Multitracer Screening: Brain Delivery of Trace Elements by Eight Different Administration Methods

Trace elements are closely associated with the normal functioning of the brain. Therefore, it is important to determine how trace elements enter, accumulate, and are retained in the brain. Using the multitracer technique, which allows simultaneous tracing of many elements and comparison of their behavior under identical experimental conditions, we examined the influence of different administration methods, i.e., intravenous (IV), intraperitoneal (IP), intramuscular (IM), subcutaneous (SC), intracutaneous (IC), intranasal (IN), peroral (PO), and percutaneous (PC) administration, on the uptake of trace elements. A multitracer solution containing 16 radionuclides (i.e., ⁷Be, ⁴⁶Sc, ⁴⁸V, ⁵¹Cr, ⁵⁴Mn, ⁵⁹Fe, ⁵⁶Co, ⁶⁵Zn, ⁷⁴As, ⁷⁵Se, ⁸³Rb, ⁸⁵Sr, ⁸⁸Y, ⁸⁸Zr, ^95mTc, and ¹⁰³Ru) was used. The results indicated that the ⁸³Rb brain uptake rate with intranasal administration was approximately twice those obtained with the other administration methods. This result indicated that a portion of Rb was delivered into the brain circumventing the blood circulation and that delivery could be accomplished mainly by olfactory transport. Multitracer screening of trace element delivery revealed differences in brain uptake pathways among administration methods.     

Correlation between serum cholesterols and trace element uptake in liver,kidney, and blood of hypercholesterolemic mice

The radioactive multitracer technique was applied to the simultaneous determination of the uptake of 17 trace elements (Be, Na, Sc, V, Cr, Mn, Fe, Co, Zn, As, Se, Rb, Sr, Y, Zr, Nb, and Ru) in the liver, kidney, and blood of hypercholesterolemic model mice. The uptakes of Be, Sc, V, Cr, Fe, As, Rb, Y, Zr, Nb, and Ru in liver increased with an increasing feeding period of a cholesterol-rich diet, whereas the uptakes of Zn and Se decreased. Feeding of the diet resulted in a marked increase in serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol. The metabolism of trace elements between cholesterolemic and normal mice was compared with respect to their serum cholesterol levels. A significant positive correlation was found between the concentration of serum triglycerides and liver uptakes of Cr, Fe, and As and a negative correlation for the uptake of Zn. A significant positive correlation was found between the concentrations of serum high- and low-density lipoprotein cholesterols and kidney uptakes of Cr and Rb. A negative correlation was found between the uptake of Be in the blood and the concentration of serum triglycerides. These results suggest that cholesterolemia have some specific effects on the metabolism of some elements.     

Preliminary study on the relationship between osteoporosis and trace elements with rat models

Thirty rats were divided randomly into five groups and fed with different feeds. They were killed after 2 mo. Right thighs of these rats were taken as samples. Bone mineral densities of these samples were measured by the double-energy x-ray bone mineral densitometer, and trace elements contents of the samples were analyzed by neutron activation analysis. Results of the experiments showed that some elements were well correlated with others, and there were obvious variances between some elements of the normal group and those of other four groups.     

A survey of trace elements in pteridophytes

Concentration of 11 trace elements (Ca, Sc, Cr, Fe, Co, Zn, Rb, Cs, Ba, La, and Ce) in 96 pteridophytes (fern and fern ally species) was determined by instrumental neutron activation analysis to evaluate a concentration range for each element and also to find species characteristic in the uptake of trace elements. Asplenium trichomanes was found to accumulate Sc, Cr, and Co to the highest concentrations among 96 pteridophytes. The highest concentration of Ca and Zn was observed for Asplenium obscurum. The other Pteridophytes exhibited only one element whose concentration was the highest. A positive correlation was found between the concentrations of Fe and Sc, and also between the concentrations of Cr and Co. The remarkable accumulation of lanthanides (La and Ce) was observed mainly in diversifying genera (Polystichum and Dryopteris in Dryopteridaceae, Diplazium in Woodsiaceae, and Asplenium in Aspleniaceae).     

