Cadmium (Cd) is toxic to the kidney and a major part of the body burden occurs here. Cd in urine (U-Cd) and blood (B-Cd) are widely-used biomarkers for assessing Cd exposure or body burden. However, ...empirical general population data on the relationship between Cd in kidney (K-Cd), urine, and blood are scarce. Our objectives were to determine the relationship between cadmium in kidney, urine, and blood, and calculate the elimination half-time of Cd from the kidney.
Kidney cortex biopsies, urine, and blood samples were collected from 109 living kidney donors. Cd concentrations were determined and the relationships between K-Cd, U-Cd, and B-Cd were investigated in regression models. The half-time of K-Cd was estimated from the elimination constant.
There was a strong association between K-Cd and U-Cd adjusted for creatinine (rp=0.70, p<0.001), while the association with B-Cd was weaker (rp=0.44, p<0.001). The relationship between K-Cd and U-Cd was nonlinear, with slower elimination of Cd at high K-Cd. Estimates of the K-Cd half-time varied between 18 and 44years. A K-Cd of 25μg/g corresponds to U-Cd of 0.42μg/g creatinine in overnight urine (U-Cd/K-Cd ratio: about 1:60). Multivariate models showed Cd in blood and urinary albumin as determinants for U-Cd excretion.
In healthy individuals with low-level Cd exposure, there was a strong correlation between Cd in kidney and urine, especially after adjustment for creatinine. Urinary Cd was also affected by Cd in blood and urinary albumin. Previous estimates of the U-Cd/K-Cd ratio may underestimate K-Cd at low U-Cd.
► The first study of the relation between Cd in kidney, blood and urine at low U-Cd ► Simultaneous samples were collected from healthy kidney donors. ► There was a nonlinear relationship between cadmium in kidney and urine. ► Estimates of the kidney cadmium half-time were 18–44years, depending on model used. ► Previous data seem to underestimate kidney cadmium at low urinary cadmium.
A biokinetic study of (209)Po in man Henricsson, Fredrik; Ranebo, Ylva; Hansson, Mats ...
The Science of the total environment,
10/2012, Letnik:
437C
Journal Article
Recenzirano
Five adult volunteers participated in a biokinetic study of radioactive polonium. Portions of about 10Bq of (209)Po were orally administrated to four of the volunteers in a single ingestion. The ...fifth volunteer ingested a daily amount of 53mBq of 209Po for 243d to study the time to achieve equilibrium between intake and excretion for protracted intakes. For the subjects ingesting single intakes of (209)Po complete sampling of urine and feces was subsequently collected the first few days upon the ingestion. The samples were processed with radiochemical extraction and analyzed with alpha spectrometry. In the study, the maximum daily excretion rates in feces were 18-50% of the ingested activity, observed within 3d after intake. Regarding the urine excretion, the daily excretion peaked, on average, at 0.15-1% of the ingested activity within two days upon intake. These results indicate an average gastro-intestinal uptake fraction of 0.46±0.08, which agrees well with earlier biokinetic studies of polonium in man.
This study investigated the human gastrointestinal uptake (f1) and subsequent whole-body retention of orally administered inorganic radioactive cobalt. Of eight adult volunteers aged between 24 and ...68 years, seven were given solutions of 57Co (T1/2 = 272 d) containing a stable cobalt carrier, and six were given carrier-free 58Co (T1/2 = 71 d). The administered activities ranged between 25 and 103 kBq. The observed mean f1, based on 6 days accumulated urinary excretion sampling and whole-body counting, was 0.028 ± 0.0048 for carrier-free 58Co, and 0.016 ± 0.0021 for carrier-associated 57Co. These values were in reasonable agreement with values reported from previous studies involving a single intake of inorganic cobalt. The time pattern of the total retention (including residual cobalt in the GI tract) included a short-term component with a biological half-time of 0.71 ± 0.03 d (average ± 1 standard error of the mean for the two nuclides), an intermediate component with a mean half-time of 32 ± 8.5 d, and a long-term component (observed in two volunteers) with half-times ranging from 80 to 720 d for the two isotopes. From the present data we conclude that for the short-lived 57Co and 58Co, more than 95% of the internal absorbed dose was delivered within 7 days following oral intake, with a high individual variation influenced by the transit time of the unabsorbed cobalt through the gastro-intestinal tract.
