A pilot study on the percutaneous absorption of microfine titanium dioxide from sunscreens.

Many Australians are being advised to apply microfine titanium dioxide sunscreen daily from the cradle to the grave. However, there is a surprising lack of data on the percutaneous absorption of microfine titanium dioxide. A prospective pilot study was conducted to analyse the percutaneous absorption of microfine titanium dioxide from sunscreens. Selected patients scheduled to have skin surgery, applied titanium dioxide sunscreen to the skin daily for 2-6 weeks prior to their operation. After excision, the stratum corneum of the sample was stripped and the titanium concentration of the remaining epidermis and dermis was measured by inductively coupled plasma-mass spectrometry. The results from this pilot study showed that levels of titanium in the epidermis and dermis of subjects who applied microfine titanium dioxide to their skin were higher than the levels of titanium found in controls. Studies with larger cohorts are necessary to establish if this absorption is statistically significant.

Blood lead concentrations of preschool children in central and southern Sydney.

OBJECTIVES: To determine the prevalence of elevated blood lead concentrations in preschool children in central and southern Sydney. PARTICIPANTS AND SETTING: Children aged from 9 months to 5 years living in 32 randomly selected geographical areas in Central and southern Sydney. METHODS: Venous blood lead concentrations were estimated by atomic absorption spectrometry. RESULTS: 953 children were identified and 726 had parental consent to participate. A blood sample for lead estimation was obtained from 718 children. The geometric mean blood level concentration was 0.34 mu mol/L (7.0 mu/dL). The proportion of children with elevated blood lead concentrations was: 16.1% (>0.48 mu mol/L [10mu/dL]), 3.9% (>0.72 mu mol/L[15mu/dL]) and 0.3% (>1.21mu mol/L [25 mu/dL], respectively. The blood lead levels for children living with a 10-km radius of the Sydney Central Business district were: 25% (>0.48 mu mol/L [10mu/dL]) and 7% (>0.72 mu mol/L [15mu/dL]), respectively. Corresponding findings for children living 10 km outside this radius were: 9% (>0.48 mu mol/L [10mu/dL]) and 1.5% (0.72 mu mol/L [15mu/dL]), respectively. CONCLUSIONS: The proportion of children with elevated blood lead concentrations in Central and Southern Sydney as a whole does not exceed current National Health and Medical Research Council (NHMRC) recommendations. However, in those areas within a 10-km radius of the Central Business District, NHMRC interventional guidelines for communities where more that 5% of children have blood lead concentrations higher than 0.72 mu mol/L (15 mu/dL) should be applied.

Spinal cord uptake of lead injected into muscle.

It has been hypothesised that some motor neuron diseases may result from lead (Pb) being retrogradely transported in axons from muscle to spinal cord. To test this hypothesis, we injected mice in the right hindlimb with 0.1 ml of 0.25% or 2.5% Pb. In some animals the sciatic nerve was cut before injection. Pb levels were measured in the lumbar and thoracic spinal cord and the kidney with atomic absorption spectrophotometry (AAS). Four weeks after injection, Pb was found in the spinal cord on AAS, with higher levels in the lumbar than the thoracic cord only in the high-Pb group. Sciatic nerve cut did not inhibit the passage of Pb to the cord. The results suggest that most Pb injected into muscle reaches the spinal cord via the blood or damaged axons, rather than via intact axons. These data do not support the hypothesis of Pb-induced motor neuron disease via retrograde axonal transport from muscle.

Selenium deficiency augments the pulmonary toxic effects of oxygen exposure in the rat.

Selenium (Se) is a component of the antioxidant enzyme glutathione peroxidase (GSHPx). We wanted to determined whether Se deficiency predisposes to pulmonary O2 toxicity. Sixteen weanling rats were fed a Se-free diet (Se-). Sixteen rats fed the same diet had drinking water supplemented with 400 micrograms.l-1 sodium selenite (Se+). After 5 weeks, rats were killed after exposure to either 95% O2 or air for 36 h. Se concentration in blood, lung, liver, heart, muscle and spleen, and blood GSHPx activity were higher in Se+ than in Se- groups. Pulmonary oedema developed in both O2-exposed groups, but was more severe in Se-O2 group than in the Se+O2 group, as judged by the presence of pleural effusions (7 out of 8 versus 0 out of 8), elevated lavage protein concentration (173 +/- 17 versus 120 +/- 14 micrograms.ml-1), and higher wet/dry weight ratio (W:D) (5.8 +/- 0.07 versus 5.4 +/- 0.07). W:D correlated inversely with lung Se content in O2-exposed rats. Both O2-exposed groups had a reduction in the amount of less aggregated lavage phospholipid (PL) compared with the Se+air group. However, the Se-O2 group had increased total PL, because of an increase in more aggregated PL. We conclude that Se deficiency exacerbates pulmonary injury in O2-exposed rats, and that O2 toxicity is associated with an altered physical form of alveolar surfactant.

