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Biomedical subjects

F W Sunderman

Publications and source records attributed to F W Sunderman.

At least 73 records · Page 4Linked to original sources
PubMed1987

Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct.

This assay of plasma lipoperoxides involves hydrolysis in dilute H3PO4 at 100 degrees C; complexation of malondialdehyde (MDA), a hydrolysis product, with thiobarbituric acid (TBA); methanol precipitation of plasma proteins; fractionation of the protein-free extract on a C18 column; and spectrophotometric quantification of the MDA-TBA adduct at 532 nm. The detection limit was 0.15 mumol of MDA per liter of plasma. Run-to-run precision (CV) averaged 8 to 13%. Analytical recovery of MDA after addition of tetraethoxypropane standards to 21 specimens of human or rat plasma averaged 98% (SD 7%). Lipoperoxide concentrations (as MDA) averaged 0.60 (SD 0.13) mumol/L in plasma specimens from 41 healthy persons and 1.4 (SD 0.3) mumol/L in plasma specimens from 12 control rats. Mean lipoperoxide concentrations were 1.5 to 2.3 times as great in plasma sampled from rats one to three days after subcutaneous administration of NiCl2 at dosages (250 to 750 mumol per kilogram body wt) previously shown to induce lipid peroxidation in lung, liver, and kidney.

Adult↗
PubMed1986

Biological monitoring of nickel.

Measurements of nickel in body fluids, excreta, and tissues from humans with occupational, environmental, and iatrogenic exposures to nickel compounds are comprehensively reviewed. Correlations between levels of human exposures to various classes of nickel compounds via inhalation, oral, or parenteral routes and the corresponding concentrations of nickel in biological samples are critically evaluated. The major conclusions include the following points: Measurements of nickel concentrations in body fluids, especially urine and serum, provide meaningful insights into the extent of nickel exposures, provided these data are interpreted with knowledge of the exposure routes, sources, and durations, the chemical identities and physical-chemical properties of the nickel compounds, and relevant clinical and physiological information, such as renal function. Nickel concentrations in body fluids should not, at present, be viewed as indicators of specific health risks, except in persons exposed to nickel carbonyl, for whom urine nickel concentrations provide prognostic guidance on the severity of the poisoning. In persons exposed to soluble nickel compounds (e.g., NiCl2, NiSO4), nickel concentrations in body fluids are generally proportional to exposure levels; absence of increased values usually indicates non-significant exposure; presence of increased values should be a signal to reduce the exposure. In persons exposed to less soluble nickel compounds (e.g., Ni3S2,NiO), increased concentrations of nickel in body fluids are indicative of significant nickel absorption and should be a signal to reduce the exposures to the lowest levels attainable with available technology; absence of increased values does not necessarily indicate freedom from the health risks (e.g., cancers of lung and nasal cavities) associated with exposures to certain relatively insoluble nickel compounds.

Alloys↗
PubMed1986

Methods for the estimation of serum magnesium in clinical laboratories.

A variety of methods have been reported for the quantitative analysis of magnesium in serum and other biological fluids. The methods may be classified into the following groups: magnesium ammonium phosphate; 8-hydroxyquinoline; titan yellow; dihydroxyazobenzene using fluorimetry; Schwarzenbach ethylenediaminetetraacetic acid; atomic emission spectrophotometry; atomic absorption spectrophotometry; ion chromatography, and carboxanilide, calmagite and related dye methods. These methods are reviewed with specific emphasis on the limitations for their use in clinical laboratories.

Azo Compounds↗
PubMed1985

Biliary excretion of nickel in rats.

Nickel (Ni) concentrations were determined by liquid scintillation spectrometry or electrothermal atomic absorption spectrophotometry in bile and plasma samples obtained from male rats following subcutaneous (s.c.) injection of 63NiCl2 (1.7 mumol/kg) or non-radioactive NiCl2 (125 or 250 mumol/kg). During the intervals from 1-6 or 11-16 h post-injection, the bile:plasma ratios of Ni concentrations ranged from 0.045-0.13, and the excretory clearance of Ni in bile ranged from 0.027-0.055 ml/h. The estimated biliary excretion of Ni in the 24 h post-injection amounted to less than 0.5% of the respective doses of NiCl2. Contrary to previous findings with other divalent metal ions, this study shows that biliary excretion is quantitatively unimportant for the elimination of exogenous Ni(II) in rats.

