Plasma Copper Concentrations Research Articles

Effect of Caffeic Acid Dietary Supplementation on the Antioxidant Defense System in Rat: Anin VivoStudy

Dietary supplementation of caffeic acid (0.2 and 0.8% w/w) in rats resulted in a statistically significant increase of α-tocopherol both in plasma and lipoprotein. While caffeic acid was not detectable in plasma under fasting conditions, in postprandial plasma it was present at micromole concentrations, doubling plasma total antioxidant capacity. Lipoproteins from caffeic acid-fed rats were more resistant than control to Cu2+-catalyzed oxidation, despite the lack of incorporation of caffeic acid in the particles. No significant effects on plasma and liver copper concentration, nor the increase in liver of Mn-superoxide dismutase reported in copper deficiency, were detected. These results demonstrate the physiological relevance of caffeic acid and its antioxidant actionin vivo,through both a direct contribution to the antioxidant defense system and a sparing effect on α-tocopherol.

Extra- and intracellular acid-base balance and ionic regulation in cod ( Gadus morhua ) during combined and isolated exposures to hypercapnia and copper

Cod (Gadus morhua) were exposed to hypercapnia (water Pco2 = 7.5 mmHg), elevated copper level (0.4 ppm) or a combination of both in order to study extra- and intracellular acid-base regulation and the influence hereupon of copper. During pure hypercapnia, the extracellular respiratory acidosis was completely compensated within 12 to 24 h via a chloride-mediated increase in extracellular [HCO3 −]. Exposure to copper in normocapnic seawater caused a large and progressive increase in plasma [Na+] and [Cl−] and a metabolic acidosis. Exposure to copper in hypercapnic seawater was associated with smaller elevations of plasma [Na+] and [Cl−] than in normocapnic seawater, showing that hypercapnia had a protective effect on the copper-induced osmoregulatory disturbances. The compensation of the hypercapnic acidosis was, however, slow and incomplete in fish exposed to both copper and hypercapnia. Extracellular pH remained depressed by 0.3 pH units after 72 h. The data reveal that acid-base regulation was immediately and persistently inhibited by copper. The limited acid-base regulation during combined copper and hypercapnia exposure was chloride-mediated as during hypercapnia alone. Intracellular pH recovery was complete and very rapid in ventricular and skeletal muscle tissues during environmental hypercapnia, whereas acid-base compensation in liver tissue was slower, the kinetics being similar to that in the extracellular compartment. Intracellular pH compensation was significantly slowed down by copper. Copper concentration increased drastically in gill tissue already at 3 h, while copper concentrations in liver, muscle and plasma were significantly elevated only after 48 h, with liver showing the largest elevation.

Postnatal caffeine effects on copper, zinc, and iron concentrations in mammary gland, milk, and plasma of lactating dams and their offspring.

Beginning on the day of delivery and until the 15th or 22nd day of lactation, one group of dams received a 20% protein diet as a basal diet and one group received the basal diet supplemented with caffeine (4 mg/100 g body weight). A correlation between caffeine concentrations in the dams' plasma and milk was observed. In the caffeine group, levels of Fe and Cu in the dams' mammary glands at day 22 were decreased. Copper levels in the milk at day 15 and Fe and Zn levels in the milk at day 22 showed a significant decrease. Copper concentration in the plasma of 15-day-old pups showed a significant decrease also, but Zn and Fe concentration showed no difference between caffeine and noncaffeine control groups. The present study shows that the dams' consumption of a caffeine-containing diet influences trace elements of mammary glands, milk, and pups' plasma.

