Internal hazardous substance burden of persons from various regions of origin--studies of lead, mercury, arsenic and cadmium exposure

AIM OF THE STUDY: The aim of this study was to investigate the concentration of metals of environmental-medical relevance in biological materials in persons seeking asylum with regard to their country of origin. COLLECTIVE AND METHOD: During medical examination after entry into Germany of persons seeking asylum, samples were taken for determination of the following biological monitoring parameters: lead in blood, and arsenic, cadmium and mercury in urine. A total of 103 males were investigated (13 from former Yugoslavia, 29 from the former USSR, 33 Africans and 28 Asians) ranging from 16 to 53 years of age (median 27 years). 34 male Germans without occupational exposure to these substances and a similar age structure (age 25-36 years; median 26 years) served as a control group. RESULTS: The countries of origin had a significant influence on all the biological monitoring parameters investigated. The mean blood lead concentration in the Asians of 75.4 micrograms/L was the highest level found, while the lowest concentration of 38.0 micrograms/L was measured in the German controls. Also the level of arsenic excreted in the urine was on average much higher in the persons seeking asylum than in the German controls. In the Africans a mean level of 9.7 micrograms/g creatinine was reached. The Germans had the lowest arsenic concentrations in urine of 5.3 micrograms/g creatinine. There were, however, considerable interindividual fluctuations, which are probably due to oral uptake of arsenic compounds as a result of eating seafoods. The highest mean concentration of mercury excreted in urine was found in the German controls. Values of 0.9 microgram/g creatinine were determined. The men seeking asylum from former Yugoslavia had significantly higher values than other groups for cadmium excreted in urine. The median of 0.6 microgram/g creatinine was nearly three times as high as found in the Germans. CONCLUSIONS: For all parameters investigated, with the exception of mercury, higher internal exposure was found in the persons seeking asylum than in the German controls. This may be due to individual life style, dietary habits or environmental conditions in the country of origin. For clinical environmental medicine, the 95th percentile, as the upper limit of the reference range, can only be regarded as an orientation aid for classifying the exposure to hazardous substances of an individual compared to other persons from the same environment.     

Efficacy of lodoxamide 0.1% versus N-acetyl aspartyl glutamic acid 6% ophthalmic solutions in patients with vernal keratoconjunctivitis

The purpose of this study was to investigate environmental lead exposure in the general Taiwanese population. A total of 8828 Taiwanese adults selected by a multistage sampling method were investigated. Characteristics of the participants were ascertained by questionnaire and 10 ml venous blood was drawn by public health nurses. The blood specimens were distributed to six laboratories for blood lead level (BLL) measurement. A quality control program was applied during the analysis of the BLLs in order to improve precision and accuracy. The arithmetic mean BLL of the 8828 Taiwanese adults was 7.70 +/- 5.23 micrograms/dl, with a maximal level of 69.1 micrograms/dl. The median was 6.5 micrograms/dl and the 90th percentile was 14.0 micrograms/dl. After logarithmic transformation, the geometric mean was 1.84 +/- 0.67 microgram/dl. This study also found that elevated BLLs were associated with certain personal characteristics, i.e., gender, ethnic group, and education level; life-style factors, such as smoking, alcohol consumption, Chinese herbal drug consumption, milk consumption, and sources of drinking water; residential location, i.e., level of urbanization; and occupational history of lead exposure. However, age, floor level of residence, distance from house to road, and betel nut consumption were not associated with elevated BLLs. These results showed that BLLs in the Taiwanese population were not higher than those in developed and developing countries. Most of the influencing factors were also found in other studies; however, local factors such as ethnic group, Chinese herbal drug consumption, and sources of drinking water are important considerations in Taiwan when examining ways to prevent overexposure to lead in the general population.     

