scholarly journals Microbicidal Power of Alpha Radiation in Sterilizing Germinating Bacillus anthracis Spores

2013 ◽  
Vol 58 (3) ◽  
pp. 1813-1815 ◽  
Author(s):  
Johanna Rivera ◽  
Alfred Morgenstern ◽  
Frank Bruchertseifer ◽  
John F. Kearney ◽  
Charles L. Turnbough ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Dependent Manner ◽  
Alpha Radiation ◽  
Content Type ◽  
Immunodominant Antigen ◽  
Spore Killing ◽  
Bacillus Anthracis Spores ◽  
A Site ◽  
Antigen Antibody ◽  
Dose Dependent

ABSTRACTRadioimmunotherapy (RIT) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver microbicidal radioactive nuclides to a site of infection. In this study, we investigated the microbicidal properties of an alpha particle-emitting213Bi-labeled monoclonal antibody (MAb), EA2-1 (213Bi-EA2-1), that binds to the immunodominant antigen onBacillus anthracisspores. Our results showed that dormant spores were resistant to213Bi-EA2-1. Significant spore killing was observed following treatment with EA2-1 labeled with 300 μCi213Bi; however, this effect was not dependent on the MAb. In contrast, when spores were germinating,213Bi-EA2-1 mediated MAb-specific killing in a dose-dependent manner. Dormant spores are very resistant to RIT, and RIT should focus on targeting vegetative cells and germinating spores.

scholarly journals Ibogaine Modifies GDNF, BDNF and NGF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits

2018 ◽  
Author(s):  
Soledad Marton ◽  
Bruno González ◽  
Sebastián Rodríguez ◽  
Ernesto Miquel ◽  
Laura Martínez Palma ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Brain Regions ◽  
Dopamine Neurons ◽  
Acute Administration ◽  
Dependent Manner ◽  
Self Administration ◽  
Seeking Behavior ◽  
A Site ◽  
Dose Dependent

<p>Ibogaine is a psychedelic alkaloid which has been subject of intense scientific research due to its reported ability to attenuate drug-seeking behavior. Recent work suggested that ibogaine effects on alcohol self-administration in rats was related to the release of Glial Cell Derived Neurotrophic Factor (GDNF) in the Ventral Tegmental Area (VTA), a mesencephalic region which hosts soma of dopamine neurons. It is well known that neurotrophic factors (NFs) mediate the neuroadaptations induced in the mesocorticolimbic dopaminergic system by repeated exposure to drugs. Although previous reports have shown ibogaine´s ability to induce GDNF expression in rat midbrain, there are no studies addressing its effect on the expression of GDNF, Brain Derived Neurotrophic Factor (BDNF) or Nerve Growth Factor (NGF) in distinct regions containing dopaminergic neurons. In this work, we examined the effect of ibogaine acute administration on the expression of these NFs in the VTA, Prefrontal Cortex (PFC), Nucleus Accumbens (NAcc) and the Substantia Nigra (SN). Thus, rats were i.p. treated with ibogaine 20 mg/kg (I<sub>20</sub>), 40 mg/kg (I<sub>40</sub>) or vehicle, and NFs expression was analyzed after 3 and 24 hours. Only at 24 h an increase of the expression for the three NFs were observed in a site and dose dependent manner. Results for GDNF showed that only I<sub>40</sub> selectively upregulated its expression in the VTA and SN. Both doses of ibogaine elicited a large increase in the expression of BDNF in the NAcc, SN and PFC, while a significant effect was found in the VTA only for I<sub>40</sub>. Finally, NGF was found to be upregulated in all regions after I<sub>40</sub>, while a selective upregulation was found in PFC and VTA for the I<sub>20</sub> treatment. An increase in the content of mature GDNF was observed in the VTA but no significant increase in the mature BDNF protein content was found in all the studied areas. Interestingly, an increase in the content of proBDNF was detected in the NAcc for both treatments. Further research is needed to understand the neurochemical bases of these changes, and to confirm their contribution to the anti-addictive properties of ibogaine. </p>

scholarly journals Fast and Sensitive Detection of Bacillus anthracis Spores by Immunoassay

