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1.
Several trace elements are essential nutrients for an optimal functioning of organs and tissues, including the immune system and the heart. The pathogenesis of some heart diseases has been associated with changes in the balance of certain trace elements. The etiology of nonrheumatic aortic valve sclerosis is unknown, however. A prospective study was performed on trace element changes in the sclerotic valves of 46 patients undergoing surgical aortic valve replacement because of aortic stenosis. Valves from 15 individual forensic cases without known cardiac disease served as controls. The contents of 15 trace elements (Al, As, Cd, Ca, Co, Cu, Fe, Pb, Mg, Mn, Hg, Se, Ag, V, and Zn) were measured by inductively coupled plasma — mass spectrometry (ICP-MS) of aortic valve tissue from both patients and forensic autopsy controls. Some trace elements showed similar concentrations in sclerotic and control valves (Al, Ag, Hg, Mn), whereas a few were moderately changed in the sclerotic as compared with the control valves, including an increase in Cd by 52% (p<0.05) and decreases in Se by 14% (p<0.05), in V by 42% (p<0,001), and in Cu by 45% (p<0.001). However, there were pronounced increases (p<0.001) in the concentrations of As (5-fold), Ca (70-fold), Co(10-fold), Fe (20-fold), Pb (8-fold), Mg (20-fold), and Zn (10-fold) in the sclerotic valves. Thus, sclerotic aortic valve disease is associated with a pronounced imbalance in several trace elements of well-known importance for cardiovascular and immune function as well as in trace elements with hitherto unknown significance.  相似文献   

2.
An association between Chlamydia pneumoniae and atherosclerotic cardiovascular diseases has been suggested. However, other factors may interact in the pathogenesis of valve sclerosis. Therefore, trace elements important for C. pneumoniae growth and host defense and markers of C. pneumoniae infection were studied in sclerotic valves and serum. Forty-six patients undergoing surgical valve replacement due to advanced aortic sclerosis were prospectively studied. Valves from 15 forensic cases with no heart valve disease and plasma from 46 healthy volunteers served as controls. C. pneumoniae was detected in 16/46 (34.8 %) sclerotic valves and in 0/15 forensic controls. IgG and IgA antibodies to C. pneumoniae were present in 54.3% and 26.1 % patients, respectively. In the patients’ valves, iron, magnesium, and zinc each correlated to calcium, a marker of the histopathological severity of disease. Patients showed 10- to 70-fold increases of these trace elements in valves and an increased copper/zinc ratio in serum. In a majority of aortic sclerosis patients, one of several markers of C. pneumoniae infection were detected and all patients had a disturbed trace element balance in valves and serum suggestive of active immune process and infection. The pattern of trace element changes was essentially similar regardless of positive makers of C. pneumoniae, suggesting a similar etiopathogenesis in both subgroups. The 20-fold increase in iron, essential for C. pneumoniae growth, in sclerotic valves suggests a new possible link to this infection in aortic sclerosis.  相似文献   

3.
4.
The occurrence of trace elements in the teeth of Steller sea lions (Eumetopias jubatus) collected from the North Pacific from 1968 to 1999 is described. Using particle-induced X-ray emission analysis, we detected eight trace elements: Ca, Mn, Fe, Cu, Zn, Br, Sr and Pb. We used a general linear model to evaluate long-term trends of trace element accumulation. Zn (Zn/Ca) and Fe (Fe/Ca) levels both varied during the last three decades, and showed significant differences between animals of different age (Fe/Ca), season (Zn/Ca and Fe/Ca), and sex (Zn/Ca); both Zn/Ca and Fe/Ca ratios were higher in young males than older males. Pb was detected in 39% of the samples from Hokkaido (Japan) and 22% of those from Alaska. The high levels of Pb recorded in 1975 were thought to be related to the use of leaded gasoline during the 1970s. Our results indicate that the levels of trace elements in the teeth of Steller sea lions can be used as indicators of temporal and spatial variations of trace element pollution.  相似文献   