Blood lead levels in Victorian children

A recent study of lead levels in the blood of Sydney schoolchildren purported to show "an alarming situation of epidemic proportions", with up to 24% of children in one survey having blood lead levels greater than 25 microgram/100 mL (1.21 mumol/L). In the present study, 446 Victorian children were tested for lead level in venous blood, showing a mean blood lead level of 11.4 microgram/100 mL (0.55 mumol/L), and only six children (1.3%) with blood lead levels in excess of 25 microgram/100 mL (1.21 mumol/L) were found. It is suggested that the blood lead levels in the Sydney study may have been falsely high because of the use of capillary blood samples which are prone to contamination.     

Side effects of antineoplastic treatment and interference with general anesthesia]

Concentrations of HCH and DDT in soil, water and whole blood were determined in two areas under malaria control. These were, (i) bioenvironmental control of malaria at BHEL, and (ii) residual spraying of insecticides in rural and urban area of Bahadrabad PHC of Hardwar district. Mean concentrations of HCH in soil and whole blood samples from BHEL was 2.26 micrograms/kg and 1.20 micrograms/l and from Bahadrabad 61.12 micrograms/kg and 24.3 micrograms/l respectively. Similarly, the mean concentration of DDT in soil and whole blood from BHEL was 3.68 micrograms/kg and 4.71 micrograms/l, while in Bahadrabad 270.51 micrograms/kg and 38.13 micrograms/l respectively. HCH and DDT were never detected in any water samples from BHEL area, while the mean concentration of these compounds in water of Bahadrabad area was 0.18 and 0.07 microgram/l respectively. Residual level of HCH and DDT were 27 and 73.5 times higher in soil and 20.2 and 8.1 times higher in whole blood samples from Bahadrabad as compared to their corresponding values from BHEL respectively.     

UK study of intrapartum care for low risk primigravidas: a survey of interventions

GH-releasing peptides (GHRPs) and their non-peptidly mimetics are synthetic molecules which possess marked, dose-related and reproducible GH-releasing effect even after oral administration. Their potent stimulatory effect on GH secretion suggested that GHRP could be useful as provocative test on the diagnosis of GH deficiency. We compared the GH response to the maximal effective dose of Hexarelin (2 micrograms/kg i.v.), an hexapeptide belonging to GHRP family, with that of GHRH (1 microgram/kg i.v.) alone and combined with arginine (ARG, 0.5 g/kg i.v.), which likely acts via inhibition of hypothalamic somatostatin release. We studied 6 prepubertal (4 boys and 2 girls, age 2.6-12.2 yr) and 6 pubertal children with normal short stature (3 boys and 3 girls, age 10.3-14.4 yr) as well as 12 normal young adults (6 males and 6 females, age 22-30 yr) and 12 normal elderly subjects (6 males and 6 females, age 53-79 yr). In prepubertal children, the GH response to HEX (19.0 +/- 4.6 micrograms/l; 611.5 +/- 121.4 micrograms/l/h) was lower than that to GHRH (27.4 +/- 12.7 micrograms/l; 1209.0 +/- 590.9 micrograms/l/h) but this difference did not attain statistical significance. Both these responses were, in turn, lower (p < 0.05) than that to ARG + GHRH (57.9 +/- 15.1 micrograms/l; 2483.6 +/- 696.6 micrograms/l/h). In pubertal children, the GH response to HEX (67.6 +/- 12.7 micrograms/l; 2755.3 +/- 547.3 micrograms/l/h) was higher than that to ARG + GHRH (49.1 +/- 8.9 micrograms/l; 2554.1 +/- 356.6 micrograms/l/h) but this difference did not attain statistical significance; both these responses were, in turn, clearly higher (p < 0.05) than that to GHRH alone (23.1 +/- 7.9 micrograms/l; 1004.8 +/- 214.3 micrograms/l/h). In young adults, the GH response to HEX 60.9 +/- 8.0 micrograms/l; 2401.0 +/- 376.2 micrograms/l/h) was similar to that to ARG + GHRH (68.9 +/- 11.7 micrograms/l; 3035.7 +/- 466.6 micrograms/l/h) and both were clearly higher (p < 0.001) than that to GHRH alone (21.6 +/- 3.6 micrograms/l; 790.0 +/- 137.0 micrograms/l/h). In elderly subjects, the GH response to HEX (22.4 +/- 4.9; 855.0 +/- 199.0 micrograms/l/h) was higher (p < 0.01) than that to GHRH (3.6 +/- 0.8 micrograms/l; 151.8 +/- 24.6 micrograms/l/h) but lower (p < 0.05) than that to ARG + GHRH (48.1 +/- 4.6 micrograms/l; 1758.2 +/- 149.1 micrograms/l/h). In conclusion, GHRPs are a powerful stimulus of GH secretion in pubertal children and young adults only. On the other hand, the age-related variations in the GH response to GHRPs probably limit their reliability for the evaluation of GH releasable pool in prepubertal children and elderly subjects.     

