The potential role of neutrophil elastase in exacerbating pulmonary infection and tissue damage in cystic fibrosis (CF) has led to proposals for treatment of lung disease in CF with the elastase inhibitor, alpha 1-proteinase inhibitor (alpha 1PI). Reports that alpha 1PI is inactivated in the CF lung suggest that the effectiveness of alpha 1PI therapy depends on the quantity of elastase present and the extent of alpha 1PI inactivation, both of which are expected to vary with disease severity. In this study we assessed the elastase-alpha 1PI profile in sputum and plasma from CF patients with various degrees of pulmonary involvement. Levels of active elastase in sputum samples increased with severity of pulmonary disease (F ratio = 5.63, p < 0.01), as did sputum levels of alpha 1PI (F ratio = 4.88, p < 0.01). A positive correlation was observed between sputum levels of active elastase and alpha 1PI (r = 0.68, p < 0.005). Plasma alpha 1PI levels were also elevated in CF patients compared with control subjects (p < 0.005), indicating a compensatory increase in plasma and sputum levels of alpha 1PI in response to increased elastase load. Molar levels of total immunogenic neutrophil elastase were, on average, 12 times higher than alpha 1PI in CF sputum. These results suggest that the major contributor to the elevated levels of active elastase observed in the CF lung is an increase in elastase release rather than inactivation of alpha 1PI.

Controlled studies with baits containing the biomarkers iophenoxic acid or tetracycline were carried out to measure bait uptake by free-living badgers. The presence of these biomarkers was determined in badger plasma and dentition. The biomarkers were then incorporated into baits to quantify bait uptake by badgers in the ®eld. Seven captive badgers were orally dosed with iophenoxic acid, which was subsequently measured in serial plasma samples for 18 weeks. Subsequently, ®eld studies using baits marked with iophenoxic acid were carried out at selected setts in two study areas. In other experiments, ®ve cagetrapped badgers were orally dosed with tetracycline and released. These badgers were subsequently retrapped and the presence of tetracycline measured in sections of canine teeth. Field trials were also carried out using baits marked with tetracycline in four separate study areas. Badgers dosed with iophenoxic acid had elevated plasma iodine in comparison to a pre-dose baseline level. The elevations in plasma iodine could be detected throughout the sampling period. Field experiments using iophenoxic acid showed that c. 80% of wild badgers had ingested the marked bait. In addition, all ®ve badgers dosed with tetracycline had tetracycline deposits in their canine teeth. Between 20% and 77.8% of badgers trapped in the tetracycline ®eld trials were positive for uptake of the tetracycline-marked bait. Variation in the percentage of badgers marked was attributed to several factors including seasonal timing of bait deployment. Our results indicated that iophenoxic acid and tetracycline were effective biomarkers of bait uptake by badgers.

A field study was carried out on Little Island (County Waterford, Ireland) in June 2000 to evaluate the potential of a bait-marking system for use in European badgers (Meles meles). Two oral biomarkers, sulfadimethoxine (SDM) and rhodamine B, were incorporated into fishmeal baits and distributed by hand at main sets in five test territories for 3 consecutive days. In parallel, non-biomarked baits were distributed at a single control territory. The objectives of the study were to: (1) assess the effects of SDM and rhodamine B on palatability and thus bait acceptance, and (2) investigate the marking capacity of SDM and rhodamine B in serum and hair samples taken from badgers. Trapping was carried out in each territory for 5 consecutive days immediately after bait distribution. Analysis of data revealed that 90-100% of baits were removed in four of the test territories and from the control territory. In the fifth test territory, 61% of baits were removed. Of the badgers (n = 26) trapped in the test territories, 18 (69%) were positive when tested for both biomarkers. In contrast, the remaining eight animals and those captured in the control territory (n = 6 badgers) were negative. In the marked animals, the highest levels of SDM were recorded in serum samples taken soon after bait distribution. Thereafter, the levels declined in each badger over the course of the study. In contrast, rhodamine B was readily detectable by fluorescence microscopy of hair samples throughout the period of study. The results indicate that SDM and rhodamine B act as systemic markers in badgers and have potential future applications for monitoring of oral vaccine uptake.

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