Brain copper, iron, magnesium, zinc, calcium, sulfur and phosphorus storage in Wilson's disease.

PROJECT: Wilson's disease (WD) is an inherited disorder of copper metabolism characterised by juvenile liver cirrhosis and by neurological symptoms. Copper levels in brain in WD have been reported to be 10 to 15 fold normal values, depending on the different brain regions. Being very few data on copper distribution in central nervous system in WD available, it seemed of interest to study the concentration of copper and of other trace elements (Zn, P, Mg, Ca, Fe and S) in the brain of a patient died for WD. PROCEDURE: a 56 year old woman affected by WD was admitted to our hospital with signs of hepatic failure and died few days later. At autopsy, a brain slice extending from the left to the right hemisphere was divided in 28 samples. On each sample Copper, Iron, Magnesium, Phosphorus, Sulphur, Zinc and Calcium were determined by Induced Coupled Plasma Atomic Emission Spectroscopy. RESULTS: the mean concentration of copper, ranging from 88 to 158 microg/g of dry tissue in all the brain specimens was higher than literature reference values, while that of the other tested elements was considerably lower. CONCLUSIONS: 1) In the brain of WD patient examined the status of trace elements was extensively altered. Further studies are necessary to correlate the concentration of trace elements with pathological lesions and with clinical pictures. 2) The elements considered in our study showed an uneven distribution in different brain areas.

Chemometric methods applied to an ICP-AES study of chemical element distributions in autopsy livers from subjects affected by Wilson and beta-thalassemia.

The concentrations of seven elements (Ca, Cu, Fe, Mg, P, S and Zn) in three autopsy livers (from two beta-thalassemic patients and one Wilson's disease patient) were determined by ICP-AES technique. At autopsy the three livers were subdivided into a large number of samples for a detailed study of the distribution of Fe and Cu, the accumulation of which characterizes the two diseases. In the same samples Ca, Mg, P, S and Zn concentrations were also determined in order to study significant variations or anomalous trends that could help identify these diseases. Our results generally show a good coincidence with literature data within the limits of sample variability. Based on Factor Analysis as well as Regression Analysis there is evidence of a high correlation between Fe and P contents in beta-thalassemia. The latter finding led us to propose tentatively an accumulation of Fe as a complex with P-containing molecules.

Uneven hepatic iron and phosphorus distribution in beta-thalassemia.

BACKGROUND/AIMS: Determination of hepatic iron concentration is crucial in the evaluation of iron-storage disease. Iron content is normally determined in a part of a needle liver biopsy and the value obtained is considered to be representative of the iron concentration in the whole liver. To evaluate the reliability of this procedure, we studied iron distribution in the liver of two beta-thalassemic patients. Since the transport of intracellular iron is mediated by phosphates, we also studied the hepatic phosphorus distribution. METHODS: At autopsy, a liver slice extending from the left to the right lobe was divided into 51 and 49 samples, respectively. Each specimen was subdivided into two parts: one of them was paraffin-embedded and utilized for the histochemical detection of iron; the second part was analyzed for iron and phosphorus content by induced coupled plasma atomic emission spectroscopy. RESULTS: The histological picture of both livers was characterized by portal and periportal fibrosis associated with iron storage of different degree, without cirrhosis. The mean iron concentration of the liver was 20,631 +/- 4903 micrograms per g of dry tissue (micrograms/g dt) and 13,901 +/- 1976 micrograms/g dt, respectively. A striking variability in iron content between samples was also found: iron concentration ranged from 11,537 to 32,347 micrograms/g dt in the first case and from 6257 to 16,493 in the second case. We even observed regional differences in iron concentration, with a preferential peripheral accumulation in both cases and a tendency of the left compartment of the liver to accumulate more iron in the first case. Histochemical analyses confirmed the uneven iron distribution even at the acinar level, showing iron mainly being stored in hepatocytes and Kupffer cells of zone 1 of the acinus, with decreasing amounts of iron in zones 2 and 3. The mean hepatic phosphorus concentration was 6662 +/- 1300 micrograms/g dt (range: 4348-9947) and 7502 +/- 986 micrograms/g dt (range: 5844-90,282), respectively. The regional distribution of phosphorus was similar to that observed for iron. A strict correlation between iron and phosphorus content was also observed. CONCLUSIONS: Our data show that: 1) iron and phosphorus are unevenly distributed in the beta-thalassemic liver, even in the non-cirrhotic stages; 2) a regional pattern of iron and phosphorus distribution is evident, characterized by higher concentrations at the periphery of the liver; 3) the observed uneven distribution of iron and phosphorus implies that their content determined in a small liver sample cannot be considered as absolutely representative of the mean hepatic iron concentration. Therefore, iron concentrations determined in a part of a needle liver biopsy should be interpreted with caution in monitoring the efficacy of the iron-chelating therapy in beta-thalassemic patients.

Characterization of the ionization and spectral properties of sulfonephthalein indicators. Correlation with substituent effects and structural features. Part II.

A spectrophotometric study is presented on the first ionization equilibrium of a class of substituted sulfonephthaleins, whose second ionization was the subject of the first part of this work. The present study was more difficult than the previous in that highly acid media and acidity functions had to be used. Nevertheless the results were of sufficient accuracy to allow the dual substituent analysis of Swain and Lupton (C.G. Swain and A.C. Lupton, Jr., J. Am. Chem. Soc., 90 (1968) 4328). Generally speaking, the dependences of equilibrium and spectral parameters on field and resonance parameters found in this and the previous paper were very similar.

Uneven hepatic copper distribution in Wilson's disease.

BACKGROUND/AIMS: Determination of hepatic copper concentration is important in the diagnosis of Wilson's disease. We studied copper distribution in the cirrhotic liver of a patient who died of Wilson's disease. METHODS: A liver slice extending from the left to the right lobe was divided into 38 samples. Each sample was analyzed for copper content by Induced Coupled Plasma Atomic Emission Spectroscopy. RESULTS: The mean copper concentration in the liver was 1370 micrograms/g dt. A striking variability, up to 2-3-fold, in copper levels was observed between the samples: the copper concentration ranged from 880 to 2100 micrograms/g dt, with significant differences even between adjacent samples. Lobar differences were also observed, with a tendency of the right lobe to accumulate more copper than the left lobe. Histochemical analyses confirmed the uneven distribution of copper even at the acinar level. Copper was mainly stored in periportal hepatocytes (zone 1) and at the periphery of the regenerating nodules. Moreover, we observed some nodules with the majority of hepatocytes full of copper granules, adjacent to areas of parenchyma negative for copper stains. CONCLUSIONS: Our data show that: 1) copper is unevenly distributed in Wilson's disease in the cirrhotic stage; 2) a lobar pattern of copper distribution is evident in this case, characterized by a higher copper concentration in the right lobe; 3) the observed lobar pattern is different from that described in the newborn liver, characterized by a higher copper content in the left compartment of the liver; 4) copper content determined in a small liver sample cannot be considered as absolutely representative of the mean hepatic copper concentration. From a practical point of view, our data show that sampling variability deserves more consideration in the diagnosis and in the monitoring of Wilson's disease. The use of hepatic copper concentration in monitoring the efficacy of the copper-chelating therapy may be unreliable, particularly in the cirrhotic stage, because of the patchy distribution of copper, as demonstrated in this study.