Age-specific reference intervals for plasma vitamins A, E and beta-carotene and for serum zinc, retinol-binding protein and prealbumin for Sydney children aged 9-62 months

Paediatric reference intervals for blood concentrations of certain nutrients are often based on either adult data or are derived from small samples of young children. Biochemical data were obtained from 467 randomly selected, healthy preschool children aged 9-62 months in Sydney, Australia. Data were obtained for plasma vitamins A, E and beta-carotene and for serum zinc, retinol-binding protein and prealbumin. Reference intervals based on the 2.5 and 97.5 centiles for age groups 9-23, 24-35, 36-47, 48-62 months and for the total group (9-62 months) were calculated. The 2.5-97.5 centiles for the whole group were: vitamin A, 0.7-1.8 mumol/l (20.05-51.56 micrograms/dl); vitamin E, 8-30 mumol/l (0.34-1.29 mg/dl); beta-carotene, 0.1-1.1 mumol/l (5.4-59.0 micrograms/dl); zinc, 9-19 mumol/l (58.8-124.2 micrograms/dl); retinol-binding protein, 14-36 mg/l; prealbumin, 104-264 mg/l. The reference intervals reported are consistent with the findings of a number of smaller studies and are likely to be an accurate reflection of the true intervals for healthy preschool children in western developed countries.     

Heterogeneity of Lyme disease spirochaetes within individual vector ticks

Nineteen workers exposed to low levels of selenium (0.047-0.202 mg/m3 air) along with 15 control subjects were studied for clinical, hematological, radiological, and neurobehavioral variables in relation to selenium concentration in hair. The levels of selenium in the hair of exposed subjects (1.44 +/- 0.37 micrograms/g) were significantly higher than those of control subjects (0.78 +/- 0.18 microgram/g). The levels of selenium in the hair of 22 nonvegetarian subjects were found to be significantly higher as compared to 12 vegetarian subjects. Complaints of weakness and/or fatigue were found to be more prevalent in the exposed subjects. The study holds promise that hair selenium may be used as a monitoring tool for low-level occupational exposure to selenium.     

Measurement of vitamin D3 metabolites in smelter workers exposed to lead and cadmium

