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•Relative humidity affects the amount of dimethyl methylphosphonate (DMMP) sorbed on office materials.•Cardboard retains captured DMMP longer than paint layer and polyurethane ...foam.•DMMP, a nerve agent simulant, was retained after 6 weeks on office materials.
Dimethyl methylphosphonate (DMMP) was used as a simulant to investigate the sorption and desorption of G-series nerve agents such as sarin (GB) released into an office space. DMMP was disseminated systematically as an aerosol and vapor on three common office materials, cardboard, polyurethane foam, and cured acrylic-based paint. The amount of DMMP initially captured on the office materials and the amount retained over a period of 10 h was tracked gravimetrically and by solvent extraction and gas chromatography/mass spectrometry (GC/MS). Physicochemical properties of the office media including the surface area per mass, polarity, and Henry’s constant were determined to help explain the capture and release of DMMP that was observed. Polyurethane foam was found to have the largest sorption capacity for DMMP in a low-humidity setting, however, cardboard was found to have the largest sorption capacity at higher humidity. A fraction of the collected DMMP desorbed with first-order kinetics from all of the office materials in an open-air atmosphere over 8 h. However, importantly for forensic purposes relevant to an indoor attack, a significant quantity (most notably on cardboard) of the nerve agent simulant was retained after 6 weeks and could be analyzed efficiently using solvent extraction followed by GC/MS.
•The BBB is a major obstacle in the treatment of CNS disorders and toxicity.•Enzymes given intranasally can treat toxicity and enzyme deficiency disorders.•Intranasally administered active enzyme ...reached all brain areas within 15min.•Therapeutic bioavailability was doubled by pretreatment with MMP-9.•Model for catalytic bioscavengers to detoxify CNS poisons and enzyme deficiencies.
The blood brain barrier (BBB) is critical for maintaining central nervous system (CNS) homeostasis by restricting entry of potentially toxic substances. However, the BBB is a major obstacle in the treatment of neurotoxicity and neurological disorders due to the restrictive nature of the barrier to many medications. Intranasal delivery of active enzymes to the brain has therapeutic potential for the treatment of numerous CNS enzyme deficiency disorders and CNS toxicity caused by chemical threat agents.
The aim of this work is to provide a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain with therapeutic bioavailability.
We tested intranasal delivery of chloramphenicol acetyltransferase (CAT), a relatively large (75kD) enzyme, in its active form into different regions of the brain. CAT was delivered intranasally to anaesthetized rats and enzyme activity was measured in different regions using a highly specific High Performance Thin Layer Chromatography (HP-TLC)-radiometry coupled assay. Active enzyme reached all examined areas of the brain within 15min (the earliest time point tested). In addition, the yield of enzyme activity in the brain was almost doubled in the brains of rats pre-treated with matrix metalloproteinase-9 (MMP-9).
Intranasal administration of active enzymes in conjunction with MMP-9 to the CNS is both rapid and effective.
The present results suggest that intranasal enzyme therapy is a promising method for counteracting CNS chemical threat poisoning, as well as for treating CNS enzyme deficiency disorders.
The essential element of any immuno-based detector device is the probe that binds analyte and, as a part of the analytical platform, generates a measurable signal. The present review summarizes the ...state of the art in development of the probes for detection of the biological threat agents: toxins, bacteria, spores and viruses. Traditionally, the probes are antibodies, which are isolated from sera of immunized animals or culture media of hybridomas. However, the “natural” antibodies may have limited application in the new generation of real-time field detectors and monitoring systems, where stress-resistant and inexpensive long-livers are required. Phage display is a newcomer in the detection area, whose expertise is development of molecular probes for targeting of various biological structures. The probes can be selection from about billion clone libraries of recombinant phages expressing on their surface a vast variety of peptides and proteins, including antigen-binding fragments of antibodies. The selection procedure, like kind of affinity chromatography, allows separating of phage binders, which are propagated in
Escherichia coli bacterial cells and purified using inexpensive technology. Although phage display traditionally is focused more on development of medical preparations and studying molecular recognition in biological systems, there are some examples of its successful use for detection, which are presented in the review. To be used as probes for detection, peptides and antibodies identified by phage display are usually chemically synthesized or produced in bacteria. Another interesting aspect is using of the selected phage itself as a probe in detector devices, like sort of substitute antibodies. This idea is illustrated in the review by “detection” of β-galactosidase from
