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H H Dieter

Publications and source records attributed to H H Dieter.

At least 19 recordsLinked to original sources
PubMed2002

Hohenheim consensus workshop: copper.

Copper (Cu) is an essential trace element with many physiological functions. Homeostatic mechanisms exist to allow Cu to act as a cofactor in enzymatic processes and to prevent accumulation of Cu to toxic levels. The aim of this commentary is to better understand the role of dietary Cu supply in deficiency and under physiological and pathological conditions. The essentiality of Cu can be attributed to its role as a cofactor in a number of enzymes that are involved in the defence against oxidative stress. Cu, however, has a second face, that of a toxic compound as it is observed with accumulating evidence in hepatic, neurodegenerative and cardiovascular diseases. The destructive potential of Cu can be attributed to inherent physico-chemical properties. The main property is its ability to take part in Fenton-like reactions in which the highly reactive and extremely deleterious hydroxyl radical is formed. Diseases caused by dietary Cu overload could be based on a genetic predisposition. Thus, an assessment of risk-groups, such as infants with impaired mechanisms of Cu homeostasis regarding detoxification, is of special interest, as their Cu intake with resuspended formula milk may be very high. This implies the need for reliable diagnostic markers to determine the Cu status. These topics were introduced at the workshop by the participants followed by extensive group discussion. The consensus statements were agreed on by all members. One of the conclusions is that a re-assessment of published data is necessary and future research is required.

Cardiovascular Diseases↗
PubMed2001

Copper in disorders with neurological symptoms: Alzheimer's, Menkes, and Wilson diseases.

Copper is an essential element for the activity of a number of physiologically important enzymes. Enzyme-related malfunctions may contribute to severe neurological symptoms and neurological diseases: copper is a component of cytochrome c oxidase, which catalyzes the reduction of oxygen to water, the essential step in cellular respiration. Copper is a cofactor of Cu/Zn-superoxide-dismutase which plays a key role in the cellular response to oxidative stress by scavenging reactive oxygen species. Furthermore, copper is a constituent of dopamine-beta-hydroxylase, a critical enzyme in the catecholamine biosynthetic pathway. A detailed exploration of the biological importance and functional properties of proteins associated with neurological symptoms will have an important impact on understanding disease mechanisms and may accelerate development and testing of new therapeutic approaches. Copper binding proteins play important roles in the establishment and maintenance of metal-ion homeostasis, in deficiency disorders with neurological symptoms (Menkes disease, Wilson disease) and in neurodegenerative diseases (Alzheimer's disease). The Menkes and Wilson proteins have been characterized as copper transporters and the amyloid precursor protein (APP) of Alzheimer's disease has been proposed to work as a Cu(II) and/or Zn(II) transporter. Experimental, clinical and epidemiological observations in neurodegenerative disorders like Alzheimer's disease and in the genetically inherited copper-dependent disorders Menkes and Wilson disease are summarized. This could provide a rationale for a link between severely dysregulated metal-ion homeostasis and the selective neuronal pathology.

Alzheimer Disease↗
PubMed1999

Early childhood cirrhoses (ECC) in Germany between 1982 and 1994 with special consideration of copper etiology.

In a multicentric retrospective clinical study with 16 pediatric centres we identified 103 cases of histologically confirmed early childhood cirrhosis (ECC) in Germany for the years 1984-1994. The most prominent diagnoses were congenital bile duct anomalies (47.5%), inborn metabolic disorders (17.5%) and unclear etiologies (17.5%). Chronic and excessive intake of copper might be discussed as an etiological factor in 8 other cases. 5 of these were proven to have coincided with very high hepatic copper contents and copper plumbing/acid well water. Their connection with copper exposure must be considered as probable, whereas 3 others were only suspected copper cases, mainly due to reliable exclusion of other etiologies. High corrosivity (base capacity) values and copper levels in the water for infants formula of 9-26.4 mg/L were determined in those probable cases for which exposure conditions could be exactly reproduced. Additional reports on copper associated ECC, either Indian Childhood Cirrhosis (ICC) from outside India or so-called Idiopathic Copper Toxicosis ( ICT ), originate from Austria, Australia, Germany, Ireland, USA.

