Intraarticular injection of a Tin-117 m radiosynoviorthesis agent in normal canine elbows causes no adverse effects.

This longitudinal prospective exploratory study used serial measurements in five dogs to evaluate safety and retention of a tin-117 m (117m Sn) colloid after intra-articular injection in normal elbow joints. Each dog was deemed healthy based on physical examination, laboratory results, and radiographic evaluation of both elbows. While anesthetized, each received an MRI of both elbows, followed by fluorine-18 fluorodeoxyglucose positron emission tomography scans of both elbow joints and associated lymph nodes. Joint fluid (0.5-1.0 mL) was withdrawn aseptically from the left elbow joint, followed by intra-articular injection of 117m Sn colloid (92.5 MBq; 1-1.5 ml). Post-injection assessments included blood counts, serum chemistry panels, urinalyses, radiographs, joint fluid analyses, MRI/positron emission tomography scans, scintigraphy, and biodistribution scans. On day 45-47, each dog was euthanized and a complete postmortem examination was performed. Tissue samples were submitted for histopathology and radioisotope retention studies. Left elbow joints were decalcified and sectioned for future autoradiography. Scintigraphy, 1 day after injection, indicated slight radioisotope escape from the joint to regional lymph nodes. Serial blood, urine, feces, and organ counts indicated >99.1% of the 117m Sn activity was retained in the joint for 45-47 days. Radiation output levels were below patient release levels the day following injection. Maximum standard uptake value for the injected joint decreased. Joint fluid cytology was unchanged. No dog exhibited lameness during the study. Absence of joint damage and lack of systemic effects after injection of the 117m Sn colloid in normal canine elbow joints indicate that this agent may be safely used for radiosynoviorthesis in dogs with osteoarthritis.

Optimization of an acidic digestion method for the determination of total Pb concentration and its isotope ratios in human blood using ICP-QMS.

Adverse effects of lead (Pb) on human health are observed even at levels below 5 µg/dL, affecting principally the children population and suggesting that there is not a safe exposure level. The determination of Pb isotopic ratios (LIRs) in biological and environmental samples, is an appropriate tool to track and control the exposure sources, because LIRs constitutes the pollutant's isotopic signature and hence can be used to identify sources of Pb emission. This study proposes the optimization of a method in order to significantly reduce the biological samples' matrix interferences, and improves precision and accuracy in the measurements of LIRs. Four total blood digestion methods were evaluated and the results were subjected to statistical methods (ANOVA) determining the combination of HNO3:H2O2 (2:1 v v-1)/g from a sample on a hot plate as the best of them. For the method's validation, detection and quantification limits, linearity range, intermediate precision and recovery were evaluated. The total Pb (PbT) and LIRs were performed by ICP-QMS, defining the optimal value of detector dead time (DT), and correcting mass bias and instrumental drift for this matrix. LIRs based on 206Pb, 207Pb and 208Pb were determined at high precision (%RSD 0.03-0.49%), than those involving 204Pb (%RSD > 0.8). The optimized methodology can be used to identify pollution sources in blood and environmental samples using LIRs (206Pb/207Pb, 207Pb/208Pb, 208Pb/206Pb, etc.) in a trustworthy and simple way, with accurate results.

Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.

A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance.

Rising environmental cadmium levels in developing countries: threat to genome stability and health.

Cadmium (Cd) is a ubiquitous environmental pollutant of increasing worldwide concern. It is thought to be of greater concern to rapidly industrializing developing countries because of the increasing pace of industrial activities in these countries with increasing consumption and release into the environment. Traditionally, health concerns in exposed human populations have revolved around the association of Cd with bone disease, emphysema and possibly hypertension. Accumulating evidence suggest that Cd is involved in the disruption of many genomic processes, the mechanisms of which are being gradually understood. Changes in DNA Methylation may be induced by cadmium leading to epigenetic alterations. Additionally, though Cd is not thought to induce reactive oxygen species (ROS) directly because it is not capable of accepting or donating electrons under physiological conditions, 8-hydroxy deoxyguanosine (8-OHdG) (a marker of oxidative stress to DNA and a risk factor for cancer among others) has been shown to be elevated in the DNA of testes from rats treated with cadmium chloride, at least in part because Cd inhibits DNA repair mechanisms.  Cadmium is also a metabolic antagonist to Zinc (Zn), an important micronutrient involved in numerous molecular activities. This antagonism alters the physiological stoichiometric relationship between Cd and Zn leading to high Cd/Zn ratio, one consequence of which is high error rate and lack of efficient DNA repair systems leading to high mutation and genome instability culminating in many carcinogenic states, particularly prostate carcinogenesis. Cadmium has also been shown to replace Zn in the tumor suppressor protein, p53 thereby impairing p53's DNA binding activity and associated repair processes. The expression of the p53 protein is significantly depressed by cadmium. Although the rising level of Cd in the environment is widely acknowledged, the occult threat it poses to genome stability largely through inhibition of normal DNA damage repair, oxidative stress and apoptosis and health is poorly recognized. This paper examines the involvement of Cd in the molecular pathways of human disease, providing insight for the prevention of genome instability and associated disease susceptibility particularly cancer across populations through micronutrient intervention, aiding upregulation of the antioxidant defense and DNA repair systems.

Lead isotopes as a supplementary tool in the routine evaluation of household lead hazards.

The advent of magnetic sector inductively coupled plasma-mass spectrometry (ICP-MS) allows rapid, accurate, and precise measurement of lead isotopes in environmental and biological samples at a lower cost than traditional methods. This may increase the feasibility of including lead isotope measurements as a routine tool to identify household sources of lead exposure to children. Here, we present three household case studies to illustrate how lead hazard evaluations by an environmental specialist could be supplemented with routine lead isotope analyses of potential lead sources and blood. Sampling for lead isotopes was undertaken following the U.S. Department of Housing and Urban Development regulatory guidelines for the evaluation of lead hazards in housing, and with the consideration of minimizing the additional costs associated with lead isotope measurements. The range of isotopic ratios within a single residence was large enough to allow the characterization of different lead sources, particularly when both major (e.g., (207)Pb/(206)Pb) and minor (e.g., (206)Pb/(204)Pb) isotope ratios were considered. These cases illustrate the utility of the lead isotope method to identify main source(s) of lead exposure to the child; discard unlikely sources of exposure to the child; point to sources of lead to dust; and substantiate or refine the environmental assessment based exclusively on lead concentrations and loadings. Thus, a more effective evaluation of household lead hazards would likely benefit from considering a) lead concentrations and loadings in and around the household environment; b) all isotopic ratios of potential lead sources within that environment; and c) information about behavioral habits, as well as an evaluation of viable pathways of exposure to the child.