5.
The concentrations of trace elements are closely related to tumor genesis, progression, and therapy. In order to establish the extent to which trace elements apply to lung cancer, 15 trace elements were determined in 60 lung tissue samples from residents of Xuanwei and Fuyuan, two counties with extremely high lung cancer incidences in Yunnan province, China. The results indicated that the levels of V, Fe, Zn, Cd, Ni, Cu, Se, and Pb in the lung cancer tissues were significantly different from those in benign tissues. Among the eight elements, the levels of V, Fe, Zn, and Cd in the lung cancer tissues were lower than those in the benign tissues, while those of Ni, Cu, Se, and Pb were higher. Multiple conditional logistic regression showed that among the 15 elements, Cu, Pb (β > 0, OR > 1), and Zn (β < 0, OR < 1) were closely related to the lung cancer. Cu and Pb were classified as risk factors for local lung cancer and Zn was identified as a protective factor. The results obtained will provide dietary suggestions in terms of how to reduce lung cancer risks by appropriately balancing the intakes of certain trace elements especially for individuals who are from those two counties.  相似文献   

6.
Most infectious diseases are accompanied by changed levels of several trace elements in the blood. However, sequential changes in trace elements in tissues harbouring bacterial infections have not been studied. In the present study the respiratory pathogen Chlamydophila pneumoniae (C. pneumoniae), adapted to C57BL/6J mice, was used to study whether the balance of trace elements is changed in infected organs. Bacteria were quantitatively measured by real-time PCR in the blood, lungs, liver, aorta, and heart on days 2, 5, and 8 of the infection. Concentrations of 13 trace elements were measured in the liver, heart, and serum by inductively coupled plasma mass-spectrometry (ICP-MS). Infected mice developed expected clinical signs of disease and bacteria were found in lungs, liver, and heart on all days. The number of bacteria peaked on day 2 in the heart and on day 5 in the liver. The copper/zinc (Cu/Zn) ratio in serum increased as a response to the infection. Cu increased in the liver but did not change in the heart. Iron (Fe) in serum decreased progressively, whereas in the heart it tended to increase, and in the liver it progressively increased. C. pneumoniae may thus cause a changed trace element balance in target tissues of infection that may be pivotal for bacterial growth.  相似文献   

7.
Concentrations of trace elements in newborns, infants, and adults may be significantly different from each other. Serum trace element reference ranges for different age groups are of value for diagnostic purposes. Inductively coupled plasma-mass spectrometry was applied to the determination of the 21 trace elements Ba, Be, Bi, Ca, Cd, Co, Cs, Cu, La, Li, Hg, Mg, Mn, Mo, Pb, Rb, Sb, Sn, Sr, TI, and Zn in a total of 117 sera of individuals representing different age groups. After microwave-assisted acid digestion with high-purity reagents, 20 umbilical cord sera, 5 sera of fully breast-fed infants, 6 sera of formula-fed infants, 66 sera of patients suffering internal diseases, and 20 sera of healthy blood donors were analyzed for trace elements. One serum and two whole-blood reference materials were analyzed for quality control. Experimental concentrations were in good agreement with certified values. Umbilical cord serum concentrations of the essential elements Ca, Co, Cu, and Mg and of the nonessential and toxic elements Ba, Be, Li, Pb, and Sb were elevated compared to the elemental concentrations in the sera of infants and adults. Serum levels of Ba, Ca, Co, Mn, Pb, and Sb of infants were much higher and serum Cu was significantly lower than in adults. Serum Cu increased significantly with age (newborns: 353 microg/L; infants: 755 microg/L; healthy adults: 810 microg/L), whereas for other trace elements no age-dependence could be established.  相似文献   

