Estimation of Mercury Body Burden from Dental Amalgam: Computer Simulation of a Metabolic Compartmental Model

1986 ◽  
Vol 65 (12) ◽  
pp. 1415-1419 ◽  
Author(s):  
M.J. Vimy ◽  
A.J. Luft ◽  
F.L. Lorscheider
Keyword(s):  
Low Dose ◽  
Body Burden ◽  
Compartment Model ◽  
Dental Amalgam ◽  
The Body ◽  
Continuous Exposure ◽  
Dental Amalgams ◽  
Wet Weight ◽  
Total Body

Estimated release rates of Hg vapor from dental amalgams permitted calculation of the potential Hg body burden by employing a four-compartment model for inorganic and elemental Hg distribution. A computer program, compatible with most personal computers, simulated the cumulative and incremental distribution in each compartment and total body accumulation between 1 and 10,000 days for different daily Hg dosages. For a given Hg dose of 30 μ g/day, metabolic compartments R1-R3 were close to equilibrium at 5, 100, and 300 days, respectively; whereas by 10,000 days, R4 closely approximated total body burden and had not yet attained equilibrium. Projected values obtained with the computer model were consistent with results obtained by another method using a standard tissue burden equation, which employed experimentally determined tissue half-lives for blood and CNS. The model predicted that continuous exposure to elemental Hg vapor, at 30 μ g/day for 10 years, would result in a total Hg body burden of 5.9 mg, of which 4.8 mg could be contained in R4. Assuming that the Hg in R4 displayed uniform distribution throughout the body, then the brain concentration was estimated to be 68 nglg wet weight. In contrast, if Hg in R4 reflected long-term preferential accumulation in brain and other neural tissue, then concentrations as high as 4.0 μ g/g could be attained. However, predictions of Hg concentrations in blood and urine were well within established ranges, and were unlikely to be of utility in assessing effects of chronic low-dose Hg exposure. It is concluded that the CNS could accumulate a substantial amount of Hg over extended time, based on low-dose elemental Hg vapor exposure via inhalation from dental amalgams.

Long-Term Accumulation of Metals in the Skeleton as Related to Osteoporotic Derangements

2020 ◽  
Vol 27 (40) ◽  
pp. 6837-6848 ◽  
Author(s):  
Geir Bjorklund ◽  
Lyudmila Pivina ◽  
Maryam Dadar ◽  
Yuliya Semenova ◽  
Salvatore Chirumbolo ◽  
...  
Keyword(s):  
Negative Impact ◽  
Age Groups ◽  
Body Burden ◽  
The Body ◽  
Metal Species ◽  
Metal Exposure ◽  
Accumulation Of Metals ◽  
Cadmium Lead ◽  
Total Body

The concentrations of metals in the environment are still not within the recommended limits as set by the regulatory authorities in various countries because of human activities. They can enter the food chain and bioaccumulate in soft and hard tissues/organs, often with a long half-life of the metal in the body. Metal exposure has a negative impact on bone health and may result in osteoporosis and increased fracture risk depending on concentration and duration of metal exposure and metal species. Bones are a long-term repository for lead and some other metals, and may approximately contain 90% of the total body burden in birds and mammals. The present review focuses on the most common metals found in contaminated areas (mercury, cadmium, lead, nickel, chromium, iron, and aluminum) and their effects on bone tissue, considering the possibility of the long-term bone accumulation, and also some differences that might exist between different age groups in the whole population.

