Quantitative Models of the Dose-Response and Time Course of Inhalational Anthrax in Humans

Anthrax poses a community health risk due to accidental or intentional aerosol release. Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. Analyses of available data from exposures and infections of humans and non-human primates are often contradictory. We review existing quantitative inhalational anthrax dose-response models in light of criteria we propose for a model to be useful and defensible. To satisfy these criteria, we extend an existing mechanistic competing-risks model to create a novel Exposure–Infection–Symptomatic illness–Death (EISD) model and use experimental non-human primate data and human epidemiological data to optimize parameter values. The best fit to these data leads to estimates of a dose leading to infection in 50% of susceptible humans (ID₅₀) of 11,000 spores (95% confidence interval 7,200–17,000), ID₁₀ of 1,700 (1,100–2,600), and ID₁ of 160 (100–250). These estimates suggest that use of a threshold to human infection of 600 spores (as suggested in the literature) underestimates the infectivity of low doses, while an existing estimate of a 1% infection rate for a single spore overestimates low dose infectivity. We estimate the median time from exposure to onset of symptoms (incubation period) among untreated cases to be 9.9 days (7.7–13.1) for exposure to ID₅₀, 11.8 days (9.5–15.0) for ID₁₀, and 12.1 days (9.9–15.3) for ID₁. Our model is the first to provide incubation period estimates that are independently consistent with data from the largest known human outbreak. This model refines previous estimates of the distribution of early onset cases after a release and provides support for the recommended 60-day course of prophylactic antibiotic treatment for individuals exposed to low doses.     

Opioid receptor labeling with the chloromethyl ketone derivative of [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAMGO) II: Covalent labeling of mu opioid binding site by 3H-Tyr-D-Ala-Gly-(Me)Phe chloromethyl ketone.

Opioid receptors of rat brain membranes were prelabeled with 3H-Tyr-D-Ala2-(Phe4)-Gly-CH2Cl, a chloromethyl ketone derivative of enkephalin, and solubilized in 1% digitonin. Hydrodynamic parameters of the receptor detergent complex derived from gel filtration and sucrose density gradient ultracentrifugation were found to be 51 A and 8.7 S, respectively, and the size was estimated to be about 200 kDa. Sodium dodecyl sulfate gel electrophoresis followed by fluorography revealed specific alkylation of a major protein at 58 kDa.     

Physiological stabilization of rabbits after shipping

Significant physiological variations that could influence experimental outcomes have been described in laboratory animals following shipping. The objective of the present study was to monitor a variety of physiologic parameters in rabbits after shipping, and to evaluate the time necessary for stabilization of these variables in the new environment. Data indicate that rabbits develop anorexia, hyperglycemia, neutrophilia, lymphopenia and elevated plasma cortisol concentrations immediately after shipping. Most of these effects abate within 2 days after arrival, suggesting that a minimum stabilization period of 48 hours after shipping is advisable prior to use of rabbits in experimental paradigms.     

Transforming growth factor beta 2 differentially modulates interleukin-1 beta- and tumour-necrosis-factor-alpha-stimulated phospholipase A2 and prostaglandin E2 synthesis in rat renal mesangial cells.

Isolated hepatocytes from streptozotocin-diabetic rats failed to respond to a glucose load with an activation of glycogen synthase. This lesion was associated with severely decreased activities of glycogen-synthase phosphatase and of glucokinase. All these defects were abolished after consumption for 13-18 days of drinking water containing Na3VO4 (0.7 mg/ml), and they were partially restored after 3.5 days, when the blood glucose concentration was already normalized. In all conditions the maximal extent of activation of glycogen synthase in cells closely parallelled the activity of glycogen-synthase phosphatase.