Imbalance Of Trace Elements Research Articles

Trace elements content and hormonal profiles in women with androgenetic alopecia

It is well-known that some trace element imbalances play a significant role in the pathomechanism of many forms of alopecia. Androgenetic alopecia, however, is a specific local sensitivity of hair follicle receptors to androgens. In a clinical and laboratory study, 153 women with androgenetic alopecia (AGA) and 32 control women were examined. In AGA patients telogen hair and vellus hair (miniaturization, D < 30 μm) significantly differed in frontal and parietal hair comparison with occipital area (20 ± 0.9% vs. 12 ± 0.5% and 33 ± 0.9% vs. 12 ± 0.6% respectively). In the AGA group levels of androstenedione and dihydrotestosterone were higher than in the control group. Hair elemental content, analyzed by ICP-MS, demonstrated a lowered Cu and Zn content in the frontal area in comparison to the occipital area. It is important to note, that the AGA patients with elevated levels of androstenedione and dihydrotestosterone presented an increased Cu content and decreased Mn, Se, Zn contents in the occipital area of scalp. The occipital level of Cu positively correlated with the concentration of free testosterone in the serum. A negative correlation between the Zn content in the occipital area and the dehydroepiandrosterone level in the blood was found. Unfortunately, a routine treatment course of AGA patients, including topical inhibitor of 5-alpha-reductase and minoxidil, had no effect on the Cu hair content in occipital and frontal areas. However, there were positive changes in the morphological structure and other trace element contents. These data led us to hypothesize a key role of Cu metabolism disturbances in the AGA onset, development of AGA, and potential pharmaceutical targets for the treatment of AGA.

Status of Some Trace Elementsin Idiopathic and Ischemic Cardiomyopathy and Coronary Artery Disease: Echocardiographic Correlation

Background:The most principal mechanisms of cardiomyopathies are;high preload and afterload and low myocardial contractility, imbalance of trace elements may cause myocardial metabolic dysfunction and may have a role in aetiology of cardiomyopathy, particulary in IDC. Trace elements are being increasingly recognized as essential mediators of the development and progression of heart diseases.Methods: Study design Multi case-control study and single center estimation of trace elements concentrations in a number of volunteer settings this study was conducted in the Department of Cardiology, Ibn Albitar Hospital, and in the Physiological Chemistry Department of the College of Medicine, Baghdad University, from June 2005 to July 2006. Subjects Twenty-five patients with IDC, 15 patients with ICM, 16 patients with coronary artery disease(CAD) who have normal LV function, and seventeen healthy individuals as controls were included in this study. Investigations included serum estimation of zinc (Zn), copper (Cu), and magnesium (Mg) concentrations in these groups of patients and controls.Results: The mean (±SD) value of serum zinc was significantly decreased in CAD patients compared with controls (P&lt; 0.003). Serum Cu values (mean±SD) were significantly higher in IDC, ICM and CAD groups than in controls (P&lt; 0.0001, P&lt; 0.002, and P&lt; 0.007, respectively). Serum Mg (mean±SD) value was significantly decreased in ICM patients compared to controls (P&lt;0.007). Furthermore, there was a significant positive correlation between serum Mg levels and the values of LVEF % in IDC patients (r=0.522, P&lt; 0.007).Conclusion: This study confirmed that heart failure (IDC and ICM) and CAD are associated with serum trace elements (Zn, C u, and Mg) abnormalities.