Removal of Vancomycin during Plasmapheresis

1997 ◽  
Vol 31 (10) ◽  
pp. 1132-1136 ◽  
Author(s):  
Syble D McClellan ◽  
Charles H Whitaker ◽  
Richard C Friedberg
Keyword(s):  
Tertiary Care ◽  
Compartment Model ◽  
The Body ◽  
Patient Specific ◽  
Pharmacokinetic Parameters ◽  
Serum Concentrations ◽  
Total Clearance ◽  
Concentration Data ◽  
Vancomycin Concentration ◽  
Total Body

OBJECTIVE: To examine the removal of vancomycin during plasmapheresis, determine whether drug administration should be withheld prior to or a supplemental dose given after the procedure, and determine whether a redistribution phenomenon in vancomycin serum concentrations occurs after plasmapheresis. DESIGN: Prospective, cohort study. SETTING: An 800-bed, tertiary-care, teaching hospital. PATIENTS: Twelve patients receiving vancomycin as prescribed who were also undergoing therapeutic plasmapheresis. METHODS: Blood samples for determination of vancomycin concentrations were obtained from each patient immediately before, during, immediately after, and 2 hours after plasmapheresis. Vancomycin concentration in plasma removed by plasmapheresis and volume of plasma removed were measured. Patient-specific pharmacokinetic parameters were determined for each patient using serum concentration data and a one-compartment model. Percent of drug removed by plasmapheresis and percent increase in vancomycin total clearance secondary to plasmapheresis were calculated. RESULTS: A mean of 6.3% of the total body store of vancomycin was removed by plasmapheresis. Vancomycin clearance during plasmapheresis averaged 1.6 L/h, which was an average increase of 285% in the total clearance of vancomycin from the body. Nine of 10 patients had a higher observed vancomycin concentration 2 hours after plasmapheresis than that predicted by degrading the concentration observed immediately after the procedure, suggesting that redistribution in serum concentrations occurs after the procedure. CONCLUSIONS: A single one-volume plasmapheresis does not remove a clinically important amount of vancomycin; therefore, supplemental dosing after the procedure is not necessary. A redistribution phenomenon in vancomycin concentrations appears to exist after plasmapheresis. Further study is needed to determine how long the redistribution phase lasts and when vancomycin concentrations should be measured after plasmapheresis.

scholarly journals Human Body Burden of Heavy Metals and Health Consequences of Pb Exposure in Guiyu, an E-Waste Recycling Town in China

2021 ◽  
Vol 18 (23) ◽  
pp. 12428
Author(s):  
Wenlong Huang ◽  
Xiaoling Shi ◽  
Kusheng Wu
Keyword(s):  
Heavy Metals ◽  
Body Burden ◽  
Local Environment ◽  
Waste Recycling ◽  
The Body ◽  
Health Consequences ◽  
Long Term Effects ◽  
Adaptive Immune ◽  
Pb Exposure

Guiyu accommodates millions of tons of e-waste from overseas and domestic sources each year and is notorious for its e-waste dismantling industry. As a consequence, Guiyu has been described as “the world’s most toxic place” and “junk town”. Informal e-waste recycling activities have caused severe pollution to the local environment and are associated with extensive health problems to the residents. This review provides updated insights on the body burden of heavy metals derived from e-waste and health outcomes resulted from lead (Pb) exposure. The review identified that Guiyu has been highly contaminated by heavy metals, especially Pb. Excessive exposure to Pb has been associated with multi-system and long-term effects in neonates and children, covering nervous, cardiovascular, adaptive immune, and hematologic systems as well as chromosome and DNA damage. Our review indicates strong associations that emphasize the need to develop strong regulations for prevention of exposure and health consequences in Guiyu and similar sites around the world.

Growth factor treatment prior to low-dose total body irradiation increases donor cell engraftment after bone marrow transplantation in mice

Blood ◽  
2002 ◽  
Vol 100 (1) ◽  
pp. 312-317 ◽  
Author(s):  
Estelle J. K. Noach ◽  
Albertina Ausema ◽  
Jan H. Dillingh ◽  
Bert Dontje ◽  
Ellen Weersing ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Growth Factors ◽  
Low Dose ◽  
Donor Cell ◽  
Hematopoietic Growth Factors ◽  
Cell Engraftment ◽  
Total Body