The reproducibility of the plasma response to a physiological dose of zinc in healthy subjects. Implications for study design.

Zinc absorption may be estimated by measuring the area under the plasma zinc curve following the ingestion of a zinc supplement. The aim of this study is to determine the reproducibility of such a response when a small dose of zinc is administered to healthy volunteers. Five female subjects were asked to consume 4.5 mg elemental zinc, and blood samples were obtained at 30 min intervals for 5 h. The experiment was repeated in the same volunteers 12-16 d later. The area under the plasma zinc curve was 30% lower after the second zinc tolerance test compared with the first (11.0 vs 15.8 mumol/l h). This difference could not be explained by differences in the fasting plasma zinc levels (12.9 mumol/L Experiment one, 15.1 mumol/L Experiment 2) nor was it related to technical or clinical parameters. The area under the curve after 5 h was strongly correlated with the response after 4 h. Hence we conclude that a small dose of zinc can be used to determine zinc absorption and a shorter experimental period may be used. However, trials must be designed to take into account the sequence variability in the response.

Striking variability of hepatic copper levels in fulminant hepatic failure.

Two cases of acute hepatic failure are reported in which the diagnosis of Wilson's disease was considered because of low serum ceruloplasmin, low serum copper levels and high 24 h urinary copper. Case 1 had Kayser-Fleischer rings, haemolysis and a high 24 h urinary copper, and so Wilson's disease was confidently diagnosed. Case 2 had high urinary copper excretion, but [64Cu] study indicated a 24:2 h ratio of 0.7 and made the diagnosis of Wilson's disease uncertain. Both patients underwent orthotopic hepatic transplantation, and multiple biopsies were taken from the resected specimen in order to estimate hepatic copper levels. In both cases, hepatic copper levels revealed considerable variation: 0.8-5.2 mumol/g dry wt (case 1) vs 0.02-12.65 mumol/g dry wt (case 2). In case 1, only two of 14 levels were within the diagnostic range for Wilson's disease (greater than 4 mumol/g dry wt), whereas hepatic copper levels in case 2 were in the Wilsonian disease range in three of 16 specimens. These results were in contrast to uniformly high hepatic copper levels in one patient with established cirrhosis secondary to Wilson's disease and two cases of primary biliary cirrhosis. This report indicates that hepatic copper levels vary greatly in acute liver failure, and that estimates from a single biopsy specimen may be misleading as to the cause of the underlying liver disease.

Serum levels of antioxidants and age-related macular degeneration.

A number of reports have suggested that oxidative damage in the retina may contribute to the pathogenesis of Age-related macular degeneration (AMD). The present study was designed to investigate the hypothesis that serum levels of the antioxidants, Vitamin E and selenium are related to the pathogenesis of AMD. Fasting bloods were obtained from 80 patients with AMD and 86 controls. Assays for serum levels of Vitamin E, selenium, cholesterol and triglycerides were performed. Assessment of patients and controls was based upon eye examination, fundus photography and medical history. No significant difference was found in serum levels of Vitamin E between subjects and controls, however, there was a borderline association between AMD and both serum selenium levels and current smoking status. The results suggest that if oxidative damage is a factor in the pathogenesis of AMD, it is not reflected in serum levels of Vitamin E; further studies are required to clarify the possible relationship between serum selenium levels, smoking and AMD.

Effects of acute illness on selenium homeostasis.

Biochemical evidence of selenium (Se) deficiency is frequent in patients with chronic malnutrition. However, the incidence of Se deficiency in acutely ill patients is unknown. In 175 consecutive ICU patients, plasma Se measured during the first week of ICU admission was 0.66 +/- 0.21 mumol/L (mean +/- SD) and was less than that measured in 57 healthy blood donors (1.05 +/- 0.21 mumol/L, p less than .001). Sixty-eight percent of plasma Se concentrations fell below the lower limit of the reference range. Plasma Se decreased with the number of weeks in the ICU (r = .33, p less than .01) with values decreasing to 0.49 +/- 0.20 mumol/L during the fourth week. Urinary Se excretion measured in a subgroup of 20 patients was related to plasma Se concentration (r = .38, p less than .05), and inversely related to N balance (r = .50, p less than .01). We conclude that decreased plasma Se concentrations are common in ICU patients and that catabolic states are associated with increased Se losses. These losses are unlikely to account for the marked reductions in plasma Se concentrations, and the findings suggest there may be significant changes in the distribution of body Se during critical illness.

Mechanisms of renal excretion of cisdichlorodiamine platinum.

Eighteen diuretic rabbits were given cisdichlorodiamine platinum (CDDP) and the clearance of plasma water platinum was determined with a simultaneous inulin clearance. The rabbits were then given probenecid (50 mg/kg) or choline (50 mg/kg) and the clearance of free platinum was calculated. CDDP has a high clearance, exceeding glomerular filtration rate. The drug appears to be secreted by the anionic transport system in the proximal tubule, as the clearance of free platinum is markedly decreased by the administration of probenecid.