8.
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.  相似文献   

9.
The present study was undertaken in order to study the effects of the broad-acting chelating agent CaNa2-EDTA on plasma trace elements and cardiovascular function in anesthetised New Zealand White rabbits. Trace elements are important for cardiovascular and immune functions and the rabbit is a well-accepted species in cardiovascular studies. The test compound CaNa2-EDTA was administered intravenously to rabbits at single doses of 4, 20, and 100 mg/kg. In addition, at 20 mg/kg, the effects of a second dose after 3 h were also investigated. Heart rate, blood pressure and body temperature were continuously monitored during a 6-h interval after injection of CaNa2-EDTA. Immediately before administration (−1 min) and at 3 and 6 h over the period of the experiment, the plasma cytokine response (tumor necrosis factor-α) and trace elements (Mn, Cu, Zn, Se, Ag, Cd, Hg, Pb) were measured. Regardless of dose, blood pressure was found to decrease, but no corresponding changes in heart rate were observed. Both a repeated administration of 20 mg/kg and a single dose of 100 mg/kg were detrimental and caused severe cardiovascular effects and lethality. α-TNF tended to increase, though only at 100 mg/kg. The electrocardiogram and body temperature were not affected by the treatment. The most pronounced trace element change was a dose-dependent increase in Mn that was equally pronounced at all time-points after the dose. There was an initial decrease in Cd at low dose levels (4 and 20 mg/kg) that turned into an increase after 6 h at 20 mg/kg and from 2 h at 100 mg/kg. A similar pattern with pronounced decreases at low dose levels was observed for Zn. Cu decreased similarly at all dose levels. For the other trace elements, no or inconsistent effects were observed. This model allows the study of concomitant cardiovascular and trace element changes during treatment with drugs and chelating agents preceding a possible lethal end point and associated pathophysiologic changes.  相似文献   

10.
Using inductively coupled plasma mass spectrometry (ICP-MS) based analytical procedures, the concentration of several trace elements (Mn, As, Pb, Co, Ni, Cu, Zn and Se) was determined in human milk samples collected from a group of healthy lactating Portuguese women (n=44), both on the 2nd day postpartum (i.e., colostrum; n=34) and at 1 month postpartum (i.e., mature milk; n=19). Blood samples (n=44), collected on the 2nd day after parturition, were also analyzed for the same trace elements. No major correlations were observed between the levels of the analyzed trace elements in blood and colostrum samples. All the studied elements, except for Co, Pb and Ni, showed a significant trend for a decrease in concentration in milk during the first month of lactation. This trend was more pronounced for Zn and Se, whose levels decreased to approximately 23% and 44% of their initial mean concentration, respectively. With the exception of Co (r=0.607) and Zn (r=0.487), no significant correlations were observed when comparing the levels of each trace element between samples of colostrum and mature milk. Several inter-element correlations were found within each type of milk sample. The most significant were: (i) Se vs Cu (r=0.828) and Se vs Co (r=0.605) in colostrum samples and (ii) Ni vs Pb (r=0.756), Ni vs Mn (r=0.743) and Se vs Co (r=0.714) in mature milk samples. An inverse correlation between Zn and Se was also found in both types of milk sample; however, it only reached statistical significance for mature milk (r=-0.624).  相似文献   

11.
This study is aimed to investigate the transfer of potentially toxic trace elements from soils to plants grown under the impact of Alaverdi's mining complex and assess the related dietary exposure to local residents. Contamination levels of potentially toxic trace elements (Cu, Ni, Pb, Zn, Hg, As, Cd) in soils and plants were determined and afterwards, transfer factors, estimated daily intakes, target hazard quotients, and hazard indexes were calculated.

Some trace elements (Pb, Zn, Cd) exceeded the maximum allowable levels. EDIs of Cu, Ni, Hg for the majority of studied fruits and vegetables exceeded the health-based guideline values. Meanwhile, in case of combined consumption of the studied food items, the estimated cumulative daily intakes exceeded health-based guideline values not only for the aforementioned trace elements but also for Zn in the following sequence: Zn > Hg > Ni > Cu. HI > 1 values highlighted the potential adverse health effects for local population through more than one trace element.