E. coli with “landscape” phage displaying a dense array of peptide binders on the surface.
► We report deep Raman spctroscopy for the standoff nonivsaive detection of concaeled chemical threat agents. ► We introduce a combined time and space resolve Raman spectrometer for the depth ...profiling of the therat agents within diffusly scattring pacakging. ► The detection was carried out from a distance of 15m by a single measurement under real life background illuminations within 5s of data acquisition. ► The new spectrometer uses nanosecond laser excitation and nanosecond gated ICCD detection. ► The new spectrometer has strong potential for national security and forensic applications.
Deep Raman spectroscopy has been utilized for the standoff detection of concealed chemical threat agents from a distance of 15m under real life background illumination conditions. By using combined time and space resolved measurements, various explosive precursors hidden in opaque plastic containers were identified non-invasively. Our results confirm that combined time and space resolved Raman spectroscopy leads to higher selectivity towards the sub-layer over the surface layer as well as enhanced rejection of fluorescence from the container surface when compared to standoff spatially offset Raman spectroscopy. Raman spectra that have minimal interference from the packaging material and good signal-to-noise ratio were acquired within 5s of measurement time. A new combined time and space resolved Raman spectrometer has been designed with nanosecond laser excitation and gated detection, making it of lower cost and complexity than picosecond-based laboratory systems.
► Impurity profiling works even after chemical is disseminated into the environment. ► Selectivity is a useful measure of impurity-profile forensic value. ► Guidance provided for optimization and use ...of impurity profiling.
Dimethyl methylphosphonate (DMMP) was used as a chemical threat agent (CTA) simulant for a first look at the effects of real-world factors on the recovery and exploitation of a CTA's impurity profile for source matching. Four stocks of DMMP having different impurity profiles were disseminated as aerosols onto cotton, painted wall board, and nylon coupons according to a thorough experimental design. The DMMP-exposed coupons were then solvent extracted and analyzed for DMMP impurities by comprehensive 2D gas chromatography/mass spectrometry (GC×GC/MS). The similarities between the coupon DMMP impurity profiles and the known (reference) DMMP profiles were measured by dot products of the coupon profiles and known profiles and by score values obtained from principal component analysis. One stock, with a high impurity-profile selectivity value of 0.9 out of 1, had 100% of its respective coupons correctly classified and no false positives from other coupons. Coupons from the other three stocks with low selectivity values (0.0073, 0.012, and 0.018) could not be sufficiently distinguished from one another for reliable matching to their respective stocks. The results from this work support that: (1) extraction solvents, if not appropriately selected, can have some of the same impurities present in a CTA reducing a CTA's useable impurity profile, (2) low selectivity among a CTA's known impurity profiles will likely make definitive source matching impossible in some real-world conditions, (3) no detrimental chemical–matrix interference was encountered during the analysis of actual office media, (4) a short elapsed time between release and sample storage is advantageous for the recovery of the impurity profile because it minimizes volatilization of forensic impurities, and (5) forensic impurity profiles weighted toward higher volatility impurities are more likely to be altered by volatilization following CTA exposure.
This manuscript discusses the phytochemical analysis of stinging plants and/or their biological toxins as novel future bio-threat agents that may be used for self-defence purpose. The selected ...stinging plants namely,
Urtica dioica
L.,
Tragia involucrata
L.,
Carduus nutans
L. and
Mucuna pruriens
(L.) DC, have dual role as nutraceutical and ethno-pharmacological uses apart from their less-explored stinging property. The phytochemical analyses of their secondary metabolites including phenolics, terpene and N-containing compounds were measured.