OBJECTIVES: To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D3. METHODS: Blood and urinary cadmium and urinary total proteins were measured in 59 smelter workers occupationally exposed to lead and cadmium. In 19 of these workers, the plasma vitamin D3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25-dihydroxycholecalciferol (24R,25(OH)2D3) and 1 alpha,25-dihydroxycholecalciferol (1 alpha, 25(OH)2D3)) were measured together with blood lead. Vitamin D3 metabolites were measured by radioimmunoassay, (RIA), lead and cadmium by atomic absorption spectrophotometry, and total proteins with a test kit. RESULTS: Ranges for plasma 25(OH)D3, 24R,25(OH)2D3 and 1 alpha,25(OH)2D3 were 1.0-51.9 ng/ml, 0.6-5.8 ng/ml, and 0.1-75.7 pg/ml, respectively. Ranges for blood lead were 1-3.7 mumol/l, (21-76 micrograms/dl), blood cadmium 6-145 nmol/l, and urinary cadmium 3-161 nmol/l. Total proteins in random urine samples were 2.1-32.6 mg/dl. Concentrations of lead and cadmium in blood showed no correlation (correlation coefficient -0.265) but there was a highly significant correlation between blood and urinary cadmium. Concentrations for 24R,25(OH)2D3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma 1 alpha,25(OH)2D3 when lead concentrations were < 1.9 mumol/l and with above normal plasma 1 alpha,25(OH)2D3 when lead concentrations were > 1.9 mumol/l, Kruskal-Wallis analysis of variance (K-W ANOVA) chi 2 = 10.3, p = 0.006. Plasma 25(OH)D3 was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)2D3, 1 alpha,25(OH)2D3, blood lead, or blood cadmium. CONCLUSION: Continuous long term exposure to cadmium may result in a state of equilibrium between blood and urinary cadmium. Cadmium concentrations in blood could be predicted from the cadmium concentration of the urine, (regression coefficient +0.35 SE 0.077). Exposure to cadmium alone decreased the concentrations of 1 alpha,25(OH)2D3 and 24R,25(OH)2D3, whereas exposure to both cadmium and lead increased the concentrations of 1 alpha,25(OH)2D3. It has been suggested that cadmium and lead interact with renal mitochondrial hydroxylases of the vitamin D3 endocrine complex. Perturbation of the vitamin D metabolic pathway by cadmium may result in health effect, such as osteoporosis or osteomalacia, risks which are possibly increased in the presence of lead.     

Survey of lead exposure around a closed lead smelter

OBJECTIVE: To test the hypothesis that elevated lead in soil is positively correlated with blood lead (BPb) levels in children in an urban population surrounding a closed lead smelter, a US Environmental Protection Agency Superfund clean-up site was surveyed. METHOD: A total of 827 volunteers including 490 children under 6 years of age participated. A questionnaire was administered. Blood lead was determined as was lead content of samples of house dust, soil, paint, and water of the participants' homes. RESULTS: The arithmetic mean venous BPb in 490 children between 6 and 72 months of age was 6.9 micrograms/dL (0.33 mumol/L) range 0.7 to 40.2 micrograms/dL (0.03 to 1.94 mumol/L). The BPb of 78 (16%) children in this group was > or = 10 micrograms/dL (0.48 mumol/L). Based on multiple regression modeling, lead in house dust accounted for 18% of the variance in BPb. Lead in paint together with the condition of the house were the main contributors to the dust lead variance (26%) with soil lead accounting for an additional 6%. Lead in paint alone accounted for 3% of the BPb variance. Lead in paint together with the condition of the house accounted for 12% of BPb variance, and lead in soil accounted for an additional 3%. Factors other than environmental lead such as education of parents, household income, and behavior were associated with BPb levels. CONCLUSIONS: The mean BPb in children was below the present level of concern of the Centers for Disease Control and Prevention. Children with BPb of > or = 10 micrograms/L (0.48 mumol/L) tended to live in poorly maintained older houses. Based on these findings lead in soil and paint in well-maintained homes contributed little to the lead exposure of children.     