Detailed investigations need to be done for the overall assessment of health risks, taking into consideration not only adverse health effects posed by more than one toxic trace element but also through other exposure pathways.  相似文献   


12.
This work is an application of energy dispersive X-ray fluorescence (EDXRF) as analytical technique for trace element determination in human tissues. Potassium (K), calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), bromine (Br), rubidium (Rb) and lead (Pb) were determined directly in blood samples from 66 mothers at delivery after full-term pregnancies. The corresponding 66 cord-blood samples of the newborns were also analysed, in order to find element correlations between maternal and newborn blood at birth. The studied samples were obtained from mothers aged between 15 and 39 years old, the gestational age being between 35 and 41 weeks and the newborns' weight between 2.310 and 4.310 kg. Samples were lyophilised and analysed without any chemical treatment. Very low levels of Pb were found both in maternal and fetal cord blood samples. Cu values ranged from 3 to 13 microg g-1, both for mothers and children. A correlation between Cu and Fe concentrations in maternal and fetal cord blood was found. Zn is considered as one of the key elements in newborn health. Concentrations between 10 and 40 microg g-1 were measured. A positive correlation between Br levels in mothers and children was observed. Positive correlations for mothers were observed between Zn and Rb as well as K and Fe. The corresponding correlations in fetal cord blood samples were not observed, however positive correlations were found between Ca and K; Cu and Fe. The mean concentrations for each element were similar in maternal and in fetal cord blood, except for Cu and Zn, being higher in maternal samples. No correlations between element concentrations and pathologies of the mothers were observed.  相似文献   

13.
The purpose of this study is to evaluate the cord blood level of toxic and trace elements and to identify their determinants in Terai, Nepal. One hundred pregnant women were recruited from one hospital in Chitwan, Nepal in 2008. The cord blood levels of toxic [lead (Pb), arsenic (As), and cadmium (Cd)], essential trace elements [zinc (Zn), selenium (Se), and copper (Cu)], demographic, socioeconomic, and behavioral variables were measured. The mean values of Pb, As, Cd, Zn, Se, and Cu in cord blood level were found as 31.7, 1.46, 0.39, 2,286, 175, and 667 μg/L, respectively. In the multivariate regression model, cord blood As levels from less educated mothers were higher than those from educated mothers (coefficient = -0.01, 95% confidence interval [CI] = -0.02-0.00). The maternal age was positively associated with the cord blood Cd level (coefficient = 0.02, 95% CI = 0.01-0.03), while it was negatively associated with the cord blood As level (coefficient = -0.01, 95% CI = -0.03--0.01). Cord blood levels of Pb, Zn, Se, and Cu were not associated with maternal age, socioeconomic status, living environment, and smoking status. As and Cd levels were relatively lower than those reported in previous studies in Asia, while the levels of Pb and the trace elements were similar. Less educated mothers are more likely to become a higher in utero As source to their fetus, and fetuses of older mothers were more likely to have higher in utero Cd exposure in Terai, Nepal.  相似文献   

14.
It is likely that most, if not all, of the elements found to be essential in animals will be shown to be so for man, and the clinical picture produced by deficiency of the elements in the human patient will differ little from that seen in the animal, although this has been established for only five elements (I, Fe, Cu, Co and Zn). However, the link between lack of a given element in the soil and a human patient is far less direct and much more complex than that met with in the animal grazing on deficient pastures, except in isolated primitive communitis. Zn is the most protean of the trace elements and has been chosen to illustrate this in human practice. Excesses of essential elements (both trace and major) give rise to toxic effects and the importance of a proper balance especially of the transitional elements in the human diet is discussed with special reference to Cu, Zn and Fe. Certain non-essential trace elements are individual and community hazards: Cd, Pb and Hg are the principal offenders for humans. Mankind is now largely dependent on grassland products, cereals and livestock with increasing dominance of the former in human nutrition. This has reduced the bioavailability of trace elements so that study of trace metals, especially Zn and Cu, in skeletal and dental remains at human burial and occupation sites should prove useful in assessing the consequences of this striking change in dietary habits.  相似文献   

