The endoglycosidase heparanase is an important in the degradation of the extracellular matrix by invading cells, notably metastatic tumor cells and migrating leukocytes. Here we report the cDNA sequence of the human platelet enzyme, which encodes a unique protein of 543 amino acids, and the identification of highly homologous sequences in activated mouse T cells and in a highly metastatic rat adenocarcinoma. Furthermore, the expression of heparanase mRNA in rat tumor cells correlates with their metastatic potential. Exhaustive studies have shown only one heparanase sequence, consistent with the idea that this enzyme is the dominant endoglucuronidase in mammalian tissues.

Four strains of Butyrivibrio fibrisolvens, transformed with a gene encoding fluoroacetate dehalogenase, maintained a combined population of 106 to 107 cells ml−1 in the rumens of test sheep. Five inoculated sheep showed markedly reduced toxicological symptoms after fluoroacetate poisoning when behavioral, physiological, and histological effects were compared with those of five uninoculated control sheep.

IMPORTANCEElevated levels of blood perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been associated with a range of adverse health outcomes. Firefighters have been exposed to PFASs in firefighting foams and have previously been shown to have higher PFAS levels in blood samples than the general population. No interventions have been shown to reduce PFAS levels. OBJECTIVE To examine the effect of blood or plasma donations on PFAS levels in firefighters in Australia. DESIGN, SETTING, AND PARTICIPANTS This 52-week, open-label, randomized clinical trial enrolled participants from May 23 to August 23, 2019. Participants were 285 Fire Rescue Victoria staff orcontractors with serum levels of perfluorooctane sulfonate (PFOS) of 5 ng/mL or more who were eligible to donate blood, had not donated blood in the 3 months prior to randomization, and were able to provide written informed consent. Analysis was performed on an intention-to-treat basis from May to July 2021. INTERVENTIONSFirefighters with baseline PFOS levels of 5 ng/mL or more were randomly assigned to donate plasma every 6 weeks for 12 months, donate blood every 12 weeks for 12 months, or be observed only. MAIN OUTCOMES AND MEASURESThe primary end points were changes in the serum PFOS and perfluorohexane sulfonic acid (PFHxS) levels after 12 months of plasma or blood donations or after observation only. Secondary end points included changes in serum PFAS levels from week 52 to week 64, changes in other PFASs, and changes in complete blood count, biochemistry, thyroid function, and lipid profile from screening to week 52. RESULTSA total of 285 firefighters (279 men [97.9%]; mean [SD] age, 53.0 [8.4] years) were enrolled; 95 were randomly assigned to donate plasma, 95 were randomly assigned to donate blood, and 95 were randomly assigned to be observed. The mean level of PFOS at 12 months was significantly reduced by plasma donation (-2.9 ng/mL; 95% CI, -3.6 to -2.3 ng/mL; P < .001) and blood donation (-1.1 ng/mL; 95% CI, -1.5 to -0.7 ng/mL; P < .001) but was unchanged in the observation group. The mean level of PFHxS was significantly reduced by plasma donation (-1.1 ng/mL; 95% CI, -1.6 to -0.7 ng/mL; P < .001), but no significant change was observed in the blood donation or observation groups. Analysis between groups indicated that plasma donation had a larger treatment effect than blood donation, but both were significantly more efficacious than observation in reducing PFAS levels. (continued) Key Points Question Can levels of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in the blood be reduced by blood or plasma donations? Findings In this randomized clinical trial of 285 firefighters, both blood and plasma donations resulted in significantly lower PFAS levels than observation alone. Plasma donation was the most effective intervention, reducing mean serum perfluorooctane sulfonate levels by 2.9 ng/mL compared with a 1.1-ng/mL reduction with blood donation, a significant difference; similar changes were seen with other PFASs. Meaning Blood or pl...

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IntroductionPerfluoroalkyl and polyfluoroalkyl substances (PFAS) are a diverse group of compounds that have been used in hundreds of industrial applications and consumer products including aqueous film-forming foam (AFFF) for many years. Multiple national and international health and environmental agencies have accepted that PFAS exposures are associated with numerous adverse health effects. Australian firefighters have been shown to have elevated levels of PFAS in their blood, specifically perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), due to the historical use of AFFF. While PFAS concentrations decline over time once the source of exposure has been removed, their potential adverse health effects are such that it would be prudent to develop an intervention to lower levels at a faster rate than occurs via natural elimination rates.Methods and analysisThis is a randomised controlled trial of current and former Australian firefighters in the Metropolitan Fire Brigade/Fire Rescue Victoria, and contractors, with previous occupational exposure to PFAS and baseline elevated PFOS levels. The study is investigating whether whole blood donation every 12 weeks or plasma donation every 6 weeks will significantly reduce PFAS levels, compared with a control group. We have used covariate-adaptive randomisation to balance participants’ sex and blood PFAS levels between the three groups and would consider a 25% reduction in serum PFOS and PFHxS levels to be potentially clinically significant after 12 months of whole blood or plasma donation. A secondary analysis of health biomarkers is being made of changes between screening and week 52 in all three groups.Ethics and disseminationThis trial has been approved by Macquarie University Human Research Ethics Committee (reference number: 3855), final protocol V.2 dated 12 June 2019. Study results will be disseminated via peer-reviewed publications and presentations at conferences.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12619000204145).