Low-dose growth hormone-releasing hormone tests: a dose-response study

We have evaluated parameters of the serum growth hormone (GH) concentration response to saline and 1-, 10- and 100-micrograms intravenous bolus doses of amide analogue of GH-releasing hormone (GHRH (1-29)NH2) given in random order to 10 adult male volunteers of median body weight 68 (60-90)kg. Compared with saline, both 10- and 100-micrograms GHRH(1-29)NH2 doses (but not 1 microgram) resulted in significant peak GH responses (means and 95% confidence intervals: 24.03 (11.22-51.29) vs 26.09 (16.40-41.50) mU/l, respectively). Although the average rate of serum GH rise was similar after both 10 micrograms (2.05 (1.13-2.97) mU.l-1.min-1) and 100 micrograms of GHRH(1-29)NH2 (1.52 (0.69-2.35) mU.l-1.min-1; ANOVA F = 0.93, p = 0.35), the average rate of serum GH decline after peak GH was slower after the higher dose (10 micrograms vs 100 micrograms: 0.65 (0.40-0.90) vs 0.37 (0.23-0.50) mU.l-1.min-1; ANOVA F = 5.14, p = 0.04), suggesting continued GH secretion. Increasing GHRH(1-29)NH2 doses delayed the time to peak GH (1 microgram: 7.00 (3.50-10.52) min; 10 micrograms: 15.80 (13.62-17.98) min; 100 micrograms: 24.80 (18.40-31.12) min) and serum GH levels were still elevated significantly 2 h after injection of 100 micrograms GHRH(1-29)NH2 compared with other doses (saline: 0.98 (0.48-2.04) mU/l; 1 microgram: 0.68 (0.48-0.93) mU/l; 10 micrograms: 1.07 (0.56-2.04) mU/l; 100 micrograms: 5.01 (2.34-10.86) mU/l; ANOVA F = 11.10, p < 0.001). In a second study we tested five adult male volunteers with lower doses (0.5-10 micrograms) of GHRH(1-29)NH2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid

Elevated plasma homocysteine, an independent risk factor for cardiovascular disease (CVD) can be lowered by administration of pharmacological doses of folic acid. The effect of lower doses in apparently normal subjects is currently unknown but is highly relevant to the question of food fortification. Healthy male volunteers (n = 30) participated in a chronic intervention study (26 weeks). Folic acid supplements were administered daily at doses increasing from 100 micrograms (6 weeks), to 200 micrograms (6 weeks), to 400 micrograms (14 weeks). Fasting blood samples collected before, during and 10 weeks post intervention were analysed for plasma homocysteine, serum and red-cell folate levels. Results, expressed as tertiles of baseline plasma homocysteine concentration, showed significant (p < or = 0.001) homocysteine lowering in the top (10.90 +/- 0.83 mumol/l) and middle (9.11 +/- 0.49 mumol/l) tertiles only. In the low tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84 mumol/l, no significant response was observed. Of the three folic acid doses, 200 micrograms appeared to be as effective as 400 micrograms, while 100 micrograms was clearly not optimal. There is thus a minimal level of plasma homocysteine below which folic acid has no further lowering effect, probably because an optimal folate status has been reached. A dose as low as 200 micrograms/day of folic acid is effective in lowering plasma homocysteine concentrations in apparently normal subjects. Any public health programme for lowering homocysteine levels, with the goal of diminishing CVD risk, should not be based on unnecessarily high doses of folic acid.     

Dose-response relationship between total cadmium intake and metallothioneinuria using logistic regression analysis

The dose-response relationship for environmental cadmium exposure was assessed using logistic regression analysis. The prevalence of metallothioneinuria was employed as a response variable, while age and total cadmium intake, calculated from the average cadmium concentration in rice and duration of residence in the cadmium-polluted area, were used as explanatory variables. The target population comprised of 1843 cadmium-exposed and 240 non-exposed inhabitants of Ishikawa, Japan. The individuals were divided into 96 subgroups by sex, age (4 categories), cadmium concentrations in rice (3 categories) and length of residence in the polluted area (4 categories). Only total cadmium intake had a significant association with the prevalence of metallothioneinuria. In the non-exposed subjects total cadmium intakes corresponding to 2.5% prevalence of metallothioneinuria were calculated. Based on metallothionein levels expressed as either microgram/l urine or microgram/g creatinine, the total intakes were: 2.221 or 2.207 g in men and 2.365 or 0.319 g in women, respectively. Most of these values were similar to those reported by us previously, employing simple regression analysis. It is concluded, therefore, that a maximum allowable intake of about 2 g cadmium is a reasonable estimate for preventing the cadmium-induced renal dysfunction.     

