIV-Infected Women in Sub-Saharan Africa: Prevalence and Infant Outcomes. C Kilewo, UCM Natchu, A Young, D Donnell, E Brown, JS Read, U Sharma, BH Chi, R Goldenberg, I Hoffman, TE Taha, WW Fawzi ...

Sub-lethal effects of neonicitinoids on the alfalfa leafcutter bee, Megachile rotundata

Science.gov (United States)

Neonicotinoids are commonly used pesticides in U.S. agriculture. For many beneficial insect species, lethal effects of neonicotinoids are well-documented; however, much less is known about sublethal exposure. The alfalfa leaf cutter bee Megachile rotundata is a managed pollinator that constructs com...

Behavioral responses of the estuarine calanoid copepod Eurytemora affinis to sub-lethal concentrations of waterborne pollutants

International Nuclear Information System (INIS)

Michalec, François-Gaël; Holzner, Markus; Menu, Dominique; Hwang, Jiang-Shiou; Souissi, Sami

2013-01-01

Highlights: •We studied the effects of sub-lethal exposure to pollutants on Eurytemora affinis swimming behavior. •Nonylphenol, cadmium and polycyclic aromatic hydrocarbons caused hyperactivity. •Effects were observable within 30 min of exposure and persisted during a depuration period. •The response resembles an escape reaction allowing copepods to evade stressful conditions. -- Abstract: Estuarine waters contain a variety of chemicals which affect to various extents the behavior of aquatic organisms. Little is known, however, on the behavioral response of copepods. The present study shows the results of laboratory experiments investigating the immediate effects of sub-lethal concentrations of three commonly found contaminants on the three-dimensional swimming behavior of the estuarine calanoid copepod Eurytemora affinis. Nonylphenol at 2 μg L −1 , cadmium at 45 ng L −1 and a mixture of low to medium molecular weight polycyclic aromatic hydrocarbons at 40 ng L −1 all affected the swimming behavior of E. affinis adults, increasing both swimming speed and activity. In most cases, effects were observable within 30 min of exposure and persisted or faded during a period of depuration in uncontaminated water of similar duration. In ovigerous females exposed to Cd and PAHs, effects appeared to be more pronounced during the depuration period, suggesting that carrying ovisacs may impair recovery. We quantified differences in the distribution of swimming speed values by considering the relative frequencies of periods of break, slow and fast swimming and we observed a trend toward faster movements in the presence of pollutants. The degree of trajectory complexity, estimated through their fractal dimension, was unaffected by pollutants. Since both narcotic and non-narcotic pollutants induced hyperactivity, our results suggest that changes in behavior after a short-term exposure may be independent of the general mode of action of the chemicals. The increase in

Behavioral responses of the estuarine calanoid copepod Eurytemora affinis to sub-lethal concentrations of waterborne pollutants

Energy Technology Data Exchange (ETDEWEB)

Michalec, François-Gaël [Université Lille Nord de France, F-59000 Lille (France); USTL, LOG, Station Marine de Wimereux, F-62930 Wimereux (France); CNRS, UMR 8187, F-62930 Wimereux (France); National Taiwan Ocean University, Institute of Marine Biology, Keelung, Taiwan, ROC (China); Holzner, Markus [Institute of Environmental Engineering, ETH Zürich (Switzerland); Menu, Dominique [Université Lille Nord de France, F-59000 Lille (France); USTL, LOG, Station Marine de Wimereux, F-62930 Wimereux (France); CNRS, UMR 8187, F-62930 Wimereux (France); Hwang, Jiang-Shiou [National Taiwan Ocean University, Institute of Marine Biology, Keelung, Taiwan, ROC (China); Souissi, Sami, E-mail: sami.souissi@univ-lille1.fr [Université Lille Nord de France, F-59000 Lille (France); USTL, LOG, Station Marine de Wimereux, F-62930 Wimereux (France); CNRS, UMR 8187, F-62930 Wimereux (France)

2013-08-15

Highlights: •We studied the effects of sub-lethal exposure to pollutants on Eurytemora affinis swimming behavior. •Nonylphenol, cadmium and polycyclic aromatic hydrocarbons caused hyperactivity. •Effects were observable within 30 min of exposure and persisted during a depuration period. •The response resembles an escape reaction allowing copepods to evade stressful conditions. -- Abstract: Estuarine waters contain a variety of chemicals which affect to various extents the behavior of aquatic organisms. Little is known, however, on the behavioral response of copepods. The present study shows the results of laboratory experiments investigating the immediate effects of sub-lethal concentrations of three commonly found contaminants on the three-dimensional swimming behavior of the estuarine calanoid copepod Eurytemora affinis. Nonylphenol at 2 μg L{sup −1}, cadmium at 45 ng L{sup −1} and a mixture of low to medium molecular weight polycyclic aromatic hydrocarbons at 40 ng L{sup −1} all affected the swimming behavior of E. affinis adults, increasing both swimming speed and activity. In most cases, effects were observable within 30 min of exposure and persisted or faded during a period of depuration in uncontaminated water of similar duration. In ovigerous females exposed to Cd and PAHs, effects appeared to be more pronounced during the depuration period, suggesting that carrying ovisacs may impair recovery. We quantified differences in the distribution of swimming speed values by considering the relative frequencies of periods of break, slow and fast swimming and we observed a trend toward faster movements in the presence of pollutants. The degree of trajectory complexity, estimated through their fractal dimension, was unaffected by pollutants. Since both narcotic and non-narcotic pollutants induced hyperactivity, our results suggest that changes in behavior after a short-term exposure may be independent of the general mode of action of the chemicals. The

Matrix metalloproteinase-9 plays a role in protecting zebrafish from lethal infection with Listeria monocytogenes by enhancing macrophage migration.

Science.gov (United States)

Shan, Ying; Zhang, Yikai; Zhuo, Xunhui; Li, Xiaoliang; Peng, Jinrong; Fang, Weihuan

2016-07-01

Zebrafish could serve as an alternative animal model for pathogenic bacteria in multiple infectious routes. Our previous study showed that immersion infection in zebrafish with Listeria monocytogenes did not cause lethality but induced transient expression of several immune response genes. We used an Affymetrix gene chip to examine the expression profiles of genes of zebrafish immersion-infected with L. monocytogenes. A total of 239 genes were up-regulated and 56 genes down-regulated compared with uninfected fish. Highest expression (>20-fold) was seen with the mmp-9 gene encoding the matrix metalloproteinase-9 (Mmp-9) known to degrade the extracellular matrix proteins. By morpholino knockdown of mmp-9, we found that the morphants showed rapid death with much higher bacterial load after intravenous or intraventricular (brain ventricle) infection with L. monocytogenes. Macrophages in mmp-9-knockdown morphants had significant defect in migrating to the brain cavity upon intraventricular infection. Decreased migration of murine macrophages with knockdown of mmp-9 and cd44 was also seen in transwell inserts with 8-μm pore polycarbonate membrane, as compared with the scrambled RNA. These findings suggest that Mmp-9 is a protective molecule against infection by L. monocytogenes by engaging in migration of zebrafish macrophages to the site of infection via a non-proteolytic role. Further work is required on the molecular mechanisms governing Mmp-9-driven macrophage migration in zebrafish. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genome Replikin Count Predicts Increased Infectivity/Lethality of Viruses

OpenAIRE

Samuel Bogoch; Elenore S. Bogoch

2012-01-01

The genomes of all groups of viruses whose sequences are listed on Pubmed, specimens since 1918, analyzed by a software from Bioradar UK Ltd., contain Replikins which range in concentration from a Replikin Count (number of Replikins per 100 amino acids) of less than 1 to 30 (see accompanying communications for higher Counts in tuberculosis, malaria, and cancer, associated with higher lethality). Counts of less than 4.0 were found in ‘resting’ virus states; Counts greater than 4....

Quantitative biokinetic analysis of radioactively labelled, inhaled Titanium dioxide Nanoparticles in a rat model

Energy Technology Data Exchange (ETDEWEB)

Kreyling, Wolfgang G.; Wenk, Alexander; Semmler-Behnke, Manuela [Helmholtz Zentrum Muenchen, Deutsches Forschungszentrum fuer Gesundheit und Umwelt GmbH (Germany). Inst. fuer Lungenbiologie und Erkrankungen, Netzwerk Nanopartikel und Gesundheit

2010-09-15

The aim of this project was the determination of the biokinetics of TiO{sub 2} nanoparticles (NP) in the whole body of healthy adult rats after NP administration to the respiratory tract - either via inhalation or instillation. We developed an own methodology to freshly synthesize and aerosolize TiO{sub 2}-NP in our lab for the use of inhalation studies. These NP underwent a detailed physical and chemical characterization providing pure polycrystalline anatase TiO{sub 2}-NP of about 20 nm (geometric standard deviation 1.6) and a specific surface area of 270 m{sup 2}/g. In addition, we developed techniques for sufficiently stable radioactive {sup 48}V labelling of the TiO{sub 2} NP. The kinetics of solubility of {sup 48}V was thoroughly determined. The methodology of quantitative biokinetics allows for a quantitative balance of the retained and excreted NP in control of the administered NP dose and provides a much more precise determination of NP fractions and concentrations of NP in organs and tissues of interest as compared to spotting biokinetics studies. Small fractions of TiO{sub 2}-NP translocate across the air-blood-barrier and accumulate in secondary target organs, soft tissue and skeleton. The amount of translocated TiO{sub 2}-NP is approximately 2% of TiO{sub 2}-NP deposited in the lungs. A prominent fraction of these translocated TiO{sub 2}-NP was found in the remainder. Smaller amounts of TiO{sub 2}-NP accumulate in secondary organs following particular kinetics. TiO{sub 2}-NP translocation was grossly accomplished within the first 2-4 hours after inhalation followed by retention in all organs and tissues studied without any detectable clearance of these biopersistent TiO{sub 2}-NP within 28 days. Therefore, our data suggest crossing of the air-blood-barrier of the lungs and subsequent accumulation in secondary organs and tissues depends on the NP material and its physico-chemical properties. Furthermore, we extrapolate that during repeated or chronic

Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia.

Science.gov (United States)

Baral, Pankaj; Umans, Benjamin D; Li, Lu; Wallrapp, Antonia; Bist, Meghna; Kirschbaum, Talia; Wei, Yibing; Zhou, Yan; Kuchroo, Vijay K; Burkett, Patrick R; Yipp, Bryan G; Liberles, Stephen D; Chiu, Isaac M

2018-05-01

Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1 + nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1 + -neuron ablation increased survival, cytokine induction, and lung bacterial clearance. Nociceptors suppressed the recruitment and surveillance of neutrophils, and altered lung γδ T cell numbers, which are necessary for immunity. Vagal ganglia TRPV1 + afferents mediated immunosuppression through release of the neuropeptide calcitonin gene-related peptide (CGRP). Targeting neuroimmunological signaling may be an effective approach to treat lung infections and bacterial pneumonia.

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

OpenAIRE

Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

2012-01-01

Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT) and cardiac-specific catalase overexpression mice were challenged...

Reproductive health and family planning needs among HIV-infected women in Sub-Saharan Africa.

Science.gov (United States)

Sarnquist, Clea C; Rahangdale, Lisa; Maldonado, Yvonne

2013-03-01

Review key topics and recent literature regarding reproductive health and family planning needs for HIV-infected women in Sub-Saharan Africa. Electronic searches performed in PubMed, JSTOR, and Web of Science; identified articles reviewed for inclusion. Most HIV-infected women in Sub-Saharan Africa bear children, and access to antiretroviral therapy may increase childbearing desires and/or fertility, resulting in greater need for contraception. Most contraceptive options can be safely and effectively used by HIV-infected women. Unmet need for contraception is high in this population, with 66- 92% of women reporting not wanting another child (now or ever), but only 20-43% using contraception. During pregnancy and delivery, HIV-infected women need access to prevention of mother-to-child transmission (PMTCT) services, a skilled birth attendant, and quality post-partum care to prevent HIV infection in the infant and maximize maternal health. Providers may lack resources as well as appropriate training and support to provide such services to women with HIV. Innovations in biomedical and behavioral interventions may improve reproductive healthcare for HIV-infected women, but in Sub-Saharan Africa, models of integrating HIV and PMTCT services with family planning and reproductive health services will be important to improve reproductive outcomes. HIV-infected women in Sub-Saharan Africa have myriad needs related to reproductive health, including access to high-quality family planning information and options, high-quality pregnancy care, and trained providers. Integrated services that help prevent unintended pregnancy and optimize maternal and infant health before, during and after pregnancy will both maximize limited resources as well as provide improved reproductive outcomes.

Effective lethal mutagenesis of influenza virus by three nucleoside analogs.

Science.gov (United States)

Pauly, Matthew D; Lauring, Adam S

2015-04-01

Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many RNA viruses. This approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. We investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. All three drugs were active against a panel of seasonal H3N2 and laboratory-adapted H1N1 strains. We found that each drug increased the frequency of mutations in influenza virus populations and decreased the virus' specific infectivity, indicating a mutagenic mode of action. We were able to drive viral populations to extinction by passaging influenza virus in the presence of each drug, indicating that complete lethal mutagenesis of influenza virus populations can be achieved when a sufficient mutational burden is applied. Population-wide resistance to these mutagenic agents did not arise after serial passage of influenza virus populations in sublethal concentrations of drug. Sequencing of these drug-passaged viral populations revealed genome-wide accumulation of mutations at low frequency. The replicative capacity of drug-passaged populations was reduced at higher multiplicities of infection, suggesting the presence of defective interfering particles and a possible barrier to the evolution of resistance. Together, our data suggest that lethal mutagenesis may be a particularly effective therapeutic approach with a high genetic barrier to resistance for influenza virus. Influenza virus is an RNA virus that causes significant morbidity and mortality during annual epidemics. Novel therapies for RNA viruses are needed due to the ease with which these viruses evolve resistance to existing therapeutics. Lethal mutagenesis is a broad-spectrum strategy that exploits the high mutation rate and the low

Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

Directory of Open Access Journals (Sweden)

Carlos Eduardo Tosta

1983-03-01

Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.Estudou-se o efeito da infecção causada por espécie letal (Plasmodium berghei e não- letal (P. yoelii de plasmódio sobre o sistema de fagócitos mononucleares de camundongo BALB/c. O P. yoelii causou maior e mais prolongada expansão e ativação do sistema de macrófagos. As duas mais importantes populações de fagócitos esplênicos - macrófagos de polpa vermelha e da zona marginal - exibiam maior aumento do número de células nesta infecção. Durante a evolução da malária por P. berghei, o baço foi progressivamente ocupado por tecido hematopoiético e, na fase terminal da infecção, observou-se significativa depleção dos linfócitos e macrófagos esplênicos. Os dados apresentados indicam que a evolução da malária depende do tipo de interação entre o plasmódio e o sistema de fagócitos mononucleares.

The Effect of A Single Sub-Lethal Dose of Whole Body Irradiation on the Small Intestine of Rats

International Nuclear Information System (INIS)

Al-Ramli, M. A.; Kubba, M. A.; Al-Bassam, L. S.; Belhaj, K.; Al-shawish, N. M.

2007-01-01

The effect of whole body radiation with a single sub-lethal dose at 4 Gy on rat small intestine was studied histologically and quantitatively. Irradiated animals were euthanized at 24 hours, 3, 7, 14, 21 and 28 days post- irradiation. Crypts of Leiberkuhn and peyer's patches were especially targeted by irradiation. The crypts showed severe cellular fragmentation in the germinal cellular compartments twenty Four hours after irradiation resulting in partial denudation of villi especially at their Tips. At three days, these cells resumed their proliferative activity with the appearance of unusually large numbers of mitotic figures. Cellular regeneration in the crypts and on the villous surface showed improvement with advancing time till day 28 when the villi had complete epithelial covering and the proliferative activity of the germinal cryptic cells returned to normal. The quantitative study included the measurement of about fifty villi at each time after irradiation. A significant decrease in villous length was noticed at twenty four hours post-irradiation compared to the control values. The length of villi plateaued at about this level till day twenty one when it slightly increased to reach a sub normal mean length on day 28. We concluded that whole body irradiation with a single dose at 4 Gy was enough to induce cryptic cellular necrosis with sloughing of epithelial villous columnar covering. This cellular damage was, however, sub- total since quick regenerative cellular activity was noticed three days post-irradiation. The decrease in the villous length paralleled the cryptic cellular damage whereas full recovery was not achieved despite obvious cellular regeneration.

Lethality Index 2008-2014: Less shootings, same lethality, more opacity

Directory of Open Access Journals (Sweden)

Carlos Silva Forné

2017-11-01

Full Text Available This article evaluates the use of lethal force by Mexican federal security forces during shootings with presumed members of organized crime from 2008-2014. The authors use official data and press reports on deaths and wounded in shootings to construct indicators such as the number of dead civilians over the number of dead officials from the federal security forces and the number of dead civilians over the number of wounded civilians. In a context where certain factors that contribute to an excessive use of force become more common, the results of the study show a growing use of lethal force. This raises questions over the possible excessive use of lethal force as a normal or systematic practice. The study also shows a growing context of opacity in the information available to evaluate the use of lethal force and the general lack of a legal framework to regulate the use of lethal force in Mexico.

Inhaled antibiotics in the treatment of non-cystic fibrosis bronchiectasis: clinical and drug delivery perspectives.

Science.gov (United States)

Sugianto, Tiffanie Daisy; Chan, Hak-Kim

2016-01-01

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic, progressive, suppurative lung disease characterized by permanent dilatation of bronchial subdivisions, which further causes accumulation of sputum and bacterial infections. The advent of inhaled antibiotics over the past two decades has been expected to effectively attenuate the problem of chronic bacterial infections in CF and NCFB subjects with higher, local drug concentrations and minimal systemic side effects. This review summarizes and evaluates current clinical evidence of efficacy and adverse effects of inhaled antibiotics in NCFB, as well as ongoing preclinical and clinical studies, followed by a discussion of issues and challenges in clinical practice and drug delivery strategies, together with future research directions. The evidence base of the clinical efficacy of inhaled antibiotics in NCFB is limited and the degrees of reported clinical benefits have been modest and conflicting. Challenges surrounding inhaled antibiotics application and development include the lack of knowledge of disease factors and optimum management strategies, unreceptive lung pathophysiology and the lack of factors that support compliance and tolerability. Nonetheless, research continues to give birth to new clinical findings and novel formulations such as combination antibiotics and sustained-release formulations, which add great value to the development of efficacious, safe and convenient inhalable antibiotics of the future.

Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence

Science.gov (United States)

Lacalle Muls, Helena; Costello, Richard W.; Reilly, Richard B.

2018-01-01

Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be

Rabies Virus Antibodies from Oral Vaccination as a Correlate of Protection against Lethal Infection in Wildlife

Directory of Open Access Journals (Sweden)

Susan M. Moore

2017-07-01

Full Text Available Both cell-mediated and humoral immune effectors are important in combating rabies infection, although the humoral response receives greater attention regarding rabies prevention. The principle of preventive vaccination has been adopted for strategies of oral rabies vaccination (ORV of wildlife reservoir populations for decades to control circulation of rabies virus in free-ranging hosts. There remains much debate about the levels of rabies antibodies (and the assays to measure them that confer resistance to rabies virus. In this paper, data from published literature and our own unpublished animal studies on the induction of rabies binding and neutralizing antibodies following oral immunization of animals with live attenuated or recombinant rabies vaccines, are examined as correlates of protection against lethal rabies infection in captive challenge settings. Analysis of our studies suggests that, though serum neutralization test results are expected to reflect in vivo protection, the blocking enzyme linked immunosorbent assay (ELISA result at Day 28 was a better predictor of survival. ELISA kits may have an advantage of greater precision and ability to compare results among different studies and laboratories based on the inherent standardization of the kit format. This paper examines current knowledge and study findings to guide meaningful interpretation of serology results in oral baiting monitoring.

Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems

Directory of Open Access Journals (Sweden)

Piyush Mehta

2016-01-01

Full Text Available Administration of drug molecules by inhalation route for treatment of respiratory diseases has the ability to deliver drugs, hormones, nucleic acids, steroids, proteins, and peptides, particularly to the site of action, improving the efficacy of the treatment and consequently lessening adverse effects of the treatment. Numerous inhalation delivery systems have been developed and studied to treat respiratory diseases such as asthma, COPD, and other pulmonary infections. The progress of disciplines such as biomaterials science, nanotechnology, particle engineering, molecular biology, and cell biology permits further improvement of the treatment capability. The present review analyzes modern therapeutic approaches of inhaled drugs with special emphasis on novel drug delivery system for treatment of various respiratory diseases.

Evaluation of Expedient Decontamination Options with Activated Peroxide-based Liquid Sporicides

Science.gov (United States)

2013-02-05

Figure 2-1) that are typical of the materials found in residential dwellings and meet industry standards or specifications for indoor use. Documented...Anthrax inhalation and lethal human infection. Lancet, 2002. 359(9307): p. 710-1. 14. Glassman, H.N., Industrial inhalation anthrax. Bacteriol. Rev...Begin by donning PPE (gloves, lab coat, and protective eyewear ). 2. Clean the workspace by wiping with pAB, next with DI water , and lastly with a 70

Maternal Antibody-Mediated Disease Enhancement in Type I Interferon-Deficient Mice Leads to Lethal Disease Associated with Liver Damage.

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Julia María Martínez Gómez

2016-03-01

Full Text Available Epidemiological studies have reported that most of the severe dengue cases occur upon a secondary heterologous infection. Furthermore, babies born to dengue immune mothers are at greater risk of developing severe disease upon primary infection with a heterologous or homologous dengue virus (DENV serotype when maternal antibodies reach sub-neutralizing concentrations. These observations have been explained by the antibody mediated disease enhancement (ADE phenomenon whereby heterologous antibodies or sub-neutralizing homologous antibodies bind to but fail to neutralize DENV particles, allowing Fc-receptor mediated entry of the virus-antibody complexes into host cells. This eventually results in enhanced viral replication and heightened inflammatory responses. In an attempt to replicate this ADE phenomenon in a mouse model, we previously reported that upon DENV2 infection 5-week old type I and II interferon (IFN receptors-deficient mice (AG129 born to DENV1-immune mothers displayed enhancement of disease severity characterized by increased virus titers and extensive vascular leakage which eventually led to the animals' death. However, as dengue occurs in immune competent individuals, we sought to reproduce this mouse model in a less immunocompromised background. Here, we report an ADE model that is mediated by maternal antibodies in type I IFN receptor-deficient A129 mice. We show that 5-week old A129 mice born to DENV1-immune mothers succumbed to a DENV2 infection within 4 days that was sub-lethal in mice born to naïve mothers. Clinical manifestations included extensive hepatocyte vacuolation, moderate vascular leakage, lymphopenia, and thrombocytopenia. Anti-TNFα therapy totally protected the mice and correlated with healthy hepatocytes. In contrast, blocking IL-6 did not impact the virus titers or disease outcome. This A129 mouse model of ADE may help dissecting the mechanisms involved in dengue pathogenesis and evaluate the efficacy of

More Human, More Humane: A New Approach for Testing Airborne Pollutants

OpenAIRE

Potera, Carol

2007-01-01

People not only inhale airborne contaminants but also absorb them through the skin. Both routes can set off localized toxic reactions or damage internal organs such as the liver, kidney, and brain. Conventional tests of the toxicity of gases and vapors, in which laboratory animals are exposed to lethal or sub-lethal doses of chemicals, have been criticized as expensive, unethical, inhumane, and time-consuming. Now researchers at the University of New South Wales (UNSW) in Sydney, Australia, h...

Development of Liposomal Ciprofloxacin to Treat Lung Infections

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David Cipolla

2016-03-01

Full Text Available Except for management of Pseudomonas aeruginosa (PA in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively. Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin® that are in development by Aradigm Corporation are described here.

Inhalation Therapy in Horses.

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Cha, Mandy L; Costa, Lais R R

2017-04-01

This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.

Inhalation of primary motor vehicle emissions: Effects of urbanpopulation and land area

Energy Technology Data Exchange (ETDEWEB)

Marshall, Julian D.; McKone, Thomas E.; Nazaroff, William W.

2004-06-14

Urban population density can influence transportation demand, as expressed through average daily vehicle-kilometers traveled per capita (VKT). In turn, changes in transportation demand influence total passenger vehicle emissions. Population density can also influence the fraction of total emissions that are inhaled by the exposed urban population. Equations are presented that describe these relationships for an idealized representation of an urban area. Using analytic solutions to these equations, we investigate the effect of three changes in urban population and urban land area (infill, sprawl, and constant-density growth) on per capita inhalation intake of primary pollutants from passenger vehicles. The magnitude of these effects depends on density-emissions elasticity ({var_epsilon}{sub e}), a normalized derivative relating change in population density to change in vehicle emissions. For example, if urban population increases, per capita intake is less with infill development than with constant-density growth if {var_epsilon}{sub e} is less than -0.5, while for {var_epsilon}{sub e} greater than -0.5 the reverse is true.

Characterization of the Outer Membrane Proteome of Leptospira interrogans Expressed during Acute Lethal Infection▿

OpenAIRE

Nally, Jarlath E.; Whitelegge, Julian P.; Bassilian, Sara; Blanco, David R.; Lovett, Michael A.

2006-01-01

Pathogenic Leptospira species adapt to a wide range of environmental conditions during disease transmission and infection. While the proteome of in vitro cultivated Leptospira has been characterized in several studies to date, relatively little is known of the proteome as expressed by Leptospira during disease processes. Isolates of Leptospira obtained from patients suffering the severe pulmonary form of leptospirosis cause acute lethal infection in guinea pigs and chronic asymptomatic infect...

Time- and concentration-dependent genomic responses of the rat airway to inhaled nickel subsulfide

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Efremenko, A.Y., E-mail: aefremenko@thehamner.org [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Campbell, J.L.; Dodd, D.E. [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Oller, A.R. [NiPERA, Inc., 2525 Meridian Parkway, Suite 240, Durham, NC 27713 (United States); Clewell, H.J. [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

2014-09-15

Objective: To provide insights into the mode of action for Ni{sub 3}S{sub 2} lung carcinogenicity by examining gene expression changes in target cells after inhalation exposure. Methods: Gene expression changes were determined in micro-dissected lung broncho-alveolar cells from Fischer 344 rats following inhalation of Ni{sub 3}S{sub 2} at 0.0, 0.04, 0.08, 0.15, and 0.60 mg/m{sup 3} (0.03, 0.06, 0.11, and 0.44 mg Ni/m{sup 3}) for one and four weeks (6 h/day, 5 days/week). Results: Broncho-alveolar lavage fluid evaluation and lung histopathology provided evidence of inflammation only at the two highest concentrations, which were similar to those tested in the 2-year bioassay. The number of statistically significant up- and down-regulated genes decreased markedly from one to four weeks of exposure, suggesting adaptation. Cell signal pathway enrichment at both time-points primarily reflected responses to toxicity, including inflammatory and proliferative signaling. While proliferative signaling was up-regulated at both time points, some inflammatory signaling reversed from down-regulation at 1 week to up-regulation at 4 weeks. Conclusions: These results support a mode of action for Ni{sub 3}S{sub 2} carcinogenicity driven by chronic toxicity, inflammation and proliferation, leading to mis-replication, rather than by direct genotoxicity. Benchmark dose (BMD) analysis identified the lowest pathway transcriptional BMD exposure concentration as 0.026 mg Ni/m{sup 3}, for apoptosis/survival signaling. When conducted on the basis of lung Ni concentration the lowest pathway BMD was 0.64 μg Ni/g lung, for immune/inflammatory signaling. Implications: These highly conservative BMDs could be used to derive a point of departure in a nonlinear risk assessment for Ni{sub 3}S{sub 2} toxicity and carcinogenicity. - Highlights: • The mode of action for lung carcinogenicity of inhaled Ni{sub 3}S{sub 2} was investigated in rats. • Gene expression changes were determined in micro

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

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

2014-02-01

The relationship between exposure time (LT50) and lethal exposure concentration (LC50) has been evaluated over relatively long exposure times using a novel parameter, Normal Life Expectancy (NLT), as a long term toxicity point. The model equation, ln(LT50) = aLC50(ν) + b, where a, b and ν are constants, was evaluated by plotting lnLT50 against LC50 using available toxicity data based on inhalation exposure from 7 species of mammals. With each specific toxicant a single consistent relationship was observed for all mammals with ν always mammals and then be extended to estimate toxicity at any exposure time with other mammals. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

New baculovirus recombinants expressing Pseudorabies virus (PRV) glycoproteins protect mice against lethal challenge infection.

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Grabowska, Agnieszka K; Lipińska, Andrea D; Rohde, Jörg; Szewczyk, Boguslaw; Bienkowska-Szewczyk, Krystyna; Rziha, Hanns-Joachim

2009-06-02

The present study demonstrates the protective potential of novel baculovirus recombinants, which express the glycoproteins gB, gC, or gD of Pseudorabies virus (PRV; Alphaherpesvirus of swine) and additionally contain the glycoprotein G of Vesicular Stomatitis Virus (VSV-G) in the virion (Bac-G-PRV). To evaluate the protective capacity, mixtures of equal amounts of the PRV gB-, gC-, and gD-expressing baculoviruses were used for immunization. Three intramuscular immunizations with that Bac-G-PRV mixture could protect mice against a lethal PRV challenge infection. To achieve complete protection high titers of Bac-G-PRV and three immunizations were necessary. This immunization with Bac-G-PRV resulted in the induction of high titers of PRV-specific serum antibodies of the IgG2a subclass and of interferon (IFN)-gamma, indicating a Th1-type immune response. Moreover, splenocytes of immunized mice exhibited natural killer cell activity accompanied by the production of IFN-alpha and IFN-gamma. Collectively, the presented data demonstrate for the first time that co-expression of VSV-G in baculovirus recombinant vaccines can improve the induction of a protective immune response against foreign antigens.

Additional burden of asymptomatic and sub-patent malaria infections during low transmission season in forested tribal villages in Chhattisgarh, India.

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Chourasia, Mehul Kumar; Raghavendra, Kamaraju; Bhatt, Rajendra M; Swain, Dipak Kumar; Meshram, Hemraj M; Meshram, Jayant K; Suman, Shrity; Dubey, Vinita; Singh, Gyanendra; Prasad, Kona Madhavinadha; Kleinschmidt, Immo

2017-08-08

The burden of sub-patent malaria is difficult to recognize in low endemic areas due to limitation of diagnostic tools, and techniques. Polymerase chain reaction (PCR), a molecular based technique, is one of the key methods for detection of low parasite density infections. The study objective was to assess the additional burden of asymptomatic and sub-patent malaria infection among tribal populations inhabiting three endemic villages in Keshkal sub-district, Chhattisgarh, India. A cross-sectional survey was conducted in March-June 2016, during the low transmission season, to measure and compare prevalence of malaria infection using three diagnostics: rapid diagnostic test, microscopy and nested-PCR. Out of 437 individuals enrolled in the study, 103 (23.6%) were malaria positive by PCR and/or microscopy of whom 89.3% were Plasmodium falciparum cases, 77.7% were afebrile and 35.9% had sub-patent infections. A substantial number of asymptomatic and sub-patent malaria infections were identified in the survey. Hence, strategies for identifying and reducing the hidden burden of asymptomatic and sub-patent infections should focus on forest rural tribal areas using more sensitive molecular diagnostic methods to curtail malaria transmission.

Inhalants in Peru.

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Lerner, R; Ferrando, D

1995-01-01

In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon

Ants defend aphids against lethal disease

Science.gov (United States)

Nielsen, Charlotte; Agrawal, Anurag A.; Hajek, Ann E.

2010-01-01

Social insects defend their own colonies and some species also protect their mutualist partners. In mutualisms with aphids, ants typically feed on honeydew produced by aphids and, in turn guard and shelter aphid colonies from insect natural enemies. Here we report that Formica podzolica ants tending milkweed aphids, Aphis asclepiadis, protect aphid colonies from lethal fungal infections caused by an obligate aphid pathogen, Pandora neoaphidis. In field experiments, bodies of fungal-killed aphids were quickly removed from ant-tended aphid colonies. Ant workers were also able to detect infective conidia on the cuticle of living aphids and responded by either removing or grooming these aphids. Our results extend the long-standing view of ants as mutualists and protectors of aphids by demonstrating focused sanitizing and quarantining behaviour that may lead to reduced disease transmission in aphid colonies. PMID:19923138

Hydrazine inhalation hepatotoxicity.

Science.gov (United States)

Kao, Yung Hsiang; Chong, C H; Ng, W T; Lim, D

2007-10-01

Abstract Hydrazine is a hazardous chemical commonly used as a reactant in rocket and jet fuel cells. Animal studies have demonstrated hepatic changes after hydrazine inhalation. Human case reports of hydrazine inhalation hepatotoxicity are rare. We report a case of mild hepatotoxicity following brief hydrazine vapour inhalation in a healthy young man, which resolved completely on expectant management.

Quantitative analysis of dynamic airway changes after methacholine and salbutamol inhalation on xenon-enhanced chest CT

Energy Technology Data Exchange (ETDEWEB)

Park, Sang Joon; Goo, Jin Mo; Kim, Jong Hyo; Park, Eun-Ah [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Lee, Chang Hyun [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Jung, Jae-Woo; Park, Heung-Woo [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of); Cho, Sang-Heon [Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of)

2012-11-15

To investigate the dynamic changes in airways in response to methacholine and salbutamol inhalation and to correlate the xenon ventilation index on xenon-enhanced chest CTs in asthmatics. Thirty-one non-smokers (6 normal, 25 asthmatics) underwent xenon-enhanced chest CT and pulmonary function tests. Images were obtained at three stages (basal state, after methacholine inhalation and after salbutamol inhalation), and the total xenon ventilation index (TXVI) as well as airway values were measured and calculated. The repeated measures ANOVA and Spearman's correlation coefficient were used for statistical analysis. TXVI in the normal group did not significantly change (P > 0.05) with methacholine and salbutamol. For asthmatics, however, the TXVI significantly decreased after methacholine inhalation and increased after salbutamol inhalation (P < 0.05). Of the airway parameters, the airway inner area (IA) significantly increased after salbutamol inhalation in all airways (P < 0.01) in asthmatics. Airway IA, wall thickness and wall area percentage did not significantly decrease after methacholine inhalation (P > 0.05). IA of the large airways was well correlated with basal TXVI, FEV{sub 1} and FVC (P < 0.05). Airway IA is the most reliable parameter for reflecting the dynamic changes after methacholine and salbutamol inhalation, and correlates well with TXVI in asthmatics on xenon-enhanced CT. (orig.)

An antivector vaccine protects against a lethal vector-borne pathogen.

Directory of Open Access Journals (Sweden)

Milan Labuda

2006-04-01

Full Text Available Vaccines that target blood-feeding disease vectors, such as mosquitoes and ticks, have the potential to protect against the many diseases caused by vector-borne pathogens. We tested the ability of an anti-tick vaccine derived from a tick cement protein (64TRP of Rhipicephalus appendiculatus to protect mice against tick-borne encephalitis virus (TBEV transmitted by infected Ixodes ricinus ticks. The vaccine has a "dual action" in immunized animals: when infested with ticks, the inflammatory and immune responses first disrupt the skin feeding site, resulting in impaired blood feeding, and then specific anti-64TRP antibodies cross-react with midgut antigenic epitopes, causing rupture of the tick midgut and death of engorged ticks. Three parameters were measured: "transmission," number of uninfected nymphal ticks that became infected when cofeeding with an infected adult female tick; "support," number of mice supporting virus transmission from the infected tick to cofeeding uninfected nymphs; and "survival," number of mice that survived infection by tick bite and subsequent challenge by intraperitoneal inoculation of a lethal dose of TBEV. We show that one dose of the 64TRP vaccine protects mice against lethal challenge by infected ticks; control animals developed a fatal viral encephalitis. The protective effect of the 64TRP vaccine was comparable to that of a single dose of a commercial TBEV vaccine, while the transmission-blocking effect of 64TRP was better than that of the antiviral vaccine in reducing the number of animals supporting virus transmission. By contrast, the commercial antitick vaccine (TickGARD that targets only the tick's midgut showed transmission-blocking activity but was not protective. The 64TRP vaccine demonstrates the potential to control vector-borne disease by interfering with pathogen transmission, apparently by mediating a local cutaneous inflammatory immune response at the tick-feeding site.

Adherence to tobramycin inhaled powder vs inhaled solution in patients with cystic fibrosis: analysis of US insurance claims data

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Hamed K

2017-04-01

Full Text Available Kamal Hamed,1 Valentino Conti,2 Hengfeng Tian,1 Emil Loefroth3 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Global Service Center, Dublin, Ireland; 3Novartis Sverige AB, Täby, Sweden Purpose: Tobramycin inhalation powder (TIP, the first dry-powder inhaled antibiotic for pulmonary Pseudomonas aeruginosa infection, is associated with reduced treatment burden, increased patient satisfaction, and higher self-reported adherence for cystic fibrosis (CF patients. We compared adherence in CF patients newly treated with TIP with those newly treated with the traditional tobramycin inhalation solution (TIS, using US insurance claims data.Patients and methods: From the Truven MarketScan® database, we identified CF patients chronically infected with P. aeruginosa who had been prescribed TIP between May 1, 2013 to December 31, 2014, or TIS between September 1, 2010 to April 30, 2012 with at least 12 months of continuous medical and pharmacy benefits prior to and following prescription. TIP and TIS adherence levels were assessed.Results: A total of 145 eligible patients were identified for the TIP cohort and 306 for the TIS cohort. Significant differences in age distribution (25.0 vs 21.9 years for TIP vs TIS, respectively, P=0.017, type of health plan (P=0.014, employment status (72.4% vs 63.4% of TIP vs TIS patients in full-time employment, P=0.008, and some comorbidities were observed between the two cohorts. Although a univariate analysis found no significant differences between TIP and TIS (odds ratio [OR] 1.411, 95% confidence interval [CI] 0.949–2.098, TIP was moderately associated with higher adherence levels compared with TIS in a multivariable analysis, once various demographic and clinical characteristics were adjusted for. These included geographic location (OR: 1.566, CI: 1.016–2.413 and certain comorbidities.Conclusion: This study of US patient data supports previous findings that TIP is associated with better

Clostridium sordellii lethal toxin kills mice by inducing a major increase in lung vascular permeability.

