Engineering of Paraoxonases for Pre- and Post-treatment of Intoxication by a Broad Spectrum of Nerve Agents and Pesticides

2013 ◽  
Author(s):  
Dan Tawfik ◽  
Joel L. Sussman
Keyword(s):  
Broad Spectrum ◽  
Nerve Agents ◽  
Post Treatment

scholarly journals Microbiome Compositions and Resistome Levels after Antibiotic Treatment of Critically Ill Patients: An Observational Cohort Study

2021 ◽  
Vol 9 (12) ◽  
pp. 2542
Author(s):  
Karen Leth Nielsen ◽  
Markus Harboe Olsen ◽  
Albert Pallejá ◽  
Søren Røddik Ebdrup ◽  
Nikolaj Sørensen ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Broad Spectrum ◽  
Selection Pressure ◽  
Shannon Index ◽  
Post Treatment ◽  
Neurointensive Care ◽  
Resistant Bacteria ◽  
Metagenomic Sequencing ◽  
Narrow Spectrum ◽  
Broad Spectrum Treatment

Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This study aimed to investigate how broad- and narrow-spectrum antibiotics affect the gut microbiome and the resistome in antibiotic naïve patients during neurointensive care. Patients admitted to the neurointensive care unit were treated with broad-spectrum (meropenem or piperacillin/tazobactam) or narrow-spectrum antibiotic treatment (including ciprofloxacin, cefuroxime, vancomycin and dicloxacillin) according to clinical indications. A rectal swab was collected from each patient before and after 5–7 days of antibiotic therapy (N = 34), respectively. Shotgun metagenomic sequencing was performed and the composition of metagenomic species (MGS) was determined. The resistome was characterized with CARD RGI software and the CARD database. As a measure for selection pressure in the patient, we used the sum of the number of days with each antibiotic (antibiotic days). We observed a significant increase in richness and a tendency for an increase in the Shannon index after narrow-spectrum treatment. For broad-spectrum treatment the effect was more diverse, with some patients increasing and some decreasing in richness and Shannon index. This was studied further by comparison of patients who had gained or lost >10 MGS, respectively. Selection pressure was significantly higher in patients with decreased richness and a decreased Shannon index who received the broad treatment. A decrease in MGS richness was significantly correlated to the number of drugs administered and the selection pressure in the patient. Bray–Curtis dissimilarities were significant between the pre- and post-treatment of samples in the narrow group, indicating that the longer the narrow-spectrum treatment, the higher the differences between the pre- and the post-treatment microbial composition. We did not find significant differences between pre- and post-treatment for both antibiotic spectrum treatments; however, we observed that most of the antibiotic class resistance genes were higher in abundance in post-treatment after broad-spectrum treatment.

scholarly journals A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents

2019 ◽  
Vol 32 (4) ◽  
pp. 169-174 ◽  
Author(s):  
Dragana Despotović ◽  
Einav Aharon ◽  
Artem Dubovetskyi ◽  
Haim Leader ◽  
Yacov Ashani ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Entire Range ◽  
Nerve Agents ◽  
Ester Bond ◽  
Minimal Impact ◽  
Entire Spectrum ◽  
Enzyme Cocktail ◽  
Enzymatic Detoxification ◽  
Single Enzyme

Abstract Nerve agents are organophosphates (OPs) that potently inhibit acetylcholinesterase, and their enzymatic detoxification has been a long-standing goal. Nerve agents vary widely in size, charge, hydrophobicity and the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Here, we describe a mixture of three previously developed variants of the bacterial phosphotriesterase (Bd-PTE) that are highly stable and nearly sequence identical. This mixture enables effective detoxification of a broad spectrum of known threat agents—GA (tabun), GB (sarin), GD (soman), GF (cyclosarin), VX and Russian-VX. The potential for dimer dissociation and exchange that could inactivate Bd-PTE has minimal impact, and the three enzyme variants are as active in a mixture as they are individually. To our knowledge, this engineered enzyme ‘cocktail’ comprises the first solution for enzymatic detoxification of the entire range of threat nerve agents.

scholarly journals A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents

2019 ◽  
Author(s):  
Dragana Despotovic ◽  
Einav Aharon ◽  
Artem Dubovetskyi ◽  
Haim Leader ◽  
Yacov Ashani ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Entire Range ◽  
Nerve Agents ◽  
Ester Bond ◽  
Minimal Impact ◽  
Entire Spectrum ◽  
Enzyme Cocktail ◽  
Enzymatic Detoxification ◽  
Single Enzyme

AbstractNerve agents are organophosphates that potently inhibit acetylcholinesterase and their enzymatic detoxification has been a long-standing goal. Nerve agents vary widely in size, charge, hydrophobicity, and the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Here, we describe a mixture of three previously developed variants of the bacterial phosphotriesterase (Bd-PTE) that are highly stable and nearly sequence identical. This mixture enables effective detoxification of a broad spectrum of known threat agents – GA (tabun), GB (sarin), GD (soman), GF (cyclosarin), VX, and Russian-VX. The potential for dimer dissociation and exchange that could inactivate Bd-PTE has minimal impact, and the three enzyme variants are as active in a mixture as they are individually. To our knowledge, this engineered enzyme ‘cocktail’ comprises the first solution for enzymatic detoxification of the entire range of threat nerve agents.