Interleukin-6 and interleukin-8 in the urine of children with acute pyelonephritis

Interleukin-6 (IL-6) and interleukin-8 (IL-8) are important mediators of the inflammatory response in serious bacterial infections. We studied the levels of these two cytokines (standardised for urinary creatinine) in the urine of infants and children during and 6 weeks after acute pyelonephritis and in non-renal febrile controls and healthy children without apparent infection. IL-6 was detected in the urine of 52% of children with pyelonephritis compared with 15% of other children (P < 0.001). The median urinary IL-6 level in acute pyelonephritis was 4 pg/mumol compared with undetectable levels in the control group (P < 0.001). IL-8 was detected in 98% of children with pyelonephritis and 42% of other children (P < 0.001). The median concentration of IL-8 was 188 pg/mumol in pyelonephritis; it was undetectable in controls (P < 0.001). IL-8 levels were higher in children less than 1 year of age (P < 0.001).     

Influence of prenatal exposure to low levels of lead on the neuro-behavioral development of neonates

OBJECTIVES: To study the effects on the neuro-behavioral development of neonates exposed to low levels of lead in utero. METHODS: 131 neonates were selected and their umbilical blood lead level was determined by Atomic Absorption Spectrometer. The neurobehavioral-cognitive performance of neonates was evaluated by Neonatal Behavioral Neurological Assessment (NBNA). RESULTS: NBNA scores in neonates with blood lead levels greater than or equal to 0.29 mumol/L were markedly lower than those with less than 0.14 mumol/L, and the difference was highly significant. CONCLUSION: Blood lead levels of less than 0.48 mumol/L could still have harmful effects on the development of children.     

Developmental pattern of fetal growth hormone, insulin-like growth factor I, growth hormone binding protein and insulin-like growth factor binding protein-3

AIMS: To evaluate the developmental pattern of fetal growth hormone (GH), insulin-like growth factor I (IGF-I), GH binding protein (GHBP) and IGF binding protein-3 (IGF-3); to determine the implications for fetal growth. METHODS: Serum GH, IGF-I, GHBP and IGFBP-3 were measured in 53 fetuses, 41 aged 20-26 weeks (group A) and 12 aged 31-38 weeks (group B). Fetal blood samples were obtained by direct puncture of the umbilical vein in utero. Fetal blood samples were taken to rule out beta thalassaemia, chromosome alterations, mother to fetus transmissible infections, and for maternal rhesus factor. GHBP was determined by gel filtration chromatography of serum incubated overnight with 125I-GH. GH, IGF-I and IGFBP-3 were determined by radioimmunoassay. RESULTS: Fetal serum GH concentrations in group A (median 29 micrograms/l, range 11-92) were significantly higher (P < 0.01) than those of group B (median 16.7 micrograms/l, range 4.5-29). IGF-I in group A (median 20 micrograms/l, range 4.1-53.3) was significantly lower (P < 0.01) than in group B (median 75.2 micrograms/l, range 27.8-122.3). Similarly, IGFBP-3 concentrations in group A (median 950 micrograms/l, range 580-1260) were significantly lower than those of group B (median 1920 micrograms/l, range 1070-1770). There was no significant difference between GHBP values in group A (median 8.6%, range 6.6-12.6) and group B (median 8.3%, range 6-14.3). Gestational age correlated positively with IGF-I concentrations (P < 0.0001) and IGFBP-3 (P < 0.0001) and negatively with GH (P < 0.0001). GHBP values did not correlate with gestational age. Multiple regression analysis showed a negative correlation between GH:IGF-I ratio and fetal growth indices CONCLUSIONS: The simultaneous evaluation of fetal GH, IGF-I, IGFBP-3 and GHBP suggests that the GH-IGF-I axis might already be functional in utero. The progressive improvement in the efficiency of this axis in the last part of gestation does not seem to be due to an increase in GH receptors.     