Animals↗
PubMed1985

63Ni content of renal parenchyma and nuclei from 63NiCl2-treated rats.

The time-course and dose-effect relationships for 63Ni uptake in renal parenchyma and nuclei were delineated in 63NiCl2-treated rats, based upon isolation of renal nuclei by sucrose gradient centrifugation and measurements of 63Ni by liquid scintillation counting. In 5 groups of rats killed 2 to 24 hours after 63NiCl2 injection (36 mumol/kg, im), 63Ni content of renal parenchyma (mean +/- SD) diminished from 3.0 +/- 0.3% of the dose at 2 hours to 0.9 +/- 0.3% of the dose at 24 hours; nuclear 63Ni content diminished from 10.5 +/- 4.4 pmol/10(6) nuclei at 2 hours to 3.0 +/- 0.3 pmol/10(6) nuclei at 24 hours. In 8 groups of rats killed 2 hours after injection of 63NiCl2 at dosages from 3 to 250 mumol/kg, 63Ni concentrations in renal nuclei increased progressively from 1.1 +/- 0.3 pmol/10(6) nuclei at 3 mumol/kg to 32.1 +/- 1.7 pmol/10(6) nuclei at 250 mumol/kg. Nuclear 63Ni content generally averaged 1.9 to 2.4% of total renal 63Ni; significantly higher mean values (3.4 +/- 1.0%) were observed in rats killed 48 hours after 5 daily injections of 63NiCl2 (1.1 mumol/kg/day). Combined administration of diethyldithiocarbamate (DDC, 1.33 mmol/kg, im) and 63NiCl2 (36 mumol/kg, im) increased 63Ni uptake in renal nuclei (4.8 +/- 1.4% of renal 63Ni; P less than 0.05 versus corresponding value of 2.0 +/- 0.2% in rats that received 63NiCl2, alone). Enhanced nuclear uptake of 63Ni evidently explains the synergistic effect of DDC and NiCl2 on induction of heme oxygenase activity in rat kidney.

Animals↗
PubMed1985

Nickel concentrations in serum of patients with acute myocardial infarction or unstable angina pectoris.

Nickel was measured, by electrothermal atomic absorption spectrophotometry, in sera from (a) 30 healthy adults, (b) 54 patients with acute myocardial infarction, (c) 33 patients with unstable angina pectoris without infarction, and (d) five patients with coronary atherosclerosis who developed cardiac ischemia during treadmill exercise. Mean (and SD) concentrations in Group a were 0.3 (0.3) microgram/L (range less than 0.05-1.1 microgram/L). Within 72 h after hospital admission, hypernickelemia (Ni greater than or equal to 1.2 microgram/L) was found in 41 patients of group b (76%) and in 16 patients of group c (48%). Hypernickelemia was found before and after exercise in one patient of Group d (20%). Peak values averaged 3.0 micrograms/L (range 0.4-21 micrograms/L) in Group b, 1.5 microgram/L (range less than 0.05-3.3 micrograms/L) in Group c. In Group b, the mean time interval between the peak values for creatine kinase activity and for nickel was 18 h. Serum nickel concentrations were unrelated to age, sex, time of day, cigarette smoking, medications, clinical complications, or outcome. Mechanisms and sources of release of nickel into the serum of patients with acute myocardial infarction or unstable angina pectoris are conjectural, but hypernickelemia may be related to the pathogenesis of ischemic myocardial injury.

Adult↗
PubMed1984

Effects of diethyldithiocarbamate and nickel chloride on glutathione and trace metal concentrations in rat liver.