Ultrastructure of bronchopulmonary lavage cells from bovines administered 3-methylindole: II. 24 hours post-treatment

1984 ◽  
Vol 42 ◽  
pp. 202-203
Author(s):  
Amreek Singh ◽  
Judith M. McLaren ◽  
Onkar S. Atwal ◽  
Peter Eyre
Keyword(s):  
Plasma Cells ◽  
Ciliated Cell ◽  
Lavage Fluid ◽  
Treated Group ◽  
Post Treatment ◽  
Lung Edema ◽  
Ciliated Cells ◽  
Thin Sections ◽  
Variable Diameter ◽  
Cell Pellet

Introduction3-methylindole (MI), a rumen metabolite of the amino acid L-tryptophan, has been shown to produce bovine pulmonary edema and emphysema. The airways contain free and exfoliated cells. A morphologic analysis of these cells may complement the understanding of the mechanism of lung edema. Ultrastructure of the bronchopulmonary lavage (BL) cells 24 h following MI oral administration to calves is described in this experiment. The 12 hours post-treatment results were described earlier.Materials and MethodsTwo Holstein-Friesian calves were each administered an oral dose of 0.2 g MI/Kg body weight and another two calves served as controls. The animals were euthanized with sodium pentabarbitol 24 h after receiving the compound. The lungs and trachea were removed and 0.1 M sodium phosphate buffered saline was infused into the lungs through the trachea. Glutaraldehyde fixative was added to the recovered BL fluid so as to form a 1% solution. The fluid was centrifuged and the resulting cell pellet was suspended in the buffer. The procedures were repeated on the suspension; the pellet was post-fixed in osmium tetroxide and was processed by conventional methods of section preparations for TEM examination. Lung samples from caudal lobes were fixed in 1.5% glutaraldehyde to obtain tissue sections for TEM.Results and DiscussionPulmonary alveolar macrophages (AM), neutrophils, ciliated epithelial cells, globule leukocytes and plasma cells were recovered from the BL fluid of the control and Mi-administered calves. Ciliated cells and globule leukocytes could not be harvested from the controls. The AM obtained from the treated calves (Fig. 1) in comparison with similar cells from the controls were larger, and contained large membrane-limited inclusions (phagolysosomes). There was a remarkable similarity between the lavaged AM and the AM studied in thin sections of lung (cf. Fig. 1 and Fig. 2). The neutrophil was the second most abundant cell type retrieved from the lavage fluid from the calves of control or treated group. Except for scanty pseudopodia in the neutrophils obtained from the Mi-receiving calves, the cells appeared unaltered (Fig. 3). Ciliated cells were abundant in the BL fluid of Mi-ingesting calves. A heterogeneous collection of vesicles filled the ciliated cell cytoplasm (Fig. 3). Globule leukocytes were commonly observed among BL cells of treated calves. The globule leukocytes were ca. 15 μm in diameter and contained round or elliptical nuclei with conspicuous nucleoli. The cytoplasmic granules, which are a prominent feature of globule leukocytes, were electron-opaque and had a variable diameter (0.5-3.0 μm). A one-line account of globule leukocytes in the bronchi of steers administered MI has appeared. Plasma cells were rare. Ultrastructure of BL cells is compatible with their response to chemical insult by MI.

A Strengths-Based Approach to Autism: Neurodiversity and Partnering With the Autism Community

2017 ◽  
Vol 2 (1) ◽  
pp. 56-68 ◽  
Author(s):  
Amy L. Donaldson ◽  
Karen Krejcha ◽  
Andy McMillin
Keyword(s):  
Broad Spectrum ◽  
First Language ◽  
Family Members ◽  
Community Identity ◽  
Speech Language Pathologists

The autism community represents a broad spectrum of individuals, including those experiencing autism, their parents and/or caregivers, friends and family members, professionals serving these individuals, and other allies and advocates. Beliefs, experiences, and values across the community can be quite varied. As such, it is important for the professionals serving the autism community to be well-informed about current discussions occurring within the community related to neurodiversity, a strengths-based approach to partnering with autism community, identity-first language, and concepts such as presumed competence. Given the frequency with which speech-language pathologists (SLPs) serve the autism community, the aim of this article is to introduce and briefly discuss these topics.

Continuous Positive Airway Pressure (CPAP) Therapy for the Treatment of Hypernasality: A Single Case Study

2014 ◽  
Vol 24 (2) ◽  
pp. 48-58 ◽  
Author(s):  
Lakshmi Kollara ◽  
Graham Schenck ◽  
Jamie Perry
Keyword(s):  
Continuous Positive Airway Pressure ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Single Case ◽  
Treatment Method ◽  
Post Treatment ◽  
Subjective Perception ◽  
Cpap Therapy ◽  
Long Term Follow Up

Studies have investigated the applications of Continuous Positive Airway Pressure (CPAP) therapy in the treatment of hypernasality due to velopharyngeal dysfunction (VPD; Cahill et al., 2004; Kuehn, 1991; Kuehn, Moon, & Folkins, 1993; Kuehn et al., 2002). The purpose of this study was to examine the effectiveness of CPAP therapy to reduce hypernasality in a female subject, post-traumatic brain injury (TBI) and pharyngeal flap, who presented with signs of VPD including persistent hypernasality. Improvements in mean velopharyngeal orifice size, subjective perception of hypernasality, and overall intelligibility were observed from the baseline to 8-week post-treatment assessment intervals. Additional long-term assessments completed at 2, 3, and 4 months post-treatment indicated decreases in immediate post-treatment improvements. Results from the present study suggest that CPAP is a safe, non-invasive, and relatively conservative treatment method for reduction of hypernasality in selected patients with TBI. More stringent long-term follow up may indicate the need for repeated CPAP treatment to maintain results.

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