Trace Element Status in Hemodialysis Patients

Patients with chronic kidney disease undergoing hemodialysis (HD) are potentially at risk of deficiency and excess of trace elements. HD exposes patients to large volumes of water (>120 l/week) in the form of dialysate. Although levels of certain ions (such as potassium and calcium) are carefully regulated in dialysate, many others are measured infrequently, if ever. As a result, substances in lower concentrations in the dialysis may be leached from the body. Conversely, toxic trace elements present in water but not in blood may accumulate and cause toxicity. Given that essential trace elements play key roles in multiple biological systems including immunological defense against oxidation and infection, it has been hypothesized that the increased morbidity and mortality seen in HD patients may in part be due to the imbalance of trace elements that has not been recognized. A recent systematic review has shown that compared with healthy controls, HD patients have significantly lower blood levels of zinc, manganese, and selenium, while blood levels of lead are likely to accumulate. Other trace elements, such as mercury and arsenic, are biologically plausible causes of excess mortality in dialysis patients, but available evidence is inconclusive as to whether they consistently accumulate in this population. Whether altered trace element levels are potentially reversible causes of adverse clinical outcomes in dialysis patients remains to be determined. This review highlights key issues related to this hypothesis, with special emphasis on zinc, manganese, selenium, lead, mercury, and arsenic.

Soils and geomedicine

Geomedicine is the science dealing with the influence of natural factors on the geographical distribution of problems in human and veterinary medicine. Discussions on potential harmful impacts on human and animal health related to soil chemistry are frequently focused on soil pollution. However, problems related to natural excess or deficiency of chemical substances may be even more important in a global perspective. Particularly problems related to trace element deficiencies in soils have been frequently reported in agricultural crops as well as in livestock. Deficiencies in plants are often observed for boron, copper, manganese, molybdenum, and zinc. In animals deficiency problems related to cobalt, copper, iodine, manganese, and selenium are well known. Toxicity problems in animals exposed to excess intake have also been reported, e.g., for copper, fluorine, and selenium. Humans are similar to mammals in their relations to trace elements and thus likely to develop corresponding problems as observed in domestic animals if their supply of food is local and dependent on soils providing trace element imbalances in food crops. In large parts of Africa, Asia, and Latin America, people depend on locally grown food, and geomedical problems are common in these parts of the world. Well-known examples are Keshan disease in China associated with selenium deficiency, large-scale arsenic poisoning in Bangladesh and adjacent parts of India, and iodine deficiency disorders in many countries. Not all essential elements are derived only from the soil minerals. Some trace elements such as boron, iodine, and selenium are supplied in significant amounts to soils by atmospheric transport from the marine environment, and deficiency problems associated with these elements are therefore generally less common in coastal areas than farther inland. For example, iodine deficiency disorders in humans are most common in areas situated far from the ocean. There is still a great need for further research on geomedical problems.

Trace element levels in alopecia areata

Alopecia areata (AA) is a recurrent, nonscarring type of hair loss considered to be an autoimmune process. Though its etiopathology is not fully understood, there are claims that imbalance of trace elements may trigger the onset of AA. The aim of the present study was to assess the levels of zinc, copper, and magnesium in the serum of AA patients. Fifty AA patients (34 men and 16 women), and fifty age and sex matched healthy control subjects were studied. Samples were analyzed using atomic absorption spectrometric methods. Serum zinc levels were significantly decreased (P < 0.05) in AA patients whose disease was extensive, prolonged, and resistant to treatment, whereas serum copper and magnesium levels showed insignificant rise compared to controls. We conclude that copper and magnesium levels are not altered in AA, but the decreased zinc levels found in our study may merit further investigation of the relationship.

Association Between Copper Excess, Zinc Deficiency, and TP53 Mutations in Esophageal Squamous Cell Carcinoma From Kashmir Valley, India—A High Risk Area