2012 ◽  
Vol 78 (18) ◽  
pp. 6491-6498 ◽  
Author(s):  
Nathalie Morel ◽  
Hervé Volland ◽  
Julie Dano ◽  
Patricia Lamourette ◽  
Patricia Sylvestre ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Electrical Current ◽  
Biological Weapons ◽  
Meso Scale Discovery ◽  
Simple Method ◽  
Content Type ◽  
Bacillus Anthracis Spores ◽  
Luminescent Signal ◽  
Sample Purification ◽  
Phosphate Buffered Saline

ABSTRACTBacillus anthracisis one of the most dangerous potential biological weapons, and it is essential to develop a rapid and simple method to detectB. anthracisspores in environmental samples. The immunoassay is a rapid and easy-to-use method for the detection ofB. anthracisby means of antibodies directed against surface spore antigens. With this objective in view, we have produced a panel of monoclonal antibodies againstB. anthracisand developed colorimetric and electrochemiluminescence (ECL) immunoassays. Using Meso Scale Discovery ECL technology, which is based on electrochemiluminescence (ECL) detection utilizing a sulfo-Tag label that emits light upon electrochemical stimulation (using a dedicated ECL plate reader, an electrical current is placed across the microplate with electrodes integrated into the bottom of the plate, resulting in a series of electrically induced reactions leading to a luminescent signal), a detection limit ranging between 0.3 × 103and 103CFU/ml (i.e., 30 to 100 spores per test), depending on theB. anthracisstrain assayed, was achieved. In complex matrices (5 mg/ml of soil or simulated powder), the detection level (without any sample purification or concentration) was never altered more than 3-fold compared with the results obtained in phosphate-buffered saline.

scholarly journals Intracellular Free Iron and Its Potential Role in Ultrahigh-Pressure-Induced Inactivation of Escherichia coli

2012 ◽  
Vol 79 (2) ◽  
pp. 722-724 ◽  
Author(s):  
Yuan Yan ◽  
Joy G. Waite-Cusic ◽  
Periannan Kuppusamy ◽  
Ahmed E. Yousef
Keyword(s):  
Escherichia Coli ◽  
Iron Chelator ◽  
Ultrahigh Pressure ◽  
Dependent Manner ◽  
Paramagnetic Resonance ◽  
Free Iron ◽  
Content Type ◽  
E Coli ◽  
Electron Paramagnetic ◽  
Dose Dependent

ABSTRACTIntracellular free iron ofEscherichia coliwas determined by whole-cell electron paramagnetic resonance spectrometry. Ultrahigh pressure (UHP) increased both intracellular free iron and cell lethality in a pressure-dose-dependent manner. The iron chelator 2,2′-dipyridyl protected cells against UHP treatments. A mutation that produced iron overload conditions sensitizedE. colito UHP treatment.

scholarly journals Silver Nanoparticles Decrease the Viability of Cryptosporidium parvum Oocysts

2015 ◽  
Vol 82 (2) ◽  
pp. 431-437 ◽  
Author(s):  
Pamela Cameron ◽  
Birgit K. Gaiser ◽  
Bidha Bhandari ◽  
Paul M. Bartley ◽  
Frank Katzer ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Cryptosporidium Parvum ◽  
Silver Ions ◽  
Protozoan Parasite ◽  
Dependent Manner ◽  
Oocyst Wall ◽  
Content Type ◽  
Chlorine Disinfection ◽  
High Concentrations ◽  
Dose Dependent