Science.gov (United States)

Geny, Blandine; Khun, Huot; Fitting, Catherine; Zarantonelli, Leticia; Mazuet, Christelle; Cayet, Nadège; Szatanik, Marek; Prevost, Marie-Christine; Cavaillon, Jean-Marc; Huerre, Michel; Popoff, Michel R

2007-03-01

When intraperitoneally injected into Swiss mice, Clostridium sordellii lethal toxin reproduces the fatal toxic shock syndrome observed in humans and animals after natural infection. This animal model was used to study the mechanism of lethal toxin-induced death. Histopathological and biochemical analyses identified lung and heart as preferential organs targeted by lethal toxin. Massive extravasation of blood fluid in the thoracic cage, resulting from an increase in lung vascular permeability, generated profound modifications such as animal dehydration, increase in hematocrit, hypoxia, and finally, cardiorespiratory failure. Vascular permeability increase induced by lethal toxin resulted from modifications of lung endothelial cells as evidenced by electron microscopy. Immunohistochemical analysis demonstrated that VE-cadherin, a protein participating in intercellular adherens junctions, was redistributed from membrane to cytosol in lung endothelial cells. No major sign of lethal toxin-induced inflammation was observed that could participate in the toxic shock syndrome. The main effect of the lethal toxin is the glucosylation-dependent inactivation of small GTPases, in particular Rac, which is involved in actin polymerization occurring in vivo in lungs leading to E-cadherin junction destabilization. We conclude that the cells most susceptible to lethal toxin are lung vascular endothelial cells, the adherens junctions of which were altered after intoxication.

Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

Science.gov (United States)

Kreijtz, J H C M; Bodewes, R; van den Brand, J M A; de Mutsert, G; Baas, C; van Amerongen, G; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

2009-08-06

The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the

Phyto-inhalation for treatment of complications of acute respiratory viral diseases

Directory of Open Access Journals (Sweden)

I.B. Ershova

2017-03-01

Full Text Available Inhalations (inhalation of medicinal substances are one of the effective ways to treat upper respiratory tract diseases and colds. Inhalation therapy is used to treat rhinitis, sinusitis, tonsillitis, pharyngitis, laryngitis, bronchitis and pneumonia, which can be complications of acute respiratory viral infections. The main rules of inhalation are as follows to conduct the procedure better after 1.5 hours after eating; clothes should not impede breathing; the procedure can be carried out only while sitting or standing; solution for the inhaler for treatment of bronchitis should be fresh; it is necessary to strictly keep the prescribed dosage; the time of the procedure should also be respected — usually it is from 1 to 4 minutes, sometimes for adults up to 10 minutes, for children the inhalation period is shorter — 1–2 minutes. Contraindications to inhalation are body temperature above 37.5 degrees; propensity to nasal blee­ding in a patient; propensity to increased arterial pressure, with cardiovascular failure; purulent inflammation of the tonsils; respiratory failure. The procedure should be stopped immediately in case of appearance of adverse symptoms such as shortness of breath, dizziness, difficulty in breathing. Therefore, inhalations must be prescribed by a doctor after examination of a patient. During inhalations in rhinitis, you should try to inhale the vapor through the nose. For effective treatment of rhinitis, inhalations from conife­rous plants are very suitable: fir, pine, juniper, larch, from steamed dried chamomile flowers, mint, and blackberry leaves. Honey inhalations can be used for the treatment of acute and chronic diseases of the upper respiratory tract (tonsillitis, pharyngitis, laryngitis and tracheitis. Medical herbal inhalation for children should be carried out from the age of two years. This must be done under the constant supervision of an adult. Leaves of coniferous trees: pine, fir, if or juniper, cedar

Induction of dominant lethal mutations by gamma irradiation of Gallus domesticus spermatozoa

Energy Technology Data Exchange (ETDEWEB)

Baumgartner, J; Grom, A; Csuka, J; Kindlova, L [Poultry Research Institute, Ivanka pri Dunaji (Czechoslovakia)

1977-01-01

Mixed semen of Gallus domesticus cocks was gamma irradiated in vitro with exposures of 500, 1000, 2000, and 3000 R at the exposure rate of 5.86 Rs/sup -1/. After the irradiation the semen was applied to experimental and control layer hens, the embryonic mortality in F/sub 1/ was observed, the total number of incubated eggs was 3344. Irradiation with 500 R had a favourable influence on embryonic vitality, the exposures 1000, 2000, and 3000 R resulted in increased embryonic mortality, for 2100 R a 50% mortality of offspring was found. Induced dominant lethality was manifest during embryonic and oviduct development. The frequency of induced dominant lethality for exposures used was 19.2, 9.9, 48.3, and 69.1%, the values of mutation rate were 0.087, 0.104, 0.659, and 1.174. The mutation rate had a linear course, the value of the lethal hit per gamete for 1 R was 1.04x10/sup -4/.

Theories of Lethal Mutagenesis: From Error Catastrophe to Lethal Defection.

Science.gov (United States)

Tejero, Héctor; Montero, Francisco; Nuño, Juan Carlos

2016-01-01

RNA viruses get extinct in a process called lethal mutagenesis when subjected to an increase in their mutation rate, for instance, by the action of mutagenic drugs. Several approaches have been proposed to understand this phenomenon. The extinction of RNA viruses by increased mutational pressure was inspired by the concept of the error threshold. The now classic quasispecies model predicts the existence of a limit to the mutation rate beyond which the genetic information of the wild type could not be efficiently transmitted to the next generation. This limit was called the error threshold, and for mutation rates larger than this threshold, the quasispecies was said to enter into error catastrophe. This transition has been assumed to foster the extinction of the whole population. Alternative explanations of lethal mutagenesis have been proposed recently. In the first place, a distinction is made between the error threshold and the extinction threshold, the mutation rate beyond which a population gets extinct. Extinction is explained from the effect the mutation rate has, throughout the mutational load, on the reproductive ability of the whole population. Secondly, lethal defection takes also into account the effect of interactions within mutant spectra, which have been shown to be determinant for the understanding the extinction of RNA virus due to an augmented mutational pressure. Nonetheless, some relevant issues concerning lethal mutagenesis are not completely understood yet, as so survival of the flattest, i.e. the development of resistance to lethal mutagenesis by evolving towards mutationally more robust regions of sequence space, or sublethal mutagenesis, i.e., the increase of the mutation rate below the extinction threshold which may boost the adaptability of RNA virus, increasing their ability to develop resistance to drugs (including mutagens). A better design of antiviral therapies will still require an improvement of our knowledge about lethal

Deposition, translocation and effects of transuranic particles inhaled by experimental animals

International Nuclear Information System (INIS)

Craig, D.K.; Ballou, J.E.; Dagle, G.E.; Mahlum, D.D.; Park, J.F.; Sanders, C.L.; Sikov, M.R.; Stuart, B.O.

1977-01-01

Inhalation exposure constitutes the most likely route of entrance for transuranics into the body. Cancer is the most likely consequence of exposure, but several thousand workers have been exposed during the last 30 yrs without, so far, evidence of exposure-related effects. Several soluble and insoluble transuranic compounds have been studied in rodents and dogs, either alone or combined with exposure to other materials (e.g., PuO/sub 2/--UO/sub 2/ fuel and Na). These studies have provided a wide variety of spatial and temporal dose distribution patterns in the lung. The distribution and total initial deposition in the respiratory tract is a function of the physical characteristics of the inhaled aerosols (size distribution, shape, hygroscopicity) and of the morphology and physiology of the animal. Translocation rates, organ and tissue distribution and excretion in urine and feces, are a function of the physicochemical characteristics of the deposited material (solubility, specific activity, chemical compound, etc.). Differences in rate of translocation of the solubilized material, primarily to the liver and bone, determines the radiation dose to the various tissues involved. Insoluble particles of plutonium dioxide are transferred to the thoracic lymph nodes, which may be functionally destroyed as a consequence. Radiation pneumonitis and pulmonary fibrosis are the main causes of death in animals with cumulative radiation doses to the lung of a few thousand rads. The most significant long-term effect of inhaled transuranic compounds in animals is the development of lung and bone tumors. The main type of lung tumor in both dog and rat is the bronchioloalveolar carcinoma (adenocarcinoma). However, tumor type is a function of radiation dose and dose-distribution at high doses. Bone ranks next to lung as the tissue developing the most tumors following inhalation of transuranics

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya.

Science.gov (United States)

Hilker, Frank M; Allen, Linda J S; Bokil, Vrushali A; Briggs, Cheryl J; Feng, Zhilan; Garrett, Karen A; Gross, Louis J; Hamelin, Frédéric M; Jeger, Michael J; Manore, Carrie A; Power, Alison G; Redinbaugh, Margaret G; Rúa, Megan A; Cunniffe, Nik J

2017-10-01

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with large holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Inhaled Antibiotics in the Treatment of Nosocomial Pneumonia

OpenAIRE

A. N. Kuzovlev; V. V. Moroz; A. M. Golubev; S. G. Polovnikov

2013-01-01

Nosocomial pneumonia is the most common nosocomial infection in intensive care units. Rational antibiotic therapy is the basis for the treatment of nosocomial pneumonia. There is currently a challenge of the pathogens of nosocomial pneumonia being resistant to most of the antibiotics recommended for its treatment. Inhaled antibiotics used in combination with systemic drugs are an effective and safe treatment for nosocomial pneumonia. This review of literature characterizes the current possibi...

Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model

Directory of Open Access Journals (Sweden)

Grassian Vicki H

2011-09-01

Full Text Available Abstract Background Human exposure to nanoparticles (NPs and environmental bacteria can occur simultaneously. NPs induce inflammatory responses and oxidative stress but may also have immune-suppressive effects, impairing macrophage function and altering epithelial barrier functions. The purpose of this study was to assess the potential pulmonary effects of inhalation and instillation exposure to copper (Cu NPs using a model of lung inflammation and host defense. Methods We used Klebsiella pneumoniae (K.p. in a murine lung infection model to determine if pulmonary bacterial clearance is enhanced or impaired by Cu NP exposure. Two different exposure modes were tested: sub-acute inhalation (4 hr/day, 5 d/week for 2 weeks, 3.5 mg/m3 and intratracheal instillation (24 hr post-exposure, 3, 35, and 100 μg/mouse. Pulmonary responses were evaluated by lung histopathology plus measurement of differential cell counts, total protein, lactate dehydrogenase (LDH activity, and inflammatory cytokines in bronchoalveolar lavage (BAL fluid. Results Cu NP exposure induced inflammatory responses with increased recruitment of total cells and neutrophils to the lungs as well as increased total protein and LDH activity in BAL fluid. Both inhalation and instillation exposure to Cu NPs significantly decreased the pulmonary clearance of K.p.-exposed mice measured 24 hr after bacterial infection following Cu NP exposure versus sham-exposed mice also challenged with K.p (1.4 × 105 bacteria/mouse. Conclusions Cu NP exposure impaired host defense against bacterial lung infections and induced a dose-dependent decrease in bacterial clearance in which even our lowest dose demonstrated significantly lower clearance than observed in sham-exposed mice. Thus, exposure to Cu NPs may increase the risk of pulmonary infection.

The radiobiology of laser-driven particle beams: focus on sub-lethal responses of normal human cells

International Nuclear Information System (INIS)

Manti, L.; Perozziello, F.M.; Romagnani, L.; Borghesi, M.; Doria, D.; Candiano, G.; Cirrone, G.A.P.; Leanza, R.; Romano, F.; Scuderi, V.; Tramontana, A.; Chaudhary, P.; Gwynne, D.; Prise, K. M.

2017-01-01

Accelerated proton beams have become increasingly common for treating cancer. The need for cost and size reduction of particle accelerating machines has led to the pioneering investigation of optical ion acceleration techniques based on laser-plasma interactions as a possible alternative. Laser-matter interaction can produce extremely pulsed particle bursts of ultra-high dose rates (≥ 10 9 Gy/s), largely exceeding those currently used in conventional proton therapy. Since biological effects of ionizing radiation are strongly affected by the spatio-temporal distribution of DNA-damaging events, the unprecedented physical features of such beams may modify cellular and tissue radiosensitivity to unexplored extents. Hence, clinical applications of laser-generated particles need thorough assessment of their radiobiological effectiveness. To date, the majority of studies have either used rodent cell lines or have focussed on cancer cell killing being local tumour control the main objective of radiotherapy. Conversely, very little data exist on sub-lethal cellular effects, of relevance to normal tissue integrity and secondary cancers, such as premature cellular senescence. Here, we discuss ultra-high dose rate radiobiology and present preliminary data obtained in normal human cells following irradiation by laser-accelerated protons at the LULI PICO2000 facility at Laser Lab Europe, France.

Genotoxic endpoints in the earthworms sub-lethal assay to evaluate natural soils contaminated by metals and radionuclides

International Nuclear Information System (INIS)

Lourenco, Joana I.; Pereira, Ruth O.; Silva, Ana C.; Morgado, Jose M.; Carvalho, Fernando P.; Oliveira, Joao M.; Malta, Margarida P.; Paiva, Artur A.; Mendo, Sonia A.; Goncalves, Fernando J.

2011-01-01

Eisenia andrei was exposed, for 56 days, to a contaminated soil from an abandoned uranium mine and to the natural reference soil LUFA 2.2. The organisms were sampled after 0, 1, 2, 7, 14 and 56 days of exposure, to assess metals bioaccumulation, coelomocytes DNA integrity and cytotoxicity. Radionuclides bioaccumulation and growth were also determined at 0 h, 14 and 56 days of exposure. Results have shown the bioaccumulation of metals and radionuclides, as well as, growth reduction, DNA damages and cytotoxicity in earthworms exposed to contaminated soil. The usefulness of the comet assay and flow cytometry, to evaluate the toxicity of contaminants such as metals and radionuclides in earthworms are herein reported. We also demonstrated that DNA strand breakage and immune cells frequency are important endpoints to be employed in the earthworm reproduction assay, for the evaluation of soil geno and cytotoxicity, as part of the risk assessment of contaminated areas. This is the first study that integrates DNA damage and cytotoxicity evaluation, growth and bioaccumulation of metals and radionuclides in a sub lethal assay, for earthworms exposed to soil contaminated with metals and radionuclides.

Genotoxic endpoints in the earthworms sub-lethal assay to evaluate natural soils contaminated by metals and radionuclides

Energy Technology Data Exchange (ETDEWEB)

Lourenco, Joana I., E-mail: joanalourenco@ua.pt [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Pereira, Ruth O., E-mail: ruthp@ua.pt [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Silva, Ana C., E-mail: ana.cmj@ua.pt [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Morgado, Jose M., E-mail: jmtmorgado@gmail.com [Centro de Histocompatibilidade do Centro, Praceta Prof. Mota Pinto, Edificio S. Jeronimo, 4o piso, Apartado 9041, 3001-301 Coimbra (Portugal); Carvalho, Fernando P., E-mail: fernando.carvalho@itn.pt [Instituto Tecnologico Nuclear, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Oliveira, Joao M., E-mail: joaomota@itn.pt [Instituto Tecnologico Nuclear, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Malta, Margarida P., E-mail: margm@itn.pt [Instituto Tecnologico Nuclear, Estrada Nacional 10, 2686-953 Sacavem (Portugal); Paiva, Artur A., E-mail: apaiva@histocentro.min-saude.pt [Centro de Histocompatibilidade do Centro, Praceta Prof. Mota Pinto, Edificio S. Jeronimo, 4o piso, Apartado 9041, 3001-301 Coimbra (Portugal); Mendo, Sonia A., E-mail: smendo@ua.pt [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Goncalves, Fernando J., E-mail: fjmg@ua.pt [CESAM and Departamento de Biologia, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal)

2011-02-15

Eisenia andrei was exposed, for 56 days, to a contaminated soil from an abandoned uranium mine and to the natural reference soil LUFA 2.2. The organisms were sampled after 0, 1, 2, 7, 14 and 56 days of exposure, to assess metals bioaccumulation, coelomocytes DNA integrity and cytotoxicity. Radionuclides bioaccumulation and growth were also determined at 0 h, 14 and 56 days of exposure. Results have shown the bioaccumulation of metals and radionuclides, as well as, growth reduction, DNA damages and cytotoxicity in earthworms exposed to contaminated soil. The usefulness of the comet assay and flow cytometry, to evaluate the toxicity of contaminants such as metals and radionuclides in earthworms are herein reported. We also demonstrated that DNA strand breakage and immune cells frequency are important endpoints to be employed in the earthworm reproduction assay, for the evaluation of soil geno and cytotoxicity, as part of the risk assessment of contaminated areas. This is the first study that integrates DNA damage and cytotoxicity evaluation, growth and bioaccumulation of metals and radionuclides in a sub lethal assay, for earthworms exposed to soil contaminated with metals and radionuclides.

Effects of radiation on the R/sub 1/ and R/sub 2/ progenies of Pennisetum typhoides S. and H

Energy Technology Data Exchange (ETDEWEB)

Das, L D.V. [Tamil Nadu Agricultural Univ., Coimbatore (India)

1978-05-01

Dry seeds of cumbu strains HB3 and MS7625 were irradiated with different doses of X- and gamma rays. The survival, growth reduction and pollen sterility of R/sub 1/ plants were estimated. The seeds from each R/sub 1/ plant were sown in the field and all clearly deviating plants were scored as morphological mutants. Gamma rays were found to be more effective than X-rays with respect to R/sub 1/ lethality, growth reduction, pollen sterility, and R/sub 2/ mutant frequency. In addition, the survival frequency of the R/sub 1/ plants was reduced to zero per cent when the exposure was increased to 30 and 40 kR of gamma rays. The response of the two strains clearly deviated in X-rays and gamma rays. HB3 showed a lower percentage of lethality, lesser growth reduction and lower pollen sterility. While the relation between R/sub 1/ pollen sterility and the R/sub 2/ mutant frequency was established, it was found that HB3 segregates greater number of mutants than MS7625. The possibility for this might be due to the hybrid parentage of HB3.

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

Science.gov (United States)

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.

DUST-BATHING BEHAVIORS OF AFRICAN HERBIVORES AND THE POTENTIAL RISK OF INHALATIONAL ANTHRAX.

Science.gov (United States)

Barandongo, Zoe R; Mfune, John K E; Turner, Wendy C

2018-01-01

:  Anthrax in herbivorous wildlife and livestock is generally assumed to be transmitted via ingestion or inhalation of Bacillus anthracis spores. Although recent studies have highlighted the importance of the ingestion route for anthrax transmission, little is known about the inhalational route in natural systems. Dust bathing could aerosolize soilborne pathogens such as B. anthracis, exposing dust-bathing individuals to inhalational infections. We investigated the potential role of dust bathing in the transmission of inhalational anthrax to herbivorous wildlife in Etosha National Park, Namibia, an area with endemic seasonal anthrax outbreaks. We 1) cultured soils from dust-bathing sites for the presence and concentration of B. anthracis spores, 2) monitored anthrax carcass sites, the locations with the highest B. anthracis concentrations, for evidence of dust bathing, including a site where a zebra died of anthrax on a large dust bath, and 3) characterized the ecology and seasonality of dust bathing in plains zebra ( Equus quagga), blue wildebeest ( Connochaetes taurinus), and African savanna elephant ( Loxodonta africana) using a combination of motion-sensing camera traps and direct observations. Only two out of 83 dust-bath soils were positive for B. anthracis, both with low spore concentrations (≤20 colony-forming units per gram). We also detected no evidence of dust baths occurring at anthrax carcass sites, perhaps due to carcass-induced changes in soil composition that may deter dust bathing. Finally, despite observing some seasonal variation in dust bathing, preliminary evidence suggests that the seasonality of dust bathing and anthrax mortalities are not correlated. Thus, although dust bathing creates a dramatic cloud of aerosolized soil around an individual, our microbiologic, ecologic, and behavioral results in concert demonstrate that dust bathing is highly unlikely to transmit inhalational anthrax infections.

The Effects of Inhaled Steroids on Recurrent Wheeze After Acute Bronchiolitis

Directory of Open Access Journals (Sweden)

Patricia Green MD

2015-07-01

Full Text Available 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.

Dry powder inhalation of antibiotics : A promising approach for treatment of infectious diseases

NARCIS (Netherlands)

Hoppentocht, Marcel

2016-01-01

In the thesis of Marcel Hoppentocht the feasibility to treat bacterial infections effectively with inhaled dry powder antibiotics is explored. Most antibiotics are currently administered pulmonary by wet nebulisation or via the parenteral route and both methods have numerous disadvantages. For

Developments and strategies for inhaled antibiotic drugs in tuberculosis therapy : A critical evaluation

NARCIS (Netherlands)

Hoppentocht, M; Hagedoorn, P; Frijlink, H W; de Boer, A H

2014-01-01

Inhaled antibiotics have been a valuable tool in treating pulmonary infections in cystic fibrosis patients for decades, and the pulmonary route is now becoming increasingly interesting for other infectious diseases like tuberculosis too. Especially with multidrug and extensively drug-resistant

A prophylactic multivalent vaccine against different filovirus species is immunogenic and provides protection from lethal infections with Ebolavirus and Marburgvirus species in non-human primates.

Directory of Open Access Journals (Sweden)

Benoit Callendret

Full Text Available The search for a universal filovirus vaccine that provides protection against multiple filovirus species has been prompted by sporadic but highly lethal outbreaks of Ebolavirus and Marburgvirus infections. A good prophylactic vaccine should be able to provide protection to all known filovirus species and as an upside potentially protect from newly emerging virus strains. We investigated the immunogenicity and protection elicited by multivalent vaccines expressing glycoproteins (GP from Ebola virus (EBOV, Sudan virus (SUDV, Taï Forest virus (TAFV and Marburg virus (MARV. Immune responses against filovirus GP have been associated with protection from disease. The GP antigens were expressed by adenovirus serotypes 26 and 35 (Ad26 and Ad35 and modified Vaccinia virus Ankara (MVA vectors, all selected for their strong immunogenicity and good safety profile. Using fully lethal NHP intramuscular challenge models, we assessed different vaccination regimens for immunogenicity and protection from filovirus disease. Heterologous multivalent Ad26-Ad35 prime-boost vaccination regimens could give full protection against MARV (range 75%-100% protection and EBOV (range 50% to 100% challenge, and partial protection (75% against SUDV challenge. Heterologous multivalent Ad26-MVA prime-boost immunization gave full protection against EBOV challenge in a small cohort study. The use of such multivalent vaccines did not show overt immune interference in comparison with monovalent vaccines. Multivalent vaccines induced GP-specific antibody responses and cellular IFNγ responses to each GP expressed by the vaccine, and cross-reactivity to TAFV GP was detected in a trivalent vaccine expressing GP from EBOV, SUDV and MARV. In the EBOV challenge studies, higher humoral EBOV GP-specific immune responses (p = 0.0004 were associated with survival from EBOV challenge and less so for cellular immune responses (p = 0.0320. These results demonstrate that it is feasible to

A prophylactic multivalent vaccine against different filovirus species is immunogenic and provides protection from lethal infections with Ebolavirus and Marburgvirus species in non-human primates.

Science.gov (United States)

Callendret, Benoit; Vellinga, Jort; Wunderlich, Kerstin; Rodriguez, Ariane; Steigerwald, Robin; Dirmeier, Ulrike; Cheminay, Cedric; Volkmann, Ariane; Brasel, Trevor; Carrion, Ricardo; Giavedoni, Luis D; Patterson, Jean L; Mire, Chad E; Geisbert, Thomas W; Hooper, Jay W; Weijtens, Mo; Hartkoorn-Pasma, Jutta; Custers, Jerome; Grazia Pau, Maria; Schuitemaker, Hanneke; Zahn, Roland

2018-01-01

The search for a universal filovirus vaccine that provides protection against multiple filovirus species has been prompted by sporadic but highly lethal outbreaks of Ebolavirus and Marburgvirus infections. A good prophylactic vaccine should be able to provide protection to all known filovirus species and as an upside potentially protect from newly emerging virus strains. We investigated the immunogenicity and protection elicited by multivalent vaccines expressing glycoproteins (GP) from Ebola virus (EBOV), Sudan virus (SUDV), Taï Forest virus (TAFV) and Marburg virus (MARV). Immune responses against filovirus GP have been associated with protection from disease. The GP antigens were expressed by adenovirus serotypes 26 and 35 (Ad26 and Ad35) and modified Vaccinia virus Ankara (MVA) vectors, all selected for their strong immunogenicity and good safety profile. Using fully lethal NHP intramuscular challenge models, we assessed different vaccination regimens for immunogenicity and protection from filovirus disease. Heterologous multivalent Ad26-Ad35 prime-boost vaccination regimens could give full protection against MARV (range 75%-100% protection) and EBOV (range 50% to 100%) challenge, and partial protection (75%) against SUDV challenge. Heterologous multivalent Ad26-MVA prime-boost immunization gave full protection against EBOV challenge in a small cohort study. The use of such multivalent vaccines did not show overt immune interference in comparison with monovalent vaccines. Multivalent vaccines induced GP-specific antibody responses and cellular IFNγ responses to each GP expressed by the vaccine, and cross-reactivity to TAFV GP was detected in a trivalent vaccine expressing GP from EBOV, SUDV and MARV. In the EBOV challenge studies, higher humoral EBOV GP-specific immune responses (p = 0.0004) were associated with survival from EBOV challenge and less so for cellular immune responses (p = 0.0320). These results demonstrate that it is feasible to generate a

Ciclesonide Oral Inhalation

Science.gov (United States)

... use ciclesonide inhalation.Ciclesonide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use ciclesonide ...

Flunisolide Oral Inhalation

Science.gov (United States)

... use flunisolide inhalation.Flunisolide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use flunisolide ...

Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection

International Nuclear Information System (INIS)

Paessler, Slobodan; Yun, Nadezhda E.; Judy, Barbara M.; Dziuba, Natallia; Zacks, Michele A.; Grund, Anna H.; Frolov, Ilya; Campbell, Gerald A.; Weaver, Scott C.; Estes, D. Mark

2007-01-01

We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta (αβ) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta (γδ) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chain and a minority of vaccinated immunoglobulin heavy chain-deficient (μMT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3 + T cells are required for protection

Effect of age on the metabolism of inhaled beryllium fluoride in rats

Energy Technology Data Exchange (ETDEWEB)

Moskalev, Yu.I.; Bugryshev, P.F.; Zaikina, T.I. (Ministry of Health, Moscow (USSR). Inst. of Biophysics)

1988-01-01

The studies reported here investigated age-related differences in the distribution of {sup 7}Be following a single inhalation of carrier-free {sup 7}BeF{sub 2} by rats. Age greatly affected the amount of {sup 7}BeF{sub 2} deposited in each region of the respiratory system, the rate of beryllium translocation from the upper respiratory tract and oral cavity to the stomach, its retention in each section of the gastrointestinal tract, the distribution pattern and the routes of removal. (author).

Lethal and sub-lethal chronic effects of the herbicide diuron on seagrass

Energy Technology Data Exchange (ETDEWEB)

Negri, Andrew P., E-mail: a.negri@aims.gov.au [Australian Institute of Marine Science, Townsville, Queensland 4810 (Australia); Flores, Florita [Australian Institute of Marine Science, Townsville, Queensland 4810 (Australia); Mercurio, Phil [Australian Institute of Marine Science, Townsville, Queensland 4810 (Australia); University of Queensland and National Research Centre for Environmental Toxicology, Coopers Plains, Queensland 4108 (Australia); Mueller, Jochen F. [University of Queensland and National Research Centre for Environmental Toxicology, Coopers Plains, Queensland 4108 (Australia); Collier, Catherine J. [Centre for Tropical Water & Aquatic Ecosystem Research (TropWATER), James Cook University, Cairns, Queensland 4870 (Australia)

2015-08-15

Highlights: • We performed chronic exposures of two seagrass species to the herbicide diuron. • Diuron affected photosystem II (PSII) at 0.3 μg l{sup −1} and growth at 7.2 μg l{sup −1}. • Biomarkers indicated that carbon-assimilation from photosynthesis dropped following 0.6 μg l{sup −1} diuron exposure. • Energetic reserves in the seagrass were halved at 1.7 μg l{sup −1} after 11 weeks. • Chronic exposure to diuron is likely to enhance the impacts of low light stress during flood plumes - Abstract: Photosystem II herbicides from agricultural sources have been detected throughout nearshore tropical habitats including seagrass meadows. While PSII herbicides have been shown to inhibit growth in microalgae at low concentrations, the potential impacts of chronic low concentration exposures to seagrass health and growth have not been investigated. Here we exposed two tropical seagrass species Halodule uninervis and Zostera muelleri to elevated diuron concentrations (from 0.3 to 7.2 μg l{sup −1}) over a 79-day period followed by a 2-week recovery period in uncontaminated seawater. PAM fluorometry demonstrated rapid effect of diuron on photosystem II (PSII) in both seagrass species at 0.3 μg l{sup −1}. This effect included significant inhibition of photosynthetic efficiency (ΔF/F{sub m}′) and inactivation of PSII (F{sub v}/F{sub m}) over the 11 week exposure period. Significant mortality and reductions in growth was only observed at the highest exposure concentration of 7.2 μg l{sup −1} diuron. However, biochemical indicators demonstrated that the health of seagrass after this prolonged exposure was significantly compromised at lower concentrations. For example, the drop in C:N ratios (0.6 μg l{sup −1}) and reduced δ{sup 13}C (1.7 μg l{sup −1}) in seagrass leaves indicated reduced C-assimilation from photosynthesis. Critically, the energetic reserves of the plants (as measured by starch content in the root-rhizome complex) were

Suicide Lethality: A Concept Analysis.

Science.gov (United States)

DeBastiani, Summer; De Santis, Joseph P

2018-02-01

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

Nitrite inhalant use among young gay and bisexual men in Vancouver during a period of increasing HIV incidence

Directory of Open Access Journals (Sweden)

Mattheis Kelly

2007-03-01

Full Text Available Abstract Background Nitrite inhalants ("poppers" are peripheral vasodilators which, since the beginning of the epidemic, have been known to increase risk for acquiring HIV infection among men who have sex with men (MSM. However, few studies in recent years have characterized use. From 1999 to 2004, new HIV diagnoses among MSM in British Columbia increased 78%, prompting us to examine the prevalence and correlates of this modifiable HIV risk factor. Methods Self-administered questionnaires were completed between October 2002 and May 2004 as part of an open cohort study of HIV-seronegative young MSM. We measured nitrite inhalant use during the previous year and use during sexual encounters with casual partners specifically. Correlates of use were identified using odds ratios. Results Among 354 MSM surveyed, 31.6% reported any use during the previous year. Nitrite inhalant use during sexual encounters was reported by 22.9% of men and was strongly associated with having casual partners, with greater numbers of casual partners (including those with positive or unknown serostatus and with anal intercourse with casual partners. Nitrite inhalant use was not associated with non-use of condoms with casual sexual partners per se. Conclusion Contemporary use of nitrite inhalants amongst young MSM is common and a strong indicator of anal intercourse with casual sexual partners. Since use appears to increase the probability of infection following exposure to HIV, efforts to reduce the use of nitrite inhalants among MSM should be a very high priority among HIV prevention strategies.

CD4 T cell-mediated protection from lethal influenza: perforin and antibody-mediated mechanisms give a one-two punch.

Science.gov (United States)

Brown, Deborah M; Dilzer, Allison M; Meents, Dana L; Swain, Susan L

2006-09-01

The mechanisms whereby CD4 T cells contribute to the protective response against lethal influenza infection remain poorly characterized. To define the role of CD4 cells in protection against a highly pathogenic strain of influenza, virus-specific TCR transgenic CD4 effectors were generated in vitro and transferred into mice given lethal influenza infection. Primed CD4 effectors conferred protection against lethal infection over a broad range of viral dose. The protection mediated by CD4 effectors did not require IFN-gamma or host T cells, but did result in increased anti-influenza Ab titers compared with untreated controls. Further studies indicated that CD4-mediated protection at high doses of influenza required B cells, and that passive transfer of anti-influenza immune serum was therapeutic in B cell-deficient mice, but only when CD4 effectors were present. Primed CD4 cells also acquired perforin (Pfn)-mediated cytolytic activity during effector generation, suggesting a second mechanism used by CD4 cells to confer protection. Pfn-deficient CD4 effectors were less able to promote survival in intact BALB/c mice and were unable to provide protection in B cell-deficient mice, indicating that Ab-independent protection by CD4 effectors requires Pfn. Therefore, CD4 effectors mediate protection to lethal influenza through at least two mechanisms: Pfn-mediated cytotoxicity early in the response promoted survival independently of Ab production, whereas CD4-driven B cell responses resulted in high titer Abs that neutralized remaining virus.

Tc-99m erythromycin lactobionate inhalation scintigraphy in parenchymal lung diseases

Energy Technology Data Exchange (ETDEWEB)

Durak, Hatice E-mail: hdurak@kordon.deu.edu.tr; Aktogu, Serir; Degirmenci, Berna; Sayit, Elvan; Ertay, Tuerkan; Dereli, Sevket

1999-08-01

We have investigated Technetium 99m erythromycin lactobionate (Tc 99m EL) clearance from the lungs after inhalation, in the presence of an alveolitis. Eighteen patients (6 sarcoidosis, 7 idiopathic fibrosis, and 5 miliary tuberculosis) were imaged after the patients inhaled 1,110 MBq of Tc 99m EL. Clearance half time for the first 45 min, for 24 h, and retention at 24 h correlated with percentage of lymphocytes in bronchoalveolar lavage fluid (BAL) (r=.729, r=.883, and r=.826, respectively). There was a positive correlation between peripheral penetration (PP) and forced expiratory volume in 1 s (FEV{sub 1}) (r=.806) and forced vital capacity (FVC) (r=.781). Retention was more marked in sarcoidosis compared with tuberculosis (0.025inhalation for therapeutic purposes.

Nasal aerodynamics protects brain and lung from inhaled dust in subterranean diggers, Ellobius talpinus

NARCIS (Netherlands)

M.P. Moshkin; D.V. Petrovski; A.E. Akulov; A.V. Romashchenko; L.A. Gerlinskaya; V.L. Ganimedov; M.I. Muchnaya; A.S. Sadovsky; I.V. Koptyug; A.A. Savelov; S. Yu Troitsky; Y.M. Moshkn; V.I. Bukhtiyarov; N.A. Kolchanov; R.Z. Sagdeev; V.M. Fomin

2014-01-01

textabstractInhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to

Derangement of cellular plasma membranes due to non-lethal radiation doses

International Nuclear Information System (INIS)

Koeteles, G.J.; Kubasova, T.; Somosy, Z.; Horvath, L.

1983-01-01

Earlier observations in the laboratory on fibroblasts and various blood cells of animal and human origins pointed to alteration of concanavalin A binding sites of plasma membranes as well as to concomitant morphological changes and scanning electron microscopic appearance of cell surfaces following sub-lethal doses of X-, fission neutron and beta irradiations. The effects appeared early and existed temporarily; their intensities and the restitution of membrane function depended on radiation doses, types and conditions of cells. In the present paper further aspects of structural and functional derangements of plasma membranes are introduced which were provoked by X- and tritium beta irradiation in the dose range up to 2.5 Gy and in the concentration range from 3.7 kBq/mL, respectively. The state of membrane structure was followed by bindings of various ligands of different receptor requirements, concanavalin A, cationized ferritin and polio virus. In the case of X-irradiation the binding conditions suggest the shift of overall negative surface charges to less negative ones. It was also found that radiation-induced phenomena appear on the cell surface unevenly. Long- and short-term treatments of cells with 3 H-thymidine and 3 H-water also perturb the plasma membrane; beta irradiation affects it directly. Membrane structure and function are suggested to offer good biological models to study correlation of energy deposition and biological effects, both restricted to domains of nanometre range. The data give evidence for radiation-induced membrane alterations in the sub-lethal or non-lethal ranges which might have consequences in the development of stochastic and non-stochastic effects. (author)

Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

Energy Technology Data Exchange (ETDEWEB)

Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)

2008-07-01

Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

Gastrointestinal decontamination in healthy and lethally irradiated monkeys

International Nuclear Information System (INIS)

Hendriks, W.D.H.

1980-01-01

In periods of extreme immunosuppression, infections which are often life-threatening, frequently occur. In an attempt to prevent such infections in lethally irradiated rhesus monkeys, the animals were subjected to strict reverse isolation prior to irradiation and administrated orally with nonabsorbable antibiotics in order to eliminate their microflora. The antibiotic combination was selected on the basis of a sensitivity test and was added to the liquid food supply. To rapidly achieve a high bactericidal concentration in the intestine, the same antibiotics were additionally given orally for 5 days. The microflora was reduced rapidly; within a few days sterile cultures were obtained. Particularly after discontinuation of the administration of the additional antibiotics were colonizations found. In contrast to colonizations persisting from the first day of treatment on, the first were rather easy to suppress. (Auth.)

Inhalant allergies in children.

Science.gov (United States)

Mims, James W; Veling, Maria C

2011-06-01

Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

Inhalant Abuse and Dextromethorphan.

Science.gov (United States)

Storck, Michael; Black, Laura; Liddell, Morgan

2016-07-01

Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan. Copyright © 2016 Elsevier Inc. All rights reserved.

Inhaled Drug Delivery: A Practical Guide to Prescribing Inhaler Devices

Directory of Open Access Journals (Sweden)

Pierre Ernst

1998-01-01

Full Text Available Direct delivery of medication to the target organ results in a high ratio of local to systemic bioavailability and has made aerosol delivery of respiratory medication the route of choice for the treatment of obstructive lung diseases. The most commonly prescribed device is the pressurized metered dose inhaler (pMDI; its major drawback is the requirement that inspiration and actuation of the device be well coordinated. Other requirements for effective drug delivery include an optimal inspiratory flow, a full inspiration from functional residual capacity and a breath hold of at least 6 s. Available pMDIs are to be gradually phased out due to their use of atmospheric ozone-depleting chlorofluorocarbons (CFCs as propellants. Newer pMDI devices using non-CFC propellants are available; preliminary experience suggests these devices greatly increase systemic bioavailability of inhaled corticosteroids. The newer multidose dry powder inhalation devices (DPIs are breath actuated, thus facilitating coordination with inspiration, and contain fewer ingredients. Furthermore, drug delivery is adequate even at low inspired flows, making their use appropriate in almost all situations. Equivalence of dosing among different devices for inhaled corticosteroids will remain imprecise, requiring the physician to adjust the dose of medication to the lowest dose that provides adequate control of asthma. Asthma education will be needed to instruct patients on the effective use of the numerous inhalation devices available.