Abstract Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell engraftment. We hypothesized that treatment of recipient mice with growth factors would selectively deplete stem cells, resulting in successful long-term donor cell engraftment after transplantation. Recipient mice were treated for 1 or 7 days with growth factors (stem cell factor [SCF] plus interleukin 11 [IL-11], SCF plus Flt-3 ligand [FL], or granulocyte colony-stimulating factor [G-CSF]) prior to low-dose TBI (4 Gy). Donor cell chimerism was measured after transplantation of congenic bone marrow cells. High levels of donor cell engraftment were observed in recipients pretreated for 7 days with SCF plus IL-11 or SCF plus FL. Although 1-day pretreatments with these cytokines initially resulted in reduced donor cell engraftment, a continuous increase in time was observed, finally resulting in highly significantly increased levels of donor cell contribution. In contrast, G-CSF treatment showed no beneficial effects on long-term engraftment. In vitro stem cell assays demonstrated the effect of cytokine treatment on stem cell numbers. Donor cell engraftment and number of remaining recipient stem cells after TBI were strongly inversely correlated, except for groups treated for 1 day with SCF plus IL-11 or SCF plus FL. We conclude that long-term donor cell engraftment can be strongly augmented by treatment of recipient mice prior to low-dose TBI with hematopoietic growth factors that act on primitive cells.

In Vivo X-Ray Fluorescence Analysis for Medical Diagnosis

1979 ◽  
Vol 23 ◽  
pp. 185-191 ◽  
Author(s):  
L. Ahlgren ◽  
T. Grönberg ◽  
S. Mattsson
Keyword(s):  
Body Burden ◽  
Fluorescence Analysis ◽  
Industrial Applications ◽  
The Body ◽  
Lead Contamination ◽  
X Ray ◽  
Sensitive Function ◽  
Total Body ◽  
Medical Interest

Occupational exposure to lead is common in many industrial applications and hence it is of considerable medical interest to control the body-burden of lead in living man. More than 90 % of the lead in the body is concentrated in bone and hence in vivo measurements of the lead in the skeleton should give the most satisfactory way for estimating the body-burden. The routine method used today for checking on lead contamination is that of measurements on blood samples. However, since the concentration of lead in the blood is a sensitive function of the actual exposure conditions, this method provides only a poor indication of the total body-burden and the integrated lead exposure.

Radiation Dose Determines Degree of Donor Chimerism after Nonmyeloablative Hematopoietic Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1828-1828 ◽  
Author(s):  
Christoph Kahl ◽  
Marco Mielcarek ◽  
Mineo Iwata ◽  
Michael Harkey ◽  
Barry Storer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Radiation Dose ◽  
Low Dose ◽  
Donor Chimerism ◽  
Stem Cell Source ◽  
Cd34 Cells ◽  
Cell Source ◽  
Total Body

Abstract Efforts to replace total body irradiation (TBI) used for transplant conditioning with agents that have less acute and long-term toxicities require a better understanding of the biological effects of low dose TBI. We therefore retrospectively analyzed the role of radiation dose, stem cell source, and type of immunosuppression on both the stability and degree of donor chimerism in canine recipients of matched littermate hematopoietic cell transplants. Recipients were prepared with 200 cGy (n=26), 100 cGy (n=76) or 50 cGy (n=19) total body irradiation (TBI) at 7 cGy/min. Stem cell sources included bone marrow (BM) alone (n=58), BM plus G-CSF mobilized peripheral blood mononuclear cells (G-PBMC) (n=42), BM and CD14-depleted G-PBMC (n=13), or BM and T-cell-depleted G-PBMC (n=8). Posttransplant immunosuppression consisted of cyclosporin (CSP) only (n=53), CSP plus mycophenolate mofetil (MMF) (n=23), CSP and rapamycin (n=12), CSP, MMF and rapamycin (n=5); or CSP and MMF in combination with pretransplant immunosuppression (n=28). The percentage of donor granulocytes in the peripheral blood, as determined by PCR amplification of variable numbers of tandem repeats (VNTR), served as a marker for engraftment. TBI dose and stem cell source were both significantly associated with long-term (>26 weeks) stable engraftment in multivariate analysis (p=0.0001 and p=0.004, respectively). Among the 39 dogs with stable engraftment, however, TBI dose was the only factor examined that was associated with the degree of donor chimerism (mean % of donor granulocytes after 200 cGy, 100 cGy and 50 cGy of TBI: 65%, 52%, and 24%, respectively; p=0.008). To determine whether low-dose irradiation directly affected recipient stem/progenitor cell numbers and thereby conferred a competitive disadvantage to donor cells, CD34+ cells were isolated from two normal human donors. One preparation of CD34 cells was ex vivo irradiated (=200 cGy) and then injected into NOD/SCID beta2m-/- mice in combination with an equal number of unirradiated CD34 cells from the second donor. The contributions of each donor to human engraftment were assessed at 10 weeks by VNTR. After 200 cGy, the irradiated population contributed 74% less than expected, 24% less after 100 cGy, but only 6% less after 50 cGy. Flow analysis of Caspase-3 activation indicated that a significant percentage of cells irradiated with 200 cGy were apoptotic, and that this was associated with the loss of L-selectin and P-selectin glycoprotein ligand-1. In conclusion, our findings suggest that TBI, in addition to its well-characterized immunosuppressive effects, determines the degree of donor cell engraftment by directly compromising recipient stem cells, thereby providing a competitive advantage to donor stem cells.

