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[Intake of essential trace elements (selenium, copper and iron) in the nutrition of patients hospitalized with liver cirrhosis].

Dietary intake for three essential trace elements: selenium, copper and iron was studied in hospitalized patients receiving either ordinary meals or regimens adapted for liver cirrhosis. The aim of the study was to assess the effects of dietary manipulations: reduction in sodium intake for uncomplicated disease and protein restriction to 40 g per day in patients with hepatic encephalopathy. The meals proposed to these three groups were collected during fourteen days and daily intake for three elements was estimated by direct analysis of the assembled meals of the day. Dietary selenium was greatly affected by the restriction in protein intake contrary to copper and iron which were not significantly reduced. Moreover, overall daily trace element intake was rather low and clearly less than the most recent recommended allowances for these essential elements. Relationships between deficiency in some of these trace elements and worsening of the liver disease have been partly documented. They should encourage studies on the correction of dietary intake.

Copper

[Effects of an essential trace element agent (TE-5) for total parenteral nutrition on the mineral nutrition in rats fed a trace element-deficient diet].

TE-5 is an essential trace element agent containing iron, zinc, copper, manganese and iodine for total parenteral nutrition (TPN). We have already reported that TE-5 improved the reduction of trace element concentrations induced by TPN. However, effects of TE-5 on the changes in biological function relating to trace elements are poorly understood. The present study was designed to clarify the effects of TE-5 on these functions. Rats fed a trace element (iron, zinc, copper, manganese and iodine)-deficient diet for 7 weeks showed reductions in the following parameters: plasma and various tissue concentrations of iron, zinc, copper, manganese and iodine, growth rate, erythrocyte (iron), hemoglobin (iron), hematocrit (iron), mean corpuscular constants (iron), plasma alkaline phosphatase activity (zinc), serum ceruloplasmin concentration (copper), liver pyruvate carboxylase activity (manganese) and serum thyroxine concentration (iodine). On the other hand, when TE-5 (0.008, 0.04 and 0.2ml/kg: x 0.2, x 1 and x 5 the usual clinical dose, respectively) was intravenously administered once a day for 7 weeks under the conditions described above, there was a tendency to prevent the reductions of plasma and various tissue concentrations of iron, zinc and manganese. In addition, TE-5 prevented the reductions of growth rate, iron metabolism functions, plasma alkaline phosphatase activity, serum ceruloplasmin concentration and liver pyruvate carboxylase activity. The present study shows that TE-5 prevents both reductions of trace element contents and trace element-related functions, and suggests that TE-5 is useful for treatment of trace element deficiency in TPN.

Animal Nutritional Physiological Phenomena

[Zinc--update of an essential trace element].

Since the recognition of zinc as an essential trace element in man and animals there has been a remarkable progress in our knowledge of the role of zinc in nutritional physiology, biology and medicine during the last few decades. Highlights in zinc research, mechanisms and homeostatic regulation of zinc absorption, sources of zinc intake, dietary factors and mineral interactions affecting zinc bioavailability are reviewed in the present paper. This is followed by an overview of the biochemical functions of zinc in enzymes, gene expression, endocrinology, immunology and oxidative stress. General signs and metabolic consequences of zinc deficiency as well as excessive intake and toxicity of zinc are summarized. Furthermore, national and international dietary zinc recommendations and different methods to determine the zinc status are discussed.

Animal Nutritional Physiological Phenomena

[Essential trace elements and immunity].

The effects of zinc, iron, copper and selenium on the immune system are reviewed. Among the essential trace elements in humans, zinc, iron, copper and selenium are essential for the integrity and optimum function of the immunity. Although each element has different functions in the immune system, the deficiencies in each of these elements mainly causes the dysfunction of cell-mediated immunity. Deficiencies do not significantly effect the B cell function. These immunological abnormalities can be improved by supplementation of deficient elements. However, excess supplementation also impairs the immune system. Therefore, a proper balance of these elements is essential for maintenance of immunocompetence.

Animals

A conserved helical element is essential for internal initiation of translation of hepatitis C virus RNA.

