Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the 198 Au β-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible 198 AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors, which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed approximately 72% retention of 198 AuNP-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 d demonstrating significant inhibition of tumor growth compared to controls. This innovative nanotechnological approach serves as a basis for designing biocompatible target specific antineoplastic agents. This novel intratumorally injectable 198 AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.
Application of phosphoric acid (H3PO4) to lead (Pb)-contaminated soil may be a remedial strategy for in situ immobilization of soil Pb. Treatment homogeneity with three application methods was assessed by determining microscale pH variability through both conventional and spatial variance analyses. Soil containing an average 2570 mg Pb kg−1 near a smelter in Jasper County, Missouri, was treated with H3PO4 (10 g P kg−1) utilizing three methods: rototilling, pressure injection, and surface application. An undisturbed soil core (10 cm deep, 10 cm wide, 2.5 cm thick) was taken from each plot 30 days after treatment. Soil pH was measured at 1-cm horizontal and vertical intervals with a pH-sensitive glass microelectrode. Horizontal and vertical variations of soil pH were estimated by variance analyses, and the spatial variability was assessed by semivariogram function. Addition of H3PO4 to the soil decreased pH significantly and increased total variability in the measured zone. The pH variability in the vertical direction differed significantly, but that in the horizontal did not. Higher total variability caused by the treatment methods resulted from increased spatially dependent variability, which may be attributed to strong trends of pH with soil depth. Rototilling resulted in the lowest variation and smallest spatial variances, suggesting the most effective mixing of soil with added H3PO4 among the methods tested. This study demonstrated that microscale pH measurements and analyses of total and spatial variances may aid in assessing the efficacy of H3PO4 treatment in Pb-contaminated soil.
Although small arms ranges are known to be contaminated with lead, the full extent of metal contamination has not been described, nor has the oral bioavailability of lead in these soils. In this work, soil samples from ranges with diverse geochemical backgrounds were sieved to <250 μm and analyzed for total metal content. Soils had consistently high levels of lead and copper, ranging from 4549 to 24 484 μg/g and 223 to 2936 μg/g, respectively, while arsenic, antimony, nickel, and zinc concentrations were 100-fold lower. For lead bioavailability measurements, two widely accepted methods were used: an in vivo juvenile swine relative bioavailability method measuring lead absorption from ingested soils relative to equivalent lead acetate concentrations and an in vitro bioaccessibility procedure which measured acid-extractable lead as a percent of total lead in the soil. For eight samples, the mean relative bioavailability and bioaccessibility of lead for the eight soils was about 100% (108 ± 18% and 95 ± 6%, respectively) showing good agreement between both methods. Risk assessment and/or remediation of small arms ranges should therefore assume high bioavailability of lead.
Abstract Objective —To determine the relationship between serum and liver copper concentrations and evaluate serum copper determination for diagnosis of copper deficiency in juvenile beef calves. Design —Cross-sectional study. Animals —105 juvenile beef calves. Procedure —Copper concentrations were measured in paired liver and serum samples from 6- to 9-monthold beef calves. Regression models that predicted liver copper concentration as a function of serum copper concentration were developed. Sensitivity and specificity of serum copper concentration for detection of low liver copper concentration were determined, using a range of serum copper concentrations as test endpoints. Positive and negative predictive values were calculated. Results —The association between serum and liver copper concentrations was significant; however, regression models accounted for only a small portion of the variation in liver copper concentrations. For a serum copper concentration endpoint of 0.45 µg/g, sensitivity and specificity for detection of low liver copper concentration were 0.53 and 0.89, respectively. Positive and negative predictive values of serum copper concentration for detection of low liver copper concentration ranged from 0.37 to 0.85 and 0.63 to 0.94, respectively. Conclusions and Clinical Relevance —Regression models are inappropriate for predicting copper status as a function of serum copper concentration. Serum copper concentration is fairly specific for detection of low liver copper concentration but only marginally sensitive when serum copper concentration of 0.45 µg/g is used as a test endpoint. The value of serum copper concentration as a diagnostic indicator depends on prevalence of copper deficiency. ( J Am Vet Med Assoc 2001;218:756–760)
Arsenic (As) is one of the most widespread, toxic elements in the environment and human activities have resulted in a large number of contaminated areas. However abundant, the potential of As toxicity from exposure to contaminated soils is limited to the fraction that will dissolve in the gastrointestinal system and be absorbed into systemic circulation or bioavailable species. In part, the release of As from contaminated soil to gastrointestinal fluid depends on the form of solid phase As also termed "As speciation." In this study, 27 As-contaminated soils and solid wastes were analyzed using X-ray absorption spectroscopy (XAS) and results were compared to in vivo bioavailability values determined using the adult mouse and juvenile swine bioassays. Arsenic bioavailability was lowest for soils that contained large amounts of arsenopyrite and highest for materials that contained large amounts of ferric arsenates. Soil and solid waste type and properties rather than the contamination source had the greatest influence on As speciation. Principal component analysis determined that As(V) adsorbed and ferric arsenates were the dominant species that control As speciation in the selected materials. Multiple linear regression (MLR) was used to determine the ability of As speciation to predict bioavailability. Arsenic speciation was predictive of 27% and 16% of RBA As determined using the juvenile swine and adult mouse models, respectively. Arsenic speciation can provide a conservative estimate of RBA As using MLR for the juvenile swine and adult mouse bioassays at 55% and 53%, respectively.
