Recombinant protective antigen anthrax vaccine improves survival when administered as a postexposure prophylaxis countermeasure with antibiotic in the New Zealand white rabbit model of inhalation anthrax.

Inhalation anthrax is a potentially lethal form of disease resulting from exposure to aerosolized Bacillus anthracis spores. Over the last decade, incidents spanning from the deliberate mailing of B. anthracis spores to incidental exposures in users of illegal drugs have highlighted the importance of developing new medical countermeasures to protect people who have been exposed to "anthrax spores" and are at risk of developing disease.

Efficacy of a capsule conjugate vaccine against inhalational anthrax in rabbits and monkeys.

Bacillus anthracis, the causative agent of anthrax, is recognized as one of the most serious bioterrorism threats. The current human vaccines are based on the protective antigen component of the anthrax toxins. Concern about possible vaccine resistant strains and reliance on a single antigen has prompted the search for additional immunogens.

A short course of antibiotic treatment is effective in preventing death from experimental inhalational anthrax after discontinuing antibiotics.

Background: Postexposure prophylaxis of inhalational anthrax requires prolonged antibiotic therapy or antibiotics and vaccination. The duration of treatment for established anthrax is controversial, because retained spores may germinate and cause disease after antibiotics are discontinued. Using rhesus macaques, we determined whether a short course of antibiotic treatment, as opposed to prophylaxis, could effectively treat inhalational anthrax and prevent disease caused by the germination of spores after discontinuation of antibiotics.

Association of Bacillus anthracis capsule with lethal toxin during experimental infection.

Bacillus anthracis lethal toxin (LT) was characterized in plasma from infected African Green monkeys, rabbits, and guinea pigs. In all cases, during the terminal phase of infection only the protease-activated 63-kDa form of protective antigen (PA(63)) and the residual 20-kDa fragment (PA(20)) were detected in the plasma. No uncut PA with a molecular mass of 83 kDa was detected in plasma from toxemic animals during the terminal stage of infection.

Whole-body plethysmography in African green monkeys (Chlorocebus aethiops) with and without jackets.

Indwelling central venous catheters are often used to facilitate frequent phlebotomy while minimizing stress and anesthetic effects on animals. However, nonhuman primates with central venous catheters must wear protective jackets. Jackets routinely are removed for aerosol exposure to agents and respiratory measurements by whole-body plethysmography (WBP) because of the potentially confounding effects of jackets on these procedures.

Identification of a surrogate marker for infection in the African green monkey model of inhalation anthrax.

In 2001, a bioterrorism attack involving Bacillus anthracis spore-laced letters resulted in 22 cases of inhalation anthrax, with five fatalities. This incident identified gaps in our health care system and precipitated a renewed interest in identifying both therapeutics and rapid diagnostic assays. To address those gaps, well-characterized animal models that resemble the human disease are needed.

Nosocomial infection of Serratia marcescens may induce a protective effect in monkeys exposed to Bacillus anthracis.

This study was originally designed to collect data on the natural history of inhalational anthrax in a new nonhuman primate model. An uncontrollable event created a new experimental condition which allowed us to retrospectively evaluate the power of the innate immune system to protect from an aerosol exposure of B. anthracis.

Pathology of inhalational anthrax infection in the african green monkey.

There is a critical need for an alternative nonhuman primate model for inhalational anthrax infection because of the increasingly limited supply and cost of the current model. This report describes the pathology in 12 African green monkeys (AGMs) that succumbed to inhalational anthrax after exposure to a low dose (presented dose 200-2 x 10(4)colony-forming units [cfu]) or a high dose (presented dose 2 x 10(4)-1 x 10(7) cfu) of Bacillus anthracis (Ames strain) spores. Frequent gross lesions noted in the AGM were hemorrhage and edema in the lung, mediastinum, and mediastinal lymph nodes; pleural and pericardial effusions; meningitis; and gastrointestinal congestion and hemorrhage.

Use of a low-concentration heparin solution to extend the life of central venous catheters in African green monkeys (Chlorocebus aethiops).

Normal hematologic values for African green monkeys have been reported, but these results are confounded by the effect of chemical restraint (for example, ketamine), physical restraint, and capture stress. The dual-lumen central venous catheter, jacket, and tether combination we describe here allows intravenous fluid administration and repeated blood sampling without the use of anesthesia or inducing capture-related stress. The use of a low-concentration heparin solution for catheter maintenance significantly increased the mean patency time, compared with a saline-only catheter flush solution.

Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax.

Prevention of inhalational anthrax after Bacillus anthracis spore exposure requires a prolonged course of antibiotic prophylaxis. In response to the 2001 anthrax attack in the United States, approximately 10,000 people were offered 60 days of antibiotic prophylaxis to prevent inhalational anthrax, but adherence to this regimen was poor. We sought to determine whether a short course of antibiotic prophylaxis after exposure could protect non-human primates from a high-dose spore challenge if vaccination was combined with antibiotics.

A recombinant 63-kDa form of Bacillus anthracis protective antigen produced in the yeast Saccharomyces cerevisiae provides protection in rabbit and primate inhalational challenge models of anthrax infection.

Infection by Bacillus anthracis is preventable by prophylactic vaccination with several naturally derived and recombinant vaccine preparations. Existing data suggests that protection is mediated by antibodies directed against the protective antigen (PA) component of the anthrax toxin complex. PA is an 83-kDa protein cleaved in vivo to yield a biologically active 63-kDa protein.

Marburg and Ebola viruses as aerosol threats.

Ebola and Marburg viruses are the sole members of the genus Filovirus in the family Filoviridae. There has been considerable media attention and fear generated by outbreaks of filoviruses because they can cause a severe viral hemorrhagic fever (VHF) syndrome that has a rapid onset and high mortality. Although they are not naturally transmitted by aerosol, they are highly infectious as respirable particles under laboratory conditions.

Drinking water exposure to cadmium, an environmental contaminant, results in the exacerbation of autoimmune disease in the murine model.

Cadmium is a pervasive environmental contaminant. The primary route of exposure to the general population occurs via contaminated drinking water or food supplies. Our hypothesis was that cadmium could be a trigger for inducing autoimmune disease (AD) in genetically predisposed populations.

Differential stimulation of IgE production, STAT activation and cytokine and CD86 expression by 2,4-dinitrochlorobenzene and trimellitic anhydride.

It has been reported that dermal exposure to trimellitic anhydride (TMA, 50%), a respiratory allergen, induced greater production of serum IgE and expression of Th2 cytokines than 2,4-dinitrochlorobenzene (DNCB, 1%), a potent contact sensitizer, in female BALB/C mice. To determine if there is any strain difference, four strains (B6C3F1, C57BL/6, BDF1 and BALB/C) of female mice were employed in this study to compare the differential effects of these chemicals on the hypersensitivity responses. Serum IgE levels were increased in TMA-treated B6C3F1, C57BL/6 and BDF1 mice when compared with the DNCB treatment and vehicle controls; in contrast, no difference was observed between TMA- and DNCB-treated BALB/C mice, although both chemicals induced greater IgE production than vehicle controls.

Sodium metasilicate hypersensitivity in BALB/c mice.

Background: Sodium metasilicate (SMS) is a key ingredient for a number of industrial and consumer products. Although little is known about potential for this chemical to cause allergic reactions, a similar silicate compound, sodium silicate, was reported to elicit IgE-mediated contact urticaria.

Objective: The aim of this study was to evaluate the potential for sodium metasilicate to elicit an allergic response in female BALB/c mice after dermal exposure.

Dermal exposure to cinnamaldehyde alters lymphocyte subpopulations, number of interferon-gamma-producing cells, and expression of B7 costimulatory molecules and cytokine messenger RNAs in auricular lymph nodes of B6C3F1 mice.

Background: Although the Murine Local Lymph Node Assay (LLNA) is efficient in identifying chemicals with sensitizing potential, there is increasing need for alternative end points. Cinnamaldehyde (CIN) was chosen for evaluation based on its moderate potency and extensive use in fragrance materials.

Objectives: The purpose of the present studies is to incorporate some alternative end points, such as phenotypic analysis and cytokine production, into a modified LLNA/irritancy assay (IA) to evaluate the sensitization of female B6C3F1 mice to CIN.

Simplified method for producing permanent ruminal fistulae.

A quick and simple method for establishing permanent rumimal fistulae is described. A frozen cannula is forced into the rumen in a manner similar to the use of a trocar. Minimal equipment is required, and the entire operation can be performed in 15 to 20 min in sheep or 30 min in cattle.