Translation of hepatitis C virus (HCV) RNA is initiated by cap-independent internal ribosome binding to the 5' noncoding region (NCR). To identify the sequences and structural elements within the 5' NCR of HCV RNA that contribute to the initiation of translation, a series of point mutations was introduced within this sequence. Since the pyrimidine-rich tract is considered a characteristic feature of picornavirus internal ribosome entry site (IRES) elements, our mutational analysis focused on two putative pyrimidine tracts (Py-I and Py-II) within the HCV 5' NCR. Translational efficiency of these mutant RNAs was examined by in vitro translation and after RNA transfection into liver-derived cells. Mutational analysis of Py-I (nucleotides 120 to 130), supported by compensatory mutants, demonstrates that the primary sequence of this motif is not important but that a helical structural element associated with this region is critical for HCV IRES function. Mutations in Py-II (nucleotides 191 to 199) show that this motif is dispensable for IRES function as well. Thus, the pyrimidine-rich tract motif, which is considered as an essential element of the picornavirus IRES elements, does not appear to be a functional component of the HCV IRES. Further, the insertional mutagenesis study suggests a requirement for proper spacing between the initiator AUG and the upstream structures of the HCV IRES element for internal initiation of translation.

Base Sequence

Activation of calmodulin by the essential trace element chromium.

Chromium at very low concentrations is an essential trace element--at higher concentrations it is associated with contact dermatitis and other toxicity problems. Its ionic radius is just outside that of other metal cations which have been found to activate calmodulin in vitro. We found that chromium was able to activate calmodulin at two different concentration ranges--over the micromolar range (which would probably never be achieved in man) a small degree of activation was found--but a much greater activation (76% of the maximum possible) was also found at nanomolar concentrations of chromium. In welders, who work with stainless steel and who were not reporting any physical symptoms of chromium toxicity, red cell chromium levels were 28.2 +/- 3.3 nM (n = 22) compared to 7.5 +/- 0.7 nM (n = 11) for normal controls. Thus, the concentration of chromium experienced within the cell can be of the order which will activate calmodulin in vitro. The possibility exists, therefore, that inappropriate activation of calmodulin could be relevant to chromium biology possibly contributing to the symptoms of chromium toxicity.

Animals

The effects of platinum chemotherapy on essential trace elements.

The effects of cisplatin chemotherapy on the metabolism of essential trace elements were investigated in 12 patients before and after treatment with cisplatin. In serum, the mean post-treatment concentrations of Cu 913.91 mumol 1-1), Zn (9.57 mumol 1-1) and Mg (0.54 mumol 1-1) were significantly reduced compared with the pre-treatment levels 919.35, 11.86 and 0.67) while Se, caeruloplasmin and C-reactive protein concentrations were unaltered. Urinary excretion of Cu, Mg and Zn were enhanced. The urinary N-acetyl-beta-D-glucosaminidase activity (a marker of proximal renal tubular dysfunction) was also increased and suggests that the mechanism for decrease of certain trace elements in serum during treatment could be increased urinary excretion caused by impaired cellular metabolism. It is not clear whether the loss of trace elements via the urine has any implication for the clinical status of cancer patients treated with cisplatin.

Adolescent

Effects of aluminium on the mineral metabolism of rats in relation to age.

The present study was conducted to assess in rats the effects of chronic aluminium (Al) exposure on calcium (Ca), magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn) and iron (Fe) accumulation and urinary excretion in relation to the age of the animals. Male young (21 day old), adult (8 months), and old (16 months) rats were orally exposed to 0, 50, or 100 mg Al/kg/day for a period of 6.5 months. Urinary levels of essential elements were determined after 3 and 6.5 months of exposure, whereas tissue Ca, Mg, Mn, Cu, Zn and Fe concentrations were examined after 6.5 months of Al administration. A number of age-related changes in tissue accumulation and urinary excretion of essential elements following chronic exposure to Al were found. Concentrations of essential elements in most tissues of young Al-exposed rats were generally lower than those of adult and old rats. The highest levels of essential elements were found in old animals. Liver, testes and spleen were the tissues that showed the most remarkable increases in relation to the levels found in those tissues of young rats. Adult rats showed a pattern comparable to that of old animals for mineral metabolism in brain, whereas in bone and testes the pattern of accumulation was closer to that of young rats. While the urinary levels of Ca were generally reduced in the Al-exposed groups, no Al-associated changes were noted for Mg, Mn, Cu and Zn. In turn, after 6.5 months of Al administration Fe excretion was increased in Al-treated adult and old rats. The results of this study suggest that early stages of life cycle should be of special concern for Al-induced changes in the metabolism of essential elements.

Aging

Dietary intakes of some essential and non-essential trace elements, nitrate, nitrite and N-nitrosamines, by Dutch adults: estimated via a 24-hour duplicate portion study.