Child, Preschool↗
PubMed1997

Experimental induction of liver fibrosis in young guinea pigs by combined application of copper sulphate and aflatoxin B1.

Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administered orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B1 group, liver damage was established. In the combined group, liver injury was more frequent and more severe compared to the aflatoxin B1 group and biliary copper excretion was diminished compared with the copper group. Histologically, only the livers of this group exhibited degeneration, atrophy and steatosis of liver cells, inflammatory processes and a more or less prominent fibrosis. For childhood cirrhosis (ICC and ICT) a combined etiology--a liver damaging agent plus elevated alimentary copper--is a plausible hypothesis.

Aflatoxin B1↗
PubMed1995

Which multiple of a safe body dose derived on the basis of default factors would probably be unsafe?

This paper proposes a procedure to establish coherence between the toxicological and the legal definition of hazardous exposure situations to substances with effect threshold. This procedure is useful for defining unsafe body doses or exposure levels at and above which such situations would appear to be "sufficiently probable" in the toxicological as well as the legal sense. We propose the unsafe exposure level to be F-times higher than the safe level. F is the geometric mean of those default factors which are intended to relate the experimental or epidemiological database to the human target population. Our proposal for defining "sufficiently probable unsafe exposures" is based entirely on widely accepted toxicological conventions. It is conservative and, at the same time, flexible enough to allow F to be corrected in concert with improvements of the database. The German Federal Environmental Agency has officially adopted this proposal and is recommending it for risk assessment of environmental contaminants.

Animals↗
PubMed1994

[Criteria for the determination of chronic exposure to hazardous substances via soil ingestion].

Legally recoverable protection of human health against pollutant effects must have for the enforcement in practice a technically comprehensible toxicological basis, i.e., a coherence or connection between the toxicological and legal definition of a dangerous situation must be found. For this purpose toxicological and socially accepted reference points in the unit "mg of pollutant amount absorbed per kg of weight per day" (mg/[kg of weight x d]) may be used to assess a danger in the sense a sufficient probability a damage to human health exists after exposure to certain pollutant concentrations. Based on the plausible toxicological assumption that above this reference point in case of an undisturbed course of action and by giving consideration to all exposure pathways a threshold of harmlessness including all groups of the population would be exceeded, criteria both for non-carcinogenic and carcinogenic substances or for substances suspected to cause cancer are being developed. These criteria allow to determine from which point the existence of a danger would be assessable as "sufficiently probable", and hence the required coherence between legal and toxicological view to be established.

Animals↗
PubMed1993

[Lead in drinking water--determination of a new limit value and the problem of lead pipes].

The problem of lead in drinking water with regard to sensitive groups of the general population (e.g. unborn, babies that are not breast-fed, infants and children) is discussed. In respect of children in nurseries, the question regarding the relation of blood-lead levels to neurobehavioural deficits due to lead as well as a theoretical "tolerable" daily intake of lead is discussed. A provisional daily intake of approx. 1.2-1.3 micrograms Pb/kg body weight for children and pregnant women is proposed. For non-pregnant adults a double to three times higher intake may be tolerated (base: high blood pressure). These doses are well three times below the still recognised Provisional Tolerable Weekly Intake of led (PTWI-values, WHO), when related to daily intake. Considering the water consumption as well as the proportionate share of other exposure routes which result in the total lead exposure of risk groups, a toxicologically tolerable level of 10 micrograms Pb/l in drinking water is suggested. A reduction of the actual limiting value in drinking water (40 micrograms Pb/l) is advised. A special problem arises from lead tubes within the water distribution system. Water in stagnation as well as in use in these tubes may have enhanced lead concentrations. Therefore, it is recommended to exchange lead tubes preferentially in areas of sensitive use (e.g. as in the kitchen).

Adult↗
PubMed1993

Presence and importance of organochlorine solvents and other compounds in Germany's groundwater and drinking water.