Trace element deficiency or excess is implicated in the development or progression in some cancers. Here we report the elevated level of copper and low level of zinc in the plasma of esophageal cancer patients in Kashmir India—a high incidence area. The average level of copper was significantly higher (P < 0.0001) for patients than for controls, with a mean concentration of 169 μg/dl and 149 μg/dl for patients and controls, respectively. The control group consisted of 55 healthy individuals matched for age, sex, and place of residence of the patients. In contrast, the average level of zinc in patients was significantly lower than in controls (P < 0.0001), with a mean concentration of 86.8 μg/dl and 96.1 μg/dl for patients and controls, respectively. The levels of both copper and zinc showed significant differences based on gender and age in patients as compared to controls. Similarly, smokers depicted a significant increase in serum copper (N = 39, P = 0.002) and a decrease in serum zinc approaching level of significance in the patient group as compared to controls. The copper and zinc levels were significantly altered in patients (N = 40) when compared to controls as a function of snuff consumption. The differences in the levels of copper and zinc showed significant association with the consumption of local salted tea up to 1,500 ml per day, but the changes were insignificant beyond that. Patients with poorly differentiated tumors (N = 7) had a higher copper concentration than those with moderately or well-differentiated tumors (P < 0.0001). To validate the general notion that imbalance in copper and zinc levels may lead to higher prevalence of TP53 mutations, we compared the 3 variables, and no association was found between copper concentration and TP53 mutation status; but patients with TP53 mutant tumor had lower zinc levels than those with no mutation. In conclusion, our results point toward a role of the trace element imbalance in the esophageal tumorigenesis in high-risk Kashmiri population exposed to a range of nitroso compounds or their precursors. Further prospective cohort studies are warranted to determine whether change in the plasma zinc and copper homeostasis may represent an independent risk factor for this malignancy as well as a possible target for preventive intervention.

The Impact of Open Dumping of Poultry on the Quality of Soil and Water

Twenty poultries in Ibadan city, Nigeria were studied in respect of water use, farm operations and waste disposal. The common disposal method among the poultry farmers was open dumping of wastes. Five poultry farms were selected, one in each zone for sampling to assess both soil and water quality parameters. Water samples were collected from main water supply source from each farm. Soil samples were collected at depths 0-150mm, 150-300mm and 300-450mm in the soil profile. The samples were taken at waste dump sites (PL) and at locations about 50metres away from dump sites (NPL). Results showed that open dumping of poultry wastes has a profound impact on soil and water qualities in the immediate environment of the dumpsites. The pH values of all water samples were higher than 7.0 and turbidity values in 60% of samples were above 1.4NTU. Though soil Zn, Fe and Mn values in soil were within critical values for arable crops, values for PL sites were higher than NPL sites. The Mean values of Mn at depths 0-150mm and 150-300mm were statistically significant (P< 0.05). N, P, K in PL soil were higher than in NPL soils by as much as 23% at depths less than 300mm. N values in all samples were below the critical range of 1.5-2.0mg/l. While all these result in enriching soil fertility for arable crop production excess wastes beyond what the soil can take cause trace elements imbalance in the soil. Trace elements imbalance results in chlorosis and other pathological conditions on leaves of crops. From the outcome of this study and considering the need for ensuring an environment that is free of pollution hazards. Open dumping of poultry wastes on bare soil surface cannot be considered a satisfactory method of waste disposal Keywords: Open dumping, Poultry, Waste, Soil, Water quality Journal of Applied Science, Engineering and Technology Vol. 6 (1) 2006 pp. 27-33

The Roles of Selenium and Mercury in the Pathogenesis of Viral Cardiomyopathy

Research on the pathogenesis of nonischemic dilated cardiomyopathy (DCM) has largely been focused on the role of viral pathogens and altered immunity. Trace elements have only rarely been considered; however, clinical observations that trace elements influence cardiovascular disease have been made in populations with extreme dietary deficiency or occupational exposure. Recently, animal models of DCM have been used to explore interactions among trace elements, viral pathogens, and the immune system. Discovery of interactions of trace elements with causes for DCM has heightened awareness of potential contributions of environmental variables to DCM pathogenesis. This article reviews the present knowledge regarding trace elements, in particular selenium and mercury, in the pathogenesis of viral and immune-mediated DCM. Based on recent studies, the authors propose a novel paradigm for the pathogenesis of viral DCM that incorporates trace element imbalance and its interactions with the cellular physiology of viral-induced cardiomyocyte dysfunction.