Copper and Zinc Determination in Plasma and Corpuscular Components of Peripheral Blood of Patients with Preterminal and Terminal Renal Failure

Homeostasis of trace elements is an essential condition for the activation and regulation of metabolic processes. Its disturbance results in clinical symptoms. Since most trace elements are eliminated via the renal system, their balance is disturbed in patients with preterminal or terminal renal insufficiency. However, only a low percentage of trace elements can be detected in plasma, so that the intracellular determination of trace elements in corpuscular components in peripheral blood cells might be of interest. After blood was taken from the shunt vessel, the cells were isolated by density gradient centrifugation media. The concentrations of the trace elements copper and zinc in peripheral blood cells and plasma were determined by means of electrothermal atomic absorption spectrometry. Compared with healthy blood donors, in patients with preterminal and terminal renal insufficiency concentrations in plasma and peripheral blood cells were altered but in different directions. In renal insufficiency copper concentration in plasma (median: 13.9 mumol/l) and erythrocytes (median: 0.8 mumol/ 10(9) cells) was normal and in the lower reference range, respectively, whereas copper concentration in the platelets was elevated (median of 20 mumol/1 10(9) cells). As regards zinc, patients with preterminal and terminal renal insufficiency both suffered from low values in plasma (median: 8.6 mumol/l). In contrast, the concentration in erythrocytes and thrombocytes was elevated (medians: 17.9 mumol/10(9) cells and 14.0 mumol/10(9) cells, respectively)). In conclusion, the intracellular determination of the trace elements copper and zinc is of value for diagnosis and monitoring of the trace element deficiency status.

Changing dietary S intakes and the Cu status of grazing lambs

The effect of increasing intake of sulphur (S) as elemental‐ and thiosulphate sulphur on copper (Cu) concentrations in digesta, plasma, and liver tissue was studied in 42 lambs grazing a ryegrass/white clover pasture containing 2.6 g S, 6.2 mg Cu, and <0.5 mg Mo per kg DM. Increasing S intakes from 3.9 to 7.9 g S/day via dosing with thrice weekly S containing capsules had no effect on plasma and liver Cu concentrations at Cu intakes of 9.3 or 24.3 mg/day but significantly (P < 0.05) increased red blood cell superoxide dismutase activity, the total S, acid volatile, and free S2’ concentrations in the reticulorumen contents. It was concluded that increasing S intakes from 3.9 to 7.9 g/day had no significant effect on the Cu status of sheep grazing low Mo pasture (<0.5 mg Mo/kg DM).

Influence of Age and Sex On Copper, Zinc and Magnesium Concentrations in Plasma, Erythrocytes and Urine of Healthy Adults

Healthy men and women aged 19 to 80 years (n=122) and living without any restriction were studied to determine the age and sex dependence of plasma, erythrocyte and urine copper, zinc and magnesium concentrations and to establish correlations between these parameters. Subjects were divided into 3 groups according to age and in 6 subgroups according to sex: 1) 40 subjects (19 mean, 21 women) aged 19 to 39 years, 2) 37 subjects (20 men, 17 women) aged 40 to 59 years, and 3) 45 subjects (25 men, 20 women) aged 60 to 80 years. Plasma copper showed an age related increase, with higher concentrations in women of the first two groups. Plasma zinc and magnesium were significantly lower in the elderly. Erythrocyte zinc and magnesium increased with age while erythrocyte copper decreased in the oldest age group. Urinary excretion of copper and magnesium decereased with age. Urinary zinc excretion was significantly higher in the men of the middle-aged group. A strong negative correlation was present between plasma and erythrocyte copper and zinc in all groups, and a significant positive correlation was observed between plasma and erythrocyte magnesium and zinc in the two younger groups. Plasma zinc and magnesium were positively correlated up to 60 years. A positive correlation between urinary magnesium and copper concentrations was present only in the elderly. These findings suggest that age and sex are factors influencing trace element homeostasis and their interactions. These data may provide a reliable basis for the interpretation of trace mineral levels and interrelations in acute or chronic changes due to disease or drugs.