Organochlorine compounds are widely used in Germany although the inland production of chlorinated solvents has greatly decreased since 1985. Data on groundwater contamination are incomplete, but there are some regional data sets from the States (Länder). Approximately 25% of the groundwater samples contain more than 1 microgram/l of a single solvent, the most prominent ones being tri- and tetrachloroethene, 1,1,1-trichloroethane and dichloromethane, but also chloroform. The most important causes for contaminations of the groundwater are unprotected storage and leaking sewage systems. Abandoned waste sites are, besides chlorinated compounds, also a source of many other contaminants. A ranking procedure according to their exposure potential (concentration, incidence, toxicology) is proposed. The compound of greatest concern is vinyl chloride, which is formed from tri- and tetrachloroethene under reducing conditions in the subsoil. The most important contaminant in drinking water is tetrachloroethene followed by 1,1,1-trichloroethane and trichloroethane. Chlorobenzene may also be present on occasion, while only about 20% of the finished drinking waters contain more chloroform after treatment than before. Only about 10% of all analyses of drinking water derived from groundwater shows the presence of organochlorine solvents and most of these show total concentrations less than 2 micrograms/l. The degradation product, vinyl chloride, was found up to now only in different groundwaters. To stabilize and to improve the situation, which still is much more favorable for drinking than for groundwater, precautions are going to be taken which should assure that these and other problematic substances which endanger water are used only in closed systems and rigid safety measures be imposed on their disposal and transport.

Germany↗
PubMed1990

Effect of methoxyethanol, cyclophosphamide and cadmium on metallothionein levels during prenatal development in the mouse.

Three known teratogenic agents--methoxyethanol (ME), cyclophosphamide (CP) and cadmium (Cd)--are possible inducers of metallothionein (MT) in the embryo and/or in the fetus. Their effect on the MT levels of forelimbs, brain and liver during prenatal development and in dam's liver was studied in the mouse to elucidate whether MT could be used as an early biochemical indicator of teratogenicity. Pregnant mice were injected with 2 doses of each teratogen at different days of the middle gestational phase and their embryos and fetuses were obtained thereafter. Quantitative estimation of MT in the S9 from homogenates of the embryo/fetal tissues and organs and maternal liver showed major alterations in the dam's hepatic MT content but only small changes in prenatal MT levels. These results do not support MT as an early indicator of teratogenicity. However, a causal relationship between the maternal MT changes induced by the tested agents and their teratogenic effect could be possible.

Animals↗
PubMed1989

Characterization and development of metallothionein in fetal forelimbs, brain and liver from the mouse.

The presence of the low molecular weight protein metallothionein (MT) has been investigated in fetal forelimbs, brain and liver from the mouse with the aim of using the protein as a biochemical marker for the early recognition of potential teratogenic agents in the future. Forelimbs, brain and liver were taken from mouse fetuses at ages ranging from 12 to 18 d. Each type of organ was homogenized and centrifuged at 9000 x g. The analysis of MT in the supernatants (S9) with the Cd-heme saturation method detected in all three cases the presence of a low molecular weight, Cd-binding protein whose concentration increased with the age of the fetus. Analysis of the S9 fractions using gel- and anion exchange-chromatography and polyacrylamide gel electrophoresis demonstrated the existence of a protein analogue to the hepatic MT in forelimbs and brain.

Animals↗
PubMed1989

[Essential biochemical aspects and toxicology of copper].

Cases of chronic copper intoxication of infants via the ingestion of water, as investigated recently in certain regions of Bavaria and the EMs district, have been prompting a quest for additional risk factors which enhance the effect of copper, even though they do limit its frequency rate. The water from water wells, which had been incriminated, was never of a quality standard that would classify it as "drinking water", i.e. as potable water, so that one must consider not only physiological/biochemical but also water-conditioned/chemical causes. Copper alone as the sole risk factor--and in the concentrations considered to be suspect so far--will not suffice to explain the number of cases recorded to date. Basing on the established knowledge in toxicology and essentially of copper we arrive at the following points of attack for further research on the causes: Special kinds of copper ingestion of a chemical nature; unusual reaction of the intestinal mucosa to copper; development-conditioned variable coeruloplasmin synthesis or elimination of copper via the bile; delayed degradation of metallothioneine. Until the causes have been definitely clarified, we believe that suitable prophylactic measures should be taken in accordance with the short communication by Eife and Müller-Höcker (Dt. Arztebl. 85 (1988) 11: A 693) or the press release by the Federal Public Health Service dated 18 March 1988.

Adult↗