Concentrations of reduced glutathione (GSH) and oxidized glutathione (GSSG) and 4 trace metals (Ni, Cu, Mn, Zn) were measured in livers from rats treated with sodium diethyldithiocarbamate (DDC, 0.67 or 1.33 mmol/kg, i.m.) and NiCl2 (0.25 or 0.50 mmol/kg, s.c.), singly or in combination. In rats treated with DDC or NiCl2, singly, hepatic GSH was diminished at 4 h and returned to control levels (or slightly above) at 17 h. In rats that received DDC plus NiCl2, hepatic GSH was not diminished at 4 h after increased 1.4-1.8-fold at 17 h. Hepatic GSSG was diminished at 4 h after NiCl2 treatment and returned to control values at 17 h; hepatic GSSG did not differ from control values at 4 h or 17 h after treatment with DDC, alone or combined with NiCl2. Hepatic Ni was below the detection limit (approximately 20 nmol/g) in control and DDC-treated rats; hepatic Ni was increased to 53 +/- 26 (S.D.) nmol/g at 17 h after treatment with NiCl2 alone, and was increased 6-fold (308 +/- 63 nmol/g) in rats that received Ni plus DDC. Under the same conditions, hepatic Zn was increased 33% or 41%, respectively, in rats that received NiCl2 or DDC, singly, and was not further increased by combined treatment; hepatic Cu and Mn concentrations were unaffected by NiCl2 or DDC, singly, but were diminished in rats that received NiCl2 and DDC. This study suggests: (a) that increased hepatic uptake of Ni is largely responsible for the synergistic induction of heme oxygenase activity in rats treated with NiCl2 and DDC; and (b) that increased hepatic uptake of Zn contributes to the induction of hepatic metallothionein by NiCl2 and DDC.

Animals↗
PubMed1984

Association between erythrocytosis and renal cancers in rats following intrarenal injection of nickel compounds.

Seventeen nickel compounds were administered to Fischer-344 rats (N = 270) by intrarenal injection (7 mg Ni/rat); the compounds included nickel sulfides, selenides, arsenides, oxide, antimonide, telluride, titanate, ferronickel alloy and metallic nickel dust. Erythrocytosis, as defined by peak hematocrit values that averaged greater than 55% during 1-4 months post-injection, occurred in nine of 17 Ni-treated groups (NiS2, beta NiS, alpha Ni3S2, Ni4FeS4, NiSe, Ni3Se2, NiAsS, NiO, Ni dust). Renal cancers (N = 23) developed within 2 years post-injection in nine of 17 Ni-treated groups (NiS2, beta NiS, alpha Ni3S2, Ni4FeS4, NiSe, Ni3Se2, NiAsS, NiAs, NiFe alloy). The renal cancers included eight fibrosarcomas, five mesangial cell sarcomas, two renal cell carcinomas, two carcinosarcomas, two leiomyosarcomas, two undifferentiated sarcomas, one rhabdomyosarcoma and one nephroblastoma. No erythrocytosis or renal cancers occurred in control rats (N = 97) in three groups treated with the vehicles or metallic iron dust. Rank correlation (p less than 0.0001) was observed between the incidences of erythrocytosis and renal cancers in the 17 Ni-treated groups. Rank correlation (p less than 0.001) was observed between the present incidences of renal cancers and the sarcoma incidences previously reported following intramuscular administration of the 17 nickel compounds to Fischer-344 rats (14 mg Ni/rat). The incidences of renal cancer were not correlated with the mass-fractions of nickel in the 17 compounds, the dissolution half-times of the compounds in rat serum or renal cytosol, or the phagocytic indices of the compounds in rat peritoneal macrophages.

Animals↗
PubMed1984

Carcinogenicity of nickel compounds in animals.