Copper Deficieny in a Patient with AIDS Cholangiopathy and Cryptosporidium Diarrhea

Objective: To report a case of leukopenia caused by copper deficiency in a patient with AIDS cholangiopathy and Cryptosporidium diarrhea who required total parenteral nutrition (TPN). Case Summary: A 36-year-old white man with AIDS had Cryptosporidium diarrhea, and produced a daily stool volume of 3–5 L. He also had AIDS cholangiopathy, with intra- and extrahepatic biliary dilation and an alkaline phosphatase concentration of 3,000 U/L. He required TPN. Since copper is excreted primarily through the bile, it was omitted from his TPN. The patient then developed progressive leukopenia. His plasma copper concentration dropped to 10.2 μg/dL. Copper was subsequently added to the TPN, and the white blood cell count returned to normal. Discussion: A review of the literature showed that neither HIV infection nor AIDS is associated with copper deficiency. Copper deficiency has been reported as a rare complication of TPN or malabsorption, but it was not expected as a result of AIDS cholangiopathy. Conclusions: Copper supplementation is required in TPN in patients with chronic diarrhea and AIDS cholangiopathy. Additionally, copper deficiency is a potential cause of leukopenia in patients with AIDS who are receiving TPN or who have chronic diarrhea.

Effect of age and dietary protein level on tissue mineral levels in female rats.

Mineral (phosphorus, sulfur, potassium, calcium, magnesium, iron, zinc, copper, and manganese) concentrations were measured in plasma, and several tissues from female Wistar rats (young: 3-wk-old; mature: 6-mo-old) were fed on a dietary regimen designed to study the combined or singular effects of age and dietary protein on mineral status. Three diets, respectively, contained 5, 15, and 20% of bovine milk casein. Nephrocalcinosis chemically diagnosed by increased calcium and phosphorus in kidney was prevented in rats fed a 5% protein diet. Renal calcium and phosphorus were more accumulated in young rats than mature rats. A 5% protein diet decreased hemoglobin and blood iron. The hepatic and splenic iron was increased by a 5% protein diet in mature rats but was not altered in young rats. Mature rats had higher iron in brain, lung, heart, liver, spleen, kidney, muscle, and tibia than young rats. A 5% protein diet decreased zinc in plasma and liver. Zinc in tibia was increased with dietary protein level in young rats but was not changed in mature rats A 5% protein diet decreased copper concentration in plasma of young rats but not in mature rats. Mature rats had higher copper in plasma, blood, brain, lung, heart, liver, spleen, and kidney than young rats. With age, manganese concentration was increased in brain but decreased in lung, heart, liver, kidney, and muscle. These results suggest that the response to dietary protein regarding mineral status varies with age.

Urinary cadmium levels during pregnancy and postpartum. A longitudinal study.

It is well established that pregnancy induces physiological, metabolical and hormonal changes. As a consequence, trace metal metabolism can be affected. The aim of the present study was to assess the urinary cadmium levels in women during gestation and postpartum. The survey was conducted in a group of nonoccupationally cadmium-exposed women from Southern Catalonia (NE, Spain). Urine samples were obtained before pregnancy, during the 6th, 10th, 26th, and 30th wk of gestation, as well as during the 5th and 24th wk after delivery. Urinary cadmium levels were determined by graphite furnace atomic absorption spectrophotometry. The concentrations of zinc and copper in plasma were also measured. Moreover, to assess the effect of the diet during pregnancy, dietary ingestions of zinc, iron, and calcium were also determined. A significant decrease of plasma zinc levels could be observed during the last two trimesters of pregnancy, while plasma copper concentrations significantly increased during the same period. Urinary cadmium concentrations ranged from 0.05 to 3.79 micrograms/g creatinine (geometric mean 0.49 +/- 2.26 micrograms/g creatinine). No significant changes in urinary cadmium concentrations during pregnancy and postpartum could be observed.

Evaluation of the influence of physical activity on the plasma concentrations of several trace metals.