ABSTRACTOocysts of the waterborne protozoan parasiteCryptosporidium parvumare highly resistant to chlorine disinfection. We show here that both silver nanoparticles (AgNPs) and silver ions significantly decrease oocyst viability, in a dose-dependent manner, between concentrations of 0.005 and 500 μg/ml, as assessed by an excystation assay and the shell/sporozoite ratio. For percent excystation, the results are statistically significant for 500 μg/ml of AgNPs, with reductions from 83% for the control to 33% with AgNPs. For Ag ions, the results were statistically significant at 500 and 5,000 μg/ml, but the percent excystation values were reduced only to 66 and 62%, respectively, from 86% for the control. The sporozoite/shell ratio was affected to a greater extent following AgNP exposure, presumably because sporozoites are destroyed by interaction with NPs. We also demonstrated via hyperspectral imaging that there is a dual mode of interaction, with Ag ions entering the oocyst and destroying the sporozoites while AgNPs interact with the cell wall and, at high concentrations, are able to fully break the oocyst wall.

scholarly journals Evaluation of the Efficacy of Methyl Bromide in the Decontamination of Building and Interior Materials Contaminated with Bacillus anthracis Spores

2016 ◽  
Vol 82 (7) ◽  
pp. 2003-2011 ◽  
Author(s):  
Joseph P. Wood ◽  
Morgan Wendling ◽  
William Richter ◽  
Andrew Lastivka ◽  
Leroy Mickelsen
Keyword(s):  
Bacillus Anthracis ◽  
Methyl Bromide ◽  
Contact Time ◽  
Geobacillus Stearothermophilus ◽  
Efficacy Data ◽  
Content Type ◽  
New Information ◽  
Bacillus Anthracis Spores ◽  
Effective Use ◽  
Selection Of

ABSTRACTThe primary goal of this study was to determine the conditions required for the effective inactivation ofBacillus anthracisspores on materials by using methyl bromide (MeBr) gas. Another objective was to obtain comparative decontamination efficacy data with three avirulent microorganisms to assess their potential for use as surrogates forB. anthracisAmes. Decontamination tests were conducted with spores ofB. anthracisAmes andGeobacillus stearothermophilus,B. anthracisNNR1Δ1, andB. anthracisSterne inoculated onto six different materials. Experimental variables included temperature, relative humidity (RH), MeBr concentration, and contact time. MeBr was found to be an effective decontaminant under a number of conditions. This study highlights the important role that RH has when fumigation is performed with MeBr. There were no tests in which a ≥6-log10reduction (LR) ofB. anthracisAmes was achieved on all materials when fumigation was done at 45% RH. At 75% RH, an increase in the temperature, the MeBr concentration, or contact time generally improved the efficacy of fumigation with MeBr. This study provides new information for the effective use of MeBr at temperatures and RH levels lower than those that have been recommended previously. The study also provides data to assist with the selection of an avirulent surrogate forB. anthracisAmes spores when additional tests with MeBr are conducted.

scholarly journals Repression of Ets-2-Induced Transactivation of the Tau Interferon Promoter by Oct-4

2001 ◽  
Vol 21 (23) ◽  
pp. 7883-7891 ◽  
Author(s):  
Toshihiko Ezashi ◽  
Debjani Ghosh ◽  
R. Michael Roberts
Keyword(s):  
Luciferase Reporter ◽  
Dependent Manner ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Pou Domain ◽  
Choriocarcinoma Cells ◽  
A Site ◽  
Dose Dependent ◽  
Developmental Switch

ABSTRACT Oct-4 is a POU family transcription factor associated with potentially totipotent cells. Genes expressed in the trophectoderm but not in embryos prior to blastocyst formation may be targets for silencing by Oct-4. Here, we have tested this hypothesis with the tau interferon genes (IFNT genes), which are expressed exclusively in the trophectoderm of bovine embryos. IFNTpromoters contain an Ets-2 enhancer, located at −79 to −70, and are up-regulated about 20-fold by the overexpression of Ets-2 in human JAr choriocarcinoma cells, which are permissive for IFNTexpression. This enhancement was reversed in a dose-dependent manner by coexpression of Oct-4 but not either Oct-1 or Oct-2. When cells were transfected with truncated bovine IFNT promoters designed to eliminate potential octamer sites sequentially, luciferase reporter expression from each construct was still silenced by Oct-4. Full repression required both the N-terminal and POU domains of Oct-4, but neither domain used alone was an effective silencer. Oct-4 and Ets-2 formed a complex in vitro in the absence of DNA through binding of the POU domain of Oct-4 to a site located between the “pointed” and DNA binding domains of Ets-2. The two transcription factors were also coimmunoprecipitated after being expressed together in JAr cells. Oct-4, therefore, silences IFNT promoters by quenching Ets-2 transactivation. The POU domain most probably binds to Ets-2 directly, while the N-terminal domain inhibits transcription. These findings provide further evidence that the developmental switch to the trophectoderm is accompanied by the loss of Oct-4 silencing of key genes.

