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Modeled speciation of Hg(II) and endogenous thiols; their comparative toxicity in LLC-PK(1) cells
In vivo Hg(II) exists as a complex with endogenous ligands, not as a free ion. Previous in vitro studies have demonstrated that metal ion form has a profound influence upon toxicity. We modeled Hg(II) ligand complexes using two independently developed computer programs. Models generated at physiological pH using published Hg(II) ligand K(f)'s, predict Hg(II) primarily will exist as a Hg(thiol)₂ complex. The Hg(thiol)₂ complexes, Hg(SG)₂, Hg(Cys)₂ and Hg(CysGly)₂, were synthesized, purified and identified. Hg(II) was administered to LLC-PK cells growing in defined media either with or without exogenous thiols. Hg(II) was administered as HgCl₂, Hg(SG)₂, Hg(Cys)₂, and HgCl₂ + either 1 or 2 moles of; GSH, L-Cys, D-Cys, CysGly and albumin. The LLC-PK₁ cells were incubated in Hg(II) concentrations ranging from 0-120 μM for 20 hrs. Toxicity was determined by the XTT assay. All forms of Hg(II) were more toxic when administered to LLC-PK₁ cells growing in defined media without exogenous thiols. Under all conditions, the least toxic form of Hg(II) was the Hg(thiol)₂ complexes and the most toxic form was HgCl₂. Addition of a single thiol equivalent to LLC-PK₁ cells in thiol containing media shifted the Hg(II) dose-response curves rightward ≈ 20μ M. Addition of Hg(II):2 albumin reduced Hg(II) toxicity in both experimental protocols. A self consistent set of relative competitive or conditional Kf's for Hg(II) with GSH, L-Cys, CysGly, DMPS, DMSA and EDTA was obtained using immobilized metal ion affinity chromatography (IMAC). Determining conditional Kf's using IMAC is advantageous in that the physical nature of water associated with the packed column is similar to that found in biological conditions and buffer composition can be manipulated to resemble biological fluids. Thiol sepharose 4B (Pharmacia LKB Biotechnology Inc., Piscataway NJ), GSH immobilized to sepharose, columns were loaded with HgCl₂, or Hg(SG)₂ and the affinity of Hg for the ligands was determined by competitive displacement chromatography. Our results demonstrate that the relative ranking of Hg-ligand Kf's is DMSA and DMPS > GSH, GSH ≈ L-Cys ≈ CysGly, > EDTA. The absolute values for the relative Hg-thiol complex Kf's must be ≥ 10²¹·⁵. (Martell and Smith, 1982)
Quantitative Particle-Induced X-ray Emission Imaging of Rat Olfactory Epithelium Applied to the Permeability of Rat Epithelium to Inhaled Aluminum
Nested multigene MSP/DHPLC method for analyzing promoter hypermethylation status in clinical samples
Olfactory Bulb Uptake and Determination of Biotransfer Factors in the California Ground Squirrel ( Spermophilus beecheyi
A Novel Mass-Spring-Damper Model Analysis to Identify Landing Deficits in Athletes Returning to Sport After Anterior Cruciate Ligament Reconstruction
A mass-spring-damper (MSD) model may serve as an extension of biomechanical data from 3-dimensional motion analysis and epidemiological data which helps to delineate populations at risk for anterior cruciate ligament (ACL) injuries. The purpose of this study was to evaluate such a model. Thirty-six ACL reconstruction (ACLR) group subjects and 67 controls (CTRL) completed single-leg drop landing and single-leg broad jump tasks. Landing ground reaction force data were collected and analyzed with an MSD model. Medians, inter-quartile ranges, and limb symmetry indices (LSIs) were calculated and comparisons were made within and between groups. During a single-leg drop landing, the ACLR group had a lower spring LSI than the CTRL group (p = 0.015) and landed with decreased stiffness in the involved limb relative to the uninvolved limb (p = 0.021). The ACLR group also had an increased damping LSI relative to the CTRL group (p = 0.045). The ACLR subjects landed with increased stiffness (p = 0.006) and decreased damping (p = 0.003) in their involved limbs compared to CTRL subjects' nondominant limbs. During a single-leg forward broad jump, the ACLR group had a greater spring LSI value than the CTRL group (p = 0.045). The CTRL group also recorded decreased damping values in their nondominant limbs compared with the involved limbs of the ACLR group (p = 0.046). Athletes who have undergone ACLR display different lower-limb dynamics than healthy controls, according to an MSD model. Quadriceps dominance and leg dominance are components of ACLR athletes' landing strategies and may be identified with an MSD model and addressed during rehabilitation