Our study was carried out with the aim of evaluating the influence that the degree of physical activity may have on plasma concentrations of essential and toxic elements. Copper and zinc, elements of known importance in basic cellular processes, have been analysed as essential, and cadmium and lead as toxic for the body in abnormal doses. The study was performed on a total population of 50 healthy individuals, 34 of them professional sportsmen and the rest who undertook moderate physical activity (control group), all of them living in a polluted environment (Madrid, Spain). Sampling was conducted at the beginning of the season (October). Electro-analytical techniques of proved reliability and accuracy were used for the determination of the metals. The results were related to data obtained using graphite furnace atomic absorption spectrophotometry and by use of biological reference materials. We found significantly higher zinc plasma concentrations in the sportsmen involved in anaerobic-type training (judo, fencing) compared to those undertaking aerobic activities (endurance, cycling) (P < 0.05). The values in both cases were higher than those found in the control group. Our study showed an increase of plasma copper concentrations in professional sportsmen, especially in those performing anaerobic activities, compared to those subjects undertaking moderate activity (control group) (P < 0.05). In summary, our results showed that there were no deficiencies of copper and zinc in the athletes studied at the beginning of the season. The levels were higher than those of the control population. As for the toxic metals, cadmium and lead, we observed lower levels in the athletes than in the control group (cadmium P < 0.005, lead P < 0.05). These results may indicate the existence of possible elimination systems for these metals in athletes, when they are training in a polluted environment.

Successful Early Copper Therapy in Menkes Disease Associated with a Mutant Transcript Containing a Small In-Frame Deletion

Classical Menkes disease is a fatal X-linked neurodegenerative disorder caused by defects in a gene (MNK) that encodes a copper-transporting ATPase. Treatment with parenteral copper has been proposed for patients identified before symptoms develop. We recently described suboptimal outcomes despite early copper replacement in two classical Menkes patients whose mutation predicts little if any functional copper transporter. Here, we describe successful copper replacement therapy in a patient with Menkes disease with a splice acceptor site mutation (IVS8,AS,dup5) that causes exon-skipping and generates a mutant transcript with a small in-frame deletion in a noncritical region. The patient was diagnosed by analysis of neurochemical levels in cord blood, and parenteral copper replacement was begun at 8 days of life. Throughout infancy, he showed normal head growth, brain myelination, and age-appropriate neurodevelopment, including independent walking at 14 months of age. In contrast, his affected half-brother and first cousin with the same mutation, but who were not diagnosed and treated from an early age, showed arrested head growth, cerebral atrophy, delayed myelination, and abnormal neurodevelopment. We propose that the successful neurological outcome in this patient was related to early repletion of circulating copper levels, in combination with residual copper transport by a partially functionalMNKATPase containing the small deletion. We hypothesize that raising plasma copper concentrations in patients with Menkes disease with some residual functional gene product can increase the ligand: transporter ratio and thus alter favorably the kinetics of copper transport into and within the brain.

Plasma copper and lipid peroxidation in cigarette smokers

Plasma levels of copper and lipid peroxidation were evaluated in 14 smokers as compared to 14 nonsmokers. Plasma copper concentrations were higher in smokers than in nonsmokers (122.5 ± 19.15 vs. 101.5 ± 16.2 μg/dl, P < .01). Plasma lipoperoxidation, evaluated as fluorescent damage products of lipid peroxidation (FDPL), also was higher in smokers than in nonsmokers (20.35 ± 2.6 vs. 17.1 ± 2.95 units of relative fluorescence/ml, P < .01). A significant and positive correlation between the number of cigarettes smoked, expressed as pack years, and the levels of either FDPL ( r = .61, P < .025) or copper ( r = .55, P < .05) was found. Moreover, a significant and positive relationship between copper and FDPL values was observed in smokers ( r = .64; P < .025), but not in nonsmokers. These data indicate that cigarette smoke-related plasma oxidant load may be partly due to enhanced levels of the prooxidant metal copper, potentially suggesting the supplementation of specific antioxidants (e.g., zinc) to counteract cigarette smoke-induced oxidative stress in smokers.