Minimum concentrations of NO/sub 2/ causing acute effects on the respiratory gas exchange and airway-resistance in patients with chronic bronchitis

Energy Technology Data Exchange (ETDEWEB)

von Nieding, G; Wagner, M; Krekeler, H; Smidt, U; Muysers, K

1971-01-01

Nitrogen dioxide-air mixtures containing 0.5 to 5.0 ppM NO/sub 2/ were inhaled by 88 patients with chronic bronchitis over a 15-minute period for a total of 30 breaths during studies investigating the effects of the gas on airway resistance and respiratory gas exchange. End-expiratory oxygen pressures remained nearly constant during inhalation of 4 or 5 ppM NO/sub 2/, though significant decreases in arterial oxygen pressure accompanied by increases in end-expiratory-arterial oxygen pressure difference occurred. Inhalation of 2 ppM NO/sub 2/ did not decrease arterial oxygen pressure. Airway resistances increased significantly down to 1.5 ppM NO/sub 2/ concentrations. Lower concentrations caused no significant effects.

Effect of vaccination against sub-clinical Porcine Circovirus type 2 infection in a high-health finishing pig herd

DEFF Research Database (Denmark)

Nielsen, Gitte Blach; Nielsen, Jens Peter; Haugegaard, John

2017-01-01

During the last decade, the clinical manifestation of Porcine Circovirus type 2 (PCV2) infections has mostly changed from postweaning multisystemic wasting syndrome and high mortality to sub-clinical infections manifested only through impaired production parameters. However, co-infection with other...... respiratory pathogens often results in a larger effect on production, sometimes with clinical signs. Little is known about the impact of a moderate level PCV2 infection without co-infections, particularly in terms of feed conversion ratio and antimicrobial consumption. The purpose of the study was to evaluate...... the effect of vaccination against PCV2 in a sub-clinically infected, high-health finishing herd in terms of viral load in serum, feed conversion ratio and antimicrobial treatments. The study was conducted as a randomised clinical field trial with a parallel group design. Vaccination against PCV2...

Adaptive immunity and histopathology in frog virus 3-infected Xenopus

International Nuclear Information System (INIS)

Robert, Jacques; Morales, Heidi; Buck, Wayne; Cohen, Nicholas; Marr, Shauna; Gantress, Jennifer

2005-01-01

Xenopus has been used as an experimental model to evaluate the contribution of adaptive cellular immunity in amphibian host susceptibility to the emerging ranavirus FV3. Conventional histology and immunohistochemistry reveal that FV3 has a strong tropism for the proximal tubular epithelium of the kidney and is rarely disseminated elsewhere in Xenopus hosts unless their immune defenses are impaired or developmentally immature as in larvae. In such cases, virus is found widespread in most tissues. Adults, immunocompromised by depletion of CD8 + T cells or by sub-lethal γ-irradiation, show increased susceptibility to FV3 infection. Larvae and irradiated (but not normal) adults can be cross-infected through water by infected adult conspecifics (irradiated or not). The natural MHC class I deficiency and the absence of effect of anti-CD8 treatment on both larval CD8 + T cells and larval susceptibility to FV3 are consistent with an inefficient CD8 + T cell effector function during this developmental period

A study of the comparison between human and animal excretion data following inhalation exposure to plutonium 238 oxide aerosols

International Nuclear Information System (INIS)

Moss, W.D.; Martinez, G.; Gautier, M.A.

1985-01-01

Bioassay urine samples obtained since 1971 from eight Los Alamos employees, accidentally exposed by inhalation to high-fired plutonium-238 oxide aerosols, were studied and compared with excretion data obtained from Beagle dogs exposed to /sup 238/PuO/sub 2/ aerosols. The early period Pu human excretion data from the inhalation exposure were unexpected and were unlike previously studied occupational exposure urinary data obtained at Los Alamos. The initial urine samples collected on day one were below the detection limits of the analytical method (0.01 pCi). Within thirty days, however, detectible concentrations of Pu were measured in the urine for several of the exposed personnel. The amounts of Pu excreted continued to increase in each of the cases throughout the first year and the individual patterns of Pu excretion were similar. The human urinary excretion data was compared with similar excretion data obtained from an animal study conducted by the Inhalation Toxicology Research Institute (Me81). In the animal study, Beagle dogs received inhalation exposure to one of three sizes of monodisperse of polydisperse aerosol of /sup 238/PuO/sub 2/. Periodic sacrifice of pairs of dogs during the 4 years after the inhalation exposure provided data on the retention, translocation and mode of excretion of /sup 238/Pu. The comparison of human and animal /sup 238/Pu excretion data supported the observation that the excretion data were similar between the two species and that the animal excretion models can be applied to predict the human /sup 238/Pu excretion following inhalation exposure to high-fired oxides of /sup 238/Pu

Effect of vaccination against sub-clinical Porcine Circovirus type 2 infection in a high-health finishing pig herd

DEFF Research Database (Denmark)

Nielsen, Gitte Blach; Nielsen, Jens Peter; Haugegaard, John

2017-01-01

During the last decade, the clinical manifestation of Porcine Circovirus type 2 (PCV2) infections has mostly changed from postweaning multisystemic wasting syndrome and high mortality to sub-clinical infections manifested only through impaired production parameters. However, co-infection with oth...

In vitro and in vivo studies of the carcinogenic, toxic and genotoxic activities of the air pollutants SO sub 2 and NO sub x , separately and in combination with carcinogenic polycyclic aromatic hydrocarbons and N-nitrosamines. Pt. 4. In vivo and in vitro Studien zur karzinogenen, toxischen und genschaedigenden Kombinationswirkung von Luftschadstoffen (SO sub 2 , NO sub x , polyzyklische aromatische Kohlenwasserstoffe und N-Nitrosamine). T. 4

Energy Technology Data Exchange (ETDEWEB)

Zeller, W J; Klein, R G; Pool, B L; Schmezer, P [Deutsches Krebsforschungszentrum, Heidelberg (Germany, F.R.). Inst. fuer Toxikologie und Chemotherapie

1989-04-01

The cytotoxic activity of sulfite (product of SO{sub 2}+water) was assessed. In vitro its effects on vitality and energy household were determined in the 3 cell types used in our genotoxicity studies. It was shown: (1) Sulfite toxicity is clearly time- and dose-dependent. (2) By simultaneously determining membrane and cytoskeleton damage, a toxicity parameter is available for pRH in suspension cluture which is as sensitive as determining plating efficiency in tissue culture (FHLC, CO60). (3) The energy system is impaired by sulfite. This was shown by the depletion of intracellular ATP. Differential resistance of cells to sulfite (pRH>FHLC>CO60) is probably due to their relative contents of detoxifying sulfite oxidases. The inhalative application of SO{sub 2} (10 ppm) with and without N-nitrosodimethylamine (NDMA) (1.7 or 3 mg/kg) to SD rats did not result in any measurable toxic effects to the liver, as was determined by measuring vitality and ATP content of explanted pRH. On the other hand, low single doses of <1 mg/kg inhaled NDMA caused a high rate of DNA single strand breaks. Inhaled SO{sub 2} (10 ppm and 50 ppm for 2 weeks) did not cause DNA damage. In contrast to our previous in vitro findings, the genotoxicity of NDMA in liver cells was not measurably affected by simultaneous SO{sub 2} inhalation in an in vivo experimental set up. (orig./MG).

Evaluation of a novel educational strategy, including inhaler-based reminder labels, to improve asthma inhaler technique.

Science.gov (United States)

Basheti, Iman A; Armour, Carol L; Bosnic-Anticevich, Sinthia Z; Reddel, Helen K

2008-07-01

To evaluate the feasibility, acceptability and effectiveness of a brief intervention about inhaler technique, delivered by community pharmacists to asthma patients. Thirty-one pharmacists received brief workshop education (Active: n=16, CONTROL: n=15). Active Group pharmacists were trained to assess and teach dry powder inhaler technique, using patient-centered educational tools including novel Inhaler Technique Labels. Interventions were delivered to patients at four visits over 6 months. At baseline, patients (Active: 53, CONTROL: 44) demonstrated poor inhaler technique (mean+/-S.D. score out of 9, 5.7+/-1.6). At 6 months, improvement in inhaler technique score was significantly greater in Active cf. CONTROL patients (2.8+/-1.6 cf. 0.9+/-1.4, p<0.001), and asthma severity was significantly improved (p=0.015). Qualitative responses from patients and pharmacists indicated a high level of satisfaction with the intervention and educational tools, both for their effectiveness and for their impact on the patient-pharmacist relationship. A simple feasible intervention in community pharmacies, incorporating daily reminders via Inhaler Technique Labels on inhalers, can lead to improvement in inhaler technique and asthma outcomes. Brief training modules and simple educational tools, such as Inhaler Technique Labels, can provide a low-cost and sustainable way of changing patient behavior in asthma, using community pharmacists as educators.

Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges.

Science.gov (United States)

Lowenthal, Elizabeth D; Bakeera-Kitaka, Sabrina; Marukutira, Tafireyi; Chapman, Jennifer; Goldrath, Kathryn; Ferrand, Rashida A

2014-07-01

Worldwide, more than three million children are infected with HIV, 90% of whom live in sub-Saharan Africa. As the HIV epidemic matures and antiretroviral treatment is scaled up, children with HIV are reaching adolescence in large numbers. The growing population of adolescents with perinatally acquired HIV infection living within this region presents not only unprecedented challenges but also opportunities to learn about the pathogenesis of HIV infection. In this Review, we discuss the changing epidemiology of paediatric HIV and the particular features of HIV infection in adolescents in sub-Saharan Africa. Longstanding HIV infection acquired when the immune system is not developed results in distinctive chronic clinical complications that cause severe morbidity. As well as dealing with chronic illness, HIV-infected adolescents have to confront psychosocial issues, maintain adherence to drugs, and learn to negotiate sexual relationships, while undergoing rapid physical and psychological development. Context-specific strategies for early identification of HIV infection in children and prompt linkage to care need to be developed. Clinical HIV care should integrate age-appropriate sexual and reproductive health and psychological, educational, and social services. Health-care workers will need to be trained to recognise and manage the needs of these young people so that the increasing numbers of children surviving to adolescence can access quality care beyond specialist services at low-level health-care facilities. Copyright © 2014 Elsevier Ltd. All rights reserved.

/sup 144/Ce in tissue of beagle dogs after inhalation of CeCl/sub 3/ with special emphasis on endocrine glands and reproductive organs

Energy Technology Data Exchange (ETDEWEB)

Cuddihy, R G; Boecker, B B; McClellan, R O; Kanapilly, G M [Lovelace Foundation for Medical Education and Research, Albuquerque, N.Mex. (USA)

1976-01-01

Beagle dogs inhaled aerosols containing /sup 144/CeCl/sub 3/. Deposition of /sup 144/Ce in tissues was determined in serially sacrificed dogs to characterize radiation dose patterns at early times after exposure. Uptakes of /sup 144/Ce in endocrine glands and reproductive organs were also measured; radiation doses were calculated and those doses were compared with the doses to the major organs of deposition - lung, liver and skeleton. Integrated radiation doses in pituitary and adrenal glands, pancreas, ovaries, testes, prostate and uterus were less than 2 % of those in lung and liver, while the thyroid dose was about 30 % of the dose in liver. These findings were consistent with previously reported biological responses in beagle dogs exposed to high levels of /sup 144/CeCl/sub 3/ wherein no radiation effects related to endocrine glands or the reproductive system have been observed. Use of these results in predicting the dosimetry of /sup 144/Ce in exposed humans re-emphasized the importance of radiation damage to lung, liver, skeleton and gastrointestinal tract compared to other organ systems.

Inhalant Dependence and its Medical Consequences

Directory of Open Access Journals (Sweden)

Mehmet Hamid Boztaş

2010-12-01

Full Text Available The term of inhalants is used for matters easily vapors. Inhalants are preferred for rapid, positive reinforcement and mild high effects. Products including inhalants are cheap, accessible, legal substances and are prevalently used in community. The prevalence of inhalant use in secondary schools in Turkey is about 5.1%. Inhalant substance dependence is generally observed within 14-15 age group. Age at first use could be as low as 5 to 6 years of age. Substance dependence is more probable in adults working in substance existing places. Inhalant usage is common in disadvantaged groups, children living in street, people with history of crimes, prison, depression, suicide, antisocial attitudes and conflict of family, history of abuse, violence and any other drug dependence and isolated populations. Inhalants are absorbed from lungs, after performing their quick and short effect metabolized by cytochrom P450 enzyme system except inhalant nitrites group which has a depressing effect like alcohol. In chronic use general atrophy, ventricular dilatation and wide sulcus were shown in cerebrum, cerebellum and pons by monitoring brain. Defects are mostly in periventricular, subcortical regions and in white matter. Demyelinization, hyperintensity, callosal slimming and wearing off in white and gray matter margins was also found. Ravages of brain shown by brain monitorisation are more and serious in inhalant dependence than in other dependences. It is important to decrease use of inhalants. Different approaches should be used for subcultures and groups in prevention. Prohibiting all the matters including inhalant is not practical as there are too many substances including inhalants. Etiquettes showing harmful materials can be used but this approach can also lead the children and adolescents recognize these substances easily.. Despite determintal effects of inhalant dependence, there are not yet sufficient number of studies conducted on prevention and

Protective Monotherapy Against Lethal Ebola Virus Infection by a Potently Neutralizing Antibody

Science.gov (United States)

2016-07-11

were 49   identified and enrolled in VRC200 clinical trial #NCT00067054 after giving signed 50   informed consent . Peripheral blood mononuclear...illness 56   when administered one day after lethal challenge. Treatment with a single human 57   mAb suggests a simplified therapeutic strategy for...efforts to simplify the ZMapp regimen to contain fewer mAbs have not been successful in 75   the macaque EVD model (7). We sought to isolate

Influence of Parasitic Worm Infections on Allergy Diagnosis in Sub-Saharan Africa.

Science.gov (United States)

Amoah, Abena S; Boakye, Daniel A; Yazdanbakhsh, Maria; van Ree, Ronald

2017-09-01

Epidemiological studies from Sub-Saharan Africa indicate that allergies are on the rise in this region especially in urban compared to rural areas. This increase has been linked to improved hygiene, lifestyle changes, and lower exposure to pathogens in childhood. Reduced exposure to parasitic worm (helminth) infections and allergy outcomes has been the focus of a number of population studies over the years. Paradoxically, there are parallels in the immune responses to helminths and to allergies. Both conditions are associated with elevated levels of immunoglobulin E, high numbers of T helper 2 cells, eosinophils, and mast cells. These immune parallels have meant that the diagnosis of allergies in parts of the world where helminths are endemic can be hampered. The aim of this review is to examine observations from population studies conducted in Sub-Saharan Africa that demonstrate how helminth infections influence the parameters used to diagnose allergy outcomes in this region. We explore specifically how helminth infections hinder the in vitro diagnosis of allergic sensitization, influence the clinical manifestations of allergy, and also the effect of anthelmintic treatment on allergy outcomes. Advancing our understanding of how helminths influence allergy diagnosis is imperative for the development of improved tools to assess, diagnose, and treat allergic disorders in both helminth-endemic and non-endemic countries worldwide.

Differential replication of Foot-and-mouth disease viruses in mice determine lethality.

Science.gov (United States)

Cacciabue, Marco; García-Núñez, María Soledad; Delgado, Fernando; Currá, Anabella; Marrero, Rubén; Molinari, Paula; Rieder, Elizabeth; Carrillo, Elisa; Gismondi, María Inés

2017-09-01

Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

Mutagenesis-mediated virus extinction: virus-dependent effect of viral load on sensitivity to lethal defection.

Directory of Open Access Journals (Sweden)

Héctor Moreno

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

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy.

Science.gov (United States)

Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun

2012-11-07

Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca(2+) properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca(2+) handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, possibly through regulation of autophagy and mitochondrial function.

Galleria mellonella infection model demonstrates high lethality of ST69 and ST127 uropathogenic E. coli.

Directory of Open Access Journals (Sweden)

Majed F Alghoribi

Full Text Available Galleria mellonella larvae are an alternative in vivo model for investigating bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from five leading uropathogenic E. coli (UPEC lineages using G. mellonella larvae. Larvae were challenged with a range of inoculum doses to determine the 50% lethal dose (LD50 and for analysis of survival outcome using Kaplan-Meier plots. Virulence was correlated with carriage of a panel of 29 virulence factors (VF. Larvae inoculated with ST69 and ST127 isolates (10(4 colony-forming units/larvae showed significantly higher mortality rates than those infected with ST73, ST95 and ST131 isolates, killing 50% of the larvae within 24 hours. Interestingly, ST131 isolates were the least virulent. We observed that ST127 isolates are significantly associated with a higher VF-score than isolates of all other STs tested (P≤0.0001, including ST69 (P<0.02, but one ST127 isolate (strain EC18 was avirulent. Comparative genomic analyses with virulent ST127 strains revealed an IS1 mediated deletion in the O-antigen cluster in strain EC18, which is likely to explain the lack of virulence in the larvae infection model. Virulence in the larvae was not correlated with serotype or phylogenetic group. This study illustrates that G. mellonella are an excellent tool for investigation of the virulence of UPEC strains. The findings also support our suggestion that the incidence of ST127 strains should be monitored, as these isolates have not yet been widely reported, but they clearly have a pathogenic potential greater than that of more widely recognised clones, including ST73, ST95 or ST131.

Toxicological aspects of photocatalytic degradation of selected xenobiotics with nano-sized Mn-doped TiO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Ozmen, Murat, E-mail: murat.ozmen@inonu.edu.tr [Inonu University, Faculty of Science, Department of Biology, Malatya (Turkey); Güngördü, Abbas [Inonu University, Faculty of Science, Department of Biology, Malatya (Turkey); Erdemoglu, Sema [Inonu University, Faculty of Science, Department of Chemistry, Malatya (Turkey); Ozmen, Nesrin [Inonu University, Faculty of Education, Department of Science Teaching Program, Malatya (Turkey); Asilturk, Meltem [Akdeniz University, Department of Materials Science and Engineering, Antalya (Turkey)

2015-08-15

Highlights: • Undoped and Mn-doped TiO{sub 2} nanoparticles were synthesized and characterized. • The photocatalytic efficiency of the photocatalysts was evaluated for BPA and ATZ. • Toxicity of photocatalysts and photocatalytic by-products were determined. • Mn-doped TiO{sub 2} nanoparticles did not cause significant lethality on X. laevis. • Degradation of BPA caused a significant reduction of lethal effects. - Abstract: The toxic effects of two selected xenobiotics, bisphenol A (BPA) and atrazine (ATZ), were evaluated after photocatalytic degradation using nano-sized, Mn-doped TiO{sub 2}. Undoped and Mn-doped TiO{sub 2} nanoparticles were synthesized. The samples were characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), UV–vis-diffuse reflectance spectra (DRS), X-ray fluorescence spectroscopy (XRF), and BET surface area. The photocatalytic efficiency of the undoped and Mn-doped TiO{sub 2} was evaluated for BPA and ATZ. The toxicity of the synthesized photocatalysts and photocatalytic by-products of BPA and ATZ was determined using frog embryos and tadpoles, zebrafish embryos, and bioluminescent bacteria. Possible toxic effects were also evaluated using selected enzyme biomarkers. The results showed that Mn-doped TiO{sub 2} nanoparticles did not cause significant lethality in Xenopus laevis embryos and tadpoles, but nonfiltered samples caused lethality in zebrafish. Furthermore, Mn-doping of TiO{sub 2} increased the photocatalytic degradation capability of nanoparticles, and it successfully degraded BPA and AZT, but degradation of AZT caused an increase of the lethal effects on both tadpoles and fish embryos. Degradation of BPA caused a significant reduction of lethal effects, especially after 2–4 h of degradation. However, biochemical assays showed that both Mn-doped TiO{sub 2} and the degradation by-products caused a significant change of selected biomarkers on X. laevis tadpoles; thus, the ecological risks of Mn

Monoclonal Idiotope Vaccine against Streptococcus pneumoniae Infection

Science.gov (United States)

McNamara, Mary K.; Ward, Ronald E.; Kohler, Heinz

1984-12-01

A monoclonal anti-idiotope antibody coupled to a carrier protein was used to immunize BALB/c mice against a lethal Streptococcus pneumoniae infection. Vaccinated mice developed a high titer of antibody to phosphorylcholine, which is known to protect against infection with Streptococcus pneumoniae. Measurement of the median lethal dose of the bacteria indicated that anti-idiotope immunization significantly increased the resistance of BALB/c mice to the bacterial challenge. Antibody to an idiotope can thus be used as an antigen substitute for the induction of protective immunity.

Asymptomatic and sub-microscopic malaria infection in Kayah State, eastern Myanmar.

Science.gov (United States)

Zaw, Myo Thiha; Thant, Myo; Hlaing, Tin Maung; Aung, Naing Zin; Thu, Min; Phumchuea, Kanit; Phusri, Kanokwan; Saeseu, Teerawat; Yorsaeng, Ritthideach; Nguitragool, Wang; Felger, Ingrid; Kaewkungwal, Jaranit; Cui, Liwang; Sattabongkot, Jetsumon

2017-04-04

Myanmar has the heaviest burden of malaria in the Greater Mekong Sub-region. Asymptomatic Plasmodium spp. infections are common in this region and may represent an important reservoir of transmission that must be targeted for malaria elimination. A mass blood survey was conducted among 485 individuals from six villages in Kayah State, an area of endemic but low transmission malaria in eastern Myanmar. Malaria infection was screened by rapid diagnostic test (RDT), light microscopy and real-time polymerase chain reaction (PCR), and its association with demographic factors was explored. The prevalence of asymptomatic Plasmodium spp. infection was 2.3% (11/485) by real-time PCR. Plasmodium vivax accounted for 72.7% (8/11) and Plasmodium falciparum for 27.3% (3/11) of infections. Men were at greater risk of infection by Plasmodium spp. than women. Individuals who worked as farmers or wood and bamboo cutters had an increased risk of infection. A combination of RDT, light microscopy and PCR diagnostics were used to identify asymptomatic malaria infection, providing additional information on asymptomatic cases in addition to the routine statistics on symptomatic cases, so as to determine the true burden of disease in the area. Such information and risk factors can improve malaria risk stratification and guide decision-makers towards better design and delivery of targeted interventions in small villages, representative of Kayah State.

Eradication of Burkholderia cepacia Using Inhaled Aztreonam Lysine in Two Patients with Bronchiectasis

Directory of Open Access Journals (Sweden)

A. Iglesias

2014-01-01

Full Text Available There are not many articles about the chronic bronchial infection/colonization in patients with underlying lung disease other than cystic fibrosis (CF, especially with non-CF bronchiectasis (NCFBQ. The prevalence of B. cepacia complex is not well known in NCFBQ. The vast majority of published clinical data on Burkholderia infection in individuals with CF is comprised of uncontrolled, anecdotal, and/or single center experiences, and no consensus has emerged regarding treatment. We present two cases diagnosed with bronchiectasis (BQ of different etiology, with early pulmonary infection by B. cepacia complex, which was eradicated with inhaled aztreonam lysine.

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

Science.gov (United States)

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Tomographic measurement of cerebral blood flow by the /sup 68/Ga-labelled-microsphere and continuous-C/sup 15/O/sub 2/-inhalation methods

Energy Technology Data Exchange (ETDEWEB)

Steinling, M.; Baron, J.C.; Maziere, B.; Loc' h, C.; Lasjaunias, P.; Canabis, E.A.; Guillon, B.

1985-05-01

The measurement of cerebral blood flow (CBF) by continuous C/sup 15/O/sub 2/ inhalation has only been validated previously by indirect experimental protocols. In the present study using baboons, these measurements were compared directly with those obtained by injection of /sup 68/Ga-labelled serum-albumin microspheres in the left cardiac ventricle. Using a modified labelling technique, no elution of /sup 68/Ga occurred in vivo. Both methods provided similar regional CBF values, which could be described by a significant linear correlation (CBFsub(CO2) = 0.82 CBFsub(microspheres)+5.7; P < 0.001). The validity of the labelled-microsphere-injection method was verified. The feasibility of stable in vivo labelling of /sup 68/Ga to serum-albumin microspheres provides a reference method for organ blood-flow measurements using positron-emission tomography.

Tomographic measurement of cerebral blood flow by the /sup 68/Ga-labelled-microsphere and continuous-C/sup 15/O/sub 2/-inhalation methods

Energy Technology Data Exchange (ETDEWEB)

Steinling, M.; Baron, J.C.; Maziere, B.; Loc' h, C.; Lasjaunias, P.; Canabis, E.A.; Guillon, B.

1985-07-01

The measurement of cerebral blood flow (CBF) by continuous C/sup 15/O/sub 2/ inhalation has only been validated previously by indirect experimental protocols. In the present study using baboons, these measurements were compared directly with those obtained by injection of /sup 68/Ga-labelled serum-albumin microspheres in the left cardiac ventricle. Using a modified labelling technique, no elution of /sup 68/Ga occurred in vivo. Both methods provided similar regional CBF values, which could be described by a significant linear correlation (CBFsub(CO2)=0.82 CBFsub(microspheres)+5.7; P < 0.001). The validity of the labelled-microsphere-injection method was verified. The feasibility of stable in vivo labelling of /sup 68/Ga to serum-albumin microspheres provides a reference method for organ blood-flow measurements using positron-emission tomography.

More human, more humane: a new approach for testing airborne pollutants.

Science.gov (United States)

Potera, Carol

2007-03-01

People not only inhale airborne contaminants but also absorb them through the skin. Both routes can set off localized toxic reactions or damage internal organs such as the liver, kidney, and brain. Conventional tests of the toxicity of gases and vapors, in which laboratory animals are exposed to lethal or sub-lethal doses of chemicals, have been criticized as expensive, unethical, inhumane, and time-consuming. Now researchers at the University of New South Wales (UNSW) in Sydney, Australia, have developed an animal-free alternative that uses human cells to test the effects of exposure to airborne toxicants.

Bioaccessibility of selected trace metals in urban PM{sub 2.5} and PM{sub 10} samples: a model study

Energy Technology Data Exchange (ETDEWEB)

Falta, Thomas; Koellensperger, Gunda; Hann, Stephan [University of Natural Resources and Applied Life Sciences, Division of Analytical Chemistry, Vienna (Austria); Limbeck, Andreas [Vienna University of Technology, Institute of Chemical Technologies and Analytics, Vienna (Austria)

2008-02-15

Bioaccessibility of trace metals originating from urban particulate matter was assessed in a worst case scenario to evaluate the uptake and thus the hazardous potential of these metals via gastric juice. Sampling was performed over a period of about two months at the Getreidemarkt in downtown Vienna. Concentrations of the assayed trace metals (Ti, Cr, Mn, Co, Ni, Cu, Zn, Mo, Ag, Cd, Sn, Sb, Tl and Pb) were determined in PM{sub 2.5} and PM{sub 10} samples by ICP-MS. The metal concentrations in sampled air were in the low picogram to high nanogram per cubic metre range. The concentrations in PM{sub 2.5} samples were generally lower than those in PM{sub 10} samples. The average daily intake of these metals by inhalation for a healthy adult was estimated to be in the range of <1 ng (Tl) to >1,000 ng (Zn). To estimate the accessibility of the inhaled and subsequently ingested metals (i.e. after lung clearance had taken place) in the size range from 2.5- to 10-{mu}m aerodynamic equivalent diameter, a batch-extraction with synthetic gastric juice was performed. The data were used to calculate the bioaccessibility of the investigated trace metals. Extractable fractions ranged from 2.10% (Ti in PM{sub 2.5}) to 91.0% (Cd in PM{sub 2.5}), thus yielding bioaccessible fractions (PM{sub 2.5-10}) from 0.16 ng (Ag) to 178 ng (Cu). (orig.)

Inhalation of a dry powder ciprofloxacin formulation in healthy subjects: a phase I study.

Science.gov (United States)

Stass, Heino; Nagelschmitz, Johannes; Willmann, Stefan; Delesen, Heinz; Gupta, Abhishek; Baumann, Sybille

2013-06-01

Oral and intravenous formulations of ciprofloxacin have established efficacy and safety profiles in respiratory infections. A dry powder for inhalation (DPI) that uses Novartis' PulmoSphere™ technology has been developed to deliver high concentrations of ciprofloxacin to the lung with low systemic exposure using a portable and convenient passive dry powder inhaler (Novartis' T-326 inhaler). The primary objective was to investigate the safety and tolerability of ciprofloxacin DPI in healthy male subjects, with a secondary objective to investigate the pharmacokinetics of ciprofloxacin after ciprofloxacin DPI administration. This was a phase I, single-dose, single-site, randomized, single-blind, placebo-controlled, crossover study conducted in the hospital setting. Subjects were followed up for safety for approximately 2 weeks. Six healthy male subjects, aged 27-42 years with no history of pulmonary disease, repeated bronchitis or respiratory allergies were enrolled. In randomized order and separated by a 1-week washout period, subjects inhaled a single dose of ciprofloxacin DPI 32.5 mg or placebo from the T-326 inhaler. Primary safety parameters included vital signs, electrocardiogram, laboratory tests, adverse events and lung function (total specific resistance, thoracic gas volume and forced expiratory volume in 1 s). Plasma concentration-time data were used to calculate pharmacokinetic parameters. Ciprofloxacin DPI was well tolerated with no clinically relevant adverse effects on lung function. Estimates of lung deposition derived from physiology-based pharmacokinetic modelling suggest that approximately 40 % of the total dose of ciprofloxacin DPI reached the trachea/bronchi and alveolar space. Systemic ciprofloxacin was detected soon after inhalation [peak concentration in plasma (C(max)) 56.42 μg/L, median time to C max 0.625 h], but total systemic exposure was minimal (area under the plasma concentration-time curve 354.4 μg·h/L). Terminal elimination half

The efficacy and pharmacokinetics of brincidofovir for the treatment of lethal rabbitpox virus infection: a model of smallpox disease.

Science.gov (United States)

Trost, Lawrence C; Rose, Michelle L; Khouri, Jody; Keilholz, Laurie; Long, James; Godin, Stephen J; Foster, Scott A

2015-05-01

Brincidofovir (BCV) has broad-spectrum in vitro activity against dsDNA viruses, including smallpox, and is being developed as a treatment for smallpox as well as infections caused by other dsDNA viruses. BCV has previously been shown to be active in multiple animal models of smallpox. Here we present the results of a randomized, blinded, placebo-controlled study of the efficacy and pharmacokinetics of a novel, "humanized" regimen of BCV for treatment of New Zealand White rabbits infected with a highly lethal inoculum of rabbitpox virus, a well characterized model of smallpox. Compared with placebo, a dose-dependent increase in survival was observed in all BCV-treatment groups. Concentrations of cidofovir diphosphate (CDV-PP), the active antiviral, in rabbit peripheral blood mononuclear cells (PBMCs) were determined for comparison to those produced in humans at the dose proposed for treatment of smallpox. CDV-PP exposure in PBMCs from rabbits given BCV scaled to human exposures at the dose proposed for treatment of smallpox, which is also currently under evaluation for other indications. The results of this study demonstrate the activity of BCV in the rabbitpox model of smallpox and the feasibility of scaling doses efficacious in the model to a proposed human dose and regimen for treatment of smallpox. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... KB] Using a metered dose inhaler (inhaler in mouth) Your browser does not support iframes Using a metered dose inhaler (inhaler in mouth) [PDF – 370 KB] Your browser does not support ...

Experimental aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs.

Science.gov (United States)

Twenhafel, N A; Shaia, C I; Bunton, T E; Shamblin, J D; Wollen, S E; Pitt, L M; Sizemore, D R; Ogg, M M; Johnston, S C

2015-01-01

Eight guinea pigs were aerosolized with guinea pig-adapted Zaire ebolavirus (variant: Mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. Guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. Intracytoplasmic inclusion bodies were observed in many alveolar macrophages. Perivasculitis was noted within the lungs. These changes are unlike those of documented subcutaneously challenged guinea pigs and aerosolized filoviral infections in nonhuman primates and human cases. Similar to findings in subcutaneously challenged guinea pigs, there were only mild lesions in the liver and spleen. To our knowledge, this is the first report of aerosol challenge of guinea pigs with guinea pig-adapted Zaire ebolavirus (variant: Mayinga). Before choosing this model for use in aerosolized ebolavirus studies, scientists and pathologists should be aware that aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs. © The Author(s) 2014.

Cytoplasmic superoxide dismutase and catalase activity and resistance to radiation lethality in murine tumor cells

International Nuclear Information System (INIS)

Davy, C.A.; Tesfay, Z.; Jones, J.; Rosenberg, R.C.; McCarthy, C.; Rosenberg, S.O.

1986-01-01

Reduced species of molecular oxygen are produced by the interaction of ionizing radiation with aqueous solutions containing molecular oxygen. The enzymes catalase and superoxide dismutase (SOD) are thought to function in vivo as scavengers of metabolically produced peroxide and superoxide respectively. SOD has been shown to protect against the lethal effects of ionizing radiation in vitro and in vivo. The authors have investigated the relationship between the cytosolic SOD catalase content and the sensitivity to radiation lethality of a number of murine cell lines (402AX, EL-4, MB-2T3, MB-4, MEL, P-815, SAI, SP-2, and SV-3T3). K/sub i/(CN - ) for murine Cu-Zn-SOD was determined to be 6.8 x 10 -6 M. No cytosolic Mn-SOD activity was found in any of the cell lines studied. No correlation was found between the cytosolic Cu-Zn-SOD or cytosolic catalase activity and the resistance to radiation lethality or the murine cell lines studied

VSVΔG/EBOV GP-induced innate protection enhances natural killer cell activity to increase survival in a lethal mouse adapted Ebola virus infection.

Science.gov (United States)

Williams, Kinola J N; Qiu, Xiangguo; Fernando, Lisa; Jones, Steven M; Alimonti, Judie B

2015-02-01

Members of the species Zaire ebolavirus cause severe hemorrhagic fever with up to a 90% mortality rate in humans. The VSVΔG/EBOV GP vaccine has provided 100% protection in the mouse, guinea pig, and nonhuman primate (NHP) models, and has also been utilized as a post-exposure therapeutic to protect mice, guinea pigs, and NHPs from a lethal challenge of Ebola virus (EBOV). EBOV infection causes rapid mortality in human and animal models, with death occurring as early as 6 days after infection, suggesting a vital role for the innate immune system to control the infection before cells of the adaptive immune system can assume control. Natural killer (NK) cells are the predominant cell of the innate immune response, which has been shown to expand with VSVΔG/EBOV GP treatment. In the current study, an in vivo mouse model of the VSVΔG/EBOV GP post-exposure treatment was used for a mouse adapted (MA)-EBOV infection, to determine the putative VSVΔG/EBOV GP-induced protective mechanism of NK cells. NK depletion studies demonstrated that mice with NK cells survive longer in a MA-EBOV infection, which is further enhanced with VSVΔG/EBOV GP treatment. NK cell mediated cytotoxicity and IFN-γ secretion was significantly higher with VSVΔG/EBOV GP treatment. Cell mediated cytotoxicity assays and perforin knockout mice experiments suggest that there are perforin-dependent and -independent mechanisms involved. Together, these data suggest that NK cells play an important role in VSVΔG/EBOV GP-induced protection of EBOV by increasing NK cytotoxicity, and IFN-γ secretion.

Oral administration of Lactobacillus plantarum strain AYA enhances IgA secretion and provides survival protection against influenza virus infection in mice.

Directory of Open Access Journals (Sweden)

Yosuke Kikuchi

Full Text Available The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer's patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer's patch dendritic cells, with this production promoting IgA(+ B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection.

SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.

Science.gov (United States)

The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with mult...

Pre-natal and post-natal exposure to respiratory infection and atopic diseases development: a historical cohort study

Directory of Open Access Journals (Sweden)

Gehring Ulrike

2006-05-01

Full Text Available Abstract Background According to the hygiene hypothesis, infections in early life protect from allergic diseases. However, in earlier studies surrogate measures of infection rather than clinical infections were associated with decreased frequencies of atopic diseases. Exposure to infection indicating sub-clinical infection rather than clinical infection might protect from atopic diseases. Objective: to investigate whether exposure to acute respiratory infections within pregnancy and the first year of life is associated with atopic conditions at age 5–14 years and to explore when within pregnancy and the first year of life this exposure is most likely to be protective. Methods Historical cohort study: Population level data on acute respiratory infections from the routine reporting system of the former German Democratic Republic were linked with individual data from consecutive surveys on atopic diseases in the same region (n = 4672. Statistical analyses included multivariate logistic regression analysis and polynomial distributed lag models. Results High exposure to acute respiratory infection between pregnancy and age one year was associated with overall reduced odds of asthma, eczema, hay fever, atopic sensitization and total IgE. Exposure in the first 9 months of life showed the most pronounced effect. Adjusted odds ratio's for asthma, hay fever, inhalant sensitization and total IgE were statistical significantly reduced up to around half. Conclusion Exposure to respiratory infection (most likely indicating sub-clinical infection within pregnancy and the first year of life may be protective in atopic diseases development. The post-natal period thereby seems to be particularly important.

In vitro and in vivo studies of the carcinogenic, toxic and genotoxic activities of the air pollutants SO/sub 2/ and NO/sub x/, separately and in combination with carcinogenic polycyclic aromatic hydrocarbons and N-nitrosamines

Energy Technology Data Exchange (ETDEWEB)

Zeller, W J; Klein, R G; Pool, B L; Schmezer, P; Horsch, F; Filby, W G; Fund, N; Gross, S; Hanisch, B; Kilz, E; Seidel, A [comps.

1988-04-01

In the course of our studies directed at elucidating biological effects of the air pollutants SO/sub 2/ and NO/sub x/ it was found, that the activity of lactate dehydrogenase (LDH) is inhibited by SO/sub 2/. This effect was observed in vitro and in vivo and is based on a sulfite- and not on a sulfate-mediated action. NO/sub x/ and SO/sub 2/ reduce DNA single strand breaks induced by B(a)P in fetal hamster lung cells in vitro and SO/sub 2/ reduces DNA single strand breaks induced by AMMN in primary cultures of rat hepatocytes. The postulated mechanisms of action are discussed. Sulfite itself induces DNA-amplification in SV40 transformed CO60 cells; but an increase in the amplification rate induced by B(a)P or 7,12-DMBA was not observed. The in vitro genotoxicity (DNA single strand breaks) of 3 nitrosamines (AMMN, NDMA, NMBzA) is reduced in rat hepatocytes from donor animals pretreated with 50 ppm SO/sub 2/ for 2 weeks. Inhalation of NO/sub x/ by rats reduced the activities of AHH, NDMA-D and GST in hepatocytes and of GST in lung cells. Following SO/sub 2/ inhalation NDMA-D activity in the liver is increased and GST activity in the lung is decreased. In a current in vivo long-term inhalation study of NDMA+-SO/sub 2/ or NO/sub x/ first tumors of the nasal cavity are already observed after a total dose of 2 mg NDMA/animal.

Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

Directory of Open Access Journals (Sweden)

Kandadi Machender R

2012-11-01

Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury

Energy Technology Data Exchange (ETDEWEB)

Wigenstam, Elisabeth; Elfsmark, Linda; Koch, Bo [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden); Bucht, Anders [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden); Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå (Sweden); Jonasson, Sofia, E-mail: sofia.jonasson@foi.se [Swedish Defence Research Agency, CBRN Defence and Security, Umeå (Sweden)

2016-10-15

We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl{sub 2}) with the aim to understand the pathogenesis of the long-term sequelae of Cl{sub 2}-induced lung-injury. In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5 h up to 90 days after a single inhalation of Cl{sub 2}. A single dose of dexamethasone (10 mg/kg) was administered 1 h following Cl{sub 2}-exposure. A 15-min inhalation of 200 ppm Cl{sub 2} was non-lethal in Sprague-Dawley rats. At 24 h post exposure, Cl{sub 2}-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24 h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24 h but did not influence the AHR. Inhalation of Cl{sub 2} in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl{sub 2}-induced respiratory dysfunction. - Highlights: • Inhalation of Cl{sub 2} leads to acute lung inflammation and airway hyperreactivity. • Cl{sub 2} activates an inflammasome pathway of TGF-β induction. • Cl{sub 2} leads to a fibrotic respiratory disease. • Treatment

Electrostatic Properties of Particles for Inhalation

OpenAIRE

Rowland, Martin

2015-01-01

Dry powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs) aredevices used to deliver therapeutic agents to the lungs. Typically, inhaled activepharmaceutical ingredients (APIs) are electrically resistive materials and are prone toaccumulating electrostatic charge. The build-up of charge on inhaled therapeutics hastraditionally been viewed as a nuisance as it may result in problems such as weighingerrors, agglomeration, adhesion to surfaces and poor flow. Energetic processing st...

Inhaled americium dioxide

International Nuclear Information System (INIS)

Park, J.F.

1982-01-01

This project includes experiments to determine the effects of Zn-DTPA therapy on the retention, translocation and biological effects of inhaled 241 AmO 2 . Beagle dogs that received inhalation exposure to 241 AmO 2 developed leukopenia, clincial chemistry changes associated with hepatocellular damage, and were euthanized due to respiratory insufficiency caused by radiation pneumonitis 120 to 131 days after pulmonary deposition of 22 to 65 μCi 241 Am. Another group of dogs that received inhalation exposure to 241 AmO 2 and were treated daily with Zn-DTPA had initial pulmonary deposition of 19 to 26 μCi 241 Am. These dogs did not develop respiratory insufficiency, and hematologic and clinical chemistry changes were less severe than in the non-DTPA-treated dogs

Long-term sub second-response monitoring of gaseous ammonia in ambient air by positive inhaling ion mobility spectrometry.

Science.gov (United States)

Huang, Wei; Wang, Weiguo; Chen, Chuang; Li, Mei; Peng, Liying; Li, Hang; Liu, Jiwei; Hou, Keyong; Li, Haiyang

2017-12-01

A real-time dynamic measurements of ammonia (NH 3 ) is crucial for understanding the atmospheric nucleation process. A novel method was developed for on line monitoring at the sub-second time scale for the gaseous ammonia in ambient air for months, based on a positive inhaling ion mobility spectrometry (IMS) with a 63 Ni ion source. The selective detection of NH 3 was achieved using a high resolution IMS with an optimization of the drift tube temperature above 150°C. This method improved the peak-to-peak resolution significantly, thus avoided the interferences of the adjacent peaks to the quantitative analysis of NH 3 . The time resolution of the IMS was less than 0.1s at a data averaging of 10 times. The limit of detection (LOD) achieved at sub-ppb level while a linear response of peak intensity versus concentration of NH 3 in the range of 10-60ppb and 60-400ppb were obtained. The relative standard deviations (RSD), the confidence level and the errors were 1.06%, 95% and ± 0.21ppb by measuring 100ppb NH 3 for 100 times. The effect of ambient humidity could be greatly reduced by using the drift temperature of over 150°C. At last, the application of measuring the NH 3 concentration evolutions of Dalian city was performed from June 19 to December 3 in 2015. The results illustrated a potential method of using IMS for a real-time measuring atmospheric NH 3 at an unprecedented accuracy and sensitivity with long-term stability. Copyright © 2017 Elsevier B.V. All rights reserved.

Daily ingestion of the probiotic Lactobacillus paracasei ST11 decreases Vaccinia virus dissemination and lethality in a mouse model.

Science.gov (United States)

Dos Santos Pereira Andrade, A C; Lima, M Teixeira; Oliveira, G Pereira; Calixto, R Silva; de Sales E Souza, É Lorenna; da Glória de Souza, D; de Almeida Leite, C M; Ferreira, J M Siqueira; Kroon, E G; de Oliveira, D Bretas; Dos Santos Martins, F; Abrahão, J S

2017-02-07

Vaccinia virus (VACV) is an important pathogen. Although studies have shown relationships between probiotics and viruses, the effect of probiotics on VACV infection is unknown. Therefore, this work aims to investigate the probiotics effects on VACV infection. Mice were divided into four groups, two non-infected groups, one receiving the probiotic, the other one not receiving it, and two groups infected intranasally with VACV Western Reserve (VACV-WR) receiving or not receiving the probiotic. Viral titres in organs and cytokine production in the lungs were analysed. Lung samples were also subjected to histological analysis. The intake of probiotic results in reduction in viral spread with a significant decrease of VACV titer on lung, liver and brain of treated group. In addition,treatment with the probiotic results in attenuated mice lung inflammation showing fewer lesions on histological findings and decreased lethality in mice infected with VACV. The ingestion of Lactobacillus paracasei ST11 (LPST11) after VACV infection resulted in 2/9 animal lethality compared with 4/9 in the VACV group. This is the first study on probiotics and VACV interactions, providing not only information about this interaction, but also proposing a model for future studies involving probiotics and other poxvirus.

Batch crystallization of rifapentine for inhalable tuberculosis medication

Science.gov (United States)

Wijanarko, Anondho; Meivita, Maria Prisca; Hermansyah, Heri; Sahlan, Muhamad; Lakerveld, Richard

2018-02-01

In the midst of Tuberculosis (TB) pandemic, a research about new tuberculosis drug that results in more rapid resolution of tubercular infection is important. It will play a crucial role in accelerating the reductions in tuberculosis incidence that is occurring worldwide. The effectiveness of rifapentine has been assessed and it has been proven to be the most effective antibiotics for TB. A frequent administration and dose of rifapentine resulted in more rapid resolution of tubercular infection. However, based on former research, high exposure levels for treatment shortening may be unachievable with oral administration and might instead be achieved by direct aerosol delivery of rifapentine to the pulmonary site of infection. Therefore, with the growing interest in the effectiveness of rifapentine in frequent administration and dose, this research integrates an inhalable form of crystalline rifapentine prepared using a batch process. Moreover, this research investigates the effect of seed loading, supersaturation ratio, and residence time on the characterization of crystalline rifapentine in order to form a crystalline rifapentine in an inhalable size. The research was carried out by using anti-solvent crystallization method with acetone as a solvent and distilled water as an anti-solvent. Based on the assessment of various operating variables, it can be concluded that the optimum result was obtained at the unseeded experiment with supersaturation ratio = 1.26. Unseeded experiments are preferred because the ideal size for therapeutic aerosol was achieved in unseeded experiments. At the request of all authors the above article is being retracted due to publication without knowledge or consent from one of the principal investigators of the research listed on the article, Dr. Richard Lakerveld. This article is retracted from the scientific record with effect from 18 May 2018.

Non-lethal Clostridium sordellii bacteraemia in an immunocompromised patient with pleomorphic sarcoma.

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Bonnecaze, Alex K; Stephens, Sarah Ellen Elza; Miller, Peter John

2016-08-03

Clostridium sordellii is a spore-forming anaerobic Gram-positive rod that has rarely been reported to cause disease in humans. Resultant mortality from infection is estimated at nearly 70% and is most often correlated with gynaecological procedures, intravenous drug abuse or trauma. C. sordellii infection often presents similarly to toxic shock syndrome (TSS); notable features of infection include refractory hypotension, haemoconcentration and marked leucocytosis. Although clinically similar to TSS, a notable difference is C. sordellii infections rarely involve fever. The organism's major toxins include haemorrhagic (TcsH) and lethal factor (TcsL), which function to disrupt cytoskeletal integrity. Current literature suggests treating C. sordelli infection with a broad-spectrum penicillin, metronidazole and clindamycin. We present a case of C. sordellii bacteraemia and septic shock in an immunocompromised patient who was recently diagnosed with pleomorphic gluteal sarcoma. Despite presenting in critical condition, the patient improved after aggressive hemodynamic resuscitation, source control and intravenous antibiotic therapy. 2016 BMJ Publishing Group Ltd.

Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation

OpenAIRE

Rydman, Elina M.; Ilves, Marit; Koivisto, Antti J.; Kinaret, Pia A. S.; Fortino, Vittorio; Savinko, Terhi S.; Lehto, Maili T.; Pulkkinen, Ville; Vippola, Minnamari; Hämeri, Kaarle J.; Matikainen, Sampsa; Wolff, Henrik; Savolainen, Kai M.; Greco, Dario; Alenius, Harri

2014-01-01

Background Carbon nanotubes (CNT) represent a great promise for technological and industrial development but serious concerns on their health effects have also emerged. Rod-shaped CNT are, in fact, able to induce asbestos-like pathogenicity in mice including granuloma formation in abdominal cavity and sub-pleural fibrosis. Exposure to CNT, especially in the occupational context, happens mainly by inhalation. However, little is known about the possible effects of CNT on pulmonary allergic dise...

Cost-effectiveness of malaria preventive treatment for HIV-infected pregnant women in sub-Saharan Africa.

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Choi, Sung Eun; Brandeau, Margaret L; Bendavid, Eran

2017-10-06

Malaria is a leading cause of morbidity and mortality among HIV-infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV-infected pregnant women was assessed. A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX. Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy. In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to

Effects of Sub-lethal Concentrations of Silver Nanoparticles on a Simulated Intestinal Prokaryotic–Eukaryotic Interface

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Elisa Garuglieri

2018-01-01

Full Text Available Nanotechnology applications are expected to bring a range of benefits to the food sector, aiming to provide better quality and conservation. In this research, the physiological response of both an Escherichia coli mono-species biofilm and Caco-2 intestinal cells to sub-lethal concentrations of silver nanoparticles (AgNPs has been investigated. In order to simulate the anaerobic and aerobic compartments required for bacteria and intestinal cells growth, a simplified semi-batch model based on a transwell permeable support was developed. Interaction between the two compartments was obtained by exposing Caco-2 intestinal cells to the metabolites secreted by E. coli biofilm after its exposure to AgNPs. To the best of the authors’ knowledge, this study is the first to investigate the effect of AgNPs on Caco-2 cells that takes into consideration previous AgNP-intestinal biofilm interactions, and at concentrations mimicking real human exposure. Our data show that 1 μg/mL AgNPs in anaerobic conditions (i promote biofilm formation up to 2.3 ± 0.3 fold in the first 72 h of treatment; (ii increase reactive oxygen species (ROS production to 84 ± 21% and change the physiological status of microbial cells after 96 h of treatment; (iii seriously affect a 72-h old established biofilm, increasing the level of oxidative stress to 86 ± 21%. Moreover, the results indicate that oxygen renders the biofilm more adequate to counteract AgNP effects. Comet assays on Caco-2 cells demonstrated a protective role of biofilm against the genotoxic effect of 1 μg/mL AgNPs on intestinal epithelial cells.

Inhalants

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... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Inhalation of Hydrocarbon Jet Fuel Suppress Central Auditory Nervous System Function.

Science.gov (United States)

Guthrie, O'neil W; Wong, Brian A; McInturf, Shawn M; Reboulet, James E; Ortiz, Pedro A; Mattie, David R

2015-01-01

More than 800 million L/d of hydrocarbon fuels is used to power cars, boats, and jet airplanes. The weekly consumption of these fuels necessarily puts the public at risk for repeated inhalation exposure. Recent studies showed that exposure to hydrocarbon jet fuel produces lethality in presynaptic sensory cells, leading to hearing loss, especially in the presence of noise. However, the effects of hydrocarbon jet fuel on the central auditory nervous system (CANS) have not received much attention. It is important to investigate the effects of hydrocarbons on the CANS in order to complete current knowledge regarding the ototoxic profile of such exposures. The objective of the current study was to determine whether inhalation exposure to hydrocarbon jet fuel might affect the functions of the CANS. Male Fischer 344 rats were randomly divided into four groups (control, noise, fuel, and fuel + noise). The structural and functional integrity of presynaptic sensory cells was determined in each group. Neurotransmission in both peripheral and central auditory pathways was simultaneously evaluated in order to identify and differentiate between peripheral and central dysfunctions. There were no detectable effects on pre- and postsynaptic peripheral functions. However, the responsiveness of the brain was significantly depressed and neural transmission time was markedly delayed. The development of CANS dysfunctions in the general public and the military due to cumulative exposure to hydrocarbon fuels may represent a significant but currently unrecognized public health issue.

Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

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Wong Brian A

2005-10-01

Full Text Available Abstract Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is

Protective effect of Lactobacillus casei strain Shirota against lethal infection with multi-drug resistant Salmonella enterica serovar Typhimurium DT104 in mice.

Science.gov (United States)

Asahara, T; Shimizu, K; Takada, T; Kado, S; Yuki, N; Morotomi, M; Tanaka, R; Nomoto, K

2011-01-01

The anti-infectious activity of lactobacilli against multi-drug resistant Salmonella enterica serovar Typhimurium DT104 (DT104) was examined in a murine model of an opportunistic antibiotic-induced infection. Explosive intestinal growth and subsequent lethal extra-intestinal translocation after oral infection with DT104 during fosfomycin (FOM) administration was significantly inhibited by continuous oral administration of Lactobacillus casei strain Shirota (LcS), which is naturally resistant to FOM, at a dose of 10(8) colony-forming units per mouse daily to mice. Comparison of the anti-Salmonella activity of several Lactobacillus type strains with natural resistance to FOM revealed that Lactobacillus brevis ATCC 14869(T) , Lactobacillus plantarum ATCC 14917(T) , Lactobacillus reuteri JCM 1112(T) , Lactobacillus rhamnosus ATCC 7469(T) and Lactobacillus salivarius ATCC 11741(T) conferred no activity even when they obtained the high population levels almost similar to those of the effective strains such as LcS, Lact. casei ATCC 334(T) and Lactobacillus zeae ATCC 15820(T) . The increase in concentration of organic acids and maintenance of the lower pH in the intestine because of Lactobacillus colonization were correlated with the anti-infectious activity. Moreover, heat-killed LcS was not protective against the infection, suggesting that the metabolic activity of lactobacilli is important for the anti-infectious activity. These results suggest that certain lactobacilli in combination with antibiotics may be useful for prophylaxis against opportunistic intestinal infections by multi-drug resistant pathogens, such as DT104. Antibiotics such as FOM disrupt the metabolic activity of the intestinal microbiota that produce organic acids, and that only probiotic strains that are metabolically active in vivo should be selected to prevent intestinal infection when used clinically in combination with certain antibiotics. © 2010 The Authors. Journal of Applied Microbiology �

Lethal doses of ionizing radiation versus endogenous level of superoxide dismutase

Energy Technology Data Exchange (ETDEWEB)

Lipecka, K; Domanski, T; Dniaszewska, K; Grabowska, B; Pietrowicz, D; Lindner, P; Cisowska, B; Gorski, H [Military Medical Academy, Lodz (Poland). Inst. of Occupational Medicine

1982-06-22

The stability of superoxide dismutase (SOD) as well as its activity distribution in a human population were investigated. The SOD activity level of the erythrocytes proved to be an index for the endogenous SOD activity in the whole body. In a rat population, having similar SOD frequency distribution as a human population, the mortality due to acute irradiation depended on the SOD level; after a single acute dose approximating the lethal dose (LD/sub 50/30/) the survival depended distinctly on the endogenous SOD activity level.

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

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Blanford Simon

2012-11-01

Full Text Available Abstract 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

Toxicity of selenium (Na sub 2 SeO sub 3 ) and mercury (HgCl sub 2 ) on the planarian Dugesia gonocephala

Energy Technology Data Exchange (ETDEWEB)

Congiu, A.M.; Casu, S.; Ugazio, G. (Istituto di Genetica (Italy))

1989-10-01

The toxicity of selenium (Na{sub 2}SeO{sub 3}) and mercury (HgCl{sub 2}) was determined by using a freshwater planarian which is particularly sensitive to pollution, and belongs to a fissiparous breed of Dugesia gonocephala. The mortality and fissiparity frequency of the subjects were studied. They were exposed to intense treatments (48 hours) or for medium to long periods of time (21 days) to either the single compounds or a combination of both, and were fed or fasting. The lethal effect of sodium selenite is correlated to the food intake, whereas the toxicity of mercurous chloride is probably the result of a fixative effect which does not depend on feeding. The 21-day treatment with the first compound has a non-negligible lethal effect which is probably due to an accumulation phenomenon. At doses where an antioxidant effect prevails, fissiparity is stimulated. On the other hand, the second compound reduces reproduction frequency to half the base values. Compared to the Paracentrotus lividus, the Dugesia gonocephala offers various advantages concerning toxicological experiments; besides being easier to handle in the laboratory, it is available all year round and is not subject to seasonal cycles. It is also more susceptible to the toxic effect of mercury, which is a common and highly toxic pollutant, than the sea urchin.

Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection.

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Megan E Schmidt

2018-01-01

Full Text Available Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.

MDA5 can be exploited as efficacious genetic adjuvant for DNA vaccination against lethal H5N1 influenza virus infection in chickens.

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Matthias Liniger

Full Text Available Chickens lack the retinoic acid-inducible gene I (RIG-I and sense avian influenza virus (AIV infections by means of the melanoma differentiation-associated gene 5 product (chMDA5. Plasmid-driven expression of the N-terminal half of chMDA5 containing the caspase activation and recruitment domains [chMDA5(1-483] triggers interferon-β responses in chicken cells. We hypothesized that mimicking virus infection by chMDA5(1-483 expression may enhance vaccine-induced adaptive immunity. In order to test this, the potential genetic adjuvant properties of chMDA5(1-483 were evaluated in vivo in combination with a suboptimal quantity of a plasmid DNA vaccine expressing haemagglutinin (HA of H5N1 AIV. Co-administration of the HA plasmid with plasmid DNA for chMDA5(1-483 expression resulted in approximately 10-fold higher HA-specific antibody responses than injection of the HA plasmid mixed with empty vector DNA as control. Accordingly, compared with HA DNA vaccination alone, the chMDA5(1-483-adjuvanted HA DNA vaccine mediated enhanced protection against a lethal H5N1 challenge infection in chickens, with reduced clinical signs and cloacal virus shedding. These data demonstrate that innate immune activation by expression of signaling domains of RIG-I-like receptors can be exploited to enhance vaccine efficacy.

Understanding the gender disparity in HIV infection across countries in sub-Saharan Africa: evidence from the Demographic and Health Surveys

Science.gov (United States)

Magadi, Monica Akinyi

2011-01-01

Women in sub-Saharan Africa bear a disproportionate burden of human immunodeficiency virus (HIV) infections, which is exacerbated by their role in society and biological vulnerability. The specific objectives of this article are to (i) determine the extent of gender disparity in HIV infection; (ii) examine the role of HIV/acquired immune deficiency syndrome (AIDS) awareness and sexual behaviour factors on the gender disparity and (iii) establish how the gender disparity varies between individuals of different characteristics and across countries. The analysis involves multilevel logistic regression analysis applied to pooled Demographic and Health Surveys data from 20 countries in sub-Saharan Africa conducted during 2003–2008. The findings suggest that women in sub-Saharan Africa have on average a 60% higher risk of HIV infection than their male counterparts. The risk for women is 70% higher than their male counterparts of similar sexual behaviour, suggesting that the observed gender disparity cannot be attributed to sexual behaviour. The results suggest that the risk of HIV infection among women (compared to men) across countries in sub-Saharan Africa is further aggravated among those who are younger, in female-headed households, not in stable unions or marital partnerships or had an earlier sexual debut. PMID:21545443

Effects of sodium bicarbonate on the end-tidal CO[sub 2], PaCO[sub 2], HCO[sub 3][sup -], PH and cerebral blood flow

Energy Technology Data Exchange (ETDEWEB)

Komatani, Akio; Akutsu, Tooru; Yoshida, Michihiko; Yamaguchi, Koichi; Seo, Hiroshi (Yamagata Univ. (Japan). School of Medicine)

1992-09-01

To estimate the quantitative reactivity of cerebral blood flow (CBF), the effects of sodium bicarbonate on the end-tidal CO[sub 2], arterial partial pressure of CO[sub 2] (PaCO[sub 2]), HCO[sub 3][sup -], pH and CBF were examined. The CBF was measured by [sup 133]Xe inhalation method with ring type SPECT (HEADTOME). Activation study with sodium bicarbonate administration was performed after 30 minutes of resting study, and the reactivity of each parameters was investigated. The arterial HCO[sub 3][sup -] and pH increased with similar reactivity, but PaCO[sub 2], end-tidal CO[sub 2] and CBF in the non-injured hemisphere changed with irregular reactivity. The excellent correlation between PaCO[sub 2] and end-tidal CO[sub 2] was vanished by the administration of sodium bicarbonate. The reactivity of CBF did not correlate with reactivity of PaCO[sub 2] and end-tidal CO[sub 2], but correlated with arterial HCO[sub 3][sup -] and pH. Thus the measurement of arterial HCO[sub 3][sup -] and pH may be indispensable to estimate the CBF reactivity with the administration of sodium bicarbonate. (author).

Influence of inhaled Ca-DTPA on the long-term effects of inhaled Pu nitrate

International Nuclear Information System (INIS)

Ballou, J.E.; Dagle, G.E.; McDonald, K.E.; Buschbom, R.L.

1975-01-01

Inhaled Ca-DTPA administered to rats in 6 weekly, one-hour treatments of 3 mg/rat did not affect weight gain or life-span compared to Pu burdened animals (78 nCi ILB) or nontreated controls. In addition, the drug did not appear to promote the development of malignant lung tumors and bone tumors in Pu burdened rats although one rat exposed only to Ca-DTPA aerosols did develop a malignant lung tumor. This single lung tumor can not be considered significant although the normal incidence of this lesion is quite low. Inhaled Ca-DTPA therapy administered 20 days after Pu inhalation showed little effect in reducing the lung burden of plutonium. Skeletal deposition was decreased possibly because Ca-DTPA was administered during a time of active translocation of the inhaled Pu when Pu may have been available for chelation in the blood. Inhaled Ca-DTPA therapy did not appear to be beneficial in reducing the number of malignant lung tumors or bone tumors in plutonium burdened rats but on the other hand the chelate did not appear to promote these lesions. (U.S.)

Lethal critical body residues as measures of Cd, Pb, and Zn bioavailability and toxicity in the earthworm Eisenia fetida

Energy Technology Data Exchange (ETDEWEB)

Conder, J.M.; Lanno, R.P. [Oklahoma State Univ., Dept. of Zoology, Stillwater, OK (United States)

2003-07-01

Background. Earthworm heavy metal concentrations (critical body residues, CBRs) may be the most relevant measures of heavy metal bioavailability in soils and may be linkable to toxic effects in order to better assess soil ecotoxicity. However, as earthworms possess physiological mechanisms to secrete and/or sequester absorbed metals as toxicologically inactive forms, total earthworm metal concentrations may not relate well with toxicity. Objective. The objectives of this research were to: i) develop LD{sub 50}s (total earthworm metal concentration associated with 50% mortality) for Cd, Pb, and Zn; ii) evaluate the LD{sub 50} for Zn in a lethal Zn-smelter soil; iii) evaluate the lethal mixture toxicity of Cd, Pb, and Zn using earthworm metal concentrations and the toxic unit (TU) approach; and iv) evaluate total and fractionated earthworm concentrations as indicators of sublethal exposure. Methods. Earthworms (Eisenia fetida (Savigny)) were exposed to artificial soils spiked with Cd, Pb, Zn, and a Cd-Pb-Zn equitoxic mixture to estimate lethal CBRs and mixture toxicity. To evaluate the CBR developed for Zn, earthworms were also exposed to Zn-contaminated field soils receiving three different remediation treatments. Earthworm metal concentrations were measured using a procedure devised to isolate toxicologically active metal burdens via separation into cytosolic and pellet fractions. (orig.)

Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications.

Science.gov (United States)

Rudokas, Mindaugas; Najlah, Mohammad; Alhnan, Mohamed Albed; Elhissi, Abdelbary

2016-01-01

This is a critical review on research conducted in the field of pulmonary delivery of liposomes. Issues relating to the mechanism of nebulisation and liposome composition were appraised and correlated with literature reports of liposome formulations used in clinical trials to understand the role of liposome size and composition on therapeutic outcome. A major highlight was liposome inhalation for the treatment of lung cancers. Many in vivo studies that explored the potential of liposomes as anticancer carrier systems were evaluated, including animal studies and clinical trials. Liposomes can entrap anticancer drugs and localise their action in the lung following pulmonary delivery. The safety of inhaled liposomes incorporating anticancer drugs depends on the anticancer agent used and the amount of drug delivered to the target cancer in the lung. The difficulty of efficient targeting of liposomal anticancer aerosols to the cancerous tissues within the lung may result in low doses reaching the target site. Overall, following the success of liposomes as inhalable carriers in the treatment of lung infections, it is expected that more focus from research and development will be given to designing inhalable liposome carriers for the treatment of other lung diseases, including pulmonary cancers. The successful development of anticancer liposomes for inhalation may depend on the future development of effective aerosolisation devices and better targeted liposomes to maximise the benefit of therapy and reduce the potential for local and systemic adverse effects. © 2016 S. Karger AG, Basel.

Exposure to acrolein by inhalation causes platelet activation

International Nuclear Information System (INIS)

Sithu, Srinivas D.; Srivastava, Sanjay; Siddiqui, Maqsood A.; Vladykovskaya, Elena; Riggs, Daniel W.; Conklin, Daniel J.; Haberzettl, Petra; O'Toole, Timothy E.; Bhatnagar, Aruni; D'Souza, Stanley E.

2010-01-01

Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6 h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.

Exposure to acrolein by inhalation causes platelet activation

Energy Technology Data Exchange (ETDEWEB)

Sithu, Srinivas D [Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202 (United States); Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Srivastava, Sanjay; Siddiqui, Maqsood A; Vladykovskaya, Elena; Riggs, Daniel W; Conklin, Daniel J; Haberzettl, Petra; O' Toole, Timothy E; Bhatnagar, Aruni [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); D' Souza, Stanley E., E-mail: sedsou01@louisville.ed [Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202 (United States)

2010-10-15

Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6 h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.

Factors influencing circadian rhythms in acetaminophen lethality.

Science.gov (United States)

Schnell, R C; Bozigian, H P; Davies, M H; Merrick, B A; Park, K S; McMillan, D A

1984-01-01

Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00-18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00-06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

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

Science.gov (United States)

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

2015-01-01

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

Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model

Directory of Open Access Journals (Sweden)

O'Shaughnessy Patrick T

2011-01-01

Full Text Available Abstract Background There is increasing interest in the environmental and health consequences of silver nanoparticles as the use of this material becomes widespread. Although human exposure to nanosilver is increasing, only a few studies address possible toxic effect of inhaled nanosilver. The objective of this study was to determine whether very small commercially available nanosilver induces pulmonary toxicity in mice following inhalation exposure. Results In this study, mice were exposed sub-acutely by inhalation to well-characterized nanosilver (3.3 mg/m3, 4 hours/day, 10 days, 5 ± 2 nm primary size. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage fluid. Lungs were evaluated for histopathologic changes and the presence of silver. In contrast to published in vitro studies, minimal inflammatory response or toxicity was found following exposure to nanosilver in our in vivo study. The median retained dose of nanosilver in the lungs measured by inductively coupled plasma - optical emission spectroscopy (ICP-OES was 31 μg/g lung (dry weight immediately after the final exposure, 10 μg/g following exposure and a 3-wk rest period and zero in sham-exposed controls. Dissolution studies showed that nanosilver did not dissolve in solutions mimicking the intracellular or extracellular milieu. Conclusions Mice exposed to nanosilver showed minimal pulmonary inflammation or cytotoxicity following sub-acute exposures. However, longer term exposures with higher lung burdens of nanosilver are needed to ensure that there are no chronic effects and to evaluate possible translocation to other organs.

Inhalation Injury: State of the Science 2016.

Science.gov (United States)

Foster, Kevin N; Holmes, James H

This article summarizes research conducted over the last decade in the field of inhalation injury in thermally injured patients. This includes brief summaries of the findings of the 2006 State of the Science meeting with regard to inhalation injury, and of the subsequent 2007 Inhalation Injury Consensus Conference. The reviewed studies are categorized in to five general areas: diagnosis and grading; mechanical ventilation; systemic and inhalation therapy; mechanistic alterations; and outcomes.

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... inhaler with a spacer Your browser does not support iframes Using a metered dose inhaler with a ...

Radioactive gas inhalator

International Nuclear Information System (INIS)

LeMon, D.E.

1975-01-01

An ''inhalator'', or more particularly an apparatus for permitting a patient to inhale a radioactive gas in order to provide a diagnostic test of the patient's lung area, is described. The disclosed apparatus provides a simple, trouble-free mechanism for achieving this result; and, furthermore, provides an improved testing method. Moreover, the disclosed apparatus has the capability of gradually introducing the test condition in a manner that makes it easy for the patient to become acclimated to it. (U.S.)

Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow

Energy Technology Data Exchange (ETDEWEB)

Kelly, W.T.; Baile, E.M.; Brancatisano, A.; Pare, P.D.; Engel, L.A. (Dept. of Respiratory Medicine, Westmead Hospital, Westmead, NSW (Australia))

1992-01-01

Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators form the airways, thus affecting the duration and severity of bronchoispasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: (1) increased negative intrathoracic pressure swings (-25[+-]1 cmH[sub 2]O) induced by an inspiratory resistance; (2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and (3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition. (au).

Survival of Primates in Lethal Septic Shock Following Delayed Treatment with Steroid.

Science.gov (United States)

1981-02-26

TECHNICAL REPORT NO. 142 SURVIVAL OF PRIMATES IN LETHAL SEPTIC SHOCK FOLLOWING DELAYED TREAMENT WIn STEROID L. B. Hinshaw, L. T. Archer, B. K. Belier ...2. Schumer W: Steroids in the treatment of clinical septic shock. Ann Surg 184:333-341, 1976. 3. Hinshaw LB, Belier PK, Archer LT, Flournoy DJ, White...not preventable by antibiotic alone. Infect Immun ZS:538-5)7, 1979. 6. Hinshaw LB, Archer LT, Belier -Todd BK, Coalson .JJ, Flournoy DL, Passey R

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... metered dose inhaler with a spacer [ PDF – 377 KB] Your browser does not support iframes Cómo usar ... inhalador de dosis fija con espaciador [PDF – 343 KB] Using a metered dose inhaler (inhaler in mouth) ...

Inhaled plutonium nitrate in dogs

International Nuclear Information System (INIS)

Dagle, G.E.; Cannon, W.C.; Ragan, H.A.; Watson, C.R.; Stevens, D.L.; Cross, F.T.; Dionne, P.J.; Harrington, T.P.

1978-01-01

Beagle dogs given a single inhalation exposure to 239 Pu(NO 3 ) 4 are being observed for life-span dose-effect relationships. Lymphopenia occurred at the two highest dosage levels as early as 1 mo following exposure and was associated with neutropenia and reduction in numbers of circulatory monocytes by 4 mo postexposure. Radiation pneumonitis developed in one dog at the highest dosage level at 14 mo postexposure. More rapid translocation to skeleton and liver occurred following inhalation of 238 Pu(NO 3 ) 4 than after 239 Pu(NO 3 ) 4 inhalation

Teaching inhaler use in chronic obstructive pulmonary disease patients.

Science.gov (United States)

Lareau, Suzanne C; Hodder, Richard

2012-02-01

To review barriers to the successful use of inhalers in patients with chronic obstructive pulmonary disease (COPD), and the role of the nurse practitioner (NP) in facilitating optimum inhaler use. Review of the national and international scientific literature. Pharmacologic treatment of COPD patients comprises mainly inhaled medications. Incorrect use of inhalers is very common in these individuals. Some of the consequences of poor inhaler technique include reduced therapeutic dosing, medication adherence, and disease stability, which can lead to increased morbidity, decreased quality of life, and a high burden on the healthcare system. Knowledgeable evaluation and frequent reassessment of inhaler use coupled with education of patients, caregivers, and healthcare professionals can significantly improve the benefits COPD patients derive from inhaled therapy. Patient education is vital for correct use of inhalers and to ensure the effectiveness of inhaled medications. The NP has a critical role in assessing potential barriers to successful learning by the patient and improving inhaler technique and medication management. The NP can also facilitate success with inhaled medications by providing up-to-date inhaler education for other healthcare team members, who may then act as patient educators. ©2011 The Author(s) Journal compilation ©2011 American Academy of Nurse Practitioners.

Modeling Powassan virus infection in Peromyscus leucopus, a natural host.

Directory of Open Access Journals (Sweden)

Luwanika Mlera

2017-01-01

Full Text Available The tick-borne flavivirus, Powassan virus (POWV causes life-threatening encephalitis in humans in North America and Europe. POWV is transmitted by ixodid tick vectors that feed on small to medium-sized mammals, such as Peromyscus leucopus mice, which may serve as either reservoir, bridge or amplification hosts. Intraperitoneal and intracranial inoculation of 4-week old Peromyscus leucopus mice with 103 PFU of POWV did not result in overt clinical signs of disease. However, following intracranial inoculation, infected mice seroconverted to POWV and histopathological examinations revealed that the mice uniformly developed mild lymphocytic perivascular cuffing and microgliosis in the brain and spinal cord from 5 to 15 days post infection (dpi, suggesting an early inflammatory response. In contrast, intracranial inoculation of 4-week old C57BL/6 and BALB/c mice was lethal by 5 dpi. Intraperitoneal inoculation was lethal in BALB/c mice, but 40% (2/5 of C57BL/6 mice survived. We concluded that Peromyscus leucopus mice infected i.c. with a lethal dose of POWV support a limited infection, restricted to the central nervous system and mount an antibody response to the virus. However, they fail to develop clinical signs of disease and are able to control the infection. These results suggest the involvement of restriction factors, and the mechanism by which Peromyscus leucopus mice restrict POWV infection remains under study.

Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle

Energy Technology Data Exchange (ETDEWEB)

Smith, Carl D., E-mail: carl.d.smith179.mil@mail.mil; Wright, Linnzi K.M.; Garcia, Gregory E.; Lee, Robyn B.; Lumley, Lucille A.

2015-09-15

Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was to determine the 24-hour median lethal dose (LD{sub 50}) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD{sub 50} of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD{sub 50}s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity. - Highlights: • The LD{sub 50} of sarin was determined in female rats throughout the stages of the estrous cycle. • Females in proestrus had a significantly higher LD{sub 50} compared to estrous or ovariectomized females. • No sex differences were observed between male and female

Use of nitrite inhalants ("poppers") among American youth.

Science.gov (United States)

Wu, Li-Tzy; Schlenger, William E; Ringwalt, Chris L

2005-07-01

We examined the patterns and correlates of nitrite inhalant use among adolescents aged 12 to 17 years. Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Logistic regression was used to identify the characteristics associated with nitrite inhalant use. Among adolescents aged 12 to 17 years, 1.5% reported any lifetime use of nitrite inhalants. The prevalence of lifetime nitrite inhalant use increased to 12% and 14% among adolescents who were dependent on alcohol and any drug in the past year, respectively. Many nitrite inhalant users used at least three other types of inhalants (68%) and also met the criteria for alcohol (33%) and drug (35%) abuse or dependence. Increased odds of nitrite inhalant use were associated with residing in nonmetropolitan areas, recent utilization of mental health services, delinquent behaviors, past year alcohol and drug abuse and dependence, and multi-drug use. Adolescents who had used nitrite inhalants at least once in their lifetime tend to engage in delinquent activities and report co-occurring multiple drug abuse and mental health problems in the past year.

Age dependent systemic exposure to inhaled salbutamol

DEFF Research Database (Denmark)

Bønnelykke, Klaus; Jespersen, Jakob Jessing; Bisgaard, Hans

2007-01-01

AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing...

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

International Nuclear Information System (INIS)

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

2009-01-01

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.

Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial.

Science.gov (United States)

Basheti, Iman A; Obeidat, Nathir M; Reddel, Helen K

2017-02-09

Inhaler technique can be corrected with training, but skills drop off quickly without repeated training. The aim of our study was to explore the effect of novel inhaler technique labels on the retention of correct inhaler technique. In this single-blind randomized parallel-group active-controlled study, clinical pharmacists enrolled asthma patients using controller medication by Accuhaler [Diskus] or Turbuhaler. Inhaler technique was assessed using published checklists (score 0-9). Symptom control was assessed by asthma control test. Patients were randomized into active (ACCa; THa) and control (ACCc; THc) groups. All patients received a "Show-and-Tell" inhaler technique counseling service. Active patients also received inhaler labels highlighting their initial errors. Baseline data were available for 95 patients, 68% females, mean age 44.9 (SD 15.2) years. Mean inhaler scores were ACCa:5.3 ± 1.0; THa:4.7 ± 0.9, ACCc:5.5 ± 1.1; THc:4.2 ± 1.0. Asthma was poorly controlled (mean ACT scores ACCa:13.9 ± 4.3; THa:12.1 ± 3.9; ACCc:12.7 ± 3.3; THc:14.3 ± 3.7). After training, all patients had correct technique (score 9/9). After 3 months, there was significantly less decline in inhaler technique scores for active than control groups (mean difference: Accuhaler -1.04 (95% confidence interval -1.92, -0.16, P = 0.022); Turbuhaler -1.61 (-2.63, -0.59, P = 0.003). Symptom control improved significantly, with no significant difference between active and control patients, but active patients used less reliever medication (active 2.19 (SD 1.78) vs. control 3.42 (1.83) puffs/day, P = 0.002). After inhaler training, novel inhaler technique labels improve retention of correct inhaler technique skills with dry powder inhalers. Inhaler technique labels represent a simple, scalable intervention that has the potential to extend the benefit of inhaler training on asthma outcomes. REMINDER LABELS IMPROVE INHALER TECHNIQUE: Personalized

Effect of inhaled formyl-methionyl-leucyl-phenylalanine on airway function.