15.
BackgroundEssential trace elements and minerals play a significant role in neurodevelopment. Although certain studies demonstrated impaired essential trace element and mineral status in children with ADHD, the existing data are insufficient. The objective of the present study was to assess serum trace element and mineral levels in children with ADHD.MethodsSerum trace element and mineral levels in 68 children with ADHD and 68 neurotypical controls were assessed using ICP-MS at NexION 300D (PerkinElmer Inc., USA) equipped with ESI SC-2 DX4 autosampler (Elemental Scientific Inc., USA).ResultsSerum Cr, Mg, and Zn levels in children with ADHD were 21 % (p = 0.010), 4 % (p = 0.005), and 7 % (p = 0. 001) lower as compared to the healthy controls, respectively. In turn, serum Cu/Zn values were 11 % higher than those in the control group. Age and gender had a significant impact on serum element levels in ADHD. Particularly, preschool children were characterized by significantly increased Cu (+8 %; p = 0.034), and Cu/Zn (+19 %; p < 0.001) values, whereas serum Zn (-9 %; p = 0.004) level was decreased. In primary school-aged children only 6 % (p = 0.007) lower Mg levels were observed. Both boys and girls with ADHD were characterized by 8 % (p = 0.016) lower serum Zn levels and 10 % (p = 0.049) higher Cu/Zn values when compared to neurotypical girls. Boys with ADHD also had significantly higher Cu/Zn, exceeding the respective control values by 12 % (p = 0.021), predominantly due to a 7 % (p = 0.035) decrease in serum Zn. Serum Mg levels were also found to be significantly lower than those in neurotypical children by 5 % (p = 0.007). In adjusted regression models serum Cr (β=-0.234; p = 0.009) and Cu/Zn (β = 0.245; p = 0.029) values were significantly associated with ADHD, respectively. Two-way ANOVA revealed a significant impact of ADHD on Cr, Mg, Zn, and Cu/Zn, whereas age was associated with Cu, I, Mg, Mo, and Cu/Zn, whereas gender accounted only for variability in serum Mn levels. Principal component analysis (PCA) also revealed significant contributions of Mg, Zn, and Cu/Zn values to ADHD variability.ConclusionsHypothetically, the observed decrease of essential trace elements, namely Mg and Zn, and elevation of Cu/Zn may significantly contribute to the risk of ADHD or its severity and/or comorbidity.  相似文献   

16.
It is known that certain trace elements can affect various heart diseases. In this study, we aimed to evaluate the changes in concentrations of certain serum trace elements in patients with chronic rheumatic heart disease (RHD). Serum analysis of selenium (Se), zinc (Zn), and copper (Cu) trace elements was assayed by atomic absorption spectrophotometry. RHD patients had significantly lower serum concentrations of Se and Zn than control subjects (p < 0.05 and p < 0.001, respectively). However, the serum Cu concentration was significantly higher in RHD patients than in controls (1.93 +/- 0.59 microg/L vs 1.06 +/- 0.29 microg/L; p < 0.001). Similarly, the Cu/Zn ratio in RHD patients was higher than in control subjects (4.70 +/- 0.92 vs 1.68 +/- 0.45; p < 0.001). Additionally, no significant correlation was found among these trace element concentrations and the functional capacity classes (p > 0.05). RHD patients had decreased serum Se and Zn element concentrations and increased serum Cu element concentration. We suggest that Se and Zn deficiency might be contributory factors in the development of rheumatic heart disease, and a high Cu concentration and a high Cu/Zn ratio might reflect an ongoing inflammatory process in this disease.  相似文献   

17.
BackgroundHeavy metals that pass through the plasmalemma are expected to influence on lichen metabolic processes; however, lichens may tolerate high concentrations of metals by sequestrating them extracellularly. Heavy metal accumulation level fundamentally determine the success of lichens in the colonisation of polluted sites; however, the proportions between extra- and intracellular metal concentrations in lichen thalli are still poorly recognized. In this study metal accumulation patterns of selected toxic trace elements, i.e. Pb, Cd, and micronutrients, i.e. Zn, Cu and Ni, in Cladonia cariosa thalli were recognised in relation to extra- and intracellular fractions.MethodsThe intracellular and total concentrations of Zn, Pb, Cd, Cu and Ni in lichen thalli collected from eleven variously polluted sites were determined by means of atomic absorption spectrometry. Additionally, organic carbon and total nitrogen contents as well as pH of soil substrate were measured.ResultsThe accumulation patterns differed between studied metal elements; the major part of Zn, Pb and Cd loads was accumulated extracellularly, whereas Cu and Ni accumulation was mostly intracellular. Like toxic trace elements, Zn was accumulated mainly extracellularly at high polluted sites. The non-linear models most reliably reflect relationships between intracellular and extracellular metal contents in C. cariosa thalli. The intracellular contents of Zn, Pb, Cd and Cu increased slower at higher than at lower extracellular concentrations. Moreover, at higher total concentrations of elements in the thalli, their extracellular proportions were markedly increased.ConclusionThe results suggest that in the face of extreme Zn-enrichment, lichens demonstrate the ability to accumulate the excess of Zn outside the cells. Therefore, it can be concluded that metal accumulation depend not only on the element but also on its abundance in the environment and direct availability for lichens. The studied species showed a defence against excessive intracellular accumulation when a given element is in excess. Such capability may facilitate the colonization of extremely polluted sites by certain pioneer lichens.  相似文献   