A total of 18 nickel compounds were tested for carcinogenicity in male Fischer rats by a single i.m. injection at equivalent dosages (14 mg Ni/rat). Within two years, the following incidences of sarcomas occurred at the injection site: nickel subsulfide (alpha Ni3S2), 100%, crystalline nickel monosulfide (beta NiS), 100%; nickel ferrosulfide (Ni4FeS4), 100%; nickel oxide (NiO), 93%; nickel subselenide (Ni3Se2), 91%; nickel sulfarsenide (NiAsS), 88%; nickel disulfide (NiS2), 86%; nickel subarsenide (Ni5AS2), 85%; nickel dust, 65%; nickel antimonide (NiSb), 59%; nickel telluride (NiTe), 54%; nickel monoselenide (NiSe), 50%; nickel subarsenide (Ni11AS8), 50%; amorphous nickel monosulfide (NiS), 12%; nickel chromate (NiCrO4), 6%; nickel monoarsenide (NiAs), 0%; nickel titanate (NiTiO3), 0%, ferronickel alloy (NiFe1.6), 0%; 84 vehicle controls, 0%. Distant metastases were found in 109 of 180 sarcoma-bearing rats (61%). The nickel-induced sarcomas included rhabdomyosarcomas, 52%, fibrosarcomas, 18%, undifferentiated sarcomas, 13%, osteosarcomas, 8%, and miscellaneous and unclassified sarcomas, 9%. Kendall's rank-correlation test showed that the carcinogenic activities of the compounds were correlated (p = 0.02) with their nickel mass-fractions, but not with dissolution half-times in rat serum or renal cytosol, or with phagocytic indices by rat peritoneal macrophages in vitro. Rank-correlation (p less than 0.0001) was found between the carcinogenic activities and the potencies of the compounds to induce erythrocytosis in rats. The discovery that the carcinogenic activities of particulate nickel compounds are correlated with a physical property, namely the nickel mass-fraction, may help to elucidate the mechanisms of nickel carcinogenesis; the observation that nickel stimulation of erythropoiesis is correlated with carcinogenic activity provides a new in vivo screening test for use in determining the carcinogenic risk of nickel compounds.

Animals↗
PubMed1984

Increased immunoreactive erythropoietin in serum and kidney extracts.

Radioimmunoassay of erythropoietin (epo) was performed upon serum samples and kidney extracts from rats that received intrarenal injections of nickel subsulfide (Ni3S2, 20 mg/rat). Serum epo concentrations were significantly increased from 1 to 4 weeks after Ni3S2 injection; the highest values occurred at 3 weeks, when serum epo in 5 Ni3S2-treated rats averaged 230 mU/ml (range = 94 - 370 mU/ml); for comparison, serum epo in 21 vehicle-treated controls averaged 19 mU/ml (range = less than 14 - 56 mU/ml, P less than 0.01). In kidney extracts of 5 rats killed 3 weeks after Ni3S2 injection, epo concentrations averaged 970 mU/g (range = 210 - 1880 mU/g); for comparison, epo in kidney extracts of 6 controls averaged 99 mU/g (range = 40 - 140 mU/g, P less than 0.005). These radioimmunoassays confirm previous bioassays findings that serum epo concentrations are significantly increased in rats with Ni3S2-induced erythrocytosis. Contrary to bioassay findings, this study demonstrates increased immunoreactive epo concentrations in kidney extracts of Ni3S2-treated rats, suggesting that renal epo in Ni3S2-treated rats occurs in a form that lacks biological activity in vivo.

Animals↗
PubMed1983

Nickel induction of microsomal heme oxygenase activity in rodents.