Science.gov (United States)

Berend, N; Peters, M J; Armour, C L; Black, J L; Ward, H E

1988-01-01

Formyl-methionyl-leucyl-phenylalanine (FMLP), a synthetic, acylated tripeptide analogous to bacterial chemotactic factors, has been shown to cause bronchoconstriction in guinea pig, rabbit, and human airways in vitro. To determine whether FMLP causes bronchoconstriction in man in vivo, a preliminary study was undertaken in which five non-smokers (mean age 35 years, FEV1 94% (SEM 5%) predicted) and five smokers (mean age 34 years, FEV1 93% (6%) predicted) inhaled aerosols of FMLP. None of the subjects showed airway hyperresponsiveness to histamine (the provocative concentrations of histamine causing a fall of greater than or equal to 20% in FEV1 (PC20) were over 8 mg/ml). FMLP dissolved in 50% dimethylsulphoxide and 50% saline in concentrations of 0, 0.06, 0.12, 0.25, 0.5, 1.0, 2.0, and 4.0 mg/ml was administered to the subjects by means of a French-Rosenthal dosimeter, FEV1 being recorded after inhalation of each concentration. Dose dependent falls in FEV1 occurred in five non-smokers (geometric mean 1.76, 95% confidence limits 0.87-3.53 mg/ml) and three smokers (0.23, 0.07-0.78 mg/ml), with two smokers not responding by 20% to the highest concentration of FMLP. On a separate day the FMLP dose-response curves were repeated after nebulisation of 500 micrograms of ipratropium bromide. The PC20 FMLP in the responders more than doubled. In six additional normal subjects a histamine inhalation test was performed before and four and 24 hours after inhalation of FMLP. All subjects remained unresponsive to histamine. These results show that FMLP is a potent bronchoconstrictor in some non-asthmatic individuals in vivo and this may be important in bronchoconstriction related to infection in patients with chronic obstructive lung disease.

E-cigarette versus nicotine inhaler: comparing the perceptions and experiences of inhaled nicotine devices.

Science.gov (United States)

Steinberg, Michael B; Zimmermann, Mia Hanos; Delnevo, Cristine D; Lewis, M Jane; Shukla, Parth; Coups, Elliot J; Foulds, Jonathan

2014-11-01

Novel nicotine delivery products, such as electronic cigarettes (e-cigarettes), have dramatically grown in popularity despite limited data on safety and benefit. In contrast, the similar U.S. Food and Drug Administration (FDA)-approved nicotine inhaler is rarely utilized by smokers. Understanding this paradox could be helpful to determine the potential for e-cigarettes as an alternative to tobacco smoking. To compare the e-cigarette with the nicotine inhaler in terms of perceived benefits, harms, appeal, and role in assisting with smoking cessation. A cross-over trial was conducted from 2012 to 2013 PARTICIPANTS/INTERVENTIONS: Forty-one current smokers age 18 and older used the e-cigarette and nicotine inhaler each for 3 days, in random order, with a washout period in between. Thirty-eight participants provided data on product use, perceptions, and experiences. The Modified Cigarette Evaluation Questionnaire (mCEQ) measured satisfaction, reward, and aversion. Subjects were also asked about each product's helpfulness, similarity to cigarettes, acceptability, image, and effectiveness in quitting smoking. Cigarette use was also recorded during the product-use periods. The e-cigarette had a higher total satisfaction score (13.9 vs. 6.8 [p e-cigarette received higher ratings for helpfulness, acceptability, and "coolness." More subjects would use the e-cigarette to make a quit attempt (76 %) than the inhaler (24 %) (p e-cigarette vs. 10 % (4/38) using the inhaler (p = 0.18). The e-cigarette was more acceptable, provided more satisfaction, and had higher perceived benefit than the inhaler during this trial. E-cigarettes have the potential to be important nicotine delivery products owing to their high acceptance and perceived benefit, but more data are needed to evaluate their actual efficacy and safety. Providers should be aware of these issues, as patients will increasingly inquire about them.

Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

DEFF Research Database (Denmark)

Heijerman, Harry; Westerman, Elsbeth; Conway, Steven

2009-01-01

, mucolytics/mucous mobilizers, anti-inflammatory drugs, bronchodilators and combinations of solutions. Additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Finally, we...... review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics...

Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C<sub>82sub>(OH)>22sub> and its implication for de novo design of nanomedicine

Energy Technology Data Exchange (ETDEWEB)

Kang, S. -g.; Zhou, G.; Yang, P.; Liu, Y.; Sun, B.; Huynh, T.; Meng, H.; Zhao, L.; Xing, G.; Chen, C.; Zhao, Y.; Zhou, R.

2012-09-18

Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth-leading cause of cancer-related death in North America. Matrix metalloproteinases (MMPs) have long been targeted as a potential anticancer therapy because of their seminal role in angiogenesis and extracellular matrix (ECM) degradation of tumor survival and invasion. However, the inhibition specificity to MMPs and the molecular-level understanding of the inhibition mechanism remain largely unresolved. Here, we found that endohedral metallofullerenol Gd@C<sub>82sub>(OH)>22sub> can successfully inhibit the neoplastic activity with experiments at animal, tissue, and cellular levels. Gd@C<sub>82sub>(OH)>22sub> effectively blocks tumor growth in human pancreatic cancer xenografts in a nude mouse model. Enzyme activity assays also show Gd@C<sub>82sub>(OH)>22sub> not only suppresses the expression of MMPs but also significantly reduces their activities. We then applied large-scale molecular-dynamics simulations to illustrate the molecular mechanism by studying the Gd@C<sub>82sub>(OH)>22sub>–MMP-9 interactions in atomic detail. Our data demonstrated that Gd@C<sub>82sub>(OH)>22sub> inhibits MMP-9 mainly via an exocite interaction, whereas the well-known zinc catalytic site only plays a minimal role. Steered by nonspecific electrostatic, hydrophobic, and specific hydrogen-bonding interactions, Gd@C<sub>82sub>(OH)>22sub> exhibits specific binding modes near the ligand-specificity loop S1', thereby inhibiting MMP-9 activity. Both the suppression of MMP expression and specific binding mode make Gd@C<sub>82sub>(OH)>22sub> a potentially more effective nanomedicine for pancreatic cancer than traditional medicines, which usually target the proteolytic sites directly but fail in selective inhibition. Finally, our findings provide insights for de novo design of nanomedicines for fatal diseases such as pancreatic cancer.

Giardia duodenalis infection: risk factors for children living in sub-standard settlements in Brazil

Directory of Open Access Journals (Sweden)

Júlio César Teixeira

2007-06-01

Full Text Available The objective of the present study was to characterize Giardia duodenalis infection among children living in sub-standard settlement areas in the municipality of Juiz de Fora, Minas Gerais State, Brazil. The cross-sectional epidemiological study included 590 children from 1 to 5 years of age. Data were collected from one child per selected family through home interviews with the parent or guardian and parasitological examination of stool samples. Thirty-one putative risk factors concerning family structure, socioeconomic status, and environmental factors were analyzed by multivariate logistic regression. Prevalence of G. duodenalis infection was 18% (106 children. Four potential risk factors were heavily associated with G. duodenalis infection: number of under-five children in the same household, index child's birth order, existence of a bathroom in the home, and drinking water source.

Effects of sub-lethal levels of dichlorodiphenyltrichloroethane and dichlorodiphenyldichloroethylene on in vitro steroid biosynthesis by ovarian follicles or steroid metabolism by embryos of rainbow trout (Oncorhynchus mykiss)

Energy Technology Data Exchange (ETDEWEB)

Petkam, Rakpong [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); Renaud, Rick [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); Lin, Lucy [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); Boermans, Herman [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., N1G 2W1 (Canada); Leatherland, John [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., N1G 2W1 (Canada)]. E-mail: jleather@ovc.uoguelph.ca

2005-07-01

This study examined the possibility that DDT and DDE, at sub-lethal exposure levels, exert direct effects on the biotransformation of gonadal steroids by rainbow trout (Oncorhynchus mykiss) ovarian follicles and embryos. Ovarian follicles were co-incubated with DDT or DDE at 0.01 or 1 mg l{sup -1} to examine effects of the pesticides on basal or cAMP-activated steroidogenesis. Ovarian preparations were incubated with radiolabelled [{sup 3}H]pregnenolone ([{sup 3}H]P{sub 5}), and the tritiated metabolites of [{sup 3}H]P{sub 5} metabolism were separated using high-performance liquid chromatography (HPLC). Testosterone (T) and 17{beta}-estradiol (E{sub 2}) production were also measured using radioimmunoassay (RIA). Embryos were either exposed to the pesticides in ovo, or co-incubated in vitro with the pesticides. The effect of the pesticides on embryo steroid biotransformation was examined using a range of radioactively labelled substrates, including [{sup 3}H]P{sub 5}, [{sup 3}H]progesterone ([{sup 3}H]P{sub 4}), [{sup 3}H]T and [{sup 3}H]E{sub 2}. At the concentrations used, the pesticides had no significant effect on the relative amounts of unconjugated radiolabelled steroids formed by the biotransformation of [{sup 3}H]P{sub 5} under conditions of basal or cAMP-stimulated ovarian steroidogenesis. However, DDT and DDE appeared to reduce the basal accumulation of androgen as a product of P{sub 5} biotransformation by ovarian follicles. Basal or cAMP-stimulated total estrogen production was not affected. In addition, DDT at 1 mg l{sup -1} and DDE at 0.01 mg l{sup -1} significantly increased and decreased cAMP-stimulated T accumulation, respectively. Also DDT at 0.01 mg l{sup -1} and DDE at 1 mg l{sup -1} significantly increased and decreased basal E{sub 2} accumulation, respectively. The steroid metabolites synthesized from the different substrates by embryos were essentially similar in both controls and pesticide-exposed groups, and the survival of embryos to hatch

Inhalants

Science.gov (United States)

... uses inhalants may be unable to learn new things or may have a hard time carrying on simple conversations. If the cerebral ... get drugs on the street, it is really hard to know what you get, Sometimes, ... put in, all sorts of things could happen. And other times, one might get ...

Inhaled actinides: some safety issues and some research problems

International Nuclear Information System (INIS)

Bair, W.J.

1978-01-01

The following topics are discussed: limited research funds; risk coefficients for inhaled particles; the hot particle hypothesis; the Gofman-Martell contention; critical tissues for inhaled actinides inhalation hazards associated with future nuclear fuel cycles; and approach to be used by the inhalation panel

Superantigens Are Critical for Staphylococcus aureus Infective Endocarditis, Sepsis, and Acute Kidney Injury

Science.gov (United States)

Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R.; Merriman, Joseph A.; Stach, Christopher S.; Horswill, Alexander R.; Peterson, Marnie L.; Schlievert, Patrick M.

2013-01-01

ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. PMID:23963178

Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study.

Science.gov (United States)

Pakkasjärvi, Niklas; Ritvanen, Annukka; Herva, Riitta; Peltonen, Leena; Kestilä, Marjo; Ignatius, Jaakko

2006-09-01

Arthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987-2002 including live born infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty-nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland.

Toxicity of nanoparticulate and bulk ZnO, Al{sub 2}O{sub 3} and TiO{sub 2} to the nematode Caenorhabditis elegans

Energy Technology Data Exchange (ETDEWEB)

Wang Huanhua; Wick, Robert L. [Department of Plant, Soil and Insect Sciences, University of Massachusetts, Stockbridge Hall, Amherst, MA 01003 (United States); Xing Baoshan [Department of Plant, Soil and Insect Sciences, University of Massachusetts, Stockbridge Hall, Amherst, MA 01003 (United States)], E-mail: bx@pssci.umass.edu

2009-04-15

Limited information is available on the environmental behavior and associated potential risk of manufactured oxide nanoparticles (NPs). In this research, toxicity of nanoparticulate and bulk ZnO, Al{sub 2}O{sub 3} and TiO{sub 2} were examined to the nematode Caenorhabditis elegans with Escherichia coli as a food source. Parallel experiments with dissolved metal ions from NPs were also conducted. The 24-h median lethal concentration (LC{sub 50}) and sublethal endpoints were assessed. Both NPs and their bulk counterparts were toxic, inhibiting growth and especially the reproductive capability of the nematode. The 24-h LC{sub 50} for ZnO NPs (2.3 mg L{sup -1}) and bulk ZnO was not significantly different, but significantly different between Al{sub 2}O{sub 3} NPs (82 mg L{sup -1}) and bulk Al{sub 2}O{sub 3} (153 mg L{sup -1}), and between TiO{sub 2} NPs (80 mg L{sup -1}) and bulk TiO{sub 2} (136 mg L{sup -1}). Oxide solubility influenced the toxicity of ZnO and Al{sub 2}O{sub 3} NPs, but nanoparticle-dependent toxicity was indeed observed for the investigated NPs. - ZnO, Al{sub 2}O{sub 3} and TiO{sub 2} nanoparticles are more toxic than their bulk counterparts to the nematode, Caenorhabditis elegans.

Systematic review with meta-analysis: the risk of mother-to-child transmission of hepatitis B virus infection in sub-Saharan Africa.

Science.gov (United States)

Keane, E; Funk, A L; Shimakawa, Y

2016-11-01

The risk of mother-to-child transmission of hepatitis B virus (HBV) has been quoted as 70-90% among women positive for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), and 5-30% among HBsAg-positive HBeAg-negative women. These risks are derived from Asia; little is known about sub-Saharan Africa. To determine the risk of mother-to-child transmission in sub-Saharan Africa, according to maternal HBeAg and type of prophylaxis. We searched Medline, Global Health, Embase, African Journals Online and African Index Medicus. We included observational or interventional studies that enrolled infants of HBV-infected women, and that tested for HBsAg or HBV DNA between 3 and 12 months of age. Fifteen articles from 11 African countries were included. Among HBeAg-positive women, the pooled risk was 38.3% (95% CI: 7.0-74.4%) without prophylaxis, which was significantly lower than the lower bound of 70-90% risk in the literature (P = 0.007). Among HBeAg-negative women, the pooled risk was 4.8% (95% CI: 0.1-13.3%) without prophylaxis, which lays within the lower range of the 5-30% risk in Asia. By extrapolating the pooled transmission risks to the number of births to infectious mothers, an estimated 1% of newborns (n = 367 250) are annually infected with HBV at birth in sub-Saharan Africa. Compared to Asia, the risk of mother-to-child transmission is low in sub-Saharan Africa. However, the annual number of infants perinatally infected with HBV is twice the number of incident paediatric HIV infections in sub-Saharan Africa (n = 190 000). This highlights the importance of preventing mother-to-child transmission of HBV in sub-Saharan Africa, which has been long neglected. © 2016 John Wiley & Sons Ltd.

CD4(+) T cell-mediated protection against a lethal outcome of systemic infection with vesicular stomatitis virus requires CD40 ligand expression, but not IFN-gamma or IL-4

DEFF Research Database (Denmark)

Andersen, C; Jensen, T; Nansen, A

1999-01-01

experiments using B cell- and T cell-deficient recipients revealed that no protection could be obtained in the absence of B cells, whereas treatment with virus-specific immune (IgG) serum controlled viral spreading to the central nervous system (CNS), but did not necessarily accomplish virus elimination......To investigate the mechanism(s) whereby T cells protect against a lethal outcome of systemic infection with vesicular stomatitis virus, mice with targeted defects in genes central to T cell function were tested for resistance to i.v. infection with this virus. Our results show that mice lacking...... the capacity to secrete both IFN-gamma and perforin completely resisted disease. Similar results were obtained using IL-4 knockout mice, indicating that neither cell-mediated nor T(h)2-dependent effector systems were required. In contrast, mice deficient in expression of CD40 ligand were more susceptible than...

Toxicity of inhaled {sup 238}PuO{sub 2} in Beagle dogs: A. Monodisperse 1.5 {mu}m AMAD particles. B. Monodisperse 3.0 {mu}m particles. XV

Energy Technology Data Exchange (ETDEWEB)

Mewhinney, J A; Gillett, N A; Muggenburg, B A; Hahn, F F; Diel, J H; Mauderly, J L; Boecker, B B; McClellan, R O

1988-12-01

Beagle dogs inhaled one of two sizes of monodisperse aerosols of {sup 238}PuO{sub 2} that resulted in graded levels of {sup 238}Pu in the lung. All dogs are being studied for their life span. One hundred and thirty-seven dogs that had initial lung burdens ranging from 0.01 to 1.5 {mu}Ci {sup 238}Pu/kg body weight (0.37 to 56 kBq/kg) have died, 8 with radiation pneumonitis and pulmonary fibrosis, 8 with lung tumors, 88 with bone tumors, 10 with liver tumors, and 25 of miscellaneous causes. Eighteen control dogs have died. Observations are being continued on 8 exposed and 6 control dogs alive at 4577-5274 days after exposure. (author)

Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs

International Nuclear Information System (INIS)

Che, Magnus M.; Conti, Michele; Chanda, Soma; Boylan, Megan; Sabnekar, Praveena; Rezk, Peter; Amari, Ethery; Sciuto, Alfred M.; Gordon, Richard K.; Doctor, Bhupendra P.; Nambiar, Madhusoodana P.

2009-01-01

We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m 3 sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.

Nalidixic acid-resistant Salmonella enteric serotype typhi infection presenting with sub-intestinal obstruction and mesenteric adenitis

International Nuclear Information System (INIS)

Al-Khuwaitir, Tarig S.; Al-Zuhair, Amin A.; Al-Ghamdi, Ali G.; Khan, A.

2008-01-01

Nalidixic acid-resistant Salmonella typhi NARST infections increase minimal inhibitory concentrations of fluoroquinolones, due to chromosomal mutations in the gene encoding DNA gyrase, and can lead to a delayed treatment response. This in turn alters the course of the disease allowing for a protracted period of illness and the occurrence of complications. In this case report, we present a patient from the Indian sub-continent, who was diagnosed with NARST complicated by sub-intestinal obstruction, her diagnosis, treatment and subsequent recovery. (author)

Non-lethal heat shock increased Hsp70 and immune protein transcripts but not Vibrio tolerance in the white-leg shrimp.

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Nguyen Hong Loc

Full Text Available Non-lethal heat shock boosts bacterial and viral disease tolerance in shrimp, possibly due to increases in endogenous heat shock protein 70 (Hsp70 and/or immune proteins. To further understand the mechanisms protecting shrimp against infection, Hsp70 and the mRNAs encoding the immune-related proteins prophenoloxidase (proPO, peroxinectin, penaeidin, crustin and hemocyanin were studied in post-larvae of the white-leg shrimp Litopenaeus vannamei, following a non-lethal heat shock. As indicated by RT-qPCR, a 30 min abrupt heat shock increased Hsp70 mRNA in comparison to non-heated animals. Immunoprobing of western blots and quantification by ELISA revealed that Hsp70 production after heat shock was correlated with enhanced Hsp70 mRNA. proPO and hemocyanin mRNA levels were augmented, whereas peroxinectin and crustin mRNA levels were unchanged following non-lethal heat shock. Penaeidin mRNA was decreased by all heat shock treatments. Thirty min abrupt heat shock failed to improve survival of post-larvae in a standardized challenge test with Vibrio harveyi, indicating that under the conditions of this study, L. vannamei tolerance to Vibrio infection was influenced neither by Hsp70 accumulation nor the changes in the immune-related proteins, observations dissimilar to other shrimp species examined.

Non-Lethal Heat Shock Increased Hsp70 and Immune Protein Transcripts but Not Vibrio Tolerance in the White-Leg Shrimp

Science.gov (United States)

Loc, Nguyen Hong; MacRae, Thomas H.; Musa, Najiah; Bin Abdullah, Muhd Danish Daniel; Abdul Wahid, Mohd. Effendy; Sung, Yeong Yik

2013-01-01

Non-lethal heat shock boosts bacterial and viral disease tolerance in shrimp, possibly due to increases in endogenous heat shock protein 70 (Hsp70) and/or immune proteins. To further understand the mechanisms protecting shrimp against infection, Hsp70 and the mRNAs encoding the immune-related proteins prophenoloxidase (proPO), peroxinectin, penaeidin, crustin and hemocyanin were studied in post-larvae of the white-leg shrimp Litopenaeus vannamei, following a non-lethal heat shock. As indicated by RT-qPCR, a 30 min abrupt heat shock increased Hsp70 mRNA in comparison to non-heated animals. Immunoprobing of western blots and quantification by ELISA revealed that Hsp70 production after heat shock was correlated with enhanced Hsp70 mRNA. proPO and hemocyanin mRNA levels were augmented, whereas peroxinectin and crustin mRNA levels were unchanged following non-lethal heat shock. Penaeidin mRNA was decreased by all heat shock treatments. Thirty min abrupt heat shock failed to improve survival of post-larvae in a standardized challenge test with Vibrio harveyi, indicating that under the conditions of this study, L. vannamei tolerance to Vibrio infection was influenced neither by Hsp70 accumulation nor the changes in the immune-related proteins, observations dissimilar to other shrimp species examined. PMID:24039886

The complications of treating chronic obstructive pulmonary disease in low income countries of sub-Saharan Africa.

Science.gov (United States)

van Gemert, Frederik A; Kirenga, Bruce J; Gebremariam, Tewodros Haile; Nyale, George; de Jong, Corina; van der Molen, Thys

2018-03-01

In most low and middle-income countries, chronic obstructive pulmonary disease (COPD) is on the rise. Areas covered: Unfortunately, COPD is a neglected disease in these countries. Taking sub-Saharan Africa as an example, in rural areas, COPD is even unknown regarding public awareness and public health planning. Programs for the management of COPD are poorly developed, and the quality of care is often of a low standard. Inhaled medication is often not available or not affordable. Tobacco smoking is the most common encountered risk factor for COPD. However, in sub-Saharan Africa, household air pollution is another major risk factor for the development of COPD. Communities are also exposed to a variety of other risk factors, such as low birth weight, malnutrition, severe childhood respiratory infections, occupational exposures, outdoor pollution, human-immunodeficiency virus and tuberculosis. All these factors contribute to the high burden of poor respiratory health in sub-Saharan Africa. Expert commentary: A silent growing epidemic of COPD seems to be unravelling. Therefore, prevention and intervention programs must involve all the stakeholders and start as early as possible. More research is needed to describe, define and inform treatment approaches, and natural history of biomass-related COPD.

Ease-of-use preference for the ELLIPTA® dry powder inhaler over a commonly used single-dose capsule dry powder inhaler by inhalation device-naïve Japanese volunteers aged 40 years or older

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Komase Y

2014-12-01

Full Text Available Yuko Komase,1 Akimoto Asako,2 Akihiro Kobayashi,3 Raj Sharma4 1Department of Respiratory Internal Medicine, St Marianna University School of Medicine, Yokohama City Seibu Hospital, Yokohama, Kanagawa, Japan; 2MA Respiratory Department, Development and Medical Affairs Unit, GlaxoSmithKline KK, Tokyo, Japan; 3Biomedical Data Sciences Department, GlaxoSmithKline KK, Tokyo, Japan; 4Global Respiratory Franchise Medical Department, GSK, Stockley Park, UK Background: In patients receiving inhaled medication, dissatisfaction with and difficulty in using the inhaler can affect treatment adherence. The incidence of handling errors is typically higher in the elderly than in younger people. The aim of the study was to assess inhaler preference for and handling errors with the ELLIPTA® dry powder inhaler (DPI, (GSK, compared with the established BREEZHALER™, a single-dose capsule DPI (Novartis, in inhalation device-naïve Japanese volunteers aged ≥40 years. Methods: In this open-label, nondrug interventional, crossover DPI preference study comparing the ELLIPTA DPI and BREEZHALER, 150 subjects were randomized to handle the ELLIPTA or BREEZHALER DPIs until the point of inhalation, without receiving verbal or demonstrative instruction (first attempt. Subjects then crossed over to the other inhaler. Preference was assessed using a self-completed questionnaire. Inhaler handling was assessed by a trained assessor using a checklist. Subjects did not inhale any medication in the study, so efficacy and safety were not measured. Results: The ELLIPTA DPI was preferred to the BREEZHALER by 89% of subjects (odds ratio [OR] 70.14, 95% confidence interval [CI] 33.69–146.01; P-value not applicable for this inhaler for ease of use, by 63% of subjects (OR 2.98, CI 1.87–4.77; P<0.0001 for ease of determining the number of doses remaining in the inhaler, by 91% for number of steps required, and by 93% for time needed for handling the inhaler. The BREEZHALER was

Conference report: 1st Medicon Valley Inhalation Symposium.

Science.gov (United States)

Lastow, Orest

2013-02-01

The 1st Medicon Valley Inhalation Symposium was arranged by the Medicon Valley Inhalation Consortium. It was held at the Medicon Village site, which is the former AstraZeneca site in Lund, Sweden. It was a 1-day symposium focused on inhaled drug delivery and inhalation product development. A total of 90 delegates listened to 15 speakers. The program was organized to follow the value chain of an inhalation product development. The benefits and future opportunities of inhaled drug delivery were discussed together with some new disease areas that can be targeted with inhalation. The pros and cons of the two main formulation types; dry powder and liquid formulations, were discussed by a panel. The different requirements of the drug molecules from a pharmacology, chemical and physical perspective were explained. The modeling of the physics inside an inhaler was demonstrated and the potential strategic benefits of device design were highlighted together with the many challenges of formulation manufacturing. Lung deposition mechanisms and the difficulties of the generic bioequivalence concept were discussed. Using an anatomically correct impactor inlet is a valuable tool in lung deposition predictions and the planning of clinical trials. The management of the biological material generated in clinical studies is key to successful studies.

Workplace Inhalant Abuse in Adult Female: Brief Report

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Rohit Verma

2011-01-01

Full Text Available Inhalant abuse is the purposeful inhalation of intoxicating gases and vapors for the purpose of achieving an altered mental state. With its propensity for being yet an under-recognized form of substance use, being gateway to hard substances, cross-cultural penetration crossing socioeconomic boundaries, and causing significant morbidity and mortality in early ages, the prevention of inhalant misuse is a highly pertinent issue. This clinical report identifies a newer perspective in the emergence of inhalant abuse initiation. We report a case of an adult female with late onset of inhalant dependence developing at workplace and recommend for greater awareness, prevention, and management of this expanding substance abuse problem.

Reactivation of Immunological Response in Lethally X-Irradiated Mice Treated with Isogeneic Bone Marrow

Energy Technology Data Exchange (ETDEWEB)

Stankovic, V.; Slijepcevic, M.; Hrsak, I. [Institute Ruder Boskovic, Zagreb, Yugoslavia (Croatia)

1968-08-15

Male and female C57BL/H and CBA/H mice aged 10-12 weeks were used as recipients and donors, respectively. All recipient mice were given a lethal whole-body X-irradiation dose (850 R for C57BL and 950 R for CBA mice) followed by iv injection of 10 x 106 isogeneic eosin-negative bone-marrow cells suspended in 0.5 ml of Hank's solution. The number of eosin-positive cells was less than 10%. The state of immunological responsiveness of irradiated recipients was measured at different time intervals up to 86 days after irradiation. The immune response to bacterial antigen was measured with the titre of agglutinating antibodies in serum six days after iv antigenic stimulation with a suspension of 2 x 10{sup 7} killed Salmonella typhimurium cells. The immune response to tissue antigens was evaluated by: (a) the effectiveness of the spleen cells from isologous radiation chimeric parental mice in preventing bone marrow from F{sub 1} (C57BL x CBA) hybrid donor from therapeutically affecting lethally irradiated F j recipient mice; (b) the effectiveness of the spleen cells in inducing splenom egaly in recipient F{sub 1} hybrid mice (Simonsen test). It was found that the responsiveness to bacterial antigens reappears much earlier and increases much faster than the immunological responsiveness to tissue antigens. (author)

Public crack cocaine smoking and willingness to use a supervised inhalation facility: implications for street disorder

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Qi Jiezhi

2011-02-01

Full Text Available Abstract Background The health risks of crack cocaine smoking in public settings have not been well described. We sought to identify factors associated with public crack smoking, and assess the potential for a supervised inhalation facility to reduce engagement in this behavior, in a setting planning to evaluate a medically supervised crack cocaine smoking facility. Methods Data for this study were derived from a Canadian prospective cohort of injection drug users. Using multivariate logistic regression we identified factors associated with smoking crack cocaine in public areas. Among public crack smokers we then identified factors associated with willingness to use a supervised inhalation facility. Results Among our sample of 623 people who reported crack smoking, 61% reported recently using in public locations. In multivariate analysis, factors independently associated with public crack smoking included: daily crack cocaine smoking; daily heroin injection; having encounters with police; and engaging in drug dealing. In sub analysis, 71% of public crack smokers reported willingness to use a supervised inhalation facility. Factors independently associated with willingness include: female gender, engaging in risky pipe sharing; and having encounters with police. Conclusion We found a high prevalence of public crack smoking locally, and this behavior was independently associated with encounters with police. However, a majority of public crack smokers reported being willing to use a supervised inhalation facility, and individuals who had recent encounters with police were more likely to report willingness. These findings suggest that supervised inhalation facilities offer potential to reduce street-disorder and reduce encounters with police.

Linking sub-individual and supra-individual effects in Daphnia magna exposed to sub-lethal concentration of chlorpyrifos.

Science.gov (United States)

Ferrario, Claudia; Parolini, Marco; De Felice, Beatrice; Villa, Sara; Finizio, Antonio

2018-04-01

The main objective of the present study was to investigate possible links between sub-individual and supra-individual levels (i.e. population level) biomarkers in D. magna exposed to sublethal concentrations of the insecticide chlorpyrifos (CPF). To achieve the aim, 8-day old individuals were exposed for 96 h to two environmentally relevant concentrations of CPF (50 and 250 ng/L). Sub-individual level effects were investigated by measuring the activity of antioxidant (SOD, CAT, and GPx) and detoxifying (GST) enzymes, as well as by measuring the acetylcholinesterase (AChE) inhibition. In addition, the effects at supra-individual level were assessed by using a video-tracking system and analyzing changes in swimming capabilities (i.e. percentage of activity time, distance moved, and velocity). Our data have shown that daphnids exposed to both CPF concentrations were in a condition of stress which was highlighted by changes in both sub- and supra-individual biomarkers. Moreover, our results highlighted that the lowest tested CPF concentration did not modulate the antioxidant and detoxifying enzymes, whereas, an inhibition of AChE and a decrease of some parameters related to swimming behaviour (distance moved and velocity) were noted. On the contrary, significant changes in all the sub-individual biomarkers were measured at the highest tested concentration. In addition, organisms recovered the movement capability (distance moved) and also activate a mechanism of avoidance (increased swimming velocity). On the other hand, a reduction in the percent of active time was measured and this was attributed to the energy spent by organisms to activate antioxidant and detoxifying enzymes and the mechanism of avoidance. Based on these results, our study suggests the existence of a link between sub- and supra-individual levels, as the activation or non-activation in the antioxidant and detoxifying enzymes activities can led to different modifications of the swimming behaviour

Supercritical CO{sub 2} fluid radiochromatography system used to purify [{sup 11}C]toluene for PET

Energy Technology Data Exchange (ETDEWEB)

Muller, Ryan D.; Ferrieri, Richard A. E-mail: rferrieri@bnl.gov; Gerasimov, Madina; Garza, Victor

2002-04-01

Abuse of inhalants in today's society has become such a widespread problem among today's adolescents that in many parts of the world their use exceeds that of many other illicit drugs or alcohol. Even so, little is known how such inhalants affect brain function to an extent that can lead to an abuse liability. While methodologies exist for radiolabeling certain inhalants of interest with short-lived positron emitting radioisotopes that would allow their investigation in human subjects using positron emission tomography (PET), the purification methodologies necessary to separate these volatile substances from the organic starting materials have not been developed. We've adapted supercritical fluid technology to this specific PET application by building a preparative-scale supercritical CO{sub 2} fluid radiochromatograph, and applied it to the purification of [{sup 11}C]toluene. We've demonstrated that [{sup 11}C]toluene can be separated from the starting materials using a conventional C{sub 18} HPLC column and pure supercritical CO{sub 2} fluid as the mobile phase operating at 2000 psi and 40 deg. C. We've also shown that the purified radiotracer can be quantitatively captured on Tenax GR, a solid support material, as it exits the supercritical fluid stream, thus allowing for later desorption into a 1.5% cyclodextrin solution that is suitable for human injection, or into a breathing tube for direct inhalation.

Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

Science.gov (United States)

Jahraus, Christopher D; Schemera, Bettina; Rynders, Patricia; Ramos, Melissa; Powell, Charles; Faircloth, John; Brawner, William R

2010-07-01

Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia.

Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study.

Science.gov (United States)

Geisbert, Thomas W; Lee, Amy C H; Robbins, Marjorie; Geisbert, Joan B; Honko, Anna N; Sood, Vandana; Johnson, Joshua C; de Jong, Susan; Tavakoli, Iran; Judge, Adam; Hensley, Lisa E; Maclachlan, Ian

2010-05-29

We previously showed that small interfering RNAs (siRNAs) targeting the Zaire Ebola virus (ZEBOV) RNA polymerase L protein formulated in stable nucleic acid-lipid particles (SNALPs) completely protected guineapigs when administered shortly after a lethal ZEBOV challenge. Although rodent models of ZEBOV infection are useful for screening prospective countermeasures, they are frequently not useful for prediction of efficacy in the more stringent non-human primate models. We therefore assessed the efficacy of modified non-immunostimulatory siRNAs in a uniformly lethal non-human primate model of ZEBOV haemorrhagic fever. A combination of modified siRNAs targeting the ZEBOV L polymerase (EK-1 mod), viral protein (VP) 24 (VP24-1160 mod), and VP35 (VP35-855 mod) were formulated in SNALPs. A group of macaques (n=3) was given these pooled anti-ZEBOV siRNAs (2 mg/kg per dose, bolus intravenous infusion) after 30 min, and on days 1, 3, and 5 after challenge with ZEBOV. A second group of macaques (n=4) was given the pooled anti-ZEBOV siRNAs after 30 min, and on days 1, 2, 3, 4, 5, and 6 after challenge with ZEBOV. Two (66%) of three rhesus monkeys given four postexposure treatments of the pooled anti-ZEBOV siRNAs were protected from lethal ZEBOV infection, whereas all macaques given seven postexposure treatments were protected. The treatment regimen in the second study was well tolerated with minor changes in liver enzymes that might have been related to viral infection. This complete postexposure protection against ZEBOV in non-human primates provides a model for the treatment of ZEBOV-induced haemorrhagic fever. These data show the potential of RNA interference as an effective postexposure treatment strategy for people infected with Ebola virus, and suggest that this strategy might also be useful for treatment of other emerging viral infections. Defense Threat Reduction Agency. Copyright 2010 Elsevier Ltd. All rights reserved.

The Advantages of Low-Flow Inhalational Anesthesia

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P. Torok

2005-01-01

Full Text Available The paper deals with the economical and ecological use of inhalation anesthetics in low-flow anesthesia (LFA, 1—0.5 l/ min and high-flow anesthesia (HFA, more than 2—6 l/min. Four hundred and ninety six inhalational anesthesias lasting at least 80 minutes were analyzed in each group under consideration. The concentration of inhalation anesthetics was measures in the atmosphere of an operative theatre if inhalational anesthesia lasted more than 4 hours. There is evidence for the economical and ecological benefits in the use of LFA in terms of the availability of appropriate anesthesiological equipment, monitoring, and a highly skilled anesthesiologist.

Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

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Tongtong Zhang

2018-05-01

Full Text Available Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency. Key words: Curcumin, Dry powder inhaler, Liposome, Primary lung cancer, Pulmonary delivery

Case Report: Dual nebulised antibiotics among adults with cystic fibrosis and chronic Pseudomonas infection [version 2; referees: 1 approved, 2 approved with reservations

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Nina Mann

2018-02-01

Full Text Available Pulmonary exacerbations in adults with cystic fibrosis (CF and chronic Pseudomonas aeruginosa (Psae infection are usually treated with dual intravenous antibiotics for 14 days, despite the lack of evidence for best practice. Intravenous antibiotics are commonly associated with various systemic adverse effects, including renal failure and ototoxicity. Inhaled antibiotics are less likely to cause systematic adverse effects, yet can achieve airway concentrations well above conventional minimum inhibitory concentrations. Typically one inhaled antibiotic is used at a time, but dual inhaled antibiotics (i.e. concomitant use of two different inhaled antibiotics may have synergistic effect and achieve better results in the treatment of exacerbations. We presented anecdotal evidence for the use of dual inhaled antibiotics as an acute treatment for exacerbations, in the form of a case report. A female in her early thirties with CF and chronic Psae infection improved her FEV1 by 5% and 2% with two courses of dual inhaled antibiotics to treat exacerbations in 2016. In contrast, her FEV1 changed by 2%, –2%, 0% and 2%, respectively, with four courses of dual intravenous antibiotics in 2016. Baseline FEV1 was similar prior to all six courses of treatments. The greater FEV1 improvements with dual inhaled antibiotics compared to dual intravenous antibiotics suggest the potential role of using dual inhaled antibiotics to treat exacerbations among adults with CF and chronic Psae infection, especially since a greater choice of inhaled anti-pseudomonal antibiotics is now available. A previous study in 1985 has looked at the concomitant administration of inhaled tobramycin and carbenicillin, by reconstituting antibiotics designed for parenteral administration. To our knowledge, this is the first literature to describe the concomitant use of two different antibiotics specifically developed for delivery via the inhaled route.

