Lenticular nucleus hyperechogenicity in Wilson's disease reflects local copper, but not iron accumulation.

In patients with Wilson's disease (WD) transcranial brain sonography typically reveals areas of increased echogenicity (hyperechogenicity) of the lenticular nucleus (LN). Correlation with T2-hypointensity on magnetic resonance images suggested that LN hyperechogenicity in WD is caused by trace metal accumulation. Accumulation of both, copper and iron, in the brain of WD patients has been reported. The present study was designed to elucidate whether LN hyperechogenicity in WD reflects accumulation of copper or iron. Post-mortem brains of 15 WD patients and one non-WD subject were studied with ultrasonography in an investigator-blinded fashion. LN hyperechogenicity was measured planimetrically by manual tracing as well as using digitized image analysis. The putaminal copper content was determined in samples of 11 WD brains and the non-WD brains using inductively coupled plasma mass spectrometry, and iron content was assessed using flame atomic absorption spectroscopy. LN was normal on ultrasonography only in the non-WD brain, but abnormal (hyperechogenic) in all WD brains. Digitized image analysis measures of LN hyperechogenicity and, by trend, manual measures correlated with putaminal copper content (Pearson test; digitized: r = 0.77, p = 0.04; manual: r = 0.57, p = 0.051) but not with iron content (each, p > 0.18). LN hyperechogenicity measures were unrelated to age at death of patients, age at onset of WD, WD duration, age of brain specimen, serum copper or serum ceruloplasmin (each, p > 0.1). We conclude that LN hyperechogenicity in WD reflects copper, but not iron accumulation. Further studies are warranted to elucidate the use of transcranial brain sonography for monitoring therapeutic effects of chelating agents in WD patients.

Tobacco smoke exposure during pregnancy increases maternal blood lead levels affecting neonate birth weight.

To assess the effect of lead exposure from cigarette smoke on fetal growth, blood lead concentrations were measured using inductively coupled plasma mass spectrometry in 150 healthy pregnant women. Mean lead concentrations in plasma and whole blood were significantly higher in the smoking group compared with the nonsmoking group in each trimester of pregnancy (p < 0.001). Logistic regression analysis showed the highest impact of the number of cigarettes smoked per day for serum lead concentration (ß = 0.238; p < 0.05), while in whole blood, it was duration of smoking before conception (ß = 0.297; p < 0.001). Birth weight of the smoking mothers' infants was significantly lower (mean ± SEM, 3,192 ± 50.8 and 3,569 ± 49.6 g, respectively; p < 0.001) and negatively correlated with lead levels in plasma (r = -0.38; p < 0.001) and in whole blood (r = -0.27; p < 0.001). Therefore, it is suggested that smoking during pregnancy increases lead concentrations in maternal blood. Fetal exposure to low doses of lead in utero may be a serious risk factor causing lower birth weight.

Neurochemical and behavioral characteristics of toxic milk mice: an animal model of Wilson's disease.

Toxic milk mice have an inherited defect of copper metabolism. Hepatic phenotype of the toxic milk mice is similar to clinical findings in humans suffering from Wilson's disease (WND). In the present study, neurotransmitter system and locomotor performance in toxic milk mice was examined to verify the feasibility of this animal model for studying neuropathology of WND. Mice aged 2 and 12 months were used in the experiment. The mice were tested according to rotarod and footprint protocols. Monoamine content in brain structures was measured by high performance liquid chromatography. In order to detect neuronal loss, expression of enzymes specific for dopaminergic [tyrosine hydroxylase (TH)], noradrenergic (dopamine beta-hydroxylase) and serotoninergic [tryptophan hydroxylase (TPH)] neurons was analyzed by Western blot. The 12-month-old toxic milk mice demonstrated impaired locomotor performance in behavioral tests. Motor deficits were accompanied by increased copper and serotonin content in different brain regions and slight decrease in dopamine concentration in the striatum. The expression of TH, dopamine beta-hydroxylase and TPH in the various brain structures did not differ between toxic milk mice and control animals. Despite differences in brain pathology between humans and rodents, further exploration of neuronal injury in toxic milk mice is warranted to broaden the understanding of neuropathology in WND.

[Effect of cigarette smoking on blood lead levels in pregnant women]. / Wplyw palenia tytoniu na poziom olowiu we KRWI kobiet ciezarnych.

UNLABELLED: Tobacco smoking creates health problems which apply not only to individuals and the family but also to different ages and social groups, as well as the national economy. Epidemiologic studies conducted at the Institute of Mother and Child indicated that in Poland 25-30% women smoke during pregnancy. Lead exposure from cigarette smoke may have a negative effect on the transplacental flow of micronutrients and have an adverse influence on the growth and development of the fetus, and then on children. The aim of this study was to estimate the effect of smoking cigarettes on plasma and whole blood lead levels in pregnant women. MATERIAL AND METHODS: Eighty healthy pregnant women, patients of the Clinical Department of the Obstetrics and Gynecology Institute of Mother and Child and Warsaw Medical University, were divided into two groups: group I - tobacco smokers and group II- tobacco abstainers according to questionnaire declaration and serum cotinine concentration. Current smokers were defined as those who had smoked 5 cigarettes per day for 2 years before conception and continued smoking during pregnancy. The women exposed to environmental tobacco smoke (smoking spouse or other family members, co-workers) were excluded from the non-smoking group. All pregnant volunteers signed a written, informed consent form, approved by the Institute's Ethical Committee. The concentrations of lead in plasma and whole blood were analyzed using inductively coupled plasma mass spectrometry on spectrometer analyzer ICP MS Elan 6100 (Perking Elmer, Germany). Levels of cotinine in serum were determined by Cotinine Direct ELISA test (Calbiotech Inc. Canada). RESULTS: In the group of smoking mothers the mean serum cotinine concentration was 69.1 µg/L, whereas in the group of tobacco abstainers it was present only in trace amount. In group I we observed a significant positive correlation between serum cotinine and the number of cigarettes smoked daily (r=0.74; p<0.001), as well as the period of smoking before conception (r=0.60; p<0.001). The concentrations of lead in the plasma of smoking women were significantly higher than in the group of tobacco abstainers in each trimester of pregnancy (I trimester: 0.22 µg/dL vs 0.12 µg/dL p<0.01; II trimester: 0.19 µg/L vs 0.10 µg/L p<0.001; III trimester 0.28 µg/ dL vs 0.13 µg/dL p<0.0001). Tobacco smoking mothers also had a higher concentration of lead in whole blood as compared to pregnant non-smoking women. These differences were statistically significant and amounted to 2.15 µg/dL vs 1.28 µg/L in the first, 1.99 µg/dL vs 1.19 µg/dL in the second and 2.11 µg/dL vs 1.58 µg/dL in the third trimester of pregnancy. We observed that the level of lead was correlated with cotinine in blood, as well as with the number of cigarettes and the length of time women smoked before conception. Such an effect was observed in every trimester of gestation. A strong correlation between the number of cigarettes/day and lead concentration in plasma (r=0.57; p<0.001) and whole blood (r=0.54; p<0.001) was found in the third trimester of pregnancy. CONCLUSIONS: Tobacco smoking during pregnancy increased the concentrations in maternal blood lead. The level of lead in plasma and whole blood correlated with the degree of intensity of cigarette smoking in the pregnant women studied. It may be a result of influencing the mobilization of calcium from the bone with simultaneous release of lead deposited in the bone. Further studies are required to characterize the effect of higher lead level in the blood of mothers on the risk of premature labor, low birth weight of newborns and their inferior development.