Heme oxygenase activity was measured in tissues of rats killed after administration of NiCl2 or Ni3S2. Induction of renal heme oxygenase activity occurred 6 hr after NiCl2 injection (0.25 mmol/kg, sc), reached a maximum of five to six times the baseline activity at 17 hr, and remained significantly increased at 72 hr. Heme oxygenase activities were also increased in liver, lung, and brain at 17 hr after the NiCl2 injection; heme oxygenase activities in spleen and intestinal mucosa were unchanged. The effects of NiCl2 on heme oxygenase activities in kidney and liver were dose-related from 0.06 to 0.75 mmol/kg, sc. Three Ni chelators were administered (1 mmol/kg, im) prior to injection of NiCl2 (0.25 mmol/kg, sc); d-penicillamine partially prevented Ni induction of renal heme oxygenase activity; triethylenetetramine had no effect; sodium diethyldithiocarbamate enhanced the Ni induction of renal heme oxygenase activity (three times greater than NiCl2 alone). Intrarenal injection of Ni3S2 (10 mg/rat) caused induction of renal heme oxygenase activity at 1 week but not at 2, 3, or 4 weeks; no correlation was observed between induction of renal heme oxygenase activity and erythropoietin-mediated erythrocytosis. Hypoxia (10% O2, 12 hr/day, 7 days) did not affect renal heme oxygenase activity. Induction of renal heme oxygenase activity was observed in mice, hamsters, and guinea pigs killed 17 hr after injection of NiCl2 (0.25 mmol/kg, sc). These studies established (a) the time course, dose-effect, organ selectivity, and species susceptibility relationships for Ni induction of microsomal heme oxygenase activity, (b) the effects of Ni chelators, and (c) the lack of relationship between induction of renal heme oxygenase activity and the erythrocytosis that develops after intrarenal injection of Ni3S2.

Animals↗
PubMed1983

Organ and species specificity in nickel subsulfide carcinogenesis.

In summary, dose-response relationships have been demonstrated for Ni3S2 carcinogenesis in rats and hamsters and for transformation of Syrian hamster fetal cells by Ni3S2 in vitro. Absolute species specificity has not been observed in Ni3S2 carcinogenesis, although rats are apparently more susceptible than mice, hamsters, or rabbits. Also, significant variations have been reported in susceptibilities of rat strains to Ni3S2 carcinogenesis. Most organs of rats have been found to be susceptible to Ni3S2 carcinogenesis following direct exposure by injection or inhalation; intraocular and intramuscular routes of administration have yielded the highest tumor incidences. Finally, an experiment in hamsters has indicated that Ni3S2 may be noncarcinogenic by the oral route; further studies are needed to confirm or refute this speculation. For discussions of molecular mechanisms that may be involved in carcinogenesis by Ni3S2 and other nickel compounds, readers are referred to recent review articles (8-10).

Animals↗
PubMed1983

Synergistic induction of microsomal heme oxygenase activity in rat liver and kidney by diethyldithiocarbamate and nickel chloride.

Microsomal heme oxygenase activity was measured in liver and kidney of rats killed after administration of sodium diethyldithiocarbamate (DDC) and nickel chloride (NiCl2), singly and in combinations (DDC dosages: 0.33 to 1.33 mmol/kg, im, 17 hr before death; NiCl2 dosages: 0.125 and 0.25 mmol/kg, sc, 17 hr before death). Synergistic induction was observed at all dosage combinations. At the highest dosages of DDC and NiCl2, the dual treatments induced heme oxygenase activity 11-fold in liver and 16-fold in kidney; at the same dosages given individually, DDC induction of heme oxygenase activity was 3-fold in liver and 2-fold in kidney, and NiCl2-induction was 1.3-fold in liver and 6-fold in kidney. Synergistic induction of heme oxygenase activity in liver occurred when DDC was injected 6 hr before to 6 hr after NiCl2; synergistic induction in kidney occurred when DDC was injected 6 hr before to 3 hr after NiCl2. Actinomycin D prevented the induction of heme oxygenase activity by DDC or NiCl2, given individually; the effect of actinomycin D on synergistic induction could not be measured, since the rats all died following treatment with DDC, NiCl2, and actinomycin D. Administration of cysteine to rats, po, 18 hr before death, partially suppressed the induction of hepatic heme oxygenase activity by DDC, singly or in combination with NiCl2. Synergistic induction of hepatic heme oxygenase activity also occurred in rats that received dual injections of DDC (1.33 mmol/kg, im) and hemoglobin (0.3 g/kg, iv); the synergism of DDC and hemoglobin, although statistically significant, was small in comparison to the striking synergistic effect of DDC and NiCl2.

Animals↗