18.
The present study was conducted to compare the trace elements and oxidative status between uremic patients with and without dementia. Chronic hemodialysis patients with dementia (n = 20) and without dementia (n = 25), and age-matched healthy volunteers (n = 20) were enrolled. The nutritional status, blood levels of trace elements aluminum (Al), zinc (Zn), copper (Cu), magnesium (Mg) and iron (Fe), malondialdehyde (MDA), and protein carbonyl production, antioxidant enzymes glutathione peroxidase (GPx), and glutathione reductase (GR) activities were measured. No significant difference in nutritional status or clinical characteristics was observed between nondementia and dementia patients. However, uremic patients with dementia have significantly higher Al, Cu, and Mg and lower Zn concentrations, as well as increased Cu/Zn ratio in comparison to nondementia patients. There were statistically significant increased MDA and carbonyl production and decreased GPx and GR activities in dementia patients. Furthermore, the significant associations of Al, Mg, and Cu/Zn ratio with oxidative status in patients with dementia were noted. The dementia may initially worsen with abnormal metabolism of trace elements and oxidative stress occurrence. Our results suggest that abnormalities in trace element levels are associated with oxidative stress and may be a major risk factor in the dementia development of uremic patients.  相似文献   

19.
Trace elements and lipid peroxidation in uremic patients on hemodialysis   总被引:1,自引:0,他引:1  
Trace elements and lipid peroxidation in 26 patients with chronic renal failure treated with hemodialysis and 25 healthy subjects were observed. Both plasma and erythrocyte trace elements and plasma malon dialdehyde (MDA) were examined immediately before and after hemodialysis. Increased levels of plasma Cu, MDA, and erythrocyte Pb, Mn, Zn, and a significantly decreased plasma Se, Zn and erythrocyte Se were found in patients before hemodialysis. After a single hemodialysis, erythrocyte Mn, Cu, Zn, and plasma Cu, Al, and MDA were significantly increased whereas both plasma and erythrocyte Se were lower in patients than in healthy subjects. The level of MDA was not significantly changed during the single hemodialysis. Both plasma and erythrocyte Zn levels and plasma Cu and Al were significantly higher after hemodialysis than before hemodialysis. In conclusion, levels of trace elements are altered by hemodialysis, which may increase patient susceptibility to lipid peroxidation in uremia.  相似文献   

20.
人工饲养与野生川金丝猴体毛10种微量元素的含量及比较   总被引:2,自引:0,他引:2  
测定了秦岭人工饲养(10只)和野生(14只)川金丝猴体毛中的10种微量元素含量。锌、铁、铜、钙、镁5种元素采用火焰原子吸收法;锰、铬、铅采用石墨炉原子吸收法;铝采用等离子光谱;硒经硝解后采用原子吸收法测定。结果表明,铬、锰、镁、铅、锌和硒的含量,人工猴极显著或显著高于野生猴;铁含量,人工猴极显著低于野生猴;钙、铜和铝的含量,人工猴与野生猴无显著差异。以人类毛发10种微量元素的正常范围为参照,人工猴铅、铬、锰与锌4种含量均显著超出正常范围的上限,属于严重超量。这可能与金丝猴饲养过程中添加营养制剂有关。  相似文献   

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