Effect of endotoxin on cardiopulmonary function and biosynthesis of eicosanoids and TNFα in calves chronically depleted of copper

We evaluated the acute cardiopulmonary and biochemical (i.e. plasma concentrations of eicosanoids and serum levels of TNFα) response to an infusion of Escherichia coli endotoxin (8 μg/kg i.v.) in cattle that were adequate or deficient in liver and plasma copper (Cu) concentrations. Young calves were chronically fed diets containing normal Cu (control; n = 4) and low Cu (n = 14). After ~6 months of dietary treatment, the calves were anesthetized and evaluated from 0-4 h during endotoxemia. At 0 h, plasma Cu concentrations averaged 32.4% (P &lt; 0.05) of the control value (i.e. 0.81 ± 0.08 μg/ml). Endotoxin caused a transient, early (at 20.4 min) increase in mean pulmonary arterial pressure to 114% and 147% of baseline in normal and Cu depleted calves, respectively (P &lt; 0.05). In Cu depleted calves, endotoxin significantly decreased heart rate (0.5-1 h) and cardiac index (0.5 h) as compared to normal calves. Endotoxin caused systemic hypotension and increased TXB2 production (at 0.5 h) and these changes were potentiated in Cu depleted calves. However, after 1 h there were no statistically significant differences between the two groups of calves for any cardiopulmonary parameter evaluated nor in plasma concentrations of eicosanoids and serum levels of TNFα. We conclude that chronic dietary depletion of Cu potentiates TXB2biosynthesis and worsens the acute (≤1 h) cardiovascular response to endotoxin challenge in cattle.

Cervical and thoracic vertebral malformation ("weak neck") in Colombia lambs.

The purpose of this study is to describe a developmental defect of the caudal cervical and cranial thoracic vertebrae in 11 purebred Colombia lambs. The lambs were either affected at birth, or developed the condition within the first 18 days of age. Cervicothoracic kyphosis, with a compensatory cervical lordosis and ataxia were common; 8 lambs had abnormal head posture, characterized by inability to lift the head from the ground. One lamb had rigid head and neck, and had to move the entire body to look to the left or right. Neurological signs included ataxia, tetraparesis, diminished conscious proprioception, and increased patellar and triceps reflexes. One lamb had inspiratory stridor because of compression of the trachea in the area overlying the abnormal vertebrae (cervical vertebrae 6 [C6] and 7 [C7]). Radiographic and pathological abnormalities included malalignment and malarticulation of the caudal cervical and cranial thoracic spine, rounded cranioventral margins in the bodies of vertebrae C7 and T1, wedging of the intervertebral disc spaces between C6 and T1 vertebrae, and hypoplasia of the dens. Pathological changes in the soft tissues included hypoplasia of the cervical epaxial and hypaxial musculature, with associated focal areas of myodegeneration. Mild Wallerian axonal degeneration, compatible with a mild cord compression syndrome, was found in 3 lambs in the cervicothoracic spinal cord adjacent to the vertebral anomalies. The concentrations of copper and selenium in blood, plasma, or tissues were normal in 10 of 11 lambs. All but one of the lambs in which pedigree information was provided were genetically related. Siblings born as twins to 5 of the affected lambs were normal, but both lambs from one twin pregnancy were affected. Owners reported that breeding stock had been shared among the ranches. Because of the close familial relationships of the affected lambs, the condition is suspected to have a hereditary basis.