Duplicate portions of 24-hour diets of 110 adults have been analyzed for aluminium, cadmium, copper, lead, manganese, mercury, zinc, nitrate, nitrite and volatile N-nitrosamines. The mean daily intake of copper (1.2 mg) is only about 50% of recommended values; mean daily intakes for manganese (3.3 mg) and zinc (8.4 mg) are adequate and marginal respectively with respect to recommended amounts. For the non-essential elements Al, Cd, Hg and Pb, mean daily intakes of 3.1 mg, 0.01 mg, 0.002 mg and 0.034 mg were found, respectively. For Cd this amounts to 17% of the acceptable daily amount, for Al, Hg and Pb 5%, 5% and 8%, respectively. Since 1976-1978 the dietary intake of lead has been reduced by a factor three; for the other six elements daily dietary intakes are almost the same as in 1976-1978. Average nitrate intake was 52 mg NO3-/day, about 25% of the ADI. Only 16 diets contained a measurable amount of nitrite. The highest daily intake (0.7 mg NO2-) is less than 10% of the ADI. Volatile N-nitrosamines were detectable in two duplicate diets (NDMA and NPIP). It is estimated that the daily dietary intake of volatile N-nitrosamines is around 0.1 microgram or less.

Adult

Trace element concentration in human brain. Activation analysis of cobalt, iron, rubidium, selenium, zinc, chromium, silver, cesium, antimony and scandium.

Up to 60 tissue samples were dissected from 13 human brains in defined regions and were analysed by means of neutron activation analysis for trace element concentration of cobalt, iron, rubidium, selesium, zinc, chromium, silver, cesium, antimony and scandium. It was shown that the variation in concentration of the non-essential elements in the different brain regions was greater than the corresponding variations in concentration of the essential elements. The mean values of Fe and Rb concentrations were higher in the basal ganglia than in the cortex areas. With increasing age the Fe concentration in the human brain was found to increase and that of Rb to decrease. Comparison of the trace element concentration in corresponding areas of the right and left hemispheres showed highly significant positive correlations for the essential elements. The concentration of each of the essential elements Fe, Rb and Zn was also found to differ significantly between defined functional regions. The characteristic distribution of essential trace elements in different areas is discussed in the light of known metabolic functions of these elements.

Adult

Daily dietary intake of copper, zinc, and selenium of exclusively breast-fed infants of middle-class women in Burundi, Africa.

Copper (Cu), zinc (Zn), and selenium (Se) in human milk of middle-class Burundian women during the first 10 mo of lactation have been determined. Wet acid digestion, using nitric and perchloric acids, and atomic absorption spectrometric analysis have been used. Daily intakes have been calculated and proven to decrease from 0.39 +/- 0.05 (colostrum) to 0.16 +/- 0.02 (mature milk), 2.3 +/- 0.3 (colostrum), to 1.2 +/- 0.2 mg (mature milk) and 10.9 +/- 1.5 (colostrum) to 5.3 +/- 0.8 micrograms (mature milk) for Cu, Zn, and Se, respectively. Since values for this African country are nonexistent, intake levels are compared with literature data and found to be somewhat higher than those observed in other poorly nourished countries. The recommended safe and adequate daily intake for infants of 0-6 mo of age, as proposed by the National Research Council of the USA, is only met for Burundian infants < 1 mo of age. The function of copper (Cu) and zinc (Zn) as essential trace elements has been known for quite a number of years (1). Also, selenium (Se) is a trace element essential for the activity of glutathione peroxidase (2) and type I iodothyronine 5-deiodinase (3). For all three elements, an adequate intake is necessary for satisfactory infant growth and development (4). In view of the almost total lack of relevant data on Burundi (Africa), we have determined Cu, Zn, and Se in human milk of middle-class Burundian women during the first 10 mo of lactation (5). The aim of this study is to assess infants' elemental intake for this country and compare this with literature data on trace elemental intake of exclusively breast-fed infants.

Adult

New essential trace elements for the life sciences.

The possible importance of some new essential trace elements in nutrition is discussed. Most likely, insufficient intake of a specific trace element becomes obvious only when the body is stressed in some way that enhances the need for that element; this has been supported by recent findings with selenium. The trace elements boron and copper may be of nutritional significance in a manner similar to selenium. When the diets of animals and humans are manipulated to cause possible changes in cellular integrity or in hormone responsiveness, a large number of responses to dietary boron occur. The findings indicate that boron is important for optimal calcium and, thus, bone metabolism. High dietary cystine and fructose exacerbate the signs of copper deficiency in rats; this indicates that the response to copper deficiency by humans would vary with the amino acid and carbohydrate composition of the diet. There is some evidence that chromium, molybdenum, nickel, arsenic, and vanadium may also be of nutritional significance under stress conditions. In other words, an increasing number of studies have been performed that have examined the importance of trace element nutriture in various forms of nutritional, metabolic, hormonal, or physiologic stress in animals and humans. These studies indicate that situations will be found in which a trace element is of nutritional significance. It is likely that some of the trace elements are more important in human nutrition than is now generally acknowledged.