Uptake and distribution of trace elements in maturing soybean

The uptake and translocation of trace elements in maturing soybean plants cultivated on soil were studied over 360 h under diurnal conditions after the administration of a multitracer. The contents (%/g) of Co, Se, Rb, Sr, Ru, Rh, and Cs in all the leaves and stems collected from each node increased up to around 200 h after the administration of the multitracer and then decreased with time. The contents of Zn, Tc, and Re in the leaves and Zn in the stems continuously increased up to 360 h, but Tc and Re in the stems showed maximum content. This observation suggests the translocation of these elements from old leaves to growing leaves via stems. The relationship between the content (%/g) of an element in the seeds and pods, and the cultivation time varied depending on the kind of element and on the growth steps. Mathematical analyses were applied to the behavior of the elements in the soybean. The time dependence of the uptake rate (%/g/h) and distribution of elements in each part of the plant were characteristic of the element.     

Isolation of giant mitochondrial nucleoids from the yeastSaccharomyces cerevisiae

Summary The yeast cellsSaccharomyces cerevisiae grown up to stationary phase under either anaerobic conditions, or aerobic conditions in the presence of a respiratory inhibitor, antimycin A, had distinctive giant mitochondrial nucleoids (mt-nucleoids) (apparent diameter 0.6–0.9 m) in contrast with the small mt-nucleoids (apparent diameter 0.2–0.4 m) in respiratory-sufficient cells grown aerobically, as revealed by DAPI-fluorescence microscopy. The cytoplasmic respiratory-deficient cells (rho^– cells), which were induced by treatment of wild-type cells with ethidium bromide, showed both giant and small mt-nucleoids of irregular size. In order to examine the structural and functional differences between giant and small mt-nucleoids, the former were successfully isolated from spheroplasts of three different cells by differential centrifugation and centrifugation on a discontinuous sucrose gradient. The isolated giant mt-nucleoids were intact in the morphology and were free of significant contamination by nuclear chromatin. The number of protein components involved in each of three different giant mt-nucleoids was similar to the number in small mt-nucleoids from aerobically grown cells, though a few noticeable differences were also recognized. DNA-binding proteins with molecular masses of 67 kDa, 52 kDa, 50 kDa, 38 kDa, 26 kDa, and 20 kDa were the main components of small mt-nucleoids from aerobically grown cells as detected by chromatography on native DNA-cellulose. In contrast, the 67 kDa and 52 kDa proteins were hardly detected in corresponding fractions of giant mt-nucleoids from anaerobically grown cells and from rho^– cells grown aerobically. On the other hand, mt-nucleoids from aerobically grown cells in the presence of antimycin A seemed to lack the 67 kDa protein but to have a small amount of the 52 kDa protein. This is the first demonstration of the variance of protein species involved in yeast mt-nucleoids according to the respiratory activity of mitochondria.     

Uptake and distribution of trace metal elements in wheat seedlings

The uptake and distribution of eight metallic elements were examined in wheat seedlings for a period of 12 d with a radioactive multitracer technique. The radioactive nuclides of the seedlings were simultaneously determined by γ-ray spectrometry. All of the elements studied were taken up by the wheat seedlings and mainly accumulated in the roots. Only some elements were transported to shoots and leaves of the seedlings or bound to leaf proteins, and two elements were transported into the chloroplast. Uptake of most elements reached a maximum on the fifth or the eighth day and then gradually decreased afterward. In the cases of ^95mTc and ⁷²Se, the uptake increased continuously within 12 d without the peak uptake. The change of elemental concentrations was dependent on uptake and excretion rates. The dynamics of metal elements taken up by the wheat seedlings and their distribution in roots, shoots, and leaves were different for each element, suggesting that it may depend on the characteristics of the elements.     

Age-related changes in the concentrations of major and trace elements in the brain of rats and mice

Age-related changes in the concentrations of constituent elements in the brains of rats and mice 1 wk to 24 mo old were determined with inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES). Seventeen elements could be determined with reasonable accuracy and reproducibility. They were P, K, Na, Mg, Ca, Fe, Zn, Cu, Rb, Al, Mn, Sr, Mo, Co, Pb, Cs, and Cd in order of concentrations in the adult rat brains. In these elements, six major elements (P, K, Na, Fe, Mg, Ca) were determined with ICP-AES and the others with ICP-MS. The concentrations of each element and the pattern of age-related changes were similar between the rat and mouse brains. The elements of which concentrations decreased with aging were K and Rb. On the other hand, the concentrations of some metal elements, including Fe, Cu, Sr, and Co, appeared to increase with growth and aging. The concentrations of other elements were relatively constant throughout the age examined.     