Body temperature and thyroid hormone metabolism of copper-deficient rats

The hypothesis that the effects of copper deficiency on body temperature are mediated via the thyroid hormone system was examined in 24 male Sprague-Dawley rats, weighing 240 to 250 g, matched by weight and fed ad libitum diets containing adequate (78.7 μmol/kg), marginal (31.5 μmol/kg), or deficient (<7.9 μmol/kg) amounts of copper for 35 days. Anemia was not found in the copper-restricted groups. Plasma cholesterol concentrations increased (P < 0.05) and plasma copper, ceruloplasmin, and liver copper concentrations decreased (P < 0.05) in the rats fed the copper-restricted diet as compared with the copper-adequate diet. Cytochrome c oxidase and glutathione peroxidase activities in liver and brown adipose tissue were decreased (P < 0.05) in the copper-deprived rats. Body temperatures at 24 °C were less (P < 0.05) in the severely copperdeficient as compared with the moderately copper-deficient and copper-adequate animals. Plasma thyroxine concentrations were decreased (P < 0.05) in severely copper-deficient as compared with moderately copperdeficient and copper-adequate rats. Plasma tri-iodothyronine concentrations were reduced (P < 0.05) and plasma thyroid-stimulating hormone concentrations were elevated (P < 0.05) in both groups of copper-restricted rats relative to the copper-adequate rats. Thyroxine 5′-monodeiodinase activities in liver and brown adipose tissue were decreased (P < 0.05) in the copper-restricted animals. Hepatic triiodothyronine receptors were increased (P < 0.05) by dietary copper restriction. Body fatness was greater (P < 0.05) in copper-restricted as compared with copper-adequate rats. These findings indicate that copper deficiency without anemia decreases tissue copper and selenium status and is associated with impaired thyroid hormone metabolism and mild hypothermia in rats at maintained at 24 °C. (J. Nutr. Biochem. 6:445-451, 1995.)

Effects of low-copper diets on human immune response

We examined the effects of low-copper diets on indexes of immune response of 11 healthy men (aged 21-32 y) during a 90-d metabolic suite study. Daily copper intake for the first 24 d, next 42 d, and the last 24 d of the study was 0.66, 0.38, and 2.49 mg, respectively. Feeding the diet with 0.38 mg Cu/d was associated with a significant (P < or = 0.05) decrease in the proliferation of peripheral blood mononuclear cells cultured with phytohemagglutinin, Concanavalin A, or pokeweed, and an increase in the percentage of circulating B cells (CD 19+), but had no effect on the concentration of serum interleukin 2 receptor, the percentage of peripheral monocytes, neutrophils, CD3+, CD4+, or CD8+ T cells; or on the neutrophil phagocytic activity. Feeding 2.49 mg Cu/d for 24 d prevented further decreases in the indexes affected by the low-copper diet but did not restore them to the prestudy concentrations, even though plasma copper and ceruloplasmin concentrations were restored to normal.

Comparative effects of 6-week nicotine treatment on blood pressure and components of the antioxidant system in male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats

Hypertension, cigarette smoking, and nicotine augment the clinical significance of other risk factors associated with cardiovascular diseases by mechanisms which are poorly understood. Since altered trace element metabolism and antioxidant status have also been implicated in these diseases, the present study investigated the interaction of nicotine treatment and hypertension on tissue trace element concentrations and select indices of antioxidant status. Spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats were treated with nicotine, via a time release tablet at an average rate of 75 μg/h for 6 weeks. Systolic blood pressure in nicotine-treated SHRs was significantly higher at weeks 3 and 6 of treatment than in the SHR-controls. Blood pressure in WKY rats was not affected by nicotine. Plasma and liver iron concentrations in the nicotine-treated SHR were higher than the SHR-controls and the WKY groups. Nicotine treatment did not affect plasma and liver zinc and copper concentrations or liver manganese (Mn) concentrations. Plasma ceruloplasmin activity was increased by nicotine treatment in the SHRs. Liver Mn superoxide dismutase (MnSOD) activities and glutathione concentrations, and liver and heart glutathione reductase activities, were higher in both groups of SHRs than in the WKY groups. Red cell SOD activity in the nicotine-treated SHR was lower than in the SHR-controls. In summary, blood pressure increased more rapidly in the nicotine-treated SHRs compared to the controls. The marked effects on antioxidant status observed were attributable more to hypertension than to the nicotine treatment.