scholarly journals Virulent Bacteriophages Can Target O104:H4 Enteroaggregative Escherichia coli in the Mouse Intestine

2012 ◽  
Vol 56 (12) ◽  
pp. 6235-6242 ◽  
Author(s):  
Damien Maura ◽  
Matthieu Galtier ◽  
Chantal Le Bouguénec ◽  
Laurent Debarbieux
Keyword(s):  
Escherichia Coli ◽  
Dependent Manner ◽  
Content Type ◽  
Intestinal Pathogens ◽  
Colonization Model ◽  
Mouse Intestine ◽  
Further Development ◽  
Dose Dependent

ABSTRACTIn vivobacteriophage targeting of enteroaggregativeEscherichia coli(EAEC) was assessed using a mouse intestinal model of colonization with the O104:H4 55989Str strain and a cocktail of three virulent bacteriophages. The colonization model was shown to mimic asymptomatic intestinal carriage found in humans. The addition of the cocktail to drinking water for 24 h strongly decreased ileal and weakly decreased fecal 55989Str concentrations in a dose-dependent manner. These decreases in ileal and fecal bacterial concentrations were only transient, since 55989Str concentrations returned to their original levels 3 days later. These transient decreases were independent of the mouse microbiota, as similar results were obtained with axenic mice. We studied the infectivity of each bacteriophage in the ileal and fecal environments and found that 55989Str bacteria in the mouse ileum were permissive to all three bacteriophages, whereas those in the feces were permissive to only one bacteriophage. Our results provide the first demonstration that bacterial permissivity to infection with virulent bacteriophages is not uniform throughout the gut; this highlights the need for a detailed characterization of the interactions between bacteria and bacteriophagesin vivofor the further development of phage therapy targeting intestinal pathogens found in the gut of asymptomatic human carriers.

scholarly journals Targeting Essential Genes in Salmonella enterica Serovar Typhimurium with Antisense Peptide Nucleic Acid

2012 ◽  
Vol 56 (12) ◽  
pp. 6407-6409 ◽  
Author(s):  
Muhammad A. Soofi ◽  
Mohamed N. Seleem
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Essential Genes ◽  
Dependent Manner ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Gene Inhibition ◽  
Dose Dependent ◽  
Antisense Peptide ◽  
Great Potency

ABSTRACTWe investigated the capability of antisense peptide nucleic acids (PNAs) conjugated to the (KFF)3K cell-penetrating peptide to target possible essential genes (ligA,rpoA,rpoD,engA,tsf, andkdtA) inSalmonella entericaserovar Typhimurium and inhibit bacterial growthin vitro and in cell culture. All targeted PNA-based gene inhibition has shown great potency in gene expression inhibition in a sequence-specific and dose-dependent manner at micromolar concentrations. Among tested PNAs, the anti-rpoAand -rpoDPNAs showed the greatest potency.

scholarly journals Significant passive protective effect against anthrax by antibody to Bacillus anthracis inactivated spores that lack two virulence plasmids