Role of trace elements in primary arterial hypertension

A negative relationship between water hardness and cardiovascular mortality rate was demonstrated and became a source of interest regarding minerals and trace metals in the pathogenesis of atherosclerosis, cardiovascular diseases, and arterial hypertension. Higher incidences of sudden death, cerebrovascular diseases, arterial hypertension, and coronary heart disease have been reported in soft water areas. A major research effort has been devoted to the problem in an attempt to find a protective factor in hard water or a detrimental factor or element in soft water. The roles of calcium, magnesium, cobalt, lithium, vanadium, silicon, manganese, and copper have been considered potentially beneficial, whereas those of cadmium, lead, silver, zinc, and antimony have been considered potentially harmful. Cobalt and zinc have been attributed both roles. In the present article, the role of trace quantities of several elements in mineral water in the etiopathogenesis of primary arterial hypertension is reviewed. An erratum to this article is available at .     

INAA of trace elements in colorectal cancer patients

The concentration of trace elements in samples of both colorectal cancer tumors and normal tissues of a Mexican population were irradiated for 30 s and 4 h and their elemental content were measured by instrumental neutron activation analysis. Ca, Cu, Co, I, Mg, Se, Fe, Zn, Hg, Ba, and Cr were analyzed. Alterations in Co, Fe, I, and Ba were found in tumors with respect to normal tissues.     

Essential trace elements in humans

Serum arsenic concentrations of persons suffering from renal failure and undergoing hemodialysis treatment (n=85) and of healthy controls (n=25) were determined by hydride-generation AAS technique after microwave digestion. The results were evaluated by comparing the values of both groups, considering physiological factors and individual data, as well as comorbid conditions of the hemodialysis (HD) patients. Serum arsenic levels were diminished in the patient group compared with controls (mean values 8.5±1.8 ng/mL vs 10.6±1.3 ng/mL). Furthermore, additional diseases within the hemodialysis group, particularly injuries of the central nervous system (CNS), vascular diseases, and cancer, were correlated to occasionally markedly decreased serum arsenic concentrations. It was concluded that arsenic homeostasis is disturbed by HD treatment and certain additional diseases. Desirable arsenic concentrations in the body seem to be reasonable. This consideration results in the conclusion that arsenic could play an essential role in human health. Thus, reference arsenic concentrations in different human tissues and body fluids should be established in order to recognize not only arsenic intoxication, but also arsenic deficiency. Perhaps arsenic deficiency contributes to the increased death risk of HD patients, and therefore, arsenic supplementations for patients with extremely low serum arsenic concentrations should be taken into account.     

天门冬属九种药用植物的氨基酸和微量元素分析

百合科(Liliaceae)天门冬属(Asparagus (Tourn.)L.)植物具有悠久的药用历史,如天门冬(A.cochinchinesis (Lour) Merr.)早在汉代《神农本草经》中就被列为上品,具有滋阴、润燥、降火、止咳等功效。现代药理研究及临     

The genetics of aging in the yeastSaccharomyces cerevisiae

The yeastSaccharomyces cerevisiae possesses a finite life span similar in many attributes and implications to that of higher eukaryotes. Here, the measure of the life span is the number of generations or divisions the yeast cell has undergone. The yeast cell is the organism, simplifying many aspects of aging research. Most importantly, the genetics of yeast is highly-developed and readily applicable to the dissection of longevity. Two candidate longevity genes have already been identified and are being characterized. Others will follow through the utilization of both the primary phenotype and the secondary phenotypes associated with aging in yeast. An ontogenetic theory of longevity that follows from the evolutionary biology of aging is put forward in this article. This theory has at its foundation the asymmetric reproduction of cells and organisms, and it makes specific predictions regarding the genetics, molecular mechanisms, and phenotypic features of longevity and senescence, including these: GTP-binding proteins will frequently be involved in determining longevity, asymmetric cell division will be often encountered during embryogenesis while binary fission will be more characteristic of somatic cell division, tumor cells of somatic origin will not be totipotent, and organisms that reproduce symmetrically will not have intrinsic limits to their longevity.     

