| 1. |
- Jin, Taiyi, et al.
(författare)
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Environmental epidemiological study and estimation of benchmark dose for renal dysfunction in a cadmium-polluted area in China.
- 2004
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Ingår i: Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. - : Kluwer Academic Publishers. - 0966-0844 .- 1572-8773. ; 17:5, s. 525-30
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Tidskriftsartikel (refereegranskat)abstract
- We have performed a study aimed at investigating the critical concentration of urinary cadmium (UCd) required for the development of renal dysfunction. We studied population groups (totally 790 persons) living in two cadmium exposed areas and one control area in China. UCd, was determined as an indicator of cadmium exposure and accumulation, while the concentrations of N-acetyl-beta-D-glucosaminidase (NAG), its iso-form B (NAG-B), beta2-microglobulin (B2M), retinol binding protein (RBP), and albumin (ALB) in urine were measured as indicators of the renal effects caused by cadmium. There was a significantly increased prevalence of hyperNAGuria, hyperNAG-Buria, hyperB2Muria, hyperRBPuria and hyperALBuria with increasing levels of Cd excretion in urine. We used the benchmark dose (BMD) procedure to estimate the critical concentration of urinary cadmium in this general population. The lower confidence limit of the BMD (LBMD-05) of urinary cadmium for a 5% level of risk above the background level was estimated for each of the renal effect indicators. The BMD-05/LBMD-05 were estimated to be 4.46/3.99, 6.70/5.87, 8.36/7.31, 7.98/6.98 and 15.06/12.18 microg/g creatinine for urinary NAG-B, NAG, B2M, RBP and ALB, respectively. Our findings suggest, based on the present study, that the Lower Confidence Limit of the Population Critical Concentration of UCd (LPCCUCd-05) of tubular dysfunction for 5% excess risk level above the background may be ca. 3-4 microg/g creatinine, and that cadmium concentration in urine should be kept below this level to prevent renal tubular damage. This report is the first to use the BMD method in this field and to define the concept of critical concentration in urine.
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| 2. |
- Kozaki, Koichi, et al.
(författare)
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Blockade of platelet-derived growth factor or its receptors transiently delays but does not prevent fibrous cap formation in ApoE null mice.
- 2002
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Ingår i: The American journal of pathology. - 0002-9440. ; 161:4, s. 1395-407
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) is a potent stimulant of smooth muscle cell migration and proliferation in culture. To test the role of PDGF in the accumulation of smooth muscle cells in vivo, we evaluated ApoE -/- mice that develop complex lesions of atherosclerosis. Fetal liver cells from PDGF-B-deficient embryos were used to replace the circulating cells of lethally irradiated ApoE -/- mice. One month after transplant, all monocytes in PDGF-B -/- chimeras are of donor origin (lack PDGF), and no PDGF-BB is detected in circulating platelets, primary sources of PDGF in lesions. Although lesion volumes are comparable in the PDGF-B +/+ and -/- chimeras at 35 weeks, lesions in PDGF-B -/- chimeras contain mostly macrophages, appear less mature, and have a reduced frequency of fibrous cap formation as compared with PDGF-B +/+ chimeras. However, after 45 weeks, smooth muscle cell accumulation in fibrous caps is indistinguishable in the two groups. Comparison of elicited peritoneal macrophages by RNase protection assay shows an altered cytokine and cytokine receptor profile in PDGF-B -/- chimeras. ApoE -/- mice were also treated for up to 50 weeks with a PDGF receptor antagonist that blocks all three PDGF receptor dimers. Blockade of the PDGF receptors similarly delays, but does not prevent, accumulation of smooth muscle and fibrous cap formation. Thus, elimination of PDGF-B from circulating cells or blockade of PDGF receptors does not appear sufficient to prevent smooth muscle accumulation in advanced lesions of atherosclerosis.
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