Virulence of invasive Salmonella Typhimurium ST313 in animal models of infection.

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Girish Ramachandran

2017-08-01

Full Text Available Salmonella Typhimurium sequence type (ST 313 produces septicemia in infants in sub-Saharan Africa. Although there are known genetic and phenotypic differences between ST313 strains and gastroenteritis-associated ST19 strains, conflicting data about the in vivo virulence of ST313 strains have been reported. To resolve these differences, we tested clinical Salmonella Typhimurium ST313 and ST19 strains in murine and rhesus macaque infection models. The 50% lethal dose (LD50 was determined for three Salmonella Typhimurium ST19 and ST313 strains in mice. For dissemination studies, bacterial burden in organs was determined at various time-points post-challenge. Indian rhesus macaques were infected with one ST19 and one ST313 strain. Animals were monitored for clinical signs and bacterial burden and pathology were determined. The LD50 values for ST19 and ST313 infected mice were not significantly different. However, ST313-infected BALB/c mice had significantly higher bacterial numbers in blood at 24 h than ST19-infected mice. ST19-infected rhesus macaques exhibited moderate-to-severe diarrhea while ST313-infected monkeys showed no-to-mild diarrhea. ST19-infected monkeys had higher bacterial burden and increased inflammation in tissues. Our data suggest that Salmonella Typhimurium ST313 invasiveness may be investigated using mice. The non-human primate results are consistent with clinical data, suggesting that ST313 strains do not cause diarrhea.

Virulence of invasive Salmonella Typhimurium ST313 in animal models of infection.

Science.gov (United States)

Ramachandran, Girish; Panda, Aruna; Higginson, Ellen E; Ateh, Eugene; Lipsky, Michael M; Sen, Sunil; Matson, Courtney A; Permala-Booth, Jasnehta; DeTolla, Louis J; Tennant, Sharon M

2017-08-01

Salmonella Typhimurium sequence type (ST) 313 produces septicemia in infants in sub-Saharan Africa. Although there are known genetic and phenotypic differences between ST313 strains and gastroenteritis-associated ST19 strains, conflicting data about the in vivo virulence of ST313 strains have been reported. To resolve these differences, we tested clinical Salmonella Typhimurium ST313 and ST19 strains in murine and rhesus macaque infection models. The 50% lethal dose (LD50) was determined for three Salmonella Typhimurium ST19 and ST313 strains in mice. For dissemination studies, bacterial burden in organs was determined at various time-points post-challenge. Indian rhesus macaques were infected with one ST19 and one ST313 strain. Animals were monitored for clinical signs and bacterial burden and pathology were determined. The LD50 values for ST19 and ST313 infected mice were not significantly different. However, ST313-infected BALB/c mice had significantly higher bacterial numbers in blood at 24 h than ST19-infected mice. ST19-infected rhesus macaques exhibited moderate-to-severe diarrhea while ST313-infected monkeys showed no-to-mild diarrhea. ST19-infected monkeys had higher bacterial burden and increased inflammation in tissues. Our data suggest that Salmonella Typhimurium ST313 invasiveness may be investigated using mice. The non-human primate results are consistent with clinical data, suggesting that ST313 strains do not cause diarrhea.

Clinical and laboratory profile of different dengue sub types in dengue virus infection

OpenAIRE

Niloy Gan Chaudhuri; S. Vithyavathi; K. Sankar

2016-01-01

Background: Dengue infection, an arthropod-borne viral hemorrhagic fever is caused by Arbovirus of Flavivirus genus and transmitted by Aedes aegypti, Aedes albopictus. Liver involvement in dengue fever is manifested by the elevation of transaminases representing reactive hepatitis, due to direct attack of virus itself or the use of hepatotoxic drugs. The objective of the study was to investigate clinical and laboratory profile of different dengue sub type's patients admitted for dengue fever....

Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

Energy Technology Data Exchange (ETDEWEB)

Johnson, Reed F., E-mail: johnsonreed@mail.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Via, Laura E. [Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Kumar, Mia R.; Cornish, Joseph P. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Solomon, Jeffrey [Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD (United States); Johnson, Joshua C. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Pickel, James [Transgenic Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, MD (United States); Hensley, Lisa E. [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD (United States)

2015-11-15

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.

Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or MERS-CoV EMC/2012 isolates does not result in lethal disease

International Nuclear Information System (INIS)

Johnson, Reed F.; Via, Laura E.; Kumar, Mia R.; Cornish, Joseph P.; Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R.; Solomon, Jeffrey; Johnson, Joshua C.; Pickel, James; Hensley, Lisa E.; Jahrling, Peter B.

2015-01-01

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-CoV-EMC/2012, MERS-CoV-Jordan-n3/2012, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. - Highlights: • Common marmosets infected with MERS-EMC and MERS-JOR did not develop lethal disease. • Infected subjects developed transient signs of clinical disease. • CT indicated few differences between the infected and control groups. • Marmosets do not faithfully replicate human MERS pathogenesis.

Cytotoxicity and Hsp 70 induction in Hep G2 cells in response to zearalenone and cytoprotection by sub-lethal heat shock

International Nuclear Information System (INIS)

Hassen, Wafa; Golli, Emna El; Baudrimont, Isabelle; Mobio, A. Theophile; Ladjimi, M. Moncef; Creppy, E. Edmond; Bacha, Hassen

2005-01-01

Zearalenone (ZEN) is a mycotoxin with several adverse effects in laboratory and domestic animals. The mechanism of ZEN toxicity that involves mainly binding to oestrogen receptors and inhibition of macromolecules synthesis is not fully understood. Using human hepatocytes Hep G2 cells as a model, the aim of this work was (i) to investigate the ability of ZEN to induce heat shock proteins Hsp 70 and (ii) to find out the mechanisms of ZEN cytotoxicity by examining cell proliferation and protein synthesis. Our study demonstrated that ZEN induces Hsp 70 expression in a time and dose-dependant manner; this induction occurs at non-cytotoxic concentrations, it could be therefore considered as a biomarker of toxicity. A cytoprotective effect of Hsp 70 was elicited when Hep G2 cells were exposed to Sub-Lethal heat shock prior to ZEN treatment and evidenced by a reduced ZEN cytolethality. This cytoprotection suggests that Hsp 70 may constitute an important cellular defence mechanism. Finally, our data show that ZEN is cytotoxic in Hep G2 cells by inhibiting cell proliferation and total protein synthesis and pointed out oxidative damage as possible pathway involved in ZEN toxicity; however, other investigations are needed to further confirm Zen induced oxidative stress

Toxicity levels to humans during acute exposure to hydrogen fluoride - An update

Energy Technology Data Exchange (ETDEWEB)

Halton, D M

1995-09-01

In March 1993, the Atomic Energy Control Board (AECB) commissioned and update of a 1984 review on the acute toxicity of hydrogen fluoride (HF). The study places particular emphasis on the effects of inhalation of gaseous HF and is divided into two main parts: a literature review and a lethal concentration (LC) estimation. The literature review summarizes data under four categories: animal studies, controlled human studies, community exposure, and industrial exposure. Data in these areas were critically reviewed for their relevance to lethal concentrations at LC{sub LO}, LC{sub 10} and LC{sub 50} levels that were derived in the 1984 report. In the last ten years, only one relevant animal study has been published. No new controlled human studies were found but a community exposure incident was reported. There were three new industrial/accidental exposures reported since 1984. Evaluation of new data does not change the lethal concentration estimates made in the 1984 report, but does indicate the absence of appropriate models to estimate the lethality of irritant and corrosive gases. In the last 10 years, much literature on the evaluation of major hazards has been published and suggests that such assessments are of growing political, economic and social importance. Numerous articles have been published on the acute toxicity of HF from skin contact and chronic toxicity from repeated airborne exposure. These publications offer important insights into the nature of HF toxicity. Several avenues of investigative research are suggested. (author). 55 refs., 4 tabs.

Inhaler devices - from theory to practice

DEFF Research Database (Denmark)

Sanchis, Joaquin; Corrigan, Chris; Levy, Mark L

2013-01-01

This brief overview of the factors determining lung deposition of aerosols provides background information required by health care providers when instructing patients to use their prescribed inhalers. We discuss differences in the optimal inhalation manoeuvres for each type of aerosol generator a...

The HIV-poverty thesis re-examined: poverty, wealth or inequality as a social determinant of HIV infection in sub-Saharan Africa?

Science.gov (United States)

Fox, Ashley M

2012-07-01

Although health is generally believed to improve with higher wealth, research on HIV in sub-Saharan Africa has shown otherwise. Whereas researchers and advocates have frequently advanced poverty as a social determinant that can help to explain sub-Saharan Africa's disproportionate burden of HIV infection, recent evidence from population surveys suggests that HIV infection is higher among wealthier individuals. Furthermore, wealthier countries in Africa have experienced the fastest growing epidemics. Some researchers have theorized that inequality in wealth may be more important than absolute wealth in explaining why some countries have higher rates of infection and rapidly increasing epidemics. Studies taking a longitudinal approach have further suggested a dynamic process whereby wealth initially increases risk for HIV acquisition and later becomes protective. Prior studies, conducted exclusively at either the individual or the country level, have neither attempted to disentangle the effects of absolute and relative wealth on HIV infection nor to look simultaneously at different levels of analysis within countries at different stages in their epidemics. The current study used micro-, meso- and macro-level data from Demographic and Health Surveys (DHS) across 170 regions within sixteen countries in sub-Saharan Africa to test the hypothesis that socioeconomic inequality, adjusted for absolute wealth, is associated with greater risk of HIV infection. These analyses reveal that inequality trumps wealth: living in a region with greater inequality in wealth was significantly associated with increased individual risk of HIV infection, net of absolute wealth. The findings also reveal a paradox that supports a dynamic interpretation of epidemic trends: in wealthier regions/countries, individuals with less wealth were more likely to be infected with HIV, whereas in poorer regions/countries, individuals with more wealth were more likely to be infected with HIV. These

Swimming speed alteration of Artemia sp. and Brachionus plicatilis as a sub-lethal behavioural end-point for ecotoxicological surveys.

Science.gov (United States)

Garaventa, Francesca; Gambardella, Chiara; Di Fino, Alessio; Pittore, Massimiliano; Faimali, Marco

2010-03-01

In this study, we investigated the possibility to improve a new behavioural bioassay (Swimming Speed Alteration test-SSA test) using larvae of marine cyst-forming organisms: e.g. the brine shrimp Artemia sp. and the rotifer Brachionus plicatilis. Swimming speed was investigated as a behavioural end-point for application in ecotoxicology studies. A first experiment to analyse the linear swimming speed of the two organisms was performed to verify the applicability of the video-camera tracking system, here referred to as Swimming Behavioural Recorder (SBR). A second experiment was performed, exposing organisms to different toxic compounds (zinc pyrithione, Macrotrol MT-200, and Eserine). Swimming speed alteration was analyzed together with mortality. The results of the first experiment indicate that SBR is a suitable tool to detect linear swimming speed of the two organisms, since the values have been obtained in accordance with other studies using the same organisms (3.05 mm s(-1) for Artemia sp. and 0.62 mm s(-1) for B. plicatilis). Toxicity test results clearly indicate that swimming speed of Artemia sp. and B. plicatilis is a valid behavioural end-point to detect stress at sub-lethal toxic substance concentrations. Indeed, alterations in swimming speed have been detected at toxic compound concentrations as low as less then 0.1-5% of their LC(50) values. In conclusion, the SSA test with B. plicatilis and Artemia sp. can be a good behavioural integrated output for application in marine ecotoxicology and environmental monitoring programs.

Biodiversity of soil bacteria exposed to sub-lethal concentrations of phosphonium-based ionic liquids: Effects of toxicity and biodegradation.

Science.gov (United States)

Sydow, Mateusz; Owsianiak, Mikołaj; Framski, Grzegorz; Woźniak-Karczewska, Marta; Piotrowska-Cyplik, Agnieszka; Ławniczak, Łukasz; Szulc, Alicja; Zgoła-Grześkowiak, Agnieszka; Heipieper, Hermann J; Chrzanowski, Łukasz

2018-01-01

Little is known about the effect of ionic liquids (ILs) on the structure of soil microbial communities and resulting biodiversity. Therefore, we studied the influence of six trihexyl(tetradecyl)phosphonium ILs (with either bromide or various organic anions) at sublethal concentrations on the structure of microbial community present in an urban park soil in 100-day microcosm experiments. The biodiversity decreased in all samples (Shannon's index decreased from 1.75 down to 0.74 and OTU's number decreased from 1399 down to 965) with the largest decrease observed in the microcosms spiked with ILs where biodegradation extent was higher than 80%. (i.e. [P 66614 ][Br] and [P 66614 ][2,4,4]). Despite this general decrease in biodiversity, which can be explained by ecotoxic effect of the ILs, the microbial community in the microcosms was enriched with Gram-negative hydrocarbon-degrading genera e.g. Sphingomonas. It is hypothesized that, in addition to toxicity, the observed decrease in biodiversity and change in the microbial community structure may be explained by the primary biodegradation of the ILs or their metabolites by the mentioned genera, which outcompeted other microorganisms unable to degrade ILs or their metabolites. Thus, the introduction of phosphonium-based ILs into soils at sub-lethal concentrations may result not only in a decrease in biodiversity due to toxic effects, but also in enrichment with ILs-degrading bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhaled /sup 147/Pm and/or total-body gamma radiation: Early mortality and morbidity in rats

Energy Technology Data Exchange (ETDEWEB)

Filipy, R.E.; Lauhala, K.E.; McGee, D.R.; Cannon, W.C.; Buschbom, R.L.; Decker, J.R.; Kuffel, E.G.; Park, J.F.; Ragan, H.A.; Yaniv, S.S.; Scott, B.R.

1989-05-01

Rats were given doses of /sup 60/Co gamma radiation and/or lung burdens of /sup 147/Pm (in fused aluminosilicate particles) within lethal ranges in an experiment to determine and compare morbidity and mortality responses for the radiation insults within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Acute mortality and morbidity from inhaled promethium were caused primarily by radiation pneumonitis and pulmonary fibrosis that occurred more than 53 days after exposure. Acute mortality and morbidity from total-body gamma irradiation occurred within 30 days of exposure and resulted from the bone-marrow radiation syndrome. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell levels and by reduced body weight gain in animals that survived the acute gamma radiation syndrome. Inhaled promethium caused a loss of body weight and diminished pulmonary function, but its only effect on blood cell levels was lymphocytopenia. Combined gamma irradiation and promethium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Promethium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the later effect of promethium lung burdens. 70 refs., 68 figs., 21 tabs.

Health effects of inhaled gasoline engine emissions.

Science.gov (United States)

McDonald, Jacob D; Reed, Matthew D; Campen, Matthew J; Barrett, Edward G; Seagrave, JeanClare; Mauderly, Joe L

2007-01-01

Despite their prevalence in the environment, and the myriad studies that have shown associations between morbidity or mortality with proximity to roadways (proxy for motor vehicle exposures), relatively little is known about the toxicity of gasoline engine emissions (GEE). We review the studies conducted on GEE to date, and summarize the findings from each of these studies. While there have been several studies, most of the studies were conducted prior to 1980 and thus were not conducted with contemporary engines, fuels, and driving cycles. In addition, many of the biological assays conducted during those studies did not include many of the assays that are conducted on contemporary inhalation exposures to air pollutants, including cardiovascular responses and others. None of the exposures from these earlier studies were characterized at the level of detail that would be considered adequate today. A recent GEE study was conducted as part of the National Environmental Respiratory Center (www.nercenter.org). In this study several in-use mid-mileage General Motors (Chevrolet S-10) vehicles were purchased and utilized for inhalation exposures. An exposure protocol was developed where engines were operated with a repeating California Unified Driving Cycle with one cold start per day. Two separate engines were used to provide two cold starts over a 6-h inhalation period. The exposure atmospheres were characterized in detail, including detailed chemical and physical analysis of the gas, vapor, and particle phase. Multiple rodent biological models were studied, including general toxicity and inflammation (e.g., serum chemistry, lung lavage cell counts/differentials, cytokine/chemokine analysis, histopathology), asthma (adult and in utero exposures with pulmonary function and biochemical analysis), cardiovascular effects (biochemical and electrocardiograph changes in susceptible rodent models), and susceptibility to infection (Pseudomonas bacteria challenge). GEE resulted in

Long-term effects of aluminium dust inhalation.

Science.gov (United States)

Peters, Susan; Reid, Alison; Fritschi, Lin; de Klerk, Nicholas; Musk, A W Bill

2013-12-01

During the 1950s and 1960s, aluminium dust inhalation was used as a potential prophylaxis against silicosis in underground miners, including in Australia. We investigated the association between aluminium dust inhalation and cardiovascular, cerebrovascular and Alzheimer's diseases in a cohort of Australian male underground gold miners. We additionally looked at pneumoconiosis mortality to estimate the effect of the aluminium therapy. SMRs and 95% CI were calculated to compare mortality of the cohort members with that of the Western Australian male population (1961-2009). Internal comparisons on duration of aluminium dust inhalation were examined using Cox regression. Aluminium dust inhalation was reported for 647 out of 1894 underground gold miners. During 42 780 person-years of follow-up, 1577 deaths were observed. An indication of increased mortality of Alzheimer's disease among miners ever exposed to aluminium dust was found (SMR=1.38), although it was not statistically significant (95% CI 0.69 to 2.75). Rates for cardiovascular and cerebrovascular death were above population levels, but were similar for subjects with or without a history of aluminium dust inhalation. HRs suggested an increasing risk of cardiovascular disease with duration of aluminium dust inhalation (HR=1.02, 95% CI 1.00 to 1.04, per year of exposure). No difference in the association between duration of work underground and pneumoconiosis was observed between the groups with or without aluminium dust exposure. No protective effect against silicosis was observed from aluminium dust inhalation. Conversely, exposure to aluminium dust may possibly increase the risk of cardiovascular disease and dementia of the Alzheimer's type.

Assessing inhalation injury in the emergency room

Directory of Open Access Journals (Sweden)

Tanizaki S

2015-07-01

Full Text Available Shinsuke Tanizaki Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan Abstract: Respiratory tract injuries caused by inhalation of smoke or chemical products are related to significant morbidity and mortality. While many strategies have been built up to manage cutaneous burn injuries, few logical diagnostic strategies for patients with inhalation injuries exist and almost all treatment is supportive. The goals of initial management are to ensure that the airway allows adequate oxygenation and ventilation and to avoid ventilator-induced lung injury and substances that may complicate subsequent care. Intubation should be considered if any of the following signs exist: respiratory distress, stridor, hypoventilation, use of accessory respiratory muscles, blistering or edema of the oropharynx, or deep burns to the face or neck. Any patients suspected to have inhalation injuries should receive a high concentration of supplemental oxygen to quickly reverse hypoxia and to displace carbon monoxide from protein binding sites. Management of carbon monoxide and cyanide exposure in smoke inhalation patients remains controversial. Absolute indications for hyperbaric oxygen therapy do not exist because there is a low correlation between carboxyhemoglobin levels and the severity of the clinical state. A cyanide antidote should be administered when cyanide poisoning is clinically suspected. Although an ideal approach for respiratory support of patients with inhalation injuries do not exist, it is important that they are supported using techniques that do not further exacerbate respiratory failure. A well-organized strategy for patients with inhalation injury is critical to reduce morbidity and mortality. Keywords: inhalation injury, burn, carbon monoxide poisoning, cyanide poisoning

Inhaled plutonium oxide in dogs

International Nuclear Information System (INIS)

Anon.

1981-01-01

This project is concerned with long-term experiments to determine the life-span dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. The tissue distribution of plutonium, radiation effects in the lung and hematologic changes in plutonium-exposed beagles with lung tumors were evaluated

49 CFR 172.555 - POISON INHALATION HAZARD placard.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition to...

Lethal effects of solar radiation in proficient and deficient bacteria in repair systems

International Nuclear Information System (INIS)

Sousa Neto, A. de.

1980-01-01

A study of the lethal action of solar radiation on strains of E.coli K12, proficient or deficient in repair systems, as well as the wild type strain gene products are involved in repair of damage induced by solar radiation. The inactivation of the various bacterial strains (normalized to a dose equivalent to radiation at a wavelength 254 nm) suggests that the more energetic wavelengths of the solar spectrum (290-320 nm) could be responsible for the primary damage that occurs in the DNA. The reduction in the shoulder of the survival curve in wild type strains in indicative of induction of sub-lethal damage in this region of the curve. Analysing solar inactivation curves of the bacterial strains (normalised by spore dosimetry) together with those of the same strains irradiated with UV at 254 nm, it was evident that 254 nm is not the ideal wavelength for comparison. This analysis also indicated that in addition to damage to DNA, other factors are involved in the solar radiation inactivation of wild type strains. (author)

The potential of TiO<sub>2sub> nanoparticles as carriers for cadmium uptake in Lumbriculus variegatus and Daphnia magna

DEFF Research Database (Denmark)

Hartmann, Nanna Isabella Bloch; Legros, Samuel; Von der Kammer, Frank

2012-01-01

variegatus, was investigated both in the absence and presence of titanium dioxide (TiO2) nanoparticles (P25 Evonic Degussa, d: 30nm). The uptake of cadmium in sub-lethal concentrations was also studied in the absence and presence of 2mg/L TiO2 nanoparticles. Formation of larger nanoparticles aggregates...

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge

Science.gov (United States)

Konduru, Krishnamurthy; Shurtleff, Amy C.; Bradfute, Steven B.; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

2016-01-01

Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105−106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

Science.gov (United States)

Konduru, Krishnamurthy; Shurtleff, Amy C; Bradfute, Steven B; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

2016-01-01

Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

Directory of Open Access Journals (Sweden)

Krishnamurthy Konduru

Full Text Available Ebola virus (EBOV, a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data

49 CFR 172.429 - POISON INHALATION HAZARD label.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to complying...

Interferon-γ Inhibits Ebola Virus Infection.

Directory of Open Access Journals (Sweden)

Bethany A Rhein

Full Text Available Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

Interferon-γ Inhibits Ebola Virus Infection.

Science.gov (United States)

Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

2015-01-01

Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

A Bioprocessed Polysaccharide from Lentinus edodes Mycelia Cultures with Turmeric Protects Chicks from a Lethal Challenge of Salmonella Gallinarum.

Science.gov (United States)

Han, Dalmuri; Lee, Hyung Tae; Lee, June Bong; Kim, Yongbaek; Lee, Sang Jong; Yoon, Jang Won

2017-02-01

Our previous studies demonstrated that a bioprocessed polysaccharide (BPP) isolated from Lentinus edodes mushroom mycelia cultures supplemented with black rice bran can protect mice against Salmonella lipopolysaccharide-induced endotoxemia and reduce the mortality from Salmonella Typhimurium infection through upregulated T-helper 1 immunity. Here, we report that a BPP from L. edodes mushroom mycelia liquid cultures supplemented with turmeric (referred to as BPP-turmeric) alters chicken macrophage responses against avian-adapted Salmonella Gallinarum and protects chicks against a lethal challenge from Salmonella Gallinarum. In vitro analyses revealed that the water extract of BPP-turmeric (i) changed the protein expression or secretion profile of Salmonella Gallinarum, although it was not bactericidal, (ii) reduced the phagocytic activity of the chicken-derived macrophage cell line HD-11 when infected with Salmonella Gallinarum, and (iii) significantly activated the transcription expression of interleukin (IL)-1β, IL-10, tumor necrosis factor α, and inducible nitric oxide synthase in response to various Salmonella infections, whereas it repressed that of IL-4, IL-6, interferon-β, and interferon-γ. We also found that BPP-turmeric (0.1 g/kg of feed) as a feed additive provided significant protection to 1-day-old chicks infected with a lethal dose of Salmonella Gallinarum. Collectively, these results imply that BPP-turmeric contains biologically active component(s) that protect chicks against Salmonella Gallinarum infection, possibly by regulating macrophage immune responses. Further studies are needed to evaluate the potential efficacy of BPP-turmeric as a livestock feed additive for the preharvest control of fowl typhoid or foodborne salmonellosis.

Personal exposure to inhalable cement dust among construction workers

International Nuclear Information System (INIS)

Peters, Susan; Kromhout, Hans; Thomassen, Yngvar; Fechter-Rink, Edeltraud

2009-01-01

A case study was carried out in 2006-2007 to assess the actual cement dust exposure among construction workers involved in a full-scale construction project and as a comparison among workers involved in various stages of cement and concrete production. Full-shift personal exposure measurements were performed for several job types. Inhalable dust and cement dust (based on analysis of elemental calcium) concentrations were determined. Inhalable dust exposures at the construction site ranged from 0.05 to 34 mg/m3, with a mean concentration of 1.0 mg/m3. For inhalable cement dust mean exposure was 0.3 mg/m3 (range 0.02-17 mg/m3). Reinforcement and pouring workers had the lowest average concentrations. Inhalable dust levels in the ready-mix and pre-cast concrete plants were, on average, below 0.5 mg/m3 for inhalable dust and below 0.2 mg/m3 for inhalable cement dust. Highest dust concentrations were measured in cement production, particularly during cleaning tasks (inhalable dust GM=55 mg/m3; inhalable cement dust GM=33 mg/m3) at which point the workers wore personal protective equipment. Elemental measurements showed highest but very variable cement percentages in the cement plant and very low percentages of cement during reinforcement work and pouring.

Inducible Costimulator Expressing T Cells Promote Parasitic Growth During Blood Stage Plasmodium berghei ANKA Infection

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Gajendra M. Jogdand

2018-05-01

Full Text Available The lethality of blood stage Plasmodium berghei ANKA (PbA infection is associated with the expression of T-bet and production of cytokine IFN-γ. Expression of inducible costimulator (ICOS and its downstream signaling has been shown to play a critical role in the T-bet expression and IFN-γ production. Although earlier studies have examined the role of ICOS in the control of acute blood-stage infection of Plasmodium chabaudi chabaudi AS (a non-lethal model of malaria infection, its significance in the lethal blood-stage of PbA infection remains unclear. Thus, to address the seminal role of ICOS in lethal blood-stage of PbA infection, we treated PbA-infected mice with anti-ICOS antibody and observed that these mice survived longer than their infected counterparts with significantly lower parasitemia. Anti-ICOS treatment notably depleted ICOS expressing CD4+ and CD8+ T cells with a concurrent reduction in plasma IFN-γ, which strongly indicated that ICOS expressing T cells are major IFN-γ producers. Interestingly, we observed that while ICOS expressing CD4+ and CD8+ T cells produced IFN-γ, ICOS−CD8+ T cells were also found to be producers of IFN-γ. However, we report that ICOS+CD8+ T cells were higher producers of IFN-γ than ICOS−CD8+ T cells. Moreover, correlation of ICOS expression with IFN-γ production in ICOS+IFN-γ+ T cell population (CD4+ and CD8+ T cells suggested that ICOS and IFN-γ could positively regulate each other. Further, master transcription factor T-bet importantly involved in regulating IFN-γ production was also found to be expressed by ICOS expressing CD4+ and CD8+ T cells during PbA infection. As noted above with IFN-γ and ICOS, a positive correlation of expression of ICOS with the transcription factor T-bet suggested that both of them could regulate each other. Taken together, our results depicted the importance of ICOS expressing CD4+ and CD8+ T cells in malaria parasite growth and lethality through IFN

Evaluation of Inhaler Techniques Among Asthma Patients Seen in ...

African Journals Online (AJOL)

hanumantp

Drug inhalation is an important and a common mode of .... to evaluate the use of inhaler technique among asthma patients in a .... The median duration of the use of the inhalers is 24 ..... Scalabrini A, Cukier A. Incorrect application technique of.

Mining of lethal recessive genetic variation in Danish cattle

DEFF Research Database (Denmark)

Das, Ashutosh

2015-01-01

in fertility. The primary objective of this PhD projekt was to identify recessive lethal gentic variants in the main Danish dairy cattle breed. Holstein-Friesian utilzing next generation sequencing (NGS) data. This study shows a potential for the use of the NGS-based reverse genetic approach in identifying...... lethal or semi-lethal recessive gentic variation...

Personal exposure to inhalable cement dust among construction workers.

Science.gov (United States)

Peters, Susan; Thomassen, Yngvar; Fechter-Rink, Edeltraud; Kromhout, Hans

2009-01-01

Objective- A case study was carried out to assess cement dust exposure and its determinants among construction workers and for comparison among workers in cement and concrete production.Methods- Full-shift personal exposure measurements were performed and samples were analysed for inhalable dust and its cement content. Exposure variability was modelled with linear mixed models.Results- Inhalable dust concentrations at the construction site ranged from 0.05 to 34 mg/m(3), with a mean of 1.0 mg/m(3). Average concentration for inhalable cement dust was 0.3 mg/m(3) (GM; range 0.02-17 mg/m(3)). Levels in the ready-mix and pre-cast concrete plants were on average 0.5 mg/m(3) (GM) for inhalable dust and 0.2 mg/m(3) (GM) for inhalable cement dust. Highest concentrations were measured in cement production, particularly during cleaning tasks (inhalable dust GM = 55 mg/m(3); inhalable cement dust GM = 33 mg/m(3)) at which point the workers wore personal protective equipment. Elemental measurements showed highest but very variable cement percentages in the cement plant and very low percentages during reinforcement work and pouring. Most likely other sources were contributing to dust concentrations, particularly at the construction site. Within job groups, temporal variability in exposure concentrations generally outweighed differences in average concentrations between workers. 'Using a broom', 'outdoor wind speed' and 'presence of rain' were overall the most influential factors affecting inhalable (cement) dust exposure.Conclusion- Job type appeared to be the main predictor of exposure to inhalable (cement) dust at the construction site. Inhalable dust concentrations in cement production plants, especially during cleaning tasks, are usually considerably higher than at the construction site.

Respirable versus inhalable dust sampling

International Nuclear Information System (INIS)

Hondros, J.

1987-01-01

The ICRP uses a total inhalable dust figure as the basis of calculations on employee lung dose. This paper was written to look at one aspect of the Olympic Dam dust situation, namely, the inhalable versus respirable fraction of the dust cloud. The results of this study will determine whether it is possible to use respirable dust figures, as obtained during routine monitoring to help in the calculations of employee exposure to internal radioactive contaminants

Economic considerations in the use of inhaled anesthetic agents.

Science.gov (United States)

Golembiewski, Julie

2010-04-15

To describe the components of and factors contributing to the costs of inhaled anesthesia, basis for quantifying and comparing these costs, and practical strategies for performing pharmacoeconomic analyses and reducing the costs of inhaled anesthetic agents. Inhaled anesthesia can be costly, and some of the variable costs, including fresh gas flow rates and vaporizer settings, are potential targets for cost savings. The use of a low fresh gas flow rate maximizes rebreathing of exhaled anesthetic gas and is less costly than a high flow rate, but it provides less control of the level of anesthesia. The minimum alveolar concentration (MAC) hour is a measure that can be used to compare the cost of inhaled anesthetic agents at various fresh gas flow rates. Anesthesia records provide a sense of patterns of inhaled anesthetic agent use, but the amount of detail can be limited. Cost savings have resulted from efforts to reduce the direct costs of inhaled anesthetic agents, but reductions in indirect costs through shortened times to patient recovery and discharge following the judicious use of these agents are more difficult to demonstrate. The patient case mix, fresh gas flow rates typically used during inhaled anesthesia, availability and location of vaporizers, and anesthesia care provider preferences and practices should be taken into consideration in pharmacoeconomic evaluations and recommendations for controlling the costs of inhaled anesthesia. Understanding factors that contribute to the costs of inhaled anesthesia and considering those factors in pharmacoeconomic analyses and recommendations for use of these agents can result in cost savings.

Cell lethality after selective irradiation of the DNA replication fork

International Nuclear Information System (INIS)

Hofer, K.G.; Warters, R.L.

1985-01-01

It has been suggested that nascent DNA located at the DNA replication fork may exhibit enhanced sensitivity to radiation damage. To evaluate this hypothesis, Chinese hamster ovary cells (CHO) were labeled with 125 I-iododeoxyuridine ( 125 IUdR) either in the presence or absence of aphidicolin. Aphidicolin (5 μg/ml) reduced cellular 125 IUdR incorporation to 3-5% of the control value. The residual 125 I incorporation appeared to be restricted to low molecular weight (sub-replicon sized) fragments of DNA which were more sensitive to micrococcal nuclease attack and less sensitive to high salt DNase I digestion than randomly labeled DNA. These findings suggest that DNA replicated in the presence of aphidicolin remains localized at the replication fork adjacent to the nuclear matrix. Based on these observations an attempt was made to compare the lethal consequences of 125 I decays at the replication fork to that of 125 I decays randomly distributed over the entire genome. Regardless of the distribution of decay events, all treatment groups exhibited identical dose-response curves (D 0 : 101 125 I decays/cell). Since differential irradiation of the replication complex did not result in enhanced cell lethality, it can be concluded that neither the nascent DNA nor the protein components (replicative enzymes, nuclear protein matrix) associated with the DNA replication site constitute key radiosensitive targets within the cellular genome. (orig.)

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma ...

The use of multiple respiratory inhalers requiring different inhalation techniques has an adverse effect on COPD outcomes

Directory of Open Access Journals (Sweden)

Bosnic-Anticevich S

2016-12-01

Full Text Available Sinthia Bosnic-Anticevich,1 Henry Chrystyn,2 Richard W Costello,3,4 Myrna B Dolovich,5 Monica J Fletcher,6 Federico Lavorini,7 Roberto Rodríguez-Roisin,8 Dermot Ryan,9,10 Simon Wan Yau Ming,2 David B Price2,11 1Woolcock Institute of Medical Research, School of Medical Sciences, University of Sydney and Sydney Local Health District, Sydney, NSW, Australia; 2Observational and Pragmatic Research Institute Pte Ltd, Singapore; 3RCSI Medicine, Royal College of Surgeons, 4RCSI Education & Research Centre, Beaumont Hospital, Beaumont, Dublin, Ireland; 5Department of Medicine, Respirology, McMaster University, ON, Canada; 6Education for Health, Warwick, UK; 7Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 8Respiratory Institute, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; 9Optimum Patient Care, Cambridge, 10Centre for Population Health Sciences, University of Edinburgh, Edinburgh, 11Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: Patients with COPD may be prescribed multiple inhalers as part of their treatment regimen, which require different inhalation techniques. Previous literature has shown that the effectiveness of inhaled treatment can be adversely affected by incorrect inhaler technique. Prescribing a range of device types could worsen this problem, leading to poorer outcomes in COPD patients, but the impact is not yet known. Aims: To compare clinical outcomes of COPD patients who use devices requiring similar inhalation technique with those who use devices with mixed techniques. Methods: A matched cohort design was used, with 2 years of data from the Optimum Patient Care Research Database. Matching variables were established from a baseline year of follow-up data, and two cohorts were formed: a “similar-devices cohort” and a “mixed-devices cohort”. COPD-related events were recorded during an outcome year of follow-up. The primary outcome measure was an

Characterization of Lethal Zika Virus Infection in AG129 Mice.

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Matthew T Aliota

2016-04-01

Full Text Available Mosquito-borne Zika virus (ZIKV typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other diseases. The detection of ZIKV in fetal brain tissue supports this hypothesis. Because human infections with ZIKV historically have remained sporadic and, until recently, have been limited to small-scale epidemics, neither the disease caused by ZIKV nor the molecular determinants of virulence and/or pathogenicity have been well characterized. Here, we describe a small animal model for wild-type ZIKV of the Asian lineage.Using mice deficient in interferon α/β and Ɣ receptors (AG129 mice, we report that these animals were highly susceptible to ZIKV infection and disease, succumbing within seven to eight days. Rapid viremic dissemination was observed in visceral organs and brain; but only was associated with severe pathologies in the brain and muscle. Finally, these results were consistent across challenge routes, age of mice, and inoculum doses. These data represent a mouse model for ZIKV that is not dependent on adapting ZIKV to intracerebral passage in mice.Foot pad injection of AG129 mice with ZIKV represents a biologically relevant model for studying ZIKV infection and disease development following wild-type virus inoculation without the requirement for adaptation of the virus or intracerebral delivery of the virus. This newly developed Zika disease model can be exploited to identify determinants of ZIKV virulence and reveal molecular mechanisms that control the virus-host interaction, providing a framework for rational design of acute phase therapeutics and for vaccine efficacy testing.

HIV infection does not disproportionately affect the poorer in sub-Saharan Africa.

Science.gov (United States)

Mishra, Vinod; Assche, Simona Bignami-Van; Greener, Robert; Vaessen, Martin; Hong, Rathavuth; Ghys, Peter D; Boerma, J Ties; Van Assche, Ari; Khan, Shane; Rutstein, Shea

2007-11-01

Wealthier populations do better than poorer ones on most measures of health status, including nutrition, morbidity and mortality, and healthcare utilization. This study examines the association between household wealth status and HIV serostatus to identify what characteristics and behaviours are associated with HIV infection, and the role of confounding factors such as place of residence and other risk factors. Data are from eight national surveys in sub-Saharan Africa (Kenya, Ghana, Burkina Faso, Cameroon, Tanzania, Lesotho, Malawi, and Uganda) conducted during 2003-2005. Dried blood spot samples were collected and tested for HIV, following internationally accepted ethical standards and laboratory procedures. The association between household wealth (measured by an index based on household ownership of durable assets and other amenities) and HIV serostatus is examined using both descriptive and multivariate statistical methods. In all eight countries, adults in the wealthiest quintiles have a higher prevalence of HIV than those in the poorer quintiles. Prevalence increases monotonically with wealth in most cases. Similarly for cohabiting couples, the likelihood that one or both partners is HIV infected increases with wealth. The positive association between wealth and HIV prevalence is only partly explained by an association of wealth with other underlying factors, such as place of residence and education, and by differences in sexual behaviour, such as multiple sex partners, condom use, and male circumcision. In sub-Saharan Africa, HIV prevalence does not exhibit the same pattern of association with poverty as most other diseases. HIV programmes should also focus on the wealthier segments of the population.