Non-random distribution of the Ty1 elements within nuclear DNA of Saccharomyces cerevisiae

Ty1 homologous sequences appear to be non-randomly distributed among different density classes of nuclear yeast DNA. Characteristic patterns of Ty1 containing EcoRI fragments can be generated from the various DNA fractions. The sequences are particularly enriched in the A + T rich part of the main nuclear DNA fraction, while the frequency in the rDNA containing heavy satellite DNA is low. The transposon however, seems to be present in this dense fraction, at least for some strains.     

Studies on some trace and minor elements in blood

Blood is one of the widely used specimens for biological trace element research because of its biological significance and ease of sampling. We have conducted a study of the blood of the Kalpakkam township population for trace and minor elements. For this purpose, analytical methods have been developed and standardized in our laboratory for the elemental analysis of blood plasma and red cells. Inductively coupled plasma-mass spectrometry (ICP-MS), a relatively new technique, has been applied for the analysis of trace elements. Details regarding spectral interference and matrix interference encountered in the analysis of blood and the methods of correcting them have been discussed. Flame atomic absorption spectrometry (AAS)/atomic emission spectrometry (AES) has been applied for the determination of minor elements. Precision and accuracy of these methods have also been discussed.     

Serum changes in trace elements during thyroid cancers

The objective was to examine changes in trace elements due to thyroid cancer in humans. Serum levels and tissue contents of trace elements (Zn, Cu, Mn, Mg, Fe and Se) were measured in 43 patients with thyroid cancer before and 4 days after surgery were compared to normal values. The serum levels of zinc in cancer patients were lower than those of normal subjects. Surgical removal of the cancer resulted in the restoration of these levels. Although serum Cu levels in patients were not different from normal, but post-operatively these levels rose significantly (p < 0.001). Levels of Fe, Mg and Mn were significantly lower (p < 0.001) post-operatively. There was no significant change in Serum Se levels. The thyroid tissue contents of these trace elements did not show a difference between the normal (Juxta-tumor) thyroid tissue and the cancerous lesion. Out of the six trace elements examined, the decrease of serum levels of zinc in cancer patients may be linked to the disease condition. It is suggested that this change: (a) may be used to demonstrate successful cancer surgery and (b) may have implications for a long-term follow-up of thyroid cancer patients.     

Determination of plasma trace elements in tumor-bearing animals by proton-induced X-ray emission spectroscopy

Although altered levels of circulating essential trace elements are known to accompany malignant disease, the lack of sensitivity of conventional detection methods has generally limited their study to clinical conditions involving extensive disease (i.e., significant tumor burden). As such, the application of altered trace element levels as potential prognostic guides or as response indicators subsequent to treatment has been of limited use. During this study, proton-induced X-ray emission spectroscopy was evaluated as a tool to determine trace element imbalances in a murine tumor model. Using plasma from C57B1/6 mice bearing the syngeneic Lewis lung carcinoma (LLCa), levels of Fe, Cu, and Zn, as well as changes in the Cu/Zn ratio, were measured in animals carrying an increasing primary tumor burden. The plasma levels of Fe, Cu, and Zn were found to decrease significantly 7 d following implants of LLCa cells with no significant change observed in the Cu/Zn ratio. By d 21, however, an increase in the Cu/Zn ratio was found to accompany increased growth of the LLCa tumor; the plasma levels of Cu had returned to normal levels, whereas both the Fe and Zn plasma levels remained lowered. Collectively, the results suggest that although a net change in individual plasma trace element concentrations might not be accurately associated with tumor growth, a clear relationship was established between the Cu/Zn ratio and tumor size.     