•Gastrointestinal (GI) uptake, f1, of inorganic radioactive cobalt varies between 0.007 and 0.043 among humans.•Mean f1 among human volunteers was found to be 0.022 ± 0.003.•More than 95% of the estimated internal absorbed dose occurs within 7 d for the short-lived radionuclides 57Co and 58Co.•More than 60% of the time integrated absorbed dose from ingestion of 60Co occurs within 7 d.•Residence time of cobalt in the human GI-tract strongly influences the time integrated internal absorbed dose.
A biokinetic study of 209Po in man Henricsson, C.F.; Ranebo, Y.; Hansson, M. ...
The Science of the total environment,
2012-Oct-15, Letnik:
437
Journal Article
Recenzirano
Five adult volunteers participated in a biokinetic study of radioactive polonium. Portions of about 10Bq of 209Po were orally administrated to four of the volunteers in a single ingestion. The fifth ...volunteer ingested a daily amount of 53mBq of 209Po for 243d to study the time to achieve equilibrium between intake and excretion for protracted intakes. For the subjects ingesting single intakes of 209Po complete sampling of urine and feces was subsequently collected the first few days upon the ingestion. The samples were processed with radiochemical extraction and analyzed with alpha spectrometry. In the study, the maximum daily excretion rates in feces were 18–50% of the ingested activity, observed within 3d after intake. Regarding the urine excretion, the daily excretion peaked, on average, at 0.15–1% of the ingested activity within two days upon intake. These results indicate an average gastro-intestinal uptake fraction of 0.46±0.08, which agrees well with earlier biokinetic studies of polonium in man.
► Human metabolism of an oral intake of polonium. ► 4 individuals were administrated about 10Bq polonium-209. ► Gastro-intestinal uptake fraction, if orally administrated polonium-209 was investigated. ► The biological half-time of polonium in human body was studied.
C-peptide (CP), connecting the A and B chains in proinsulin, has been considered to possess physiological effects in diabetes. In order to prolong the half-life of CP in vivo, a long acting CP analog ...human serum albumin (HSA-CP) was obtained by direct gene fusion of a single-chain CP to HSA and expressed in host Pichia pastoris GS115. After 72 h of growth on methanol, the recombinant HSA-CP concentration reached a level of 145 mg/L, representing 70% of total proteins in culture supernatant. The recombinant fusion protein was purified by ultra filtration, Q-sepharose fast flow column and Superdex 75 size-exclusion column. It was specifically recognized by the anti-human HSA antibody and CP antibody in Western blotting assay. In vitro, the recombinant HSA-CP can stimulate HEK293 cell proliferation. In Zucker diabetic fatty (ZDF) rats, 12 weeks recombinant HSA-CP treatment could prevent the accumulation of glomerular extracellular matrix, which leads to mesangial expansion and glomerular hypertrophy. The terminal biological half-time of the protein was 3.38 plus or minus 1.87 h after single administration of 500 nmol/kg of HSA-CP in Wister rats. The pharmacokinetic analysis of the protein indicate its promising application in clinical medicine.