Inhalation drug delivery devices: technology update

Directory of Open Access Journals (Sweden)

Ibrahim M

2015-02-01

Full Text Available Mariam Ibrahim, Rahul Verma, Lucila Garcia-ContrerasDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided.Keywords: pulmonary delivery, asthma, nebulizers, metered dose inhaler, dry powder inhaler

Inhaled ciclesonide versus inhaled budesonide or inhaled beclomethasone or inhaled fluticasone for chronic asthma in adults: a systematic review

Directory of Open Access Journals (Sweden)

Halpin David MG

2006-06-01

Full Text Available Abstract Background Ciclesonide is a new inhaled corticosteroids licensed for the prophylactic treatment of persistent asthma in adults. Currently beclomethasone dipropionate, budesonide and fluticasone propionate are the most commonly prescribed inhaled corticosteroids for the treatment of asthma but there has been no systematic review comparing the effectiveness and safety ciclesonide to these agents. We therefore aimed to systematically review published randomised controlled trials of the effectiveness and safety of ciclesonide compared to alternative inhaled corticosteroids in people with asthma. Methods We performed literature searches on MEDLINE, EMBASE, PUBMED, the COCHRANE LIBRARY and various Internet evidence sources for randomised controlled trials or systematic reviews comparing ciclesonide to beclomethasone or budesonide or fluticasone in adult humans with persistent asthma. Data was extracted by one reviewer. Results Five studies met the inclusion criteria. Methodological quality was variable. There were no trials comparing ciclesonide to beclomethasone. There was no significant difference between ciclesonide and budesonide or fluticasone on the following outcomes: lung function, symptoms, quality of life, airway responsiveness to a provoking agent or inflammatory markers. However, the trials were very small in size, increasing the possibility of a type II error. One trial demonstrated that the combined deposition of ciclesonide (and its active metabolite in the oropharynx was 47% of that of budesonide while another trial demonstrated that the combined deposition of ciclesonide (and its active metabolite in the oropharynx was 53% of that of fluticasone. One trial demonstrated less suppression of cortisol in overnight urine collection after ciclesonide compared to fluticasone (geometric mean fold difference = 1.5, P Conclusion There is very little evidence comparing CIC to other ICS, restricted to very small, phase II studies of low

[Iatrogenic adrenal insufficiency secondary to an interaction between ritonavir and inhaled fluticasone. A review of the literature].

Science.gov (United States)

Gómez-Cerquera, Juan Manuel; Hernando-López, Elena; Blanco-Ramos, José Ramón

2014-12-01

Highly effective antiretroviral treatment has improved the life expectancy of human immunodeficiency virus (HIV) infected patients, but has led to an increase in the comorbidities related to aging, such as the chronic obstructive pulmonary disease (COPD). All this implies the need for a greater number of drugs and an increasing risk of drugs interactions with antiretroviral treatment, particularly protease inhibitors. We report a case of iatrogenic adrenal insufficiency interaction secondary to ritonavir and inhaled fluticasone in an HIV-infected patient with COPD. A review was made of the cases reported in adults in the medical literature (Medline) up to December 2012. A total of 34 cases were reported. The mean age was 4 years. The mean dose of ritonavir was 187 mg/day, while the fluticasone dose was 866 μg/day. The average time of the interaction between ritonavir and fluticasone was 8 months. In 85% of cases fluticasone was discontinued at the time of diagnosis of adrenal insufficiency/Cushing syndrome. Almost all (90%) patients had a complete resolution of the symptoms after changing the treatment. HIV-infected patients on antiretroviral therapy with protease inhibitor boosted with ritonavir which requires the use of inhaled corticosteroids, beclomethasone would be the best treatment option. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Lethal and sublethal effects of methoxyphenozide on the development, survival and reproduction of the fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae)

Energy Technology Data Exchange (ETDEWEB)

Zarate, N.; Diaz, O. [Universidad Autonoma de San Luis Potosi (Mexico). Facultad de Agronomia; Martinez, A.M.; Figueroa, J.I.; Pineda, S., E-mail: spineda_us@yahoo.co [Universidad Michoacana de San Nicolas de Hidalgo, Tarimbaro, Michoacan (Mexico). Inst. de Investigaciones Agropecuarias y Forestales; Schneider, M.I. [National Council of Scientific and Technical Research (CEPAVE/CCT/CONICET), La Plata (Argentina). Centro de Estudios Parasitologicos y de Vectores. Centro Cientifico Tecnologico; Smagghe, G. [Ghent University, Ghent (Belgium). Faculty of Bioscience Engineering. Lab of Agrozoology; Vinuela, E.; Budia, F. [Escuela Tecnica Superior de Ingenieros Agronomos, Madrid (Spain). Escuela Tecnica Superior de Ingenieros Agronomos. Proteccion de Cultivos

2011-01-15

The lethal and sublethal effects of the ecdysone agonist methoxyphenozide on the fall armyworm, Spodoptera frugiperda (J. E. Smith), were investigated by feeding a methoxyphenozide-treated diet to fifth instars until pupation in doses corresponding to the LC{sub 10} and LC{sub 25} for the compound. Larval mortality reached 8% and 26% in the low and high concentration groups, respectively, on the seventh day of the experiment. A progressive larval mortality of 12% for the LC{sub 10} and 60% for the LC{sub 25} was observed before pupation. Treated larvae exhibited lower pupal weights, higher pupal mortality, presence of deformed pupae, and more deformed adults than untreated larvae. The incorporation of methoxyfenozide into the diet had a significant effect on the timing of larval development. The development period for males and females was about seven days longer than the controls for both concentrations tested. In contrast, the compound affected neither pupae nor adult longevity. Finally, S. frugiperda adults that resulted from fifth instars treated with methoxyfenozide were not affected in their mean cumulative number of eggs laid per female (fecundity), nor percentages of eggs hatched (fertility), or the sex ratio. Our results suggest that the combination of lethal and sublethal effects of methoxyfenozide may have important implications for the population dynamics of the fall armyworm. (author)

Invasive aspergillosis in a user of inhaled cocaine: rhinosinusitis with bone and cartilage destruction

Directory of Open Access Journals (Sweden)

Luna Azulay-Abulafia

2014-07-01

Full Text Available Aspergillosis is an infection caused by saprophytic fungi of the genus Aspergillus, which typically occurs in immunosuppressed individuals, but has also been reported in immunocompetent patients. The main routes of entry are the respiratory tract, skin, cornea, and ear, and the infection may be localized or disseminated by contiguity or vascular invasion. We report a severe case of rhinosinusitis with cutaneous involvement, caused by invasive aspergillosis, in an immunocompetent user of inhaled cocaine. Invasive aspergillosis related to cocaine abuse has not yet been reported in the literature. After itraconazole treatment and surgical debridement, complete clinical remission was achieved. Nasal reconstruction with a skin graft over a silicone prosthesis resulted in a satisfactory esthetic outcome.

Scleral Buckle Infection With Pseudallescheria boydii.

Science.gov (United States)

Law, Janice C; Breazzano, Mark P; Eliott, Dean

2017-08-01

Pseudallescheria boydii is a ubiquitous fungus that infects soft tissues and is known to cause ocular disease, including keratitis and endophthalmitis, in rare cases. In immunocompromised hosts, P. boydii can disseminate to or from the eye and other organs with lethal consequences. Postoperative P. boydii infections have, in rare cases, complicated several types of ocular surgeries in immunocompetent patients, but never for a scleral buckle. The authors present the first case of an infected scleral buckle from P. boydii. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:676-678.]. Copyright 2017, SLACK Incorporated.

Phylogenetic Analysis of Staphylococcus aureus CC398 Reveals a Sub-Lineage Epidemiologically Associated with Infections in Horses

DEFF Research Database (Denmark)

Abdelbary, Mohamed M. H.; Wittenberg, Anne; Cuny, Christiane

2014-01-01

-allelic polymorphisms, and phylogenetic analyses revealed that an epidemic sub-clone within CC398 (dubbed 'clade (C)') has spread within and between equine hospitals, where it causes nosocomial infections in horses and colonises the personnel. While clade (C) was strongly associated with S. aureus from horses...

Inhalation Toxicology Research Institute annual report 1987-1988

International Nuclear Information System (INIS)

Mauderly, J.L.; Mewhinney, J.A.; Bechtold, W.E.; Sun, J.D.; Coons, T.A.

1988-12-01

The mission of the Inhalation Toxicology Research Institute is to investigate the magnitude of human health effects that result from the inhalation of airborne materials at home, in the work place, or in the general environment. Diseases of the respiratory tract are major causes of suffering and death, and many of these diseases are directly related to the materials that people breath. The Institute's research is directed toward obtaining a better understanding of the basic biology of the respiratory tract and the mechanisms by which inhaled materials produce respiratory disease. Special attention is focused on studying the airborne materials released by various energy technologies, as well as those associated with national defense activities. The research uses a wide-ranging, comprehensive array of investigative approaches that are directed toward characterizing the source of the airborne material, following the material through its potential transformation in the air, identifying the mechanisms that govern its inhalation and deposition in the respiratory tract, and determining the fate of these inhaled materials in the body and the health effects they produce. The ultimate objectives are to determine the roles played by inhaled materials in the development of disease processes adn to estimate the risk they pose by inhaled materials in the development of disease processes and to estimate the risk they pose to humans who may be exposed to them. This report contains brief research papers that reflect the scope and recent findings of the Institute's research funded by the U.S. Department of Energy, principally through the Office of Health and Environmental Research. The papers are divided into topical sections. The first section, Characterization of Airborne Materials and Generation of Experimental Exposure Atmospheres, reflects the Institute's capabilities for fundamental aerosol research and the application of that expertise to toxicological studies. The second

Inhalation Toxicology Research Institute annual report 1987-1988

Energy Technology Data Exchange (ETDEWEB)

Mauderly, J L; Mewhinney, J A; Bechtold, W E; Sun, J D; Coons, T A [eds.

1988-12-01

The mission of the Inhalation Toxicology Research Institute is to investigate the magnitude of human health effects that result from the inhalation of airborne materials at home, in the work place, or in the general environment. Diseases of the respiratory tract are major causes of suffering and death, and many of these diseases are directly related to the materials that people breath. The Institute's research is directed toward obtaining a better understanding of the basic biology of the respiratory tract and the mechanisms by which inhaled materials produce respiratory disease. Special attention is focused on studying the airborne materials released by various energy technologies, as well as those associated with national defense activities. The research uses a wide-ranging, comprehensive array of investigative approaches that are directed toward characterizing the source of the airborne material, following the material through its potential transformation in the air, identifying the mechanisms that govern its inhalation and deposition in the respiratory tract, and determining the fate of these inhaled materials in the body and the health effects they produce. The ultimate objectives are to determine the roles played by inhaled materials in the development of disease processes adn to estimate the risk they pose by inhaled materials in the development of disease processes and to estimate the risk they pose to humans who may be exposed to them. This report contains brief research papers that reflect the scope and recent findings of the Institute's research funded by the U.S. Department of Energy, principally through the Office of Health and Environmental Research. The papers are divided into topical sections. The first section, Characterization of Airborne Materials and Generation of Experimental Exposure Atmospheres, reflects the Institute's capabilities for fundamental aerosol research and the application of that expertise to toxicological studies. The second

[Neuromeningeal cryptococcosis in patients infected with HIV at Agadir regional hospital, (Souss-Massa, Morocco)].

Science.gov (United States)

Chadli, S; Aghrouch, M; Taqarort, N; Malmoussi, M; Ouagari, Z; Moustaoui, F; Bourouache, M; Oulkheir, S

2018-03-01

Neuromeningeal cryptococcosis (NMC) is a severe and fatal opportunistic infection. Lethality is frequent in the absence of treatment, especially in the presence of HIV co-infection. To determine the prevalence, epidemiological, clinical, biological and therapeutic aspects as well as the evolution of NMC for patients infected with HIV. This is a retrospective study of 40 cases of neuromeningeal cryptococcosis diagnosed in HIV-infected patients. Data are collected for 7 years (from January 2010 to December 2016) in the registers of the parasitology laboratory and the infectious diseases department at the regional hospital center in Agadir. A reduction in the prevalence of neuromeningeal cryptococcosis in HIV-infected patients was noted from 2010 to 2016 (3.66% to 0.83%). The overall prevalence of NMC was 1.53%. The mean age was 37±10 years old, with 90% of patients aged less than 45 years. The main clinical symptomatology was headache (75%). The main cytochemical abnormalities of cerebrospinal fluid analysis were hyperproteinorachy (60%), hypoglycorachy (63%) and lymphocytosis (50%). The mean CD4 cell count was 47/mm 3 . Patients were initially treated with amphotericin B, relayed with fluconazole. The overall lethality was 35%. Neuromeningeal cryptococcosis is a serious opportunistic infection in patients HIV-infected, and the lethality rate remains unacceptable. Fighting NMC in HIV+ patients requires early diagnosis, increased access to antiretrovirals, rapid introduction of appropriate treatment and the prescription of effective systemic antifungals. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cromolyn Oral Inhalation

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... your doctor.Cromolyn oral inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Your doctor will prescribe ...

Olodaterol Oral Inhalation

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... in a class of medications called long-acting beta-agonists (LABAs). It works by relaxing and opening ... the inhaler upright with the yellow cap closed. Turn the clear base in the direction of the ...

Ipratropium Oral Inhalation

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... with the clear end pointing upward. Place the metal canister inside the clear end of the inhaler. ... do not discard it in an incinerator or fire.Unneeded medications should be disposed of in special ...

Control beliefs and health locus of control in Ugandan, German and migrated sub-Saharan African HIV infected individuals.

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Milz, Ruth U; Husstedt, Ingo-W; Reichelt, Doris; Evers, Stefan

2016-04-01

Little is known about the influence of control beliefs on antiretroviral drug adherence in patients who migrated from sub-Saharan Africa to Europe. The aim of this study was to explore the differences in health locus of control and control beliefs between HIV infected patients from sub-Saharan Africa with and without a lifetime experience of migration. A sample of 62 HIV infected consecutive patients referred to the HIV clinics at the University Hospital of Münster (Germany) and at the Rubaga Hospital Kampala (Uganda) were enrolled into this study. We compared three groups of patients: sub-Saharan African migrants, German patients, and local Ugandan patients. We used the German health and illness related control beliefs questionnaire (KKG), the Competence and control beliefs questionnaire (FKK), and the Powe Fatalism Inventory-HIV/AIDS-Version (PFI-HIV/AIDS-Version) and translated these scales into English and Luganda. In addition, the patients' sociodemographic, acculturation, clinical, and immunological data were registered. Significant results were shown in HIV related external locus of control between migrated sub-Saharan African and local Ugandan patients compared to German patients. General control beliefs showed no significant differences. In the PFI-HIV-Version, there was a significant difference between migrated sub-Saharan African and Ugandan patients compared to German patients. Our data suggest that the experience of migration does not influence the locus of control. Compared to German HIV patients, African patients in general showed a significantly higher external health locus of control which might have implications for drug adherence. Copyright © 2016 Elsevier Inc. All rights reserved.

Children Living with HIV-Infected Adults: Estimates for 23 Countries in sub-Saharan Africa.

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Short, Susan E; Goldberg, Rachel E

2015-01-01

In sub-Saharan Africa many children live in extreme poverty and experience a burden of illness and disease that is disproportionately high. The emergence of HIV and AIDS has only exacerbated long-standing challenges to improving children's health in the region, with recent cohorts experiencing pediatric AIDS and high levels of orphan status, situations which are monitored globally and receive much policy and research attention. Children's health, however, can be affected also by living with HIV-infected adults, through associated exposure to infectious diseases and the diversion of household resources away from them. While long recognized, far less research has focused on characterizing this distinct and vulnerable population of HIV-affected children. Using Demographic and Health Survey data from 23 countries collected between 2003 and 2011, we estimate the percentage of children living in a household with at least one HIV-infected adult. We assess overlaps with orphan status and investigate the relationship between children and the adults who are infected in their households. The population of children living in a household with at least one HIV-infected adult is substantial where HIV prevalence is high; in Southern Africa, the percentage exceeded 10% in all countries and reached as high as 36%. This population is largely distinct from the orphan population. Among children living in households with tested, HIV-infected adults, most live with parents, often mothers, who are infected; nonetheless, in most countries over 20% live in households with at least one infected adult who is not a parent. Until new infections contract significantly, improvements in HIV/AIDS treatment suggest that the population of children living with HIV-infected adults will remain substantial. It is vital to on-going efforts to reduce childhood morbidity and mortality to consider whether current care and outreach sufficiently address the distinct vulnerabilities of these children.

Children Living with HIV-Infected Adults: Estimates for 23 Countries in sub-Saharan Africa.

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Susan E Short

Full Text Available In sub-Saharan Africa many children live in extreme poverty and experience a burden of illness and disease that is disproportionately high. The emergence of HIV and AIDS has only exacerbated long-standing challenges to improving children's health in the region, with recent cohorts experiencing pediatric AIDS and high levels of orphan status, situations which are monitored globally and receive much policy and research attention. Children's health, however, can be affected also by living with HIV-infected adults, through associated exposure to infectious diseases and the diversion of household resources away from them. While long recognized, far less research has focused on characterizing this distinct and vulnerable population of HIV-affected children.Using Demographic and Health Survey data from 23 countries collected between 2003 and 2011, we estimate the percentage of children living in a household with at least one HIV-infected adult. We assess overlaps with orphan status and investigate the relationship between children and the adults who are infected in their households.The population of children living in a household with at least one HIV-infected adult is substantial where HIV prevalence is high; in Southern Africa, the percentage exceeded 10% in all countries and reached as high as 36%. This population is largely distinct from the orphan population. Among children living in households with tested, HIV-infected adults, most live with parents, often mothers, who are infected; nonetheless, in most countries over 20% live in households with at least one infected adult who is not a parent.Until new infections contract significantly, improvements in HIV/AIDS treatment suggest that the population of children living with HIV-infected adults will remain substantial. It is vital to on-going efforts to reduce childhood morbidity and mortality to consider whether current care and outreach sufficiently address the distinct vulnerabilities of these

Nicotine Oral Inhalation

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... with a smoking cessation program, which may include support groups, counseling, or specific behavioral change techniques. Nicotine inhalation ... and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or ...

Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

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Liling Yang

2017-10-01

Full Text Available Background/Aims: Forsythia suspensa Vahl. (Oleaceae fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN, the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF

CLINICAL INFECTION OF TWO CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS) WITH ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 1B.

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Fuery, Angela; Tan, Jie; Peng, RongSheng; Flanagan, Joseph P; Tocidlowski, Maryanne E; Howard, Lauren L; Ling, Paul D

2016-03-01

The ability of prior infection from one elephant endotheliotropic herpesvirus (EEHV) type to protect against clinical or lethal infection from others remains an important question. This report describes viremia and subsequent shedding of EEHV1B in two juvenile 4-yr-old Asian elephants within 3 wk or 2 mo following significant infections caused by the rarely seen EEHV4. High levels of EEHV1B shedding were detected in the first elephant prior to emergence of infection and viremia in the second animal. The EEHV1B virus associated with both infections was identical to the strain causing infection in two herd mates previously. High EEHV viremia correlated with leukopenia and thrombocytopenia, which was followed by leukocytosis and thrombocytosis when clinical signs started to resolve. The observations from these cases should be beneficial for helping other institutions monitor and treat elephants infected with EEHV1, the most common virus associated with lethal hemorrhagic disease.

Identification of a sub-population of B cells that proliferates after infection with epstein-barr virus

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Ye Jianjiang

2011-02-01

Full Text Available Abstract Background Epstein-Barr virus (EBV-driven B cell proliferation is critical to its subsequent persistence in the host and is a key event in the development of EBV-associated B cell diseases. Thus, inquiry into early cellular events that precede EBV-driven proliferation of B cells is essential for understanding the processes that can lead to EBV-associated B cell diseases. Methods Infection with high titers of EBV of mixed, primary B cells in different stages of differentiation occurs during primary EBV infection and in the setting of T cell-immunocompromise that predisposes to development of EBV-lymphoproliferative diseases. Using an ex vivo system that recapitulates these conditions of infection, we correlated expression of selected B cell-surface markers and intracellular cytokines with expression of EBV latency genes and cell proliferation. Results We identified CD23, CD58, and IL6, as molecules expressed at early times after EBV-infection. EBV differentially infected B cells into two distinct sub-populations of latently infected CD23+ cells: one fraction, marked as CD23hiCD58+IL6- by day 3, subsequently proliferated; another fraction, marked as CD23loCD58+, expressed IL6, a B cell growth factor, but failed to proliferate. High levels of LMP1, a critical viral oncoprotein, were expressed in individual CD23hiCD58+ and CD23loCD58+ cells, demonstrating that reduced levels of LMP1 did not explain the lack of proliferation of CD23loCD58+ cells. Differentiation stage of B cells did not appear to govern this dichotomy in outcome either. Memory or naïve B cells did not exclusively give rise to either CD23hi or IL6-expressing cells; rather memory B cells gave rise to both sub-populations of cells. Conclusions B cells are differentially susceptible to EBV-mediated proliferation despite expression of viral gene products known to be critical for continuous B cell growth. Cellular events, in addition to viral gene expression, likely play a

Lethality of Rendang packaged in multilayer retortable pouch with sterilization process

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Praharasti, A. S.; Kusumaningrum, A.; Frediansyah, A.; Nurhikmat, A.; Khasanah, Y.; Suprapedi

2017-01-01

Retort Pouch had become a choice to preserve foods nowadays, besides the used of the can. Both had their own advantages, and Retort Pouch became more popular for the reason of cheaper and easier to recycle. General Method usually used to estimate the lethality of commercial heat sterilization process. Lethality value wa s used for evaluating the efficacy of the thermal process. This study aimed to find whether different layers of pouch materials affect the lethality value and to find differences lethality in two types of multilayer retort pouch, PET/Aluminum Foil/Nylon/RCPP and PET/Nylon/Modified Aluminum/CPP. The result showed that the different layer arrangement was resulted different Sterilization Value (SV). PET/Nylon/Modified Aluminum/CPP had better heat penetration, implied by the higher value of lethality. PET/Nylon/Modified Aluminum/CPP had the lethality value of 6,24 minutes, whereas the lethality value of PET/Aluminum Foil/Nylon/RCPP was 3,54 minutes.

Primary aspergillosis of vocal cord: Long-term inhalational steroid use can be the miscreant

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Arpita Saha

2015-12-01

Full Text Available Primary laryngeal aspergillosis is extremely rare, especially in an immunocompetent host. It is commonly found as a part of systemic infection in immunocompromised patients. A case of vocal cord aspergillosis with no systemic extension in an immunocompetent patient on long-term steroid metered dose inhaler (MDI is presented here, because of its rarity. The present case is a 28-year-old asthmatic female who was on inhalational steroid for 8 years, presented with sudden onset of severe dysphonia for 5 days. Fiberoptic laryngoscopy demonstrated whitish plaque involving right vocal cord, clinically suggestive of fungal laryngitis. Microlaryngeal laser surgery was performed with stripping of the plaque. Histopathology demonstrated ulcerated hyperplastic squamous epithelium with masses of fungal hyphae, which was confirmed to be Aspergillus species on fungal culture. This rare but serious adverse effect of long-term steroid MDI use must be kept in mind while treating an asthmatic patient. We also present a brief review of literature of laryngeal aspergillosis.

Experimental infection with Klebsiella pneumoniae and its gentamicin therapy in guinea pigs 60Co irradiated with 4 Gy

International Nuclear Information System (INIS)

Kallay, Z.; Trnovec, T.; Durisova, M.; Mazurova, E.; Navarova, J.; Plskova, M.; Kettner, M.

1982-01-01

Sublethal irradiation was used to suppress the immunity response of the organism. Following the development of infection with Klebsiella pneumoniae the therapeutical effect was compared of intramuscular administration and of inhalation of gentamicin. Intramuscular administration was statistically significant for reducing the mortality of infected guinea pigs as against non-treated animals at days 7 to 10 after irradiation. Administration by inhalation had the same effect between days 12 and 25 after irradiation. The weight and blood counts of the animals were observed during the experiment. (M.D.)

Detection of sites of infection in mice using {sup 99m}Tc-labeled PN{sub 2}S-PEG conjugated to UBI and {sup 99m}Tc-UBI: a comparative biodistribution study

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Melendez-Alafort, Laura [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy)], E-mail: lmalafort@yahoo.com; Nadali, Anna; Pasut, Gianfranco; Zangoni, Elena [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy); De Caro, Raffaele [Department of Anatomy and Physiology, University of Padua, 35131 Padova (Italy); Cariolato, Luca [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy); Giron, Maria Cecilia [Department of Pharmacology and Anesthesiology, University of Padua, 35131 Padova (Italy); Castagliuolo, Ignazio [Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, 35131 Padova (Italy); Veronese, Francesco M.; Mazzi, Ulderico [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy)

2009-01-15

The antimicrobial peptide ubiquicidin (UBI) directly labeled with technetium-99m ({sup 99m}Tc) has recently been shown to be specifically taken up at sites of infection; however, its chemical structure is not well defined. To address this problem, the aim of the present study was to label UBI using poly(ethyleneglycol)-N-(N-(3-diphenylphosphinopropionyl)glycyl) -S-tritylcysteine ligand (PEG-PN{sub 2}S) in order to compare its ability to detect infection sites with that of {sup 99m}Tc-UBI. Methods: The PN{sub 2}S-PEG-UBI conjugate was prepared and labeled with {sup 99m}Tc, and its radiochemical purity was subsequently assessed. The stability of the conjugate to cysteine challenge and dilution with both saline solution and phosphate buffer was determined and serum stability and protein binding were also assessed. In vivo studies were carried out in healthy mice to study the biodistribution of {sup 99m}Tc-PN{sub 2}S-PEG-UBI and its precursor {sup 99m}Tc-PN{sub 2}S-PEG and in infected mice to compare the uptakes of {sup 99m}Tc-UBI and {sup 99m}Tc-PN{sub 2}S-PEG-UBI at the site of infection using scintigraphic imaging and ex vivo tissue counting. Results: {sup 99m}Tc-PN{sub 2}S-PEG-UBI was obtained with high radiochemical purity (98{+-}1%) and high stability. The amphiphilic nature of the conjugate leads to a tendency to form micellar aggregates that explain the high protein binding values obtained. Biodistribution studies in mice showed low renal clearance followed by a predominant reticuloendothelial system clearance that limits its application in the abdominal area. Statistical analysis revealed no significant difference between {sup 99m}Tc-UBI and {sup 99m}Tc-PN{sub 2}S-PEG-UBI uptake in infected mouse thigh, and the site of infection was clearly visualized using scintigraphic imaging. Conclusions: {sup 99m}Tc-PN{sub 2}S-PEG-UBI proved to be as effective as {sup 99m}Tc-UBI in detecting sites of infection; however, the well-defined chemical structure of {sup 99m}Tc-PN{sub

Novel Tissue Level Effects of the Staphylococcus aureus Enterotoxin Gene Cluster Are Essential for Infective Endocarditis.

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Stach, Christopher S; Vu, Bao G; Merriman, Joseph A; Herrera, Alfa; Cahill, Michael P; Schlievert, Patrick M; Salgado-Pabón, Wilmara

2016-01-01

Superantigens are indispensable virulence factors for Staphylococcus aureus in disease causation. Superantigens stimulate massive immune cell activation, leading to toxic shock syndrome (TSS) and contributing to other illnesses. However, superantigens differ in their capacities to induce body-wide effects. For many, their production, at least as tested in vitro, is not high enough to reach the circulation, or the proteins are not efficient in crossing epithelial and endothelial barriers, thus remaining within tissues or localized on mucosal surfaces where they exert only local effects. In this study, we address the role of TSS toxin-1 (TSST-1) and most importantly the enterotoxin gene cluster (egc) in infective endocarditis and sepsis, gaining insights into the body-wide versus local effects of superantigens. We examined S. aureus TSST-1 gene (tstH) and egc deletion strains in the rabbit model of infective endocarditis and sepsis. Importantly, we also assessed the ability of commercial human intravenous immunoglobulin (IVIG) plus vancomycin to alter the course of infective endocarditis and sepsis. TSST-1 contributed to infective endocarditis vegetations and lethal sepsis, while superantigens of the egc, a cluster with uncharacterized functions in S. aureus infections, promoted vegetation formation in infective endocarditis. IVIG plus vancomycin prevented lethality and stroke development in infective endocarditis and sepsis. Our studies support the local tissue effects of egc superantigens for establishment and progression of infective endocarditis providing evidence for their role in life-threatening illnesses. In contrast, TSST-1 contributes to both infective endocarditis and lethal sepsis. IVIG may be a useful adjunct therapy for infective endocarditis and sepsis.

A whiff of death: fatal volatile solvent inhalation abuse.

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Steffee, C H; Davis, G J; Nicol, K K

1996-09-01

Inhalation abuse of volatile solvents, previously known generically as "glue sniffing," is typically pursued by adolescents. A wide range of legal, easily obtained products containing volatile substances are available for abuse. We report two illustrative cases of fatal volatile substance abuse: gasoline sniffing in a 20-year-old man and aerosol propellant gas inhalation (aerosol air freshener) in a 16-year-old girl with underlying reactive airway disease. Although the ratio of deaths to nonfatal inhalation escapades is extremely low, volatile solvent abuse carries the risk of sudden death due to cardiac arrest after a dysrhythmia or vasovagal event, central nervous system respiratory depression, hypoxia and hypercapnia due to the techniques of inhalation, and other mechanisms. Investigation of the patient's substance abuse history, examination of the scene of death, and special toxicologic analyses are critical to identifying volatile substance inhalation abuse as the cause of death because anatomic autopsy findings will typically be nonspecific. Above all, physicians must suspect the diagnosis of volatile substance inhalation abuse, especially in any case of sudden death involving an otherwise healthy young person.

[Bladder tumor lethality. Results in the autonomous community of Rioja between 1975-1991].

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Fernández Fernández, A; Gil Fabra, J; Fernández Ruíz, M; Angulo Castellanos, M G; Blanco Martín, E; Otero Mauricio, G

1998-01-01

Between 1975-1991, a total of 557 cases of bladder carcinoma were identified in the Autonomous Community of La Rioja (CAR) which were followed up to December 1994. The overall lethality was 21.9%. 492 cases with 22.35% lethality were identified in males. In females, however, there was 65 cases with 18.46% lethality. The comparison of males and females lethality resulted in p = 0.525. Lethality between cases diagnosed within each 5-year period analyzed is: 1975-1981: 177 cases, lethality 23.72%. 1982-1986: 168 cases, lethality 30.95%. 1987-1991: 212 cases, lethality 13.20%. Between the first and the second 5-year periods, p = 0.132; between the first and third 5-year periods p = 0.007 and between the second and third 5-year periods p CAR for a 22.35% lethality. Lethality is higher in males that in females but the difference is not statistically significant. In the last 5-year period assessed, 1987-1991, a reduction of lethality from bladder neoplasms has been documented.

Inhaler technique maintenance: gaining an understanding from the patient's perspective.

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Ovchinikova, Ludmila; Smith, Lorraine; Bosnic-Anticevich, Sinthia

2011-08-01

The aim of this study was to determine the patient-, education-, and device-related factors that predict inhaler technique maintenance. Thirty-one community pharmacists were trained to deliver inhaler technique education to people with asthma. Pharmacists evaluated (based on published checklists), and where appropriate, delivered inhaler technique education to patients (participants) in the community pharmacy at baseline (Visit 1) and 1 month later (Visit 2). Data were collected on participant demographics, asthma history, current asthma control, history of inhaler technique education, and a range of psychosocial aspects of disease management (including adherence to medication, motivation for correct technique, beliefs regarding the importance of maintaining correct technique, and necessity and concern beliefs regarding preventer therapy). Stepwise backward logistic regression was used to identify the predictors of inhaler technique maintenance at 1 month. In total 145 and 127 participants completed Visits 1 and 2, respectively. At baseline, 17% of patients (n = 24) demonstrated correct technique (score 11/11) which increased to 100% (n = 139) after remedial education by pharmacists. At follow-up, 61% (n = 77) of patients demonstrated correct technique. The predictors of inhaler technique maintenance based on the logistic regression model (X(2) (3, N = 125) = 16.22, p = .001) were use of a dry powder inhaler over a pressurized metered-dose inhaler (OR 2.6), having better asthma control at baseline (OR 2.3), and being more motivated to practice correct inhaler technique (OR 1.2). Contrary to what is typically recommended in previous research, correct inhaler technique maintenance may involve more than repetition of instructions. This study found that past technique education factors had no bearing on technique maintenance, whereas patient psychosocial factors (motivation) did.

Inhaled antibiotics in non-cystic fibrosis bronchiectasis: A meta-analysis.

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Xu, Li; Zhang, Fei; Du, Shuai; Yu, Qi; Chen, Lin; Long, Li-Hui; Li, Ya-Ming; Jia, Ai-Hua

2016-09-01

To evaluate the efficacy and safety of inhaled antibiotics for the treatment of non-cystic fibrosis bronchiectasis (NCFB). Pubmed, Cochrane library, Embase, Elsevier, OVID, Springerlink, Web of knowledge and NEJM were searched for randomized controlled trials (RCTs) on inhaled antibiotics in treatment of NCFB from inception until April 2015. Meta-analysis was conducted to assess the efficacy and safety of inhaled antibiotics in the treatment of NCFB. Twelve RCTs involving 1154 participants were included. They showed that inhaled antibiotics were more effective in reduction of sputum bacterial density, eradication of P. aeruginosa, prolonged time to exacerbation and reduction of new pathogens emergence with no significant difference in adverse events compared with control groups. However, we did not find significant benefits of inhaled antibiotics in reducing the risk of acute exacerbation, improving health-related quality of life and reduction of P. aeruginosa resistance. Moreover, inhaled antibiotics exerted a statistically significant reduction in FEV1%. Inhaled antibiotics may be an alternative pathway to inhibit airway inflammation with no more adverse events in patients with NCFB.

[Efficacy of systemic glucocorticoids combined with inhaled steroid on children with acute laryngitis].

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Chen, Q P; Zhou, R F; Zhang, Y M; Yang, L

2018-01-07

Objective: To evaluate the efficacy of systemic glucocorticoid (steroid) combined with high dose inhaled steroid in the treatment of children with acute laryngitis. Methods: A total of 78 children with acute laryngitis were randomly divided into study group( n =40) and control group( n =38) between November 2016 and April 2017. In addition to routine treatment of anti infection and symptomatic treatment, Dexamethasone injection(0.3-0.5 mg/kg, 1-3 d, according to the patient's condition) was provided to each group. In addition to the treatment mentioned above, the study group were assigned to receive 1.0 mg Budesonide suspension for inhalation, oxygen-driven atomizing inhalation, every/30 minutes, 2 times in a row, after that every 12 hours. The improvement of inspiratory dyspnea, hoarseness, barking cough and wheezing of both groups was evaluated at 30 min, 1 h, 2 h, 6 h, 12 h, 24 h and 72 h after treatment.Sigmaplot 11.5 software was used to analyze the data. Results: No significant difference was detected in terms of inspiratory dyspnea, hoarseness, barking cough or stridor score before treatment between the two groups( P >0.05). Compared with those before treatment, symptoms of inspiratory dyspnea, hoarseness, barking cough and stridor score of both groups improved markedly at 12 h and 24 h after treatment( P dyspnea, hoarseness, barking cough or stridor score at each time point after treatment between the two groups( P >0.05). The effective rate was 92.50% and 92.11% in study group and control group, respectively, and no significant difference was noted ( P >0.05). Conclusion: Compared with single systemic glucocorticoid, systemic glucocorticoids combined with inhaled steroid possessed similar efficacy in treating acute laryngitis and relieving laryngeal obstruction of children.

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

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Westerik, Janine A. M.; Carter, Victoria; Chrystyn, Henry; Burden, Anne; Thompson, Samantha L.; Ryan, Dermot; Gruffydd-Jones, Kevin; Haughney, John; Roche, Nicolas; Lavorini, Federico; Papi, Alberto; Infantino, Antonio; Roman-Rodriguez, Miguel; Bosnic-Anticevich, Sinthia; Lisspers, Karin; Ställberg, Björn; Henrichsen, Svein Høegh; van der Molen, Thys; Hutton, Catherine; Price, David B.

2016-01-01

Abstract Objective: Correct inhaler technique is central to effective delivery of asthma therapy. The study aim was to identify factors associated with serious inhaler technique errors and their prevalence among primary care patients with asthma using the Diskus dry powder inhaler (DPI). Methods: This was a historical, multinational, cross-sectional study (2011–2013) using the iHARP database, an international initiative that includes patient- and healthcare provider-reported questionnaires from eight countries. Patients with asthma were observed for serious inhaler errors by trained healthcare providers as predefined by the iHARP steering committee. Multivariable logistic regression, stepwise reduced, was used to identify clinical characteristics and asthma-related outcomes associated with ≥1 serious errors. Results: Of 3681 patients with asthma, 623 (17%) were using a Diskus (mean [SD] age, 51 [14]; 61% women). A total of 341 (55%) patients made ≥1 serious errors. The most common errors were the failure to exhale before inhalation, insufficient breath-hold at the end of inhalation, and inhalation that was not forceful from the start. Factors significantly associated with ≥1 serious errors included asthma-related hospitalization the previous year (odds ratio [OR] 2.07; 95% confidence interval [CI], 1.26–3.40); obesity (OR 1.75; 1.17–2.63); poor asthma control the previous 4 weeks (OR 1.57; 1.04–2.36); female sex (OR 1.51; 1.08–2.10); and no inhaler technique review during the previous year (OR 1.45; 1.04–2.02). Conclusions: Patients with evidence of poor asthma control should be targeted for a review of their inhaler technique even when using a device thought to have a low error rate. PMID:26810934

Clinical effectiveness of the Respimat® inhaler device in managing chronic obstructive pulmonary disease: evidence when compared with other handheld inhaler devices

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et al

2011-02-01

Full Text Available Felix SF Ram1, Celso R Carvallho2, John White31School of Health and Social Services, Massey University, Auckland, New Zealand; 2Department of Physical Therapy, School of Medicine, University of São Paulo, Brazil; 3York Hospitals NHS Foundation Trust, York Hospital, York, UKObjectives: Medication for the management of chronic obstructive pulmonary disease (COPD may be delivered by a number of different inhaler devices. This study was undertaken to determine the clinical effectiveness of the Respimat® handheld inhaler device compared with other handheld inhaler devices for the delivery of medication in stable COPD.Methodology: A systematic review of high-quality randomized controlled clinical trials comparing Respimat with other inhaler devices using the same medication was performed. Studies were searched for in the Cochrane Central Register of Controlled Trials as well as other relevant electronic databases. Manufacturers of inhaled COPD medication were also contacted for potential trials.Results: Seven studies of high methodological quality with 3813 participants were included in the review. Three trials used Handihaler® as the comparator inhaler, three used a chlorofluorocarbon metered-dose inhaler (CFC-MDI, and one trial used a hydroflouroalkane (HFA-MDI. When Respimat was compared with Handihaler, the following reported outcomes were not significantly different: trough forced expiratory volume in 1 second (FEV1 (weighted mean difference [WMD] 0.01 L; P = 0.14, trough forced vital capacity (FVC (WMD 0.001 L: P = 0.88, peak FEV1 (WMD 0.01 L: P = 0.08, peak FVC (WMD 0.01 L: P = 0.55, morning peak expiratory flow rate (PEFR (WMD 5.06 L/min: P = 0.08, and evening PEFR (WMD 4.39 L/min: P = 0.15. Furthermore, there were no differences when Respimat was compared with Handihaler for risk of exacerbations (relative risk [RR] 0.94: P = 0.81, dry mouth (RR 1.57: P = 0.34, or nasopharyngitis (RR 1.42: P = 0.22. For Respimat compared with CFC-MDI, the

Contemporary issues on the epidemiology and antiretroviral adherence of HIV-infected adolescents in sub-Saharan Africa: a narrative review

OpenAIRE

Adejumo, Olurotimi A; Malee, Kathleen M; Ryscavage, Patrick; Hunter, Scott J; Taiwo, Babafemi O

2015-01-01

Introduction: Adolescents are a unique and sometimes neglected group in the planning of healthcare services. This is the case in many parts of sub-Saharan Africa, where more than eight out of ten of the world's HIV-infected adolescents live. Although the last decade has seen a reduction in AIDS-related mortality worldwide, largely due to improved access to effective antiretroviral therapy (ART), AIDS remains a significant contributor to adolescent mortality in sub-Saharan Africa. Although ina...