Abdominal Aortic Aneurysm or Aortic Occlusive Disease: Role of Trace Element Imbalance

The nature of the relationship between atheromatous disease and degenerative aneurysm is yet to be defined. The purpose of this study was to compare tissue Fe, Cu, Zn, and thiobarbituric acid reactive substances (TBARS) levels (as a marker of lipid peroxidation) in the abdominal aorta in relation to the development of aneurysmal and occlusive disease in the infrarenal aorta. This was a prospective clinical study in an institutional referral center, in hospitalized patients. Eighty male patients who underwent surgery for abdominal aortic aneurysm (AAA) or aortic occlusive disease (AOD) were included in the study. Age, risk factors and comorbid conditions were recorded, including diabetes mellitus, hypertension, coronary artery disease, smoking, and chronic obstructive pulmonary disease. Aortic wall biopsies were collected at operation from the anterolateral section of the infrarenal aorta. Tissue Fe, Cu, Zn, and TBARS levels were determined. The mean age of the AAA group was 66.2 (56-75) years and of the AOD group 57.8 (47-72) years (p <0.001). There was a higher prevalence of hypertension in AAA patients compared to AOD patients (62.5%, 35% respectively; p <0.05). The comparison of tissue Zn levels showed no significant difference. Tissue levels of Fe, Cu, and TBARS were found to be higher in the AAA group, compared with the AOD group (p<0.001 for each). These results suggest that higher oxidative stress as a result of higher Fe and Cu levels in the AAA, compared with AOD, may be one of the contributing factors in aneurysmal formation as a result of promoted wall erosion.

Copper, Zinc, Selenium, Cadmium and Lead Levels in plasma of Hemodialysis Patients.

Introduction: Hemodialysis patients are at risk of developing trace elements imbalance and increase in heavy metals. Objective: The objective of this study was to asses plasma levels of copper, zinc, selenium, cadmium and lead of hemodialysis patients. Design: The study comprised 40 patients aged 27-65 years under regular hemodialysis for 1.8-13 years and 28 healthy age and sex matched the control. Copper, zinc, selenium, cadmium and lead plasma levels were determined by atomic absorption spectrophotometry. Results: Levels of copper, zinc and selenium were significantly decreased in dialysis patients compared with the control group; the percentage decrease was 25.5%, 20.4% and 19.0% for copper zinc and selenium, respectively. Moreover, cadmium and lead plasma levels showed significant increases among hemodialysis patients versus their matched controls with percentage of 144.6% and 28.1% for cadmium and lead, respectively. Conclusions: Levels of trace elements are altered and heavy metals showed increased plasma levels by hemodialysis. Regular monitoring of trace elements and heavy metals in hemodialytic patients is advisable.

Copper, Zinc, Selenium, Cadmium and Lead Levels in plasma of Hemodialysis Patients.

Introduction: Hemodialysis patients are at risk of developing trace elements imbalance and increase in heavy metals. Objective: The objective of this study was to asses plasma levels of copper, zinc, selenium, cadmium and lead of hemodialysis patients. Design: The study comprised 40 patients aged 27-65 years under regular hemodialysis for 1.8-13 years and 28 healthy age and sex matched the control. Copper, zinc, selenium, cadmium and lead plasma levels were determined by atomic absorption spectrophotometry. Results: Levels of copper, zinc and selenium were significantly decreased in dialysis patients compared with the control group; the percentage decrease was 25.5%, 20.4% and 19.0% for copper zinc and selenium, respectively. Moreover, cadmium and lead plasma levels showed significant increases among hemodialysis patients versus their matched controls with percentage of 144.6% and 28.1% for cadmium and lead, respectively. Conclusions: Levels of trace elements are altered and heavy metals showed increased plasma levels by hemodialysis. Regular monitoring of trace elements and heavy metals in hemodialytic patients is advisable.