Peptide growth factors in normal and hypertrophied bladder

The pharmacokinetics of oral zidovudine in HIV-infected children and adults are reported. Fourty-six patients were investigated. For data analysis three groups of similar size were formed: young children 4 months-4 years, n = 15 (group 1), older children up to 13 years, n = 16 (group 2) and young adults, n = 15 (group 3). After a single oral dose repeated blood samples were taken 1/2 hourly during a period of 4 hours and zidovudine concentrations in plasma were determined by high performance liquid chromatography. For better comparison of dose dependent parameters peak concentrations (Cmax) and the area under the time-concentration curves (AUC) were normalized either to the dose/body weight (bw) or the dose/body surface area (bs), respectively. Time to reach peak concentrations and mean terminal elimination half-life times (t1/2 beta = 63.4 +/- 47.6, 74.9 +/- 54.9 and 56.9 +/- 16.4 min in group 1, 2 and 3, respectively, mean +/- SD) were not significantly different between the three groups. With normalization to dose/bw young children in comparison to adults had significantly lower Cmax (2.7 +/- 1.3 vs. 4.6 +/- 2.4 mumol/l, p = 0.016) and AUC (226 +/- 108 vs. 373 +/- 224 mumol.min/l, p = 0.038). Group 2 gave intermediate values. However, with normalization to dose/bs differences in Cmax (6.5 +/- 3.3, 7.3 +/- 4.2 and 6.8 +/- 3.6 mumol/l, in group 1, 2, and 3, respectively) and AUC (563 +/- 313, 691 +/- 351 and 555 +/- 342 mumol.min/l, in group 1, 2 and 3) were not significant between the three groups. It is likely that changes in body water content with age may account for most of these differences observed. In conclusion, a similar pharmacokinetic profile was found in children older than 3 months as compared to older children or adults.     

Radioimmunoassay of glutathione peroxidase in human serum

Glutathione peroxidase (GSHPx) was purified from human serum and used for immunization of rabbits. Antiserum bound up to 75% of added 125I-GSHPx after precipitation with a second antibody. Human serum, but not sera from eight animal species, inhibited the binding of labelled GSHPx, indicating that the antiserum did not react with GSHPx from these species. GSHPx could be measured in less than 10 microliters of human serum by radioimmunoassay. In sera with widely varying selenium concentrations (0.1-2.9 mumol/l) the amount of GSHPx protein (0.3-6.3 mg/l) was strongly correlated with GSHPx activity (r = 0.94) and it was also correlated with serum selenium concentrations (r = 0.64). This indicates that GSHPx protein may be a valuable biological marker of selenium status. In samples with serum selenium concentrations of 0.8-1.2 mumol/l, the concentration of GSHPx was 3.3 (0.4) mg/l (mean (S.D.)), or 0.04 (0.005) mumol/l. This corresponded to 0.16 (0.02) mumol/l of GSHPx selenium and 16% (2.8)% of total serum selenium. The data suggest that the method can be used to measure the proportion of serum selenium that is located in GSHPx. Following storage of serum at room temperature, both serum GSHPx protein and activity declined, but addition of glutathione protected both GSHPx protein and activity.     

Evaluation of bosentan, pinacidil and nitroprusside on human pulmonary arteries: comparison with rat pulmonary arteries

OBJECTIVE: The general objective of the Etude du Viellissement Arterial (EVA) program is to follow vascular aging and the decline in cognitive functions at the cerebrovascular level longitudinally over a 4-year period. One of the specific objectives of this EVA study is to examine epidemiologically the relationship between the markers of oxidative stress (lipid peroxidation), the antioxidant micronutrient status (particularly of selenium, vitamin E, and the carotenoids) and the prevalence of chronic disorders occurring during the pre-aging period. METHODS: 1389 subjects aged from 59 to 71 years were studied. RESULTS: The concentration of plasma lipid peroxides was higher than in young adults (2.91 +/- 0.38, men; 2.97 +/- 0.40, women (mumol/l). On the other hand, plasma Se (1.09 +/- 0.21, men; 1.10 +/- 0.19, women (mumol/l)), erythrocyte vitamin E (5.32 +/- 1.29, men; 5.52 +/- 1.28, women (mumol/l)), and total plasma carotenoids (2.19 +/- 0.98, men; 3.07 +/- 1.33, women (mumol/l)) were comparable to values in young adults. In our cohort, 40% of subjects had unremarkable medical histories. The disorders most often encountered were lipemia (29.8% of men, 36.1% of women), and hypertension (28.9% of men, 30.4% of women). CONCLUSION: Se and vitamin E levels were raised in cases of lipemia, especially in those treated with fibrates. The mechanism of the increase is unknown. In hypertensives and diabetics, there was a decrease in total carotenoids associated with increased peroxidative risk.     