Interactive Effects of Dietary Copper, Water Copper, and Eimeria spp. Infection on Growth, Water Intake, and Plasma and Liver Copper Concentrations of Poults

The effects of dietary Cu, water Cu, and coccidial infection on poult growth performance and selected tissue mineral concentrations were investigated in a 10-d experiment using 200 5-d-old Nicholas toms (five replicates of 5 poults each; initial weight = 85 g). Uninfected and coccidiosis-infected (Eimeria meleagrimitis, Eimeria dispersa, Eimeria adenoeides, and Eimeria gallopavonis; cocci) poults were assigned to two levels of dietary Cu [Basal (B) and B + 204 mg Cu/kg diet on Days 1 to 10] and two levels of water Cu (0 and 103 mg Cu/kg water on Days 6 to 10). Dietary Cu and water Cu (main effects) did not affect (P > .10) gain, feed intake, gain:feed, water intake, hemoglobin, hematocrit, or liver Fe and Zn concentrations. Dietary Cu and water Cu increased (P < .03) liver and plasma Cu concentrations. The combination of dietary Cu and water Cu increased plasma Cu more than the sum of the Cu additions (dietary Cu by water Cu, P < .08). Coccidial infection reduced (P < .07) gain, feed intake, gain:feed, water intake, and hemoglobin, and increased (P < .02) liver Zn. Water Cu reduced water intake in uninfected poults but increased water intake in coccidiosis-infected poults (water Cu by cocci, P < .07). Water Cu increased hemoglobin in uninfected poults but decreased hemoglobin in coccidiosis-infected poults (water Cu by cocci, P < .07). Water Cu increased plasma Cu and liver Cu more in coccidiosis-infected poults than in uninfected poults (water Cu by cocci, P < .02). Simultaneous supplementation of feed and water with Cu increases plasma and liver Cu concentrations in coccidiosis-infected poults.

Plasma copper and iron changes in sheep after left lung inhalation injury: effect of the thromboxane antagonist BM 13.177 (Solutroban).

A significant decline in plasma concentrations of copper and iron were observed in sheep exposed to preferential smoke inhalation of the left lung. The decline was evident 30 minutes after smoke inhalation, and the levels of both trace metals persisted at quite low levels for up to the 18-hour time interval after injury. From that time a gradual recover for copper but not for iron levels was observed so that by 24 hours the levels of copper were in the same range of those at baseline. Copper and iron levels showed an inverse correlation to airway peak and plateau pressures and left lung vascular resistance index and a direct correlation to left lung blood flow. Administration of BM 13.177 (Solutroban), a thromboxane antagonist, before exposure to smoke inhalation protected the sheep from the decline of copper and iron levels in plasma. In these animals airway peak and plateau pressure, left lung vascular resistance, and blood flow were also unmodified. Lipid peroxidation of the lung tissue by oxygen free radicals were lower than in those animals that did not receive BM 13.177. There was likewise a tendency of a decreased wet-to-dry weight ratios in the animals treated with BM 13.177. BM 13.177 treatment in an inhalation injury model might partly protect lung damage and parallels unchanged plasma copper and iron levels. The plasma copper and iron may therefore be an indicator of acute lung damage.

Influence of age and health on immune functions and trace elements.

Apparently healthy elderly donors were screened according to a simple protocol that included clinical examination and the determination of hematological and biochemical values. This screening was performed to detect subclinical alterations which might interfere with immune responses and trace element status. The elderly were divided into two groups. The first group consisted of 22 (age 76 +/- 1 years) positively selected elderly (PSE), i.e. healthy subjects with no hematological and laboratory alterations, the second one comprised 13 (age 75 +/- 1 years) negatively selected elderly (NSE). Data were then compared with those obtained from 40 (age 35 +/- 2 years) healthy young controls. In both groups of elderly donors, plasma zinc levels were normal, while plasma copper concentrations were increased. Intracellular values of zinc and copper in mono- and polymorphonuclear cells from both groups of elderly were within reference limits. After in vitro activation, granulocyte chemiluminescence activity was impaired only in NSE. A decrement in the number of circulating CD3 lymphocytes and an increase in CD8d, CD57 cells were found in PSE, while NSE showed an increased number of CD3,DR cells and CD8d, CD57, CD8b,CD57 and CD16,CD56 positive cells. Our results indicate that only plasma copper levels were affected by age, whereas subclinical alterations in hematological or biochemical values appear to impair immune responses in the elderly.