Comparison of status epilepticus models induced by pilocarpine and nerve agents - a systematic review of the underlying aetiology and adopted therapeutic approaches.

Among potential radiological, nuclear, biological and chemical weapons, cholinergic nerve agents from chemical weapons remain a realistic terrorist threat due to its combination of high lethality, demonstrated use and relative abundance of un-destroyed stockpiles in various militaries around the world. While current fielded antidotes are able to mitigate acute poisoning, effective neuroprotection in the field remains a challenge amongst subjects with established status epilepticus following nerve agent intoxication. Due to ethical, safety and surety issues, extensive preclinical and clinical research on cholinergic nerve agents is not possible. This may have been a contributory factor for the slow progress in uncovering new neuroprotectants for nerve agent casualties with established status epilepticus. To overcome this challenge, comparative research with surrogate chemicals that produce similar hypercholinergic toxicity but with less security concerns would be a useful approach forward. In this paper, we will systemically compare the mechanism of seizure generation, propagation and the subsequent clinical, hematologic, and metabolic, biochemical, neuroinflammatory changes and current therapeutic approaches reported in pilocarpine, soman, and sarin models of seizures. This review will be an important first step in closing this knowledge gap among different closely related models of seizures and neurotoxicity. Hopefully, it will spur further efforts in using surrogate cholinergic models by the wider scientific community to expedite the development of a new generation of antidotes that are better able to protect against delayed neurological effects inflicted by nerve agents.

High responsivity GaNAsSb p-i-n photodetectors at 1.3 microm grown by radio-frequency nitrogen plasma-assisted molecular beam epitaxy.

GaNAsSb/GaAs p-i-n photo notdetectors with an intrinsic GaNAsSb photoabsorption layer grown at 350 degrees C, 400 degrees C, 440 degrees C and 480 degrees C, have been prepared using radio-frequency nitrogen plasma-assisted molecular beam epitaxy in conjunction with a valved antimony cracker source. The i-GaNAsSb photoabsorption layer contains 3.3% of nitrogen and 8% of antimony, resulting in DC photo-response up to wavelengths of 1350 nm. The device with i-GaNAsSb layer grown at 350 degrees C exhibits extremely high photoresponsivity of 12A/W at 1.3 microm. These photodetectors show characteristics which strongly suggest the presence of carrier avalanche process at reverse bias less than 5V.

Investigation of Semiconductor Quantum Dots for Waveguide Electroabsorption Modulator.

In this work, we investigated the use of 10-layer InAs quantum dot (QD) as active region of an electroabsorption modulator (EAM). The QD-EAM is a p-i-n ridge waveguide structure with intrinsic layer thickness of 0.4 mum, width of 10 mum, and length of 1.0 mm. Photocurrent measurement reveals a Stark shift of ~5 meV (~7 nm) at reverse bias of 3 V (75 kV/cm) and broadening of the resonance peak due to field ionization of electrons and holes was observed for E-field larger than 25 kV/cm. Investigation at wavelength range of 1,300-1320 nm reveals that the largest absorption change occurs at 1317 nm. Optical transmission measurement at this wavelength shows insertion loss of ~8 dB, and extinction ratio of ~5 dB at reverse bias of 5 V. Consequently, methods to improve the performance of the QD-EAM are proposed. We believe that QDs are promising for EAM and the performance of QD-EAM will improve with increasing research efforts.

Acetylcholinesterase-independent action of diisopropyl-flurophosphate in the rat aorta.

Recent studies have shown that many organophosphates can bind competitively and noncompetitively to membrane muscarinic receptors. The present study investigated the responses of the rat aortic rings to diisopropyl-flurophosphate (DFP), an organophsophorus cholinesterase inhibitor, and the possible involvement of muscarinic receptors. DFP caused a concentration-dependent contraction when added cumulatively from 10(-8) to 10(-4) M. This contraction was inhibited in a noncompetitive manner by high concentrations of atropine (1.5 x 10(-6) and 1.8 x 10(-6) M) but was unaffected by similar concentrations of selective muscarinic receptor subtype antagonists, pirenzepine, 11-2[2-[(diethylamino)methyl]-1-piperidinyl]acetyl-5, 11-dihydro-6H-rido[2,3-b][1,4]benzodiazepin-6-one (AF-DX116) and 4-Diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP). Phentolamine, an alpha-adrenoceptor antagonist, was able to inhibit the DFP-induced contraction in a noncompetitive manner at a concentration of 10(-7) M. These findings suggested that the DFP-induced contraction in the rat aortic rings was mediated by norepinephrine that was released from sympathetic nerve terminals present in the aortic rings.

Wound dressing with sustained anti-microbial capability.

To overcome current limitations in wound dressings for treating mustard-burn induced septic wound injuries, a nonadherent wound dressing with sustained anti-microbial capability has been developed. The wound dressing consists of two layers: the upper layer is a carboxymethyl-chitin hydrogel material, while the lower layer is an anti-microbial impregnated biomaterial. The hydrogel layer acts as a mechanical and microbial barrier, and is capable of absorbing wound exudate. In physiological fluid, the carboxymethylated-chitin hydrogel swells considerably, imbibing up to 4 times its own weight of water and is also highly porous to water vapor. The moisture permeability of the dressing prevents the accumulation of fluid in heavily exudating wounds seen in second-degree burns. The lower layer, fabricated from chitosan acetate foam, is impregnated with chlorhexidine gluconate. From the in vitro release studies, the loading concentration was optimized to deliver sufficient anti-microbial drug into the wound area to sustain the anti-microbial activity for 24 h. The anti-microbial activity of the dressing against Pseudomonas aeruginosa and Staphylococcus aureus was tested using the Bauer-Kirby Disk Diffusion Test.