Survey of Strontium in Mineral Waters Sold in Japan: Relations of Strontium to Other Minerals and Evaluation of Mineral Water as a Possible Dietary Source of Strontium

The concentrations of strontium, calcium, and magnesium in 33 brands of natural mineral waters commercially available in Japan were determined by inductively coupled plasma-atomic emission spectrometry. The geometric mean values were 94.4 microg/L for strontium, 19.1 mg/L for calcium, and 2.82 mg/L for magnesium. Wide confidence intervals of 1.96-4539 microg/L for strontium, 0.865-421 mg/L for calcium, and 0.064-123 mg/L for magnesium were observed. The significant linear relationships among the three elements over a wide distribution range suggest that the synchronized variations of these elements are regulated by the natural ecosystem and not from accidental contamination from human activities or exceptionally high natural sources. Using the results of multiple linear regression analysis, the strontium concentration can be predicted by that of calcium with the appropriate power function. The results of this study suggest that mineral water can be an important nutritional source of strontium. As trace elements imbalance is often found in older patients with chronic renal failure, we propose that close attention of trace elements intake from trendy foods or beverages is necessary to prevent this hidden problem of a rapidly aging society.

Long-Term Changes in Trace Elements in Patients Undergoing Chronic Hemodialysis

Although the connection between aluminum intoxication and dialysis dementia was identified in the 1980s, understanding of trace element imbalances in hemodialysis patients is as yet incomplete. Recent application of newer inductively coupled plasma-mass spectrometry (ICP/MS) techniques has resulted in renewed study of this population. We used ICP/MS to evaluate serum concentrations of Cu, Se, Zn, Mn, and Ni in a relatively large population of hemodialysis patients compared with healthy age-matched controls. Comparisons were also done by duration of hemodialysis treatment to see whether length of treatment correlates with severity of imbalance. Patients had significantly lower concentrations of the three elements Se, Zn, and Mn. Patients had significantly higher concentrations of Ni, and there was a positive correlation between duration and severity of imbalance for this one element. There was no difference in Cu concentrations between patients and controls. Our findings confirm relative Ni excess and deficiencies of Se, Zn, and Mn in hemodialysis patients, documenting the value of ICP/MS in research work on trace element imbalances as well as clinical monitoring of individual patients.

2,3‐Dimercaptopropanol, 2,3‐Dimercaptopropane‐1‐sulfonic Acid and meso‐2,3‐Dimercaptosuccinic Acid Acute Administration Diferentially Change Biochemical Parameters in Mice

Chelating agents have been used clinically as antidotes for acute and chronic metal intoxications. These compounds not only enhance excretion but, in at least some cases, they also decrease the metal’s toxicity by preventing it from binding to cellular target molecules (Aposhian et al. 1995). Conversely, prolonged treatment with a chelating agent may lead to haematopoietic disorders (Flora & Kumar 1993), impairment of cellular metabolism, and synthesis of DNA, RNA and protein (Fischer et al. 1975), or trace element imbalance (Cantilena & Klaassen 1982). One of these metal chelators, 2,3-dimercaptopropanol (BAL), has the capacity to ameliorate the deleterious effects of metals intoxications, but it has a low therapeutic index (Andersen 1989). Despite relevant evidence of the BAL therapeutic use, obtained from in vivo and in vitro animal data as well as clinical accounts, its use as treatment for poisoning has been halted by data suggesting serious neurotoxicity (Pepin et al. 1995; Nogueira et al. 2000, 2001a&b). Other chelating agents, such as 2,3-dimercapto-1-propanesulfonic acid (DMPS, DimavalA) and meso-2,3-dimercaptosuccinic acid (DMSA, succimer) are less toxic and more effective chelating agents than the chemically analogous BAL (Aposhian et al. 1995). DMPS is registered in Germany for the treatment of mercury intoxication (Clarkson et al. 1981) or lead poisoning in children and adults (Kemper et al. 1990). Clinical reliance on DMSA, an orally administered chelating, has expanded greatly during the last years particularly after its approval for the clinical use against childhood lead poisoning by US Food and Drug Administration (FDA) (Jorgensen 1993). In the present investigation a number of toxicological par-

The distribution patterns of trace elements in the blood and organs in a rabbit experimental model of copper pollution and study of haematology and biochemistry parameters