Humanitarian Algorithms : A Codified Key Safety Switch Protocol for Lethal Autonomy

OpenAIRE

Nyagudi, Nyagudi Musandu

2014-01-01

With the deployment of lethal autonomous weapons, there is the requirement that any such platform complies with the precepts of International Humanitarian Law. Humanitarian Algorithms[9: p. 9] ensure that lethal autonomous weapon systems perform military/security operations, within the confines of International Humanitarian Law. Unlike other existing techniques of regulating lethal autonomy this scheme advocates for an approach that enables Machine Learning. Lethal autonomous weapons must be ...

A chimeric measles virus with canine distemper envelope protects ferrets from lethal distemper challenge.

Science.gov (United States)

Rouxel, Ronan Nicolas; Svitek, Nicholas; von Messling, Veronika

2009-08-06

CDV infects a broad range of carnivores, and over the past decades it has caused outbreaks in a variety of wild carnivore populations. Since the currently available live-attenuated vaccine is not sufficiently safe in these highly susceptible species, we produced a chimeric virus combining the replication complex of the measles Moraten vaccine strain with the envelope of a recent CDV wild type isolate. The resulting virus did not cause disease or immunosuppression in ferrets and conferred protection from challenge with a lethal wild type strain, demonstrating its potential value for wildlife conservation efforts.

Inhaling habits among smokers of different types of cigarette

Energy Technology Data Exchange (ETDEWEB)

Wald, N.J.; Idle, M.; Boreham, J.; Bailey, A.

1980-12-01

Inhaling habits were studied in 1316 men who freely smoked their usual brands of cigarette. An index of inhaling was calculated for each person by dividing the estimated increase in carboxyhaemoglobin level from a standard number of cigarettes by the carbon monoxide yield of the cigarette smoked. Smokers of ventilated filter cigarettes inhaled 82% more than smokers of plain cigarettes (p less than 0.001) and those who smoked unventilated filter cigarettes inhaled 36% more (p less than 0.001). Cigarette consumption was similar among smokers of each type of cigarette. Assuming that the intake of tar and nicotine is proportional to the inhaling index, the intake in either group of filter cigarette smokers would have been less than that in plain cigarette smokers. Among smokers of unventilated cigarettes, however, the intake would not have been much less.

Opportunities for inhaler device selection in elderly patients with asthma or COPD

Directory of Open Access Journals (Sweden)

Barrons R

2015-12-01

Full Text Available Robert Barrons,1 James Wheeler,2 J Andrew Woods1 1Wingate University School of Pharmacy, Wingate, NC, USA; 2University of Tennessee Health Science Center, Nashville, TN, USA Abstract: An anticipated surge in the elderly population will be accompanied by a rise in aging patients with asthma or COPD. Clinician selection of inhalers needs to address the unique challenges to elderly patients. These challenges to the use of inhalers include diminished physical and cognitive abilities, as well as cost reimbursement issues associated with polypharmacy and the Medicare gap. Clinicians should consider patient preferences for an inhaler device that provides ease of administration, and addresses conveniences such as portability, visual, and auditory indicators of dosing completion. The addition of spacer devices resolves hand-breath coordination difficulty with pressurized metered dose inhalers, but reduces overall inhaler convenience. Soft mist inhalers (Respimat® improve ease of administration, but use may be limited by cost and formulary availability. Multiple dose dry powder inhalers provide convenience and simplified use by requiring only one to two steps prior to administration, but concerns of peak inspiratory flow requirements remain among patients with advanced age and severity of COPD. If unaddressed, these challenges to inhaler selection contribute to inappropriate use of inhalers in 41% to 69% of patients, accompanied by at least 51% non-adherence to treatment. Clinicians must first avail themselves of reputable educational resources regarding new inhaler developments and administration, for competent patient instruction. Patient education should include a checklist of inhaler technique, with physical demonstration of each device by the patient and provider. Device demonstration significantly improves inhaler technique and identifies the need for nebulization therapy. Clinician and patient knowledge of available inhalers and their

Smoke inhalation injury in a pregnant patient: a literature review of the evidence and current best practices in the setting of a classic case.

Science.gov (United States)

Roderique, Ensign Joseph D; Gebre-Giorgis, Abel A; Stewart, Dane H; Feldman, Michael J; Pozez, Andrea L

2012-01-01

For smoke inhalation injury of a pregnant woman, one must treat two patients and be aware of the potential effects of carbon monoxide (CO) and cyanide (CN) poisoning on both the mother and the fetus. In a pregnant woman, the size and age of the fetus and the degree of poisoning allow for tremendous variability in the toxicity of CO and CN and their respective treatment options. The authors will review a case of a 32-year-old woman who was at 37 weeks of gestation and admitted to the Evans-Haynes Burn Center after a house fire and received hydroxocobalamin (Cyanokit) for suspected CN poisoning. In addition, a review of the literature, current guidelines, and treatment options of inhalation injury during pregnancy will be discussed. The authors will focus only on the toxic components of smoke inhalation injury rather than the mechanical components from heat and particulate damage. Literature review clearly identifies that the treatment of pregnant women with inhalation injury remains a controversial subject. The use of hydroxocobalamin (Cyanokit) as a treatment modality for potential CN poisoning in a pregnant patient has not been reported in the literature. Animal studies have shown that combined CO and CN poisoning are more lethal than either one alone and at lower concentrations. Due to the synergistic effects of CO and CN, and because these two toxins concentrate at even higher levels in the fetus than the mother, the authors will clarify the urgent seriousness of prompt administration of hydroxocobalamin in a pregnant patient with suspected smoke inhalation injury. This case review details the treatment of a 32-year-old woman who was at 36 weeks of gestation on admission to the Evans-Haynes Burn Center. The authors will report her injuries and the course of treatment. Although burned and presenting with concomitant smoke inhalation injury, both the woman and her child fared well with no significant complications due to the smoke inhalation at 6 months of follow

Inhalation of uranium ores

International Nuclear Information System (INIS)

Stuart, B.O.; Jackson, P.O.

1975-01-01

In previous studies the biological dispositions of individual long-lived alpha members of the uranium chain ( 238 U, 234 U and 230 Th) were determined during and following repeated inhalation exposures of rats to pitchblende (26 percent U 3 O 8 ) ore. Although finely dispersed ore in secular equilibrium was inhaled, 230 Th/ 234 U radioactivity ratios in the lungs rose from 1.0 to 2.5 during 8 weeks of exposures and increased to 9.2 by four months after cessation of exposures. Marked non-equilibrium levels were also found in the tracheobronchial lymph nodes, kidneys, liver, and femur. Daily exposures of beagle dogs to high levels of this ore for 8 days resulted in lung 230 Th/ 234 U ratios of >2.0. Daily exposures of dogs to lower levels (0.1 mg/1) for 6 months, with sacrifice 15 months later, resulted in lung and thoracic lymph node 230 Th/ 234 U ratios ranging from 3.6 to 9 and nearly 7, respectively. The lungs of hamsters exposed to carnotite (4 percent U 3 O 8 ) ore in current lifespan studies show 230 Th/ 234 U ratios as high as 2.0 during daily inhalation of this ore in secular equilibrium. Beagle dogs sacrificed after several years of daily inhalations of the same carnotite ore plus radon daughters also showed marked non-equilibrium ratios of 230 Th/ 234 U, ranging from 5.6 to 7.4 in lungs and 6.2 to 9.1 in thoracic lymph nodes. This pattern of higher retention of 230 Th than 234 U in lungs, thoracic lymph nodes, and other tissues is thus consistent for two types of uranium ore among several species and suggests a reevaluation of maximum permissible air concentrations of ore, currently based only on uranium content

Non-Lethal Weapons Program

Science.gov (United States)

Sheets Frequently Asked Questions Non-Lethal Weapons FAQs Active Denial System FAQs Human Electro -Muscular Incapacitation FAQs Related Links Business Opportunities Contact JNLWD Congressional Engagement , Wednesday, Sept 20, 2017. The Active Denial System, blunt-impact munitions, dazzling lasers, LRAD 100X

Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever

Science.gov (United States)

Golden, Joseph W.; Maes, Piet; Kwilas, Steven A.; Ballantyne, John

2016-01-01

ABSTRACT Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaviruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaviruses. In the present study, we produced arenavirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junín virus (JUNV), Machupo virus (MACV), and Guanarito virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT50), exceeded 5,000 against homologous viruses. Antisera against each targeted virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (∼30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenavirus immunotherapeutic. IMPORTANCE Arenaviruses are an important family of emerging viruses. In infected humans, convalescent-phase plasma containing neutralizing antibodies can

Passive therapy with humanized anti-staphylococcal enterotoxin B antibodies attenuates systemic inflammatory response and protects from lethal pneumonia caused by staphylococcal enterotoxin B-producing Staphylococcus aureus.

Science.gov (United States)

Karau, Melissa J; Tilahun, Mulualem E; Krogman, Ashton; Osborne, Barbara A; Goldsby, Richard A; David, Chella S; Mandrekar, Jayawant N; Patel, Robin; Rajagopalan, Govindarajan

2017-10-03

Drugs such as linezolid that inhibit bacterial protein synthesis may be beneficial in treating infections caused by toxigenic Staphylococcus aureus. As protein synthesis inhibitors have no effect on preformed toxins, neutralization of pathogenic exotoxins with anti-toxin antibodies may be beneficial in conjunction with antibacterial therapy. Herein, we evaluated the efficacy of human-mouse chimeric high-affinity neutralizing anti-staphylococcal enterotoxin B (SEB) antibodies in the treatment of experimental pneumonia caused by SEB-producing S. aureus. Since HLA class II transgenic mice mount a stronger systemic immune response following challenge with SEB and are more susceptible to SEB-induced lethal toxic shock than conventional mice strains, HLA-DR3 transgenic mice were used. Lethal pneumonia caused by SEB-producing S. aureus in HLA-DR3 transgenic mice was characterized by robust T cell activation and elevated systemic levels of several pro-inflammatory cytokines and chemokines. Prophylactic administration of a single dose of linezolid 30 min prior to the onset of infection attenuated the systemic inflammatory response and protected from mortality whereas linezolid administered 60 min after the onset of infection failed to confer significant protection. Human-mouse chimeric high-affinity neutralizing anti-SEB antibodies alone, but not polyclonal human IgG, mitigated this response and protected from death when administered immediately after initiation of infection. Further, anti-SEB antibodies as well as intact polyclonal human IgG, but not its Fab or Fc fragments, protected from lethal pneumonia when followed with linezolid therapy 60 min later. In conclusion, neutralization of superantigens with high-affinity antibodies may have beneficial effects in pneumonia.

Intravenous inoculation of a bat-associated rabies virus causes lethal encephalopathy in mice through invasion of the brain via neurosecretory hypothalamic fibers.

Directory of Open Access Journals (Sweden)

Mirjam A R Preuss

2009-06-01

Full Text Available The majority of rabies virus (RV infections are caused by bites or scratches from rabid carnivores or bats. Usually, RV utilizes the retrograde transport within the neuronal network to spread from the infection site to the central nervous system (CNS where it replicates in neuronal somata and infects other neurons via trans-synaptic spread. We speculate that in addition to the neuronal transport of the virus, hematogenous spread from the site of infection directly to the brain after accidental spill over into the vascular system might represent an alternative way for RV to invade the CNS. So far, it is unknown whether hematogenous spread has any relevance in RV pathogenesis. To determine whether certain RV variants might have the capacity to invade the CNS from the periphery via hematogenous spread, we infected mice either intramuscularly (i.m. or intravenously (i.v. with the dog-associated RV DOG4 or the silver-haired bat-associated RV SB. In addition to monitoring the progression of clinical signs of rabies we used immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR to follow the spread of the virus from the infection site to the brain. In contrast to i.m. infection where both variants caused a lethal encephalopathy, only i.v. infection with SB resulted in the development of a lethal infection. While qRT-PCR did not reveal major differences in virus loads in spinal cord or brain at different times after i.m. or i.v. infection of SB, immunohistochemical analysis showed that only i.v. administered SB directly infected the forebrain. The earliest affected regions were those hypothalamic nuclei, which are connected by neurosecretory fibers to the circumventricular organs neurohypophysis and median eminence. Our data suggest that hematogenous spread of SB can lead to a fatal encephalopathy through direct retrograde invasion of the CNS at the neurovascular interface of the hypothalamus-hypophysis system

Inhalant abuse of computer cleaner manifested as angioedema.

Science.gov (United States)

Kurniali, Peter C; Henry, Letitia; Kurl, Rita; Meharg, Joseph V

2012-01-01

Inhalant abuse is the intentional inhalation of chemical vapors or volatile substance to achieve a euphoric effect. Although no statistical data are reported yet, inhalant abuse is potentially life-threatening and has resulted in a wide range of toxic effects such as central nervous system depression, seizures, aspiration, cardiac arrhythmia, asphyxiation, hypoxia, metabolic acidosis, and sudden death among others. We are reporting a 25-year-old white man who was brought to the emergency department after inhaling aerosolized computer-cleaning spray composed of difluoroethane. He was found to have marked upper and lower lip facial swelling consistent with angioedema. The patient also had a prolonged QT interval, mild inspiratory stridor, but no urticaria. In this case, we believe the difluoroethane-related angioedema represents either idiopathic or bradykinin-induced angioedema.

Inhaled plutonium nitrate in dogs

International Nuclear Information System (INIS)

Dagle, G.E.

1987-01-01

The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. They have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 3 tables

Inhaled plutonium nitrate in dogs

International Nuclear Information System (INIS)

Dagle, G.E.

1986-01-01

The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. The authors have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 4 tables

Inhaled plutonium nitrate in dogs

International Nuclear Information System (INIS)

Dagle, G.E.

1982-01-01

The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in the prediction of health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; as described in previous Annual Reports, lymphopenia and neutropenia occurred at the two highest dose levels. Radiation pneumonitis, lung cancer, and bone cancer have been observed at the highest dose levels

Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination: TORCH study results

DEFF Research Database (Denmark)

Crim, C; Calverley, P M A; Anderson, J A

2009-01-01

Inhaled corticosteroids (ICS) are important in reducing exacerbation frequency associated with chronic obstructive pulmonary disease (COPD). However, little is known about the risk of associated infections. In a post hoc analysis of the TOwards a Revolution in COPD Health (TORCH) study, we analys...... not be concluded for FP. Despite the benefits of ICS-containing regimens in COPD management, healthcare providers should remain vigilant regarding the possible development of pneumonia as a complication in COPD patients receiving such therapies....

Non-Lethal Weapons: Opportunities for R&D

Science.gov (United States)

2004-12-01

during the Vietnam War. US; emulsifying agents are used in food processing, drilling fluids, cosmetics , pharmaceuticals, heavy- duty cleaners, textile...conducted in a professional manner, with no threat to public safety or the environment. 11 References [1] Fenton , G., (2001). NLW Technology Taxonomy...W.A., Mason, R.L., Collins, K.R., (2000). Non-Lethal Applicants of Slippery Substances. NDIA Non-Lethal Defense IV. [24] Fenton , G., (2000). Overview

Role of the chemokine receptors CCR1, CCR2 and CCR4 in the pathogenesis of experimental dengue infection in mice.

Directory of Open Access Journals (Sweden)

Rodrigo Guabiraba

Full Text Available Dengue virus (DENV, a mosquito-borne flavivirus, is a public health problem in many tropical countries. Recent clinical data have shown an association between levels of different chemokines in plasma and severity of dengue. We evaluated the role of CC chemokine receptors CCR1, CCR2 and CCR4 in an experimental model of DENV-2 infection in mice. Infection of mice induced evident clinical disease and tissue damage, including thrombocytopenia, hemoconcentration, lymphopenia, increased levels of transaminases and pro-inflammatory cytokines, and lethality in WT mice. Importantly, infected WT mice presented increased levels of chemokines CCL2/JE, CCL3/MIP-1α and CCL5/RANTES in spleen and liver. CCR1⁻/⁻ mice had a mild phenotype with disease presentation and lethality similar to those of WT mice. In CCR2⁻/⁻ mice, lethality, liver damage, levels of IL-6 and IFN-γ, and leukocyte activation were attenuated. However, thrombocytopenia, hemoconcentration and systemic TNF-α levels were similar to infected WT mice. Infection enhanced levels of CCL17/TARC, a CCR4 ligand. In CCR4⁻/⁻ mice, lethality, tissue injury and systemic inflammation were markedly decreased. Despite differences in disease presentation in CCR-deficient mice, there was no significant difference in viral load. In conclusion, activation of chemokine receptors has discrete roles in the pathogenesis of dengue infection. These studies suggest that the chemokine storm that follows severe primary dengue infection associates mostly to development of disease rather than protection.

Does inhalation injury predict mortality in burns patients or require redefinition?

Directory of Open Access Journals (Sweden)

Youngmin Kim

Full Text Available Inhalation injury is known to be an important factor in predicting mortality in burns patients. However, the diagnosis is complicated by the heterogeneous presentation and inability to determine the severity of inhalation injury. The purpose of this study was to identify clinical features of inhalation injury that affect mortality and the values that could predict the outcome more precisely in burns patients with inhalation injury. This retrospective observational study included 676 burns patients who were over 18 years of age and hospitalized in the Burns Intensive Care Unit between January 2012 and December 2015. We analyzed variables that are already known to be prognostic factors (age, percentage of total body surface area (%TBSA burned, and inhalation injury and factors associated with inhalation injury (carboxyhemoglobin and PaO2/FiO2 [PF] ratio by univariate and multivariate logistic regression. Age group (odds ratio [OR] 1.069, p<0.001, %TBSA burned (OR 1.100, p<0.001, and mechanical ventilation (OR 3.774, p<0.001 were identified to be significant predictive factors. The findings for presence of inhalation injury, PF ratio, and carboxyhemoglobin were not statistically significant in multivariate logistic regression. Being in the upper inhalation group, the lower inhalation group, and having a PF ratio <100 were identified to be significant predictors only in univariate logistic regression analysis (OR 4.438, p<0.001; OR 2.379, p<0.001; and OR 2.765, p<0.001, respectively. History and physical findings are not appropriate for diagnosis of inhalation injury and do not predict mortality. Mechanical ventilation should be recognized as a risk factor for mortality in burns patients with inhalation injury.

Knowledge of spacer device, peak flow meter and inhaler technique ...

African Journals Online (AJOL)

Background: Metered dose inhalers are cornerstone in effective management of bronchial asthma when correctly used. Most studies hitherto have focused on assessing patient's knowledge of inhaler technique. We sought to assess the knowledge of inhaler technique, spacer device and peak flow meter among doctors and ...

Use of sulfur hexafluoride airflow studies to determine the appropriate number and placement of air monitors in an alpha inhalation exposure laboratory

Energy Technology Data Exchange (ETDEWEB)

Newton, G.J.; Hoover, M.D.

1995-12-01

Determination of the appropriate number and placement of air monitors in the workplace is quite subjective and is generally one of the more difficult tasks in radiation protection. General guidance for determining the number and placement of air sampling and monitoring instruments has been provided by technical reports such as Mishima, J. These two documents and other published guidelines suggest that some insight into sampler placement can be obtained by conducting airflow studies involving the dilution and clearance of the relatively inert tracer gas sulfur hexafluoride (SF{sub 6}) in sampler placement studies and describes the results of a study done within the ITRI alpha inhalation exposure laboratories. The objectives of the study were to document an appropriate method for conducting SF{sub 6} dispersion studies, and to confirm the appropriate number and placement of air monitors and air samplers within a typical ITRI inhalation exposure laboratory. The results of this study have become part of the technical bases for air sampling and monitoring in the test room.

Hypoxial death inferred from thermally induced injuries at upper lethal temperatures, in the banded killifish, Fundulus diaphanus (LeSueur)

Energy Technology Data Exchange (ETDEWEB)

Rombough, P J; Garside, E T

1977-10-01

Banded killifish, Fundulus diaphanus (LeSueur), acclimated to 25/sup 0/C were subjected to upper lethal temperatures using a 10,000 min bioassay procedure. The incipient upper lethal temperature (LT/sub 50/) was about 34.5/sup 0/C. Histologic examination of heat-treated fish revealed no obvious injury to the heart, spleen, trunk musculature, eye, naris, integument, or digestive tract. Thermal stress induced progressive injury to the gills characterized by subepithelial edema, congestion of lamellar capillaries, and delamination of the respiratory epithelium from the pillar cell system. Areas of necrosis were observed in the lobus inferior of the hypothalamus and in the medulla oblongata. The pseudobranch epithelium was necrotic. Fatty change occurred in the liver. Acinar cells of the pancreas appeared autolytic and adjacent blood vessels damaged. Degenerative tubular changes and contracted glomerular tufts were noted in the kidney. The ovary was extremely temperature sensitive and displayed severe injury to oocytes and follicular cells after relatively short exposure to temperatures near the LT/sub 50/. It is proposed that primary thermally induced injury is to the gills. This results in abnormal gas exchange and osmoregulation and leads to pathologic changes in other tissues. Hypoxia of the central nervous system appears to be the ultimate cause of death.

Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics.

Science.gov (United States)

Malik, Muhammad; Li, Liping; Zhao, Xilin; Kerns, Robert J; Berger, James M; Drlica, Karl

2014-12-01

One way to address the growing problem of antimicrobial resistance is to revive old compounds that may have intrinsic lethal activity that is obscured by protective factors. Bicyclomycin is an old inhibitor of the Rho transcription terminator that by itself shows little rapid lethal activity. However, bicyclomycin participates in bacteriostatic synergy, which raises the possibility that conditions for lethal synergy may exist, perhaps through a suppression of protective factors. Bicyclomycin was combined with bacteriostatic inhibitors of gene expression, and bactericidal activity was measured with several cultured Gram-negative pathogens. When used alone, bicyclomycin failed to rapidly kill growing cultures of Escherichia coli; however, the additional presence of bacteriostatic concentrations of tetracycline, chloramphenicol or rifampicin led to rapid killing. Four other pathogen species, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella enterica serotype Typhimurium and Shigella dysenteriae, also exhibited enhanced killing when bicyclomycin was combined with tetracycline or rifampicin. This lethal synergy was achieved at low concentrations (slightly above the MIC) for all agents tested in combinations. Follow-up work with E. coli indicated that lethal synergy arose from a blockage of transcription elongation. Moreover, lethal synergy was reduced when bicyclomycin was added 60 min before tetracycline, suggesting that bicyclomycin induces a protective factor. The action of bicyclomycin illustrates the potential present in a largely abandoned antibacterial agent; it exhibits lethal synergy when coadministered with known, bacteriostatic inhibitors of gene expression. The identification of protective factors, which are currently uncharacterized, may reveal new ways to promote the lethal action of some old antibiotics. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

Investigation of toxic effects of imidazolium ionic liquids, [bmim][BF{sub 4}] and [omim][BF{sub 4}], on marine mussel Mytilus galloprovincialis with or without the presence of conventional solvents, such as acetone

Energy Technology Data Exchange (ETDEWEB)

Tsarpali, Vasiliki; Belavgeni, Alexia; Dailianis, Stefanos, E-mail: sdailianis@upatras.gr

2015-07-15

Highlights: • The toxic effects of [bmim][BF{sub 4}] and [omim][BF{sub 4}] on mussels were investigated. • Both ILs could induce lethal and nonlethal effects on Mytilus galloprovincialis. • Different extent of IL-mediated adverse effects was observed in mussel hemocytes. • The alkyl chain length and lipophilicity of ILs are crucial for their toxicity. • Acetone influences the oxidative and genotoxic effects of [omim][BF{sub 4}]. - Abstract: This study investigated the cytotoxic, oxidative and genotoxic effects of two commonly used imidazolium ionic liquids (ILs), [bmim][BF{sub 4}] (1-butyl-3-methylimidazolium) and [omim][BF{sub 4}] (1-methyl-3-octylimidazolium tetrafluoroborate), on the marine mussel Mytilus galloprovincialis, as well as whether acetone could mediate their toxic profile. In this context, mussels were firstly exposed to different concentrations of [bmim][BF{sub 4}] or [omim][BF{sub 4}], with or without the presence of acetone (at a final concentration of 0.06% v/v), for a period of 96 h, in order to determine the concentration that causes 50% mussel mortality (LC{sub 50} values) in each case. Thereafter, mussels were exposed to sub- and non-lethal concentrations of ILs for investigating their ability to cause lysosomal membrane impairment (with the use of neutral red retention assay/NRRT), superoxide anion and lipid peroxidation byproduct (malondialdehyde/MDA) formation, as well as DNA damage and formation of nuclear abnormalities in hemocytes. The results showed that [omim][BF{sub 4}] was more toxic than [bmim][BF{sub 4}] in all cases, while the presence of acetone resulted in a slight attenuation of its toxicity. The different toxic behavior of ILs was further revealed by the significantly lower levels of NRRT values observed in [omim][BF{sub 4}]-treated mussels, compared to those occurring in [bmim][BF{sub 4}] in all cases. Similarly, [bmim][BF{sub 4}]-mediated oxidative and genotoxic effects were observed only in the highest

Inhaled plutonium oxide in dogs

International Nuclear Information System (INIS)

Park, J.F.

1985-01-01

This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols to obtain graded levels of initial lung burdens are being observed for lifespan dose-effect relationships. Mortality due to radiation pneumonitis and lung tumor increased in the four highest dose-level groups exposed to 239 PuO 2 , during the 13-yr postexposure period. During the 10 1/2 years after exposure to 238 PuO 2 , mortality due to lung and/or bone tumors increased in the three highest dose-level groups. Chronic lymphopenia, occurring 0.5 to 2 year after exposure, was the earliest observed effect after inhalation of either 239 PuO 2 or 238 PuO 2 in the four highest dose-level groups that had initial lung burdens greater than or equal to 80 nCi. 3 figures, 6 tables

Terbutaline accumulates in blood and urine following daily therapeutic inhalation

DEFF Research Database (Denmark)

Krogh, Nanna; Rzeppa, Sebastian; Dyreborg, Anders

2017-01-01

×d) of inhaled terbutaline. After inhalation of terbutaline at each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption after which they stayed inactive. Blood and urine samples were collected before and after inhalation of terbutaline. Samples were analyzed by high...

Effect of inhaled formoterol and budesonide on exacerbations of asthma

NARCIS (Netherlands)

Pauwels, RA; Lofdahl, CG; Postma, DS; Tattersfield, AE; OByrne, P; Barnes, PJ; Ullman, A

1997-01-01

Background The role of long-acting, inhaled beta(2)-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. Methods After a four-week run-in period of treatment

Copy number variation of Fc gamma receptor genes in HIV-infected and HIV-tuberculosis co-infected individuals in sub-Saharan Africa.

Directory of Open Access Journals (Sweden)

Lee R Machado

Full Text Available AIDS, caused by the retrovirus HIV, remains the largest cause of morbidity in sub-Saharan Africa yet almost all genetic studies have focused on cohorts from Western countries. HIV shows high co-morbidity with tuberculosis (TB, as HIV stimulates the reactivation of latent tuberculosis (TB. Recent clinical trials suggest that an effective anti-HIV response correlates with non-neutralising antibodies. Given that Fcγ receptors are critical in mediating the non-neutralising effects of antibodies, analysis of the extensive variation at Fcγ receptor genes is important. Single nucleotide variation and copy number variation (CNV of Fcγ receptor genes affects the expression profile, activatory/inhibitory balance, and IgG affinity of the Fcγ receptor repertoire of each individual. In this study we investigated whether CNV of FCGR2C, FCGR3A and FCGR3B as well as the HNA1 allotype of FCGR3B is associated with HIV load, response to highly-active antiretroviral therapy (HAART and co-infection with TB. We confirmed an effect of TB-co-infection status on HIV load and response to HAART, but no conclusive effect of the genetic variants we tested. We observed a small effect, in Ethiopians, of FCGR3B copy number, where deletion was more frequent in HIV-TB co-infected patients than those infected with HIV alone.

In vitro and in vivo activity of ribavirin against Andes virus infection.

Directory of Open Access Journals (Sweden)

David Safronetz

Full Text Available Pathogenic hantaviruses are a closely related group of rodent-borne viruses which are responsible for two distinct diseases in humans, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome (HPS, otherwise known as hantavirus cardiopulmonary syndrome, HCPS. The antiviral effect of ribavirin against Old World hantaviruses, most notably Hantaan virus, is well documented; however, only a few studies have addressed its inhibitory effect on New World hantaviruses. In the present study, we demonstrate that ribavirin is highly active against Andes virus (ANDV, an important etiological agent of HPS, both in vitro and in vivo using a lethal hamster model of HPS. Treatment of ANDV infected Vero E6 cells with ribavirin resulted in dose-dependent reductions in viral RNA and protein as well as virus yields with a half maximal inhibitory concentration between 5 and 12.5 µg ml(-1. In hamsters, treatment with as little as 5 mg kg(-1 day(-1 was 100% effective at preventing lethal HPS disease when therapy was administered by intraperitoneal injection from day 1 through day 10 post-infection. Significant reductions were observed in ANDV RNA and antigen positive cells in lung and liver tissues. Ribavirin remained completely protective when administered by intraperitoneal injections up to three days post-infection. In addition, we show that daily oral ribavirin therapy initiated 1 day post-infection and continuing for ten days is also protective against lethal ANDV disease, even at doses of 5 mg kg(-1 day(-1. Our results suggest ribavirin treatment is beneficial for postexposure prophylaxis against HPS-causing hantaviruses and should be considered in scenarios where exposure to the virus is probable. The similarities between the results obtained in this study and those from previous clinical evaluations of ribavirin against HPS, further validate the hamster model of lethal HPS and demonstrate its usefulness in screening antiviral agents against

Using compound SiO{sub 2}(62-68)-MgO+CaO(29-39) in the protections of ceramics of steel company to replace the CaO-Al{sub 2}O{sub 3}-SiO{sub 2} compound; Utilizacao do composto SiO{sub 2}(62-68)-MgO+CaO(29-39) nas protecoes ceramicas de empresa siderurgica em substituicao ao composto CaO-Al{sub 2}O{sub 3}-SiO{sub 2}

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Nogueira, Anderson Carvalho; Silva, Paula Cipriano da; Vernilli Junior, Fernando; Santos, Claudinei dos; Magnago, Roberto de Oliveira [Centro Universitario de Volta Redonda (UNIFOA), Volta Redonda, RJ (Brazil); Lima, Leonardo Moreira de [Universidade de Sao Paulo (USP), Lorena, SP (Brazil)

2014-12-15

This article describes the use of protective ceramic composed of SiO{sub 2}(62-68)-MgO + CaO(29-39) in the frontal region of the machines that inject mass refractory to stop racing pig iron and slag liquid in blast furnaces. The new protection model (prototype) showed a annual saving of approximately R$ 32,000.00 compared to the compound previously used CaO-Al{sub 2}O{sub 3}-SiO{sub 2}. Also had a lower toxicity, as it has in its morphology least amount of fiber. These fibers when inhaled cause damage to internal tissues of the lungs is harmful to health. There maintenance rates of production, since in all samples tested the new ceramic protection, the front part was preserved allowing the refractory mass injection quantity and pressure required for reconstitution of the length of the bore which removes iron and slag inside the high oven, allowing for a larger internal volume to produce more. The protection models were produced by Morganite-Brazil. The morphology and crystallographic characterization were characterized by Scanning Electron Microscopy and X-ray diffraction, respectively. (author)

USC-087 protects Syrian hamsters against lethal challenge with human species C adenoviruses.

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Toth, Karoly; Spencer, Jacqueline F; Ying, Baoling; Tollefson, Ann E; Hartline, Caroll B; Richard, Eric T; Fan, Jiajun; Lyu, Jinglei; Kashemirov, Boris A; Harteg, Cheryl; Reyna, Dawn; Lipka, Elke; Prichard, Mark N; McKenna, Charles E; Wold, William S M

2018-05-01

Human adenoviruses (AdV) cause generally mild infections of the respiratory and GI tracts as well as some other tissues. However, AdV can cause serious infection in severely immunosuppressed individuals, especially pediatric patients undergoing allogeneic hematopoietic stem cell transplantation, where mortality rates are up to 80% with disseminated disease. Despite the seriousness of AdV disease, there are no drugs approved specifically to treat AdV infections. We report here that USC-087, an N-alkyl tyrosinamide phosphonate ester prodrug of HPMPA, the adenine analog of cidofovir, is highly effective against multiple AdV types in cell culture. USC-087 is also effective against AdV-C6 in our immunosuppressed permissive Syrian hamster model. In this model, hamsters are immunosuppressed by treatment with high dose cyclophosphamide. Injection of AdV-C6 (or AdV-C5) intravenously leads to a disseminated infection that resembles the disease seen in humans, including death. We have tested the efficacy of orally-administered USC-087 against the median lethal dose of intravenously administered AdV-C6. USC-087 completely prevented or significantly decreased mortality when administered up to 4 days post challenge. USC-087 also prevented or significantly decreased liver damage caused by AdV-C6 infection, and suppressed virus replication even when administered 4 days post challenge. These results imply that USC-087 is a promising candidate for drug development against HAdV infections. Copyright © 2018 Elsevier B.V. All rights reserved.

Treatment of proctalgia fugax with salbutamol inhalation.

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Eckardt, V F; Dodt, O; Kanzler, G; Bernhard, G

1996-04-01

Although no generally effective treatment for proctalgia fugax is known, inhalation of salbutamol has been reported to shorten pain attacks in isolated cases. We conducted a randomized, double-blind, placebo-controlled, crossover trial of inhaled salbutamol in 18 patients with proctalgia fugax. The clinical effect was evaluated by recording the duration of severe pain and discomfort during acute attacks. In addition, anorectal motility recordings were analyzed for possible changes in anal resting tone, sphincter relaxation during rectal distension and in rectal compliance prior to and following administration of the two test substances. Sixteen patients completed all investigations. Compared to placebo, salbutamol inhalation shortened the duration of severe pain (p = 0.019). The effect was most marked in patients having prolonged attacks. In the asymptomatic state, neither salbutamol nor placebo led to a significant change in anal resting pressure, anal relaxation during rectal distension, or rectal compliance. Salbutamol also did not alter the threshold for rectal sensation. Salbutamol inhalation shortens attacks of severe pain in patients with proctalgia fugax. The mechanism of this effect remains unexplained.

Inhaled corticosteroid metered-dose inhalers: how do variations in technique for solutions versus suspensions affect drug distribution?

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Robinson, Christie A; Tsourounis, Candy

2013-03-01

To assess the literature that evaluates how variations in metered-dose inhaler (MDI) technique affect lung distribution for inhaled corticosteroids (ICSs) formulated as MDI suspensions and solutions. PubMed (up to November 2012) and Cochrane Library (up to November 2012) were searched using the terms metered-dose inhalers, HFA 134a, Asthma/*drug therapy, and inhaled corticosteroids. In addition, reference citations from publications identified were reviewed. All articles in English from the data sources that assessed MDI technique comparing total lung distribution (TLD) of MDI solutions or suspensions formulated with ICSs were included in the review. Five relevant studies were identified. Five controlled studies compared how variations in MDI technique affect TLD for ICS MDI solutions with suspensions. MDI solutions resulted in greater TLD compared with larger particle MDI suspensions. Delayed or early inspiration upon device actuation of MDI solutions resulted in less TLD than coordinated actuation, but with a 3- to 4-times greater TLD than MDI suspensions inhaled using a standard technique. A sixth study evaluated inspiratory flow rates (IFR) for small, medium, and large particles. Rapid and slow IFRs resulted in similar TLD for small particles, while far fewer particles reached the airways with medium and large particles at rapid, rather than slow, IFRs. Based on the literature evaluated, standard MDI technique should be used for ICS suspensions. ICS MDI solutions can provide a higher average TLD than larger-particle ICS suspensions using standard technique, discoordinated inspiration and medication actuation timing, or rapid and slow IFRs. ICS MDI solutions allow for a more forgiving technique, which makes them uniquely suitable options for patients with asthma who have difficultly with MDI technique.

Development of a High Efficiency Dry Powder Inhaler: Effects of Capsule Chamber Design and Inhaler Surface Modifications

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Behara, Srinivas R.B.; Farkas, Dale R.; Hindle, Michael; Longest, P. Worth

2013-01-01

Purpose The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device. Methods DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices. Results The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI. Conclusions High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD 90%, and ED > 80%. PMID:23949304

Development of a high efficiency dry powder inhaler: effects of capsule chamber design and inhaler surface modifications.

Science.gov (United States)

Behara, Srinivas R B; Farkas, Dale R; Hindle, Michael; Longest, P Worth

2014-02-01

The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device. DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices. The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI. High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD  90%, and ED > 80%.