Animals

Sequences involved in accurate and efficient transcription of human c-myc genes microinjected into frog oocytes.

By microinjecting a series of deletion mutant constructs into Xenopus laevis oocytes, transcriptional control regions, two promoters, of the human c-myc gene were defined. In the case of the first promoter, sequences between -60 and -37 relative to the transcription start site contained an element essential for promoter activity. In the case of the second promoter, sequences between -66 and -56 relative to the initiation site appeared to be involved in accurate and efficient transcription. In both cases, the region identified as the essential promoter element contained GGGCGG or GGCGGG,GC box-like sequences, suggesting that c-myc gene promoter activity may be controlled by transcription factor Sp1 binding in the microinjected oocytes.

Animals

The suitability of transfer coefficients used for stochastic calculations in radioecology.

In radioecology, stochastic calculations are used to an increasing extent. It is shown that transfer coefficients which are defined as concentration ratios are not suited for stochastic calculations, at least for essential elements and their antagonists. The reason is that essential elements are regulated in plants and animals whereby their concentrations vary within narrow limits, rather independent of the concentrations in the source compartment. For a more accurate description of the transfer of radionuclides, it is proposed to include the concentrations of the essential elements in the source and target compartments into the transfer equation which leads to the specific activity model. This model has already been proposed by Comar et al. in 1956. It seems to work accurately for the transfer into animals and their products as well as into plants. Examples of its applicability are presented and discussed. Furthermore stochastic calculations seem to be more reasonable with this model.

Animals

Risk assessment of essential trace elements: new approaches to setting recommended dietary allowances and safety limits.

By definition, every essential trace element must have a range of intakes safe from toxicity but adequate enough to meet nutrition requirements. That range is part of the total dose-response curve and its lower and upper limits are delineated on the basis of nutrition and toxicology data, respectively. Close coordination of activities to set these limits is necessary to avoid recommendations that are either impractical (narrow zones of safe and adequate intakes) or contradictory (overlapping limits, i.e., no zones of safe and adequate intakes).

Biological Availability

[Essential trace element and skin diseases].

We have described herein various skin diseases which are caused by essential trace element deposition, deficiency, allergy, etc. Pigmentation of hemochromatosis and hemosiderosis are recognized by hemosiderin deposition in the dermis. Acrodermatitis enteropathica is caused by a deficiency of Zn and is classified as either a hereditary type or as an acquired type. The former is autosomal recessive and the latter is caused by a low intake of Zn. Wilson's disease and Menkes' kinky hair syndrome, which are caused by abnormal Cu metabolism, elicit hyperpigmentation and morphological changes of the hair, respectively. It appears that kinky hair formation results from low activity of sulfhydryl oxidase which is a Cu enzyme. Bowen disease, which is carcinoma in situ, is caused by As toxicosis. Some cases, such as palmo-plantar-pustulosis, lichen planus and oral lichen planus are caused by allergies to metals used in dental surgery, especially Ni, Co, Cr and Sn.

Bowen's Disease

Silicon as an essential trace element in animal nutrition.

Within the last decade silicon has been recognized as participating in the normal metabolism of higher animals and as being an essential trace element. Silicon is found to perform an important role in connective tissue, especially in bone and cartilage. Bone and cartilage abnormalities are associated with a reduction in matrix components, resulting in the establishment of a requirement for silicon in collagen and glycosaminoglycan formation. Silicon's primary effect in bone and cartilage is on the matrix, with formation of the organic matrix appearing to be more severely affected by silicon deficiency than the mineralization process. Additional support for silicon's metabolic role in connective tissue is provided by the finding that silicon is a major ion of osteogenic cells and is present in especially high concentrations in the metabolically active state of the cell; furthermore, silicon reaches relatively high levels in the mitochondria of these cells. Further studies also indicate that silicon participates in the biochemistry of the subcellular enzyme-containing structures. Silicon also forms important interrelationships with other elements. Although it is clear from the body of recent work that silicon performs a specific metabolic function, a structural role has also been proposed for it in connective tissue. A relationship established between silicon and ageing probably relates to glycosaminoglycan changes.

Animals