M. pruriens
showed maximum total phenolic content (~1004 µg g
−1
dry wt) followed by those of
T. involucrata
,
C. nutans
and
U. dioica
. Similarly, the flavonoid content was also found highest (~500 µg of QE g
−1
dry wt) in
M. pruriens
. However, the tannin content was maximum (~654 µg g
−1
dry wt) in
T. involucrata
followed by
M. pruriens
. Likewise, the terpenoid content was maximum (~350 µg of Lil g
−1
dry wt) in
U. dioica
followed by
M. pruriens
,
T. involucrata
and
C. nutans
. FRSA was maximum (~31%) in
M. pruriens
. However, the oil content was highest in
T. involucrata
followed by
U. dioica
,
M. pruriens
and
C. nutans
. In addition, the alkaloid content was maximum (~523 µg of AE g
−1
dry wt) in
M. pruriens
. These findings clearly suggest that
M. pruriens
has higher potential for harvesting of toxic compounds as compared to other studied plants for the formulation of novel future bio-threat agents for self-defence. However, detailed work is required for identification of the precise stinging chemical components.
Stinging plants: as future bio-weapon Gupta, Sanjay Mohan; Kumar, Kamal
Journal of complementary & integrative medicine,
2016-Sep-01, Letnik:
13, Številka:
3
Journal Article
Recenzirano
In the present opinion paper, we have been introducing for the first time the stinging plants and/or their biological toxins as novel bio-threat agents that may be used for the development of ...bio-weapons for self-defence purpose. The selected studied stinging plants are having dual role as nutraceutical and ethno-pharmacological uses apart from their less explored stinging property. However, future detailed work is required for identification and characterization of the precise stinging chemical components that will be used for the formulation of novel bio-warfare agents for self-defence purpose.
The probe technique originated from early attempts of Anton van Leeuwenhoek to contrast microorganisms under the microscope using plant juices, successful staining of tubercle bacilli with synthetic ...dyes by Paul Ehrlich and discovery of a stain for differentiation of gram-positive and gram-negative bacteria by Hans Christian Gram. The technique relies on the principle that pathogens have unique structural features, which can be recognized by specifically labeled organic molecules. A hundred years of extensive screening efforts led to discovery of a limited assortment of organic probes that are used for identification and differentiation of bacteria. A new challenge—continuous monitoring of biological threats—requires long lasting molecular probes capable of tight specific binding of pathogens in unfavorable conditions. To respond to the challenge, probe technology is being revolutionized by utilizing methods of combinatorial chemistry, phage display and directed molecular evolution. This review describes how molecular evolution methods are applied for development of peptide, antibody and phage probes, and summarizes the author's own data on development of landscape phage probes against
Salmonella typhimurium. The performance of the probes in detection of
Salmonella is illustrated by a precipitation test, enzyme-linked immunosorbent assay (ELISA), fluorescence-activated cell sorting (FACS) and fluorescent, optical and electron microscopy.
Field screening tools are required which would allow first responders to quickly ascertain if a suspicious powder poses a potential threat necessitating additional testing for biological pathogens ...such as
Bacillus anthracis. In this study, three commercially available generic screening technologies were evaluated for the effectiveness to accurately differentiate between a hoax powder and a true biological threat. The BioCheck
® Kit was able to detect the following biological agents 1
×
10
8
CFU of
B. anthracis Sterne (washed 4 times), 1
×
10
7
CFU of
B. anthracis ΔSterne (washed 2 times), 1
×
10
7
CFU of
Yersinia pestis A1122, and 100
μg of ricin. The Prime Alert™ kit was able to detect 2
×
10
10
CFU of
B. anthracis ΔSterne 4×, 1
×
10
9
CFU of
B. anthracis ΔSterne 2×, and 1
×
10
8
CFU of
Y. pestis A1122. The Prime Alert™ kit was not able to detect ricin. The Profile
®-1 kit was able to detect 1
×
10
4
CFU of
B. anthracis ΔSterne 4× and
B. anthracis ΔSterne 2×, and 1
×
10
6
CFU of
Y. pestis A1122. The Profile
®-1 kit was not able to detect ricin. All of the kits showed positive results for powders containing components specifically targeted by the particular technology being used. Each technology assessed in this evaluation employs a different mechanism for the detection of biological materials and it is important that first responders are aware of the strengths and the limitations of each system so that they can effectively employ the technology to protect the homeland.
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