In a rabbit model of five copper overfeeding, we investigated the distribution pattern of trace elements of copper [Cu], zinc [Zn], chromium [Cr], manganese [Mn], and selenium [Se] in blood serum, red cell, and whole blood and in the organs: brain, gallbladder, liver, intestines, heart, kidney, lung, and spleen. Furthermore, their haematology and biochemistry parameters as well as feed consumption and weight development were also performed in this study. Changes in trace element concentrations were determined by contrast and control group. Observably, the increased concentrations of Cr were observed in the heart; that of Cu, Zn, Cr, Mn in the liver; that of Cu, Cr, Mn in the intestines; that of Cu in the spleen; that of Cu in the blood serum; and that of Cu in the whole blood. But remarkably, the decreased concentrations of Mn were observed in heart; that of Zn and Se in the encephalon; that of Cr, Mn and Se in the spleen and that of Zn in the blood serum. In the gallbladder, the concentrations of Zn, Cr, Mn, and Se were also reduced. Excessive Cu was accumulated mainly in liver, intestines, and blood serum. In contrast group, only a few changes were detected in excretion of Mn, Zn, and Cr, but increased concentrations of Cu and Se compared with the control group. For the different biochemistry parameters measured, the contrast group showed changes, mainly owing to the altered activity of enzymes induced by trace element excess and imbalance. Increased concentrations of LDL were measured in contrast group, while a substantial decrease was seen in TG and VLDL as a result of excessive Cu. Regarding haematological parameters, increased concentrations of NEUT% and EO% were found in contrast group, but considerably decreased concentrations were detected in PLT, MONO%, BASO%, MONO#, BASO#, and P-LCR, but a minor decrease was also seen in EO#. The present paper shows the effect of copper pollution in the animals and analyzes the interplay among trace elements in their bodies at length. It is significant for environment protection and toxicology study.

Effect of Hormone Replacement Therapy on the Elemental Contents of Uterine Tissue

For the past years, different therapies based on steroid hormone supplementation or modulators of estrogen receptors have been used after menopause to prevent or manage osteoporosis. Although these treatments seem to be beneficial, they have some negative effects in the uterus and breast. The objective of this study was to assess variations for the concentrations of K, Ca, Mn, Fe, Cu, Zn, and Se in uterine tissue of Wistar rats. Ovariectomized rats were subjected to estrogen, progesterone, raloxifene, and tibolone supplementation and compared with nonovariectomized control animals. Elemental contents determined by the particle-induced X-ray emission (PIXE) technique revealed major alterations in Fe, Ca, Mn, and Se in the uterus of ovariectomized rats relative to control animals. After ovariectomy, a significant increase in Ca and Fe and a significant decrease in Mn and Se contents were determined in the uterus. For the ovariectomized groups in which animals received raloxifene, tibolone, estrogen, and estrogen combined with progesterone supplementation, an overall recovery in Mn, Fe, and Se contents was verified. Elemental concentration in the progesterone-supplemented group did not significantly differ from ovariectomized animals receiving placebo. The alterations found for ovariectomized animals receiving placebo and progesterone suggest tissue impairment and trace element imbalance, contrasting with the remaining supplemented groups where an enhancement of tissue activity might justify similar concentration levels relative to controls, because most of the elemental contents altered after ovariectomy.

Trace element changes in sclerotic heart valves from patients undergoing aortic valve surgery.

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.

Hair analysis and the early detection of imbalances in trace elements for members of expeditions in Antarctica