Wet decontamination-induced stratum corneum hydration--effects on the skin barrier function to diethylmalonate.

Decontamination of chemical agents from the skin uses both dry and wet decontamination processes. Recent studies have shown that wet decontamination frequently results in stratum corneum hydration. To evaluate the hydration effect of wet decontamination on the skin barrier function and hence on the decontamination efficiency, a series of comparative studies were carried out on human skin contaminated with the nerve agent simulant diethylmalonate, using decontamination media having different salinity and surfactants. The results showed that, compared to non-decontaminated skin, remnant diethylmalonate on decontaminated skin penetrated at an accelerated rate in the immediate 2 h following decontamination. This transient enhancement effect, ranging from 20 to 98%, was depended on the nature of the decontamination media used and was more obvious in skin samples that were decontaminated 1 h postexposure. All decontamination media exhibited this effect, with the greatest enhancement observed in the following order: anionic surfactant > cationic surfactant > non-ionic surfactant > deionized water > 0.9% saline > 9% saline.

Enzyme-based microassay for accurate determination of soman in blood samples.

Successful medical therapy for nerve agent intoxication requires early diagnosis and treatment. Current clinical diagnostic methods do not permit early or definitive confirmation of intoxication. To improve the chances of successful medical therapy against nerve agent intoxication, a sensitive enzyme-based microassay for rapid and accurate quantification of residual soman levels in blood was developed. The new analytical technique is based on the linear correlation between residual eel acetylcholinesterase activities and the inhibitor concentration. Blood samples were deproteinized with perchloric acid, followed by immediate neutralization after deproteinization. The mixtures were centrifuged at 3000g and the supernatant was directly assayed for soman. The sensitivity of the technique (18-1820 pg/ml blood) is comparable to that attained by GC-FID analysis (250 pg/ml blood). To facilitate routine analysis, the linear range of the assay was optimized to span over a factor of 100 (0.1-10 nM), with a typical correlation factor of at least 0.999 (six standards). The assay accuracy, checked with four different concentrations of soman, was within +/- 10%. The assay capability in monitoring the pharmacokinetic of soman was validated using both in vitro and in vivo rat models.

Hybrid biomaterials based on the interaction of polyurethane oligomers with porcine pericardium.

Hybrid biomaterials have been produced by the interaction of polyurethane oligomers with both fresh and glutaraldehyde-fixed porcine pericardium. The hybrid biomaterials so formed were translucent with occasional white streaks and/or spots, had increased stiffness (to touch) but remained pliable. No shrinkage temperature was detected for fresh porcine pericardium hybrid up to 100 degrees C compared to porcine pericardium (approximately 67 degrees C) and glutaraldehyde-fixed porcine pericardium (approximately 87 degrees C). Amino acid analysis of the fresh porcine pericardium hybrid showed a reduction in lysine content after active isocyanate-terminated polyurethane oligomers exposure, indicating cross-linking between the polymer and tissue. Histological examination of the hybrid material shows a thin grey coating on both surfaces of the tissue, implying at least surface cross-linking of the tissue with polyurethane. The results suggest that fresh porcine pericardium can be reacted with active isocyanate-terminated polyurethane oligomers to produce hybrid biomaterials with covalent bonding.

Validation of the shrinkage temperature of animal tissue for bioprosthetic heart valve application by differential scanning calorimetry.

Shrinkage temperature is most often used to report the degree of cross-linking in glutaraldehyde-fixed animal tissue for use in bioprosthetic heart valve fabrication. Present practice utilizes the measurement of hydrothermal shrinkage observed when a sample is subjected to a temperature programme. This measurement at best gives a general indication of the efficiency of the treatment, i.e. the extent of cross-linking in the tissue. When differential scanning calorimetry has been used, the ambiguity arising from the scant reporting of the protocols used does not permit easy comparison of experimental results. This report addresses the considerations necessary to obtain optimum results in the differential scanning calorimetry experiment for the determination of shrinkage temperature in biological tissue. The shrinkage temperature of two previously unreported tissue types, porcine pericardium and equine pericardium, are provided and compared with those of bovine pericardium and porcine aortic valve leaflets.

Trivalent metal ions in the prevention of calcification in glutaraldehyde treated biological tissues. Is there a chemical correlation?

The influence of chemical factors on trivalent metal ions in the prevention of calcification of glutaraldehyde treated biological tissue has been explored. The results indicate that the chemical link lies in the hard character of the trivalent metal ions. Metal ions with the hardest character appear to have the best chance of reacting with oxygen atoms of the phosphate groups at nucleation sites of hydroxyapatite. This disrupts the nucleation and thus prevents calcification in glutaraldehyde treated biological tissue.