scholarly journals Protective Effects of Hydrogen against Low-Dose Long-Term Radiation-Induced Damage to the Behavioral Performances, Hematopoietic System, Genital System, and Splenic Lymphocytes in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Jiaming Guo ◽  
Deyun Zhao ◽  
Xiao Lei ◽  
Hainan Zhao ◽  
Yanyong Yang ◽  
...  
Keyword(s):  
Low Dose ◽  
Protective Efficacy ◽  
Forced Swim Test ◽  
Lymphocyte Transformation ◽  
Lymphocyte Transformation Test ◽  
The Body ◽  
Whole Body ◽  
Protective Effects ◽  
Multiple Systems

Molecular hydrogen (H2) has been previously reported playing an important role in ameliorating damage caused by acute radiation. In this study, we investigated the effects ofH2on the alterations induced by low-dose long-term radiation (LDLTR). All the mice in hydrogen-treated or radiation-only groups received 0.1 Gy, 0.5 Gy, 1.0 Gy, and 2.0 Gy whole-body gamma radiation, respectively. After the last time of radiation exposure, all the mice were employed for the determination of the body mass (BM) observation, forced swim test (FST), the open field test (OFT), the chromosome aberration (CA), the peripheral blood cells parameters analysis, the sperm abnormality (SA), the lymphocyte transformation test (LTT), and the histopathological studies. And significant differences between the treatment group and the radiation-only groups were observed, showing thatH2could diminish the detriment induced by LDLTR and suggesting the protective efficacy ofH2in multiple systems in mice against LDLTR.

scholarly journals In Situ Vaccination with Cpg and Anti-OX40 Antibody: Preclinical Optimization for Clinical Translation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2943-2943
Author(s):  
Idit Sagiv Barfi ◽  
Debra K. Czerwinski ◽  
Tanaya Shree ◽  
Ronald Levy
Keyword(s):  
Immune Response ◽  
Therapeutic Effect ◽  
Therapeutic Efficacy ◽  
Low Dose ◽  
The Body ◽  
Systemic Immune Response ◽  
Low Dose Radiotherapy ◽  
Untreated Tumor