Glucagon-like peptide-1 (GLP-1) is a 30-residue peptide hormone secreted by intestinal L-cells in response to nutrient ingestion. In the present study, overlapping PCR technology was employed to ...construct two GLP-1 mutants (GLP-1
A2G)
2 and human albumin (HSA) genes in vitro without linker. The spliced gene, (GLP-1
A2G)
2-HSA, was over expressed under the control of promoter AOX1 and Mat α signal peptide in
Pichia pastoris. SDS–PAGE and Western blotting were applied to assay the recombinant fusion protein in the culture broth. The results demonstrated that the recombinant (GLP-1
A2G)
2-HSA concentration in the broth could reach a level of 245.0
mg/L and the expressed fusion protein was capable of cross-reacting with anti-human GLP-1 and anti-human albumin antibody. The recombinant (GLP-1
A2G)
2-HSA protein was purified by ultrafiltration, columns of Q-sepharose fast flow and Superdex 75 size-exclusion. The recombinant (GLP-1
A2G)
2-HSA protein obtained could lower in vivo glucose concentration in blood and stimulate in vitro islet cell proliferation. In mouse model, the fusion protein was detectable in plasma even 308
h after a single subcutaneous dose of 1.25
mg/kg. The result showed that the terminal biological half-time of the protein was about 54.2
h which is 650-fold longer than that of GLP-1. The pharmacokinetic analysis of the protein suggests its promising application in clinical medicine.
Wistar male rats were exposed to 2000 ppm of methyl bromide gas for one hour (single exposure experiment) or 300 ppm of the gas for 6 hours a day, 3 days a week for 4 or 8 weeks (repeated exposure ...experiment) to investigate the metabolism of inhaled methyl bromide. After the exposure was completed, the bromine ion concentration in serum was measured up to 60 days. The serum bromine ion concentration was determined by a headspace gas chromatography-mass spectrometry after converting bromine ion to methyl bromide by adding dimethyl sulfate in the serum samples. In the single exposure experiment, the bromine ion concentration decreased quickly within one day after the end of the exposure, and then began to decrease gradually. In the repeated exposure experiment, on the other hand, the bromine ion concentration decreased almost exponentially. A two-compartment model was applied to analyze the clearance rate of bromine ion. The biological half time of serum bromine ion was 9.1 days for the single exposure and 5.4 days for the repeated exposure. The amount of cytochrome P450 (CYP) in liver microsomes was measured after the end of exposure. CYP in liver was not significantly different after the repeated exposure but it decreased after the single exposure.
Radionuclides were added to the anoxic hypolimnion of a Canadian Shield lake to simulate the nuclear fuel waste disposal scenario where radionuclides might enter the bottom waters of a lake. The ...radionuclides remained in the hypolimnion until lake mixing at autumn turnover after which
60Co was rapidly lost and
134Cs was slowly lost from the water. Only 0.4% of the
60Co and 0.6% of the
134Cs remained in the water at year 5. Highest concentrations occurred in periphyton and filter feeders,
Holopedium gibberum and clams (
Anodonata grandis grandis). From maximum annual concentrations in clam tissues, it was estimated that the availability of
60Co for uptake had a half-time (
t
1/2) of 835 days in the lake, whereas that for
134Cs was 780 days. Loss rate coefficients,
k, for the radionuclides from taxa ranged from 0.0008 to 0.0043 day
−1 (
t
1/2=161–866 days) for
60Co and from 0.0009 to 0.005 day
−1 (
t
1/2=139–770 days) for
134Cs. Cobalt-60 concentrations in forage fish were low, whereas
134Cs concentrations increased over the first year or two, then slowly declined. On the basis of
k values measured for forage fish, the biological half-time of
134Cs in forage fish ranged from 428 to 630 days. Maximum
134Cs concentrations in forage fish were higher following hypolimnetic addition than epilimnetic addition. Relatively high
134Cs concentrations in periphyton at year 5 point to the importance of benthic pathways in the recycling of contaminants to higher trophic levels. The presence of
134Cs in biota 5 years after the addition, long after concentrations were no longer detectable in surface waters, is evidence of the persistence of Cs in aquatic systems. The
k values (or
t
1/2 values) for the loss of
60Co and
134Cs from water and their uptake and loss from biota can be used to establish parameter values for assessment models. The results demonstrate that assessment models should account for the release of radionuclides from sediment and their subsequent recycling in the food chain when modeling over the long term after the end of a radionuclide release to the environment.
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