Levels of some trace elements and rheumatoid factor in sheep with brucellosis

Brucellosis is a zoonotic disease that is encountered in sheep rather frequently. In this study, 100 sheep diagnosed with brucellosis that had aborts and 40 healthy sheep were used as materials. Analyses for Cu, Zn, Fe, Cr, Ca, Mg, and K were performed with the atomic absorption spectrophotometric method on blood collected from vena jugularis of all the sheep and rheumatoid factor levels were determined by the nephelometry method. Although it was found that Cu, Ca, and rheumatoid factor values in the sera of the sheep with brucellosis were high when compared to the control group (p<0.001, p<0.05, p<0.001, respectively), their serum Zn values were low (p<0.05). No significant changes in serum Cr, Fe, K, and Mg levels were found.     

Serum and tissue levels of six trace elements and copper/zinc ratio in patients with cervical cancer and uterine myoma

The aim of this study is to investigate the relationship between trace elements and the incidence of cervical cancer. Tissue and serum levels of six elements (Cu, Zn, Fe, Mn, Ca, and Se) and the Cu/Zn ratio in 40 cases of patients with cervical cancer, 30 cases of uterine myoma, and 50 healthy subjects were measured by atomic absorption spectrophotometry; the selenium content was determined by atomic fluorescence spectrometry. The results showed that the tissue contents of Zn, Se, and Ca were significantly lower and the Cu and Fe concentrations and Cu/Zn ratio were significantly higher in cervical cancer tissue than that for paired nonlesion tissue (p<0.02 and p<0.001, respectively). The serum levels of Zn, Se, Ca, and Fe were lower and Cu and Mn levels and Cu/Zn ratio were higher in patients with cervical cancer than in healthy subjects (p<0.01 and p<0.001, respectively) and in the uterine myoma group compared with healthy subjects (p< 0.05–0.001). There are no significant differences in the contents of six elements and the Cu/Zn ratio between uterine myoma tissue and paired nonlesion tissue. The results showed also that the Fe level and Cu/Zn ratio were significantly higher and the Zn and Se levels were significantly lower in cervical cancer tissue than in uterine myoma tissue (p<0.01 and p<0.001, respectively). The serum Cu level and Cu/Zn ratio were significantly higher in the cervical cancer group than the uterine myoma group (p<0.01). Data were also analyzed using multivarate logistic regression. After adjustment for age, occupation, life habit, and other covariates for the development of cervical cancer, the odds ratios were 22.64 (95% confidence interval [CI]: 5.64–90.88, p=0.001) for Cu, 0.11 (95% CI: 0.034–0.373; p=0.005) for Zn, and 0.60 (95% CI: 0.36–0.99, p=0.01) for Se. Thus, the serum and tissue levels of Cu increase and the deficiency of Zn and Se may be risk factors for the development of cervical cancer.     

Competitive inhibition and selectivity enhancement by Ca in the uptake of inorganic elements (Be, Na, Mg, K, Ca, Sc, Mn, Co, Zn, Se, Rb, Sr, Y, Zr, Ce, Pm, Gd, Hf) by carrot (Daucus carota cv. U.S. harumakigosun)

We investigated the uptake of inorganic elements (Be, Na, Mg, K, Ca, Sc, Mn, Co, Zn, Se, Rb, Sr, Y, Zr, Ce, Pm, Gd, and Hf) and the effect of Ca on their uptake in carrots (Daucus carota cv. U.S. harumakigosun) by the radioactive multitracer technique. The experimental results suggested that Na, Mg, K, and Rb competed for the functional groups outside the cells in roots with Ca but not for the transporter-binding sites on the plasma membrrane of the root cortex cells. In contrast, Y, Ce, Pm, and Gd competed with Ca for the transporters on the plasma membrane. The selectivity, which was defined as the value obtained by dividing the concentration ratio of an elemental pair, K/Na, Rb/Na, Be/Sr, and Mg/Sr, in the presence of 0.2 and 2 ppm Ca by that of the corresponding elemental pair in the absence of Ca in the solution was estimated. The selectivity of K and Rb in roots was increased in the presence of Ca. The selectivity of Be in roots was not affected, whereas the selectivity of Mg was increased by Ca. These observations suggest that the presence of Ca in the uptake solution enhances the selectivity in the uptake of metabolically important elements against unwanted elements.