In the framework of the Human Biology and Medicine Project of the National Program for Research in Antarctica (Programma Nazionale di Ricerche in Antartide, PNRA) a study was undertaken to explore the suitability of trace element determination in human hair as a tool for the early detection of the impact of extreme environmental conditions on the health of members of the Italian and French expeditions. This study included three campaigns, namely, the 1995–1996 expedition to the Italian base of Terra Nova Bay, as well as the 1997–1998 and 1998–1999 expeditions to both the Italian base of Terra Nova Bay and the Italian–French base of Dome C. Sampling of hair of participants in the expeditions was carried out both prior to departure and at the end of the period spent at the bases. As regards storage, pre-treatment and analysis of hair samples they were performed in accordance with previously established procedures. Acid-assisted microwave digestion was adopted as the best approach for preparing solutions for subsequent analysis by inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. In the first part of this study, only the elements Ca, Cu, Fe, Mg and Zn were selected, while at a later stage it was decided to also include Co, Cr, Mn, Mo and Ni. Experimental results were subjected to basic statistical analysis to detect possible significant differences in element concentrations that occurred during the sojourn at the bases, with a view to identify possible remedial action to minimize adverse consequences.

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.

Experimental copper and chromium deficiency and additional molybdenum supplementation in goats. II. Concentrations of trace and minor elements in liver, kidneys and ribs: haematology and clinical chemistry

Since the mid-1980s a previously undescribed disease has affected moose in south-western Sweden. Investigations made to reveal evidence of a viral aetiology have proved unsuccessful. Trace element studies in apparently healthy moose shot during regular hunting suggested a trace element imbalance, with excessive molybdenum uptake causing secondary copper deficiency. The results also indicated a possible chromium deficiency. To verify this hypothesis, an experimental study was performed in male goats fed a semi-synthetic diet for 1.5 years. The animals were kept and treated in four groups: Controls, Cu-deficient group (group 1), Cr-deficient group (group 2), and combined Cu- and Cr-deficient group with additional supplementation of tetrathiomolybdate for 10 weeks at the end of the study (group 3). The present paper presents tissue contents of trace and minor elements, haematology and clinical chemical parameters. Feed consumption and weight development, as well as pathological and histopathological investigations, were also performed in this study, but these results are presented elsewhere. Changes in trace element concentrations were determined by comparing groups 1, 2 and 3 with the control group. Increased concentrations were observed for Al, Ca, Co, Fe, Mo, Pb, Se in the liver; for Al, Cd, Co, Cr, Mo in the kidneys; and for Mn and Mo in the ribs. Considerable accumulation of Mn in ribs seems to be a useful way to determine oxidative stress. Decreases in Mg and P in all organs and blood serum is characteristic of Cu deficiency and molybdenosis. Also the ratio of Ca/Mg was increased as the result of tissue lesions causing an intracellular increase in Ca and decrease in Mg. The trace element changes observed in group 1 were enhanced by the Mo supplementation in group 3, resulting in characteristic patterns, ‘spectra’ of changes. The alterations were not as remarkable in group 2 as in the two other groups. However, Cr deficiency considerably influenced Al, Co, V and to a smaller extent also Mn in ribs. In groups 1 and 2, only a few minor changes were detected in the haematological parameters, probably caused by increased adrenal activity after transportation of the animals. In group 3, severe anaemia was present but also a leukopenia. For the different clinical chemical parameters measured, all three groups showed changes, explained mainly by the altered activity of enzymes induced by trace element deficiencies and imbalance. Impaired carbohydrate and lipid metabolism was seen in groups 1 and 3, with increased concentrations of glucose, lactate and triglycerides in serum. Increased concentrations of total bilirubin were measured in all three groups (bile stasis was also seen post mortem). A considerably increased concentration of serum urea was found in group 3, although there were no indications of renal insufficiency or dehydration. Regarding hormones, a substantial decrease was seen in thyroxine (T 4) in group 3 as a result of the molybdenosis, but a minor decrease was also seen in group 1. Insulin on the other hand showed increased levels in group 3 — and especially in group 2 due to the Cr deficiency but also affected by the molybdenosis. As could be expected, Cu deficiency (groups 1 and 3) caused low levels of caeruloplasmin, secondarily affecting the Fe metabolism in these animals. Protein abnormalities, detected as altered electrophoretic patterns of serum proteins, were also seen mainly in group 3. The findings were also confirmed by multivariate data analysis, where PCA revealed the overall impact of the deficiencies, and PLS regression coefficients indicated the influence on the various analytes.