Proteins aerosolized

As with other protein toxin weapons, we expect that the generation of primary or secondary ricin aerosols, especially within an enclosed space, poses a potential biological warfare or bioterrorism risk (LeClaire and Pitt, 2005 Millard, 2005). Due to the technical challenges of generating highly toxic and persistent protein aerosols, we expect the risk of lethality to be less than the risk of operational disruption, prolonged incapacitation from ocular or respiratory tract inflammation, and increased burden on medical and logistical assets. 

Animals exposed to 150 pg of subtilisin protein. m for 15 min per day for 5 consecutive days developed immediate-onset and late-onset pulmonary responses when re-exposed to the protein aerosol (Thome et al., 1986). The immediate-onset pulmonary responses were detected as significant increases in the breathing rate. The late-onset responses were also detected as significant increases in breathing rate accompanied by febrile responses. In addition, the animals possessed allergic antibody specific to subtilisin, although not every animal with antibody developed pulmonary symptoms (Hillebrand et al., 1987). Animals exposed to 8 or 41 pg of subtilisin protein, nr3 did not experience pulmonary symptoms, but did develop low levels of antibody to subtilisin. These experiments showed that immune reactivity to this occupational allergen occurred at exposure levels lower than those required for the elicitation of pulmonary responses. 

Maa, Y.-F., Nguyen, P.-A., Sit, K Hsu, S. W 1998b. Spray-drying performance of a bench-top spray dryer for protein aerosol powder preparation. Biotech. Bioeng. 60 503-512. 

Metered-dose propellant-driven aerosols of an antigenically reactive protein have been produced by combining bovine gammaglobulin with surfactants soluble in freon or dimethylether propellants (189). Propellants for delivering protein aerosols need further development. In this study, dimethylether was most effective, but this propellant is not approved by the US Food and Dmg Administration (FDA) for respiratory aerosols. 

The ablated vapors constitute an aerosol that can be examined using a secondary ionization source. Thus, passing the aerosol into a plasma torch provides an excellent means of ionization, and by such methods isotope patterns or ratios are readily measurable from otherwise intractable materials such as bone or ceramics. If the sample examined is dissolved as a solid solution in a matrix, the rapid expansion of the matrix, often an organic acid, covolatilizes the entrained sample. Proton transfer from the matrix occurs to give protonated molecular ions of the sample. Normally thermally unstable, polar biomolecules such as proteins give good yields of protonated ions. This is the basis of matrix-assisted laser desorption ionization (MALDI). 

The lungs large, permeable surface makes systemic deUvery possible. For example, an inhaler deUvers 360 )Tg per dose of aerosolized ergotamine tartrate [379-79-3] for migraine (54), and inhalant systems deUver anesthetic gases. Research is under way on the systemic deUvery of proteins and peptides through the lungs (57,58). 

Amines Methylamine Protein decay H2SO4 aerosol —... 

The anthrax bioterrorist attacks that followed the events of September 11th 2001 resulted in a renewed interest BadUus anthracis, the causative agent of this disease. Research has focused on the development of better vaccines than the one currently available. It has been estimated that the aerosolized release of 100 kg of anthrax spores upwind of Washington DC would cause mortalities of 130,000-3,000,000 [63]. Nonetheless, wild-type Bacillus anthracis is susceptible to conventional antibiotics, including penicillin, oxyfloxacin and ciprofloxacin. The problem lies not with the bacterial infection itself, but with three proteins released by the bacteria - protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa) and edema factor (EF, 89 kDa) -known as anthrax toxins [63]. 

Spergel, J.M. et al., Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methachohne after single exposure to aerosolized antigen in mice, J. Clin Invest, 101, 1614, 1998. 

Caution Ricin is extremely toxic to cells and acts by inhibiting protein synthesis. After aerosol exposure, signs and symptoms would depend on the dose inhaled. Humans can be expected to develop severe lung inflammation with progressive cough, dyspnea, cyanosis, and pulmonary edema. 

Detector (able to broadly categorize the contents of the aerosol and lend confidence to the detection process e.g., biological material in the aerosol or not, bacteriological, spore, protein, etc.). 

Drug development, proteins in, 20 839 Drug discovery, yeasts in, 26 488 Drug dosage forms, 15 702-718 aerosols, IS 717 biotechnology and, IS 717-718 capsules, 15 708 granules, 15 702-705 liquid, 15 712-713 lyophilization, 15 716 ophthalmic, 15 716 parenteral, IS 713-716 prolonged action/controlled release solid, 15 708-712... 

For example, studies of the morphology of a number of flame-generated aggregates (different carbonaceous soots, A1203 aerosols, etc.) [203] by both TEM and ALS procedures resulted in D2 = 1.7 0.15, while analysis of silhouettes of computer models of seven proteins [211] gave a value of D2 = 1.120 0.025, etc. 

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