Abstract In-situ vaccination is a local intervention in which immune enhancing agents are injected locally into one site of tumor, triggering a T cell immune response locally that then travels to attack cancer throughout the body. We have employed a preclinical strategy whereby the same syngeneic tumor is implanted at two separate sites in the body. One tumor is then injected with the test agents and the resulting systemic immune response, if any, is detected by the regression of the distant, untreated tumor. In this test for abscopal therapeutic effects, the combination of unmethylated CG-enriched oligodeoxynucleotide (CpG) - a TLR9 ligand - and agonist anti-OX40 antibody has provided impressive results. This combination lead to durable disease control and long-term treatment-free survival in multiple mouse models of cancer. CpG induced myeloid cells to secrete cytokines, which subsequently induced OX40 expression on T cells. Thus, we hypothesized that administration sequence and timing may affect the anti-tumor responses of in-situ vaccination. In order to screen for the best sequence and timing we implanted A20 lymphoma tumors bilaterally in opposite sides of the abdomen of Balb/C mice. After tumors were established, one tumor was injected at the selected sequence and timing with the test agents and the resulting immune response was monitored by the measuring growth of the distant, untreated tumor. As opposed to our usual schedule of three injections, even a single injection of CpG (50µg) and anti-OX40 (8µg) resulted in a fully protective systemic immune response. In addition, the cured animals were protected from re-challenge with the same A20 tumor but not unrelated tumors. Decreasing the dose even further to 10µg CpG and 1µg anti-OX40 partially preserved the therapeutic response with a long-term survival of 60%. Concurrent administration of CpG and anti-OX40 resulted in eradication of both local and distant disease. Sequential administration of CpG followed by anti-OX40 preserved the therapeutic efficacy. However, the opposite order of anti-OX40 followed by CpG significantly attenuated the therapeutic effect. While CpG followed by a 24- or 48-hour-delayed anti-OX40 treatment preserved the therapeutic efficacy, a 72h delay in anti-OX40 administration resulted in reduced therapeutic effect. These data demonstrate the importance of the administration sequence for fully protective anti-tumor immune responses. Our data suggest that the anti-OX40 antibody should be administered at the same time as CpG or with only a slight delay but not in the reverse order. Low-dose radiotherapy (2×2 Gy) is an effective treatment for patients with indolent non-Hodgkin's lymphoma. This treatment results in high response rates at the treated site. Since immune infiltrating cells in the tumor microenvironment are essential for in situ vaccination of CpG and anti-OX40 we aimed to assess the effect of adding radiation in our pre-clinical models of lymphoma. We found that the addition of 2x2 Gy radiation did not interfere with the induction of a protective immune response by of CpG and anti-OX40. Given the effectiveness of low dose radiotherapy for local control and its lack of interference with the immune related abscopal response in the pre-clinical model, we are including radiation in our current clinical trials. In addition, we have incorporated our findings in the preclinical model regarding dosing and scheduling of CpG and anti-OX40 antibody to the design of our current in situ vaccination lymphoma clinical trial. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Side-Effects: Mercury Contribution to Body Burden From Dental Amalgam

1992 ◽  
Vol 6 (1) ◽  
pp. 110-113 ◽  
Author(s):  
J.W. Reinhardt
Keyword(s):  
Body Burden ◽  
Elemental Mercury ◽  
Mercury Vapor ◽  
Dental Amalgam ◽  
Human Tissues ◽  
Target Organs ◽  
Highly Sensitive ◽  
Dental Amalgams ◽  
The Central Nervous System ◽  
The Relationship

The purpose of this paper is to examine and report on studies that relate mercury levels in human tissues to the presence of dental amalgams, giving special attention to autopsy studies. Until recently, there have been few published studies examining the relationship between dental amalgams and tissue mercury levels. Improved and highly sensitive tissue analysis techniques have made it possible to measure elements in the concentration range of parts per billion. The fact that mercury can be absorbed and reach toxic levels in human tissues makes any and all exposure to that element of scientific interest. Dental amalgams have long been believed to be of little significance as contributors to the overall body burden of mercury, because the elemental form of mercury is rapidly consumed in the setting reaction of the restoration. Studies showing measurable elemental mercury vapor release from dental amalgams have raised renewed concern about amalgam safety. Mercury vapor absorption occurs through the lungs, with about 80% of the inhaled vapor being absorbed by the lungs and rapidly entering the bloodstream. Following distribution by blood circulation, mercury can enter and remain in certain tissues for longer periods of time, since the half-life of excretion is prolonged. Two of the primary target organs of concern are the central nervous system and kidneys.

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