A rare presentation of thoracic aortic dissection as detected by transoesophageal echocardiography

Sex-based differences in serum leptin concentrations have been reported in adolescence and adulthood. To discover when such differences were generated, serum leptin concentrations were measured in umbilical cord blood from 46 healthy infants and in the mother's blood at delivery. Considering the respective body weights of the mothers and infants (68.5 +/- 1.3 kg and 3.3 +/- 0.0 kg), umbilical cord concentrations of leptin were disproportionately high in the infants (9.4 +/- 1.2 micrograms/l) compared with those in the mothers (18.7 +/- 1.3 micrograms/l). There was a wide variation in the infants leptin values (1.2 +/- 56.8 micrograms/l) that did not correlate with height, weight, cephalic circumference, or any other growth-related parameter. The most striking differences emerged when results were analysed by sex: umbilical cord concentrations of leptin in the girls (12.9 +/- 2.2 micrograms/l) were significantly (P < 0.01) greater than those in the boys (6.8 +/- 0.9 micrograms/l), although no differences in leptin concentrations were observed between the mothers who gave birth to a girl (19.5 +/- 2.2 micrograms/l) and those who gave birth to a boy (18.1 +/- 1.7 micrograms/l). The sex-based differences were not attributable to any growth-related differences between the sexes, except heavier placental weights in the girls (P < 0.007) than in the boys. These differences in leptin concentrations may reflect a sex-based difference in the regulation of leptin production by the fetal adipose tissue.     

Urinary levels of 1-hydroxypyrene, 1-, 2-, 3-, and 4-hydroxyphenanthrene in females living in an industrial area of Germany

The concentrations of 1-hydroxypyrene (1-HOPYR), and 1-, 2-, 3-, and 4-hydroxyphenanthrene (HOPHE) as metabolites of pyrene and phenanthrene, were measured in urine samples collected from 124 housewives (27 smokers and 97 non-smokers) living in Bottrop, an industrial city located in the Ruhr area in Germany. The urine samples were analyzed by a very sensitive and practical high-performance liquid chromatographic (HPLC) method using a two-column switching technique and a special precolumn packing material followed by fluorescence detection. The polycyclic aromatic hydrocarbon (PAH) metabolites are selectively enrichéd on the precolumn and separated from the matrix. Therefore, laborious clean-up steps were omitted. The above-mentioned PAH metabolites could be detected in all urine samples investigated. Smokers had significantly higher urine concentrations of 1-HOPYR (median 0.48 microgram/g creatinine), 3-HOPHE (median 0.61 microgram/g creatinine), 2-HOPHE (0.41 microgram/g creatinine) and 4-HOPHE (median 0.10 microgram/g creatinine) than non-smokers (median 0.15 microgram/g creatinine, 0.31 microgram/g creatinine, 0.31 microgram/g creatinine and 0.04 microgram/g creatinine, respectively). The study shows that the influence of smoking is of such an order of magnitude that potential environmental exposure to PAH in this highly industrialized area is obscured by smoking habits. Furthermore, it can be concluded that the determination of 1-HOPYR, 1-, 2-, 3-, and 4-HOPHE in urine is a diagnostically useful method for the biological monitoring of persons environmentally exposed to PAH.