Microbiology ◽  
2006 ◽  
Vol 152 (10) ◽  
pp. 3103-3110 ◽  
Author(s):  
Jargalsaikhan Enkhtuya ◽  
Keiko Kawamoto ◽  
Yoshiyasu Kobayashi ◽  
Ikuo Uchida ◽  
Neeraj Rana ◽  
...  
Keyword(s):  
Protective Effect ◽  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Lethal Dose ◽  
Dependent Manner ◽  
Protective Effects ◽  
Virulence Plasmids ◽  
Somatic Antigens ◽  
Dose Dependent ◽  
Formalin Fixed

The protective-antigen (PA)-based cell-free vaccine is the only vaccine licensed for use against Bacillus anthracis infection in humans. Although the PA shows strong immunogenicity, the capsule or spore-associated somatic antigens may be important as additional vaccine targets for full protection against anthrax. In this study, the protective effect of spore-associated antigens against B. anthracis infection was determined. Rabbits were immunized with formalin-fixed spores of a non-toxigenic unencapsulated B. anthracis strain that lacked the two virulence plasmids pXO1 and pXO2, and the protective effects of the immune antibody were evaluated. Immunostaining and Western blot analysis revealed that the anti-B. anthracis (anti-BA)-spore IgG specifically bound to the surface of spores or endospores of B. anthracis, but not to vegetative cells, or closely related Bacillus species, such as Bacillus cereus, Bacillus subtilis and Bacillus thuringiensis. Passively transferred anti-BA-spore IgG protected mice from intraperitoneal challenge with a lethal dose of fully virulent B. anthracis spores, and increased the survival rate in a dose-dependent manner. Pre-incubation of spores with antibody also reduced their infectivity in a dose-dependent manner. The number of bacteria (c.f.u.) in spleens and livers of infected mice was significantly lower in antibody-treated mice than in untreated mice. Treatment with anti-BA-spore IgG also inhibited the germination of spores in J774.1 macrophages, suggesting that opsonization of spores promotes phagocytosis and subsequent killing by macrophages. These results indicate the usefulness of spore surface antigens as vaccine targets. In combination with major virulence factors such as the PA, spore-associated antigens may offer a safer and more effective multicomponent vaccine for B. anthracis infection.

In vitro anti-diabetic activity of Tribulus terrestrisL. fruits extracts

2019 ◽  
Vol 50 (4) ◽  
pp. 631-640
Author(s):  
Kholowd AlKhaldi ◽  
Manal Daghestani ◽  
Thanaa Al-Haddad
Keyword(s):  
Acetone Extract ◽  
Hexane Extract ◽  
Tribulus Terrestris ◽  
Dependent Manner ◽  
Inhibition Activity ◽  
Content Type ◽  
Significant Difference ◽  
Ethanol Extracts ◽  
Dose Dependent

Purpose The purpose of this paper is to evaluate the inhibition activity of Tribulus terrestris L. (T. terrestris) fruits extracts with solvents of increasing polarity against α-glucosidase and α-amylase, and to determine the inhibition mode of the most effective extract against both enzymes. Design/methodology/approach Hexane, acetone, ethanol and aqueous extracts of T. terrestris fruits were prepared using ultrasonic sequential extraction and analyzed for their α-amylase and α-glucosidase inhibitory activities by specific assay for each enzyme. The modes of inhibitions were detected using Lineweaver–Burk plots. Findings T. terrestris fruits extracts showed inhibition activity against α-glucosidase and α-amylase which was in the dose-dependent manner. Hexane extract had the highest α-glucosidase inhibition activity (IC50 = 27.28 μg/ml, p = 0.003), followed by acetone and ethanol extracts (IC50 = 60.58 μg/ml and IC50 = 84.21 μg/ml, respectively). The inhibition mode of hexane extract was noncompetitive. While acetone extract showed the highest inhibition activity against α-amylase (IC50 = 6.18 mg/ml, p = 0.002), hexane and ethanol extracts showed no significant difference (IC50 = 13.04 mg/ml and IC50 = 14.20 mg/ml, respectively, p = 0.09). The inhibition mode of acetone extract was competitive. Originality/value T. terrestris fruits extracts had strong inhibition activity against α-glucosidase and α-amylase, and they can be used as a promising anti-diabetic agent.

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