Increase In Serum Copper Research Articles

Association between serum copper levels and stroke in the general population: A nationally representative study

ObjectivesThe objective was to explore the association between serum copper levels and the prevalence of stroke. MethodsData were obtained from 3 consecutive National Health and Nutrition Examination Survey (NHANES) cycles (2011-2016). Weighted multivariable logistic regression analysis was conducted to evaluate the association between serum copper levels and self-reported stroke. ResultsA total of 5,151 adults met the inclusion criteria. A total of 181 (3.51%) stroke patients were identified. In comparison to individuals with serum copper levels in the lowest tertile (<16.4 µmol/l), those with levels in the middle tertile (16.4-19.8 µmol/l) had an odds ratio (OR) of 0.99 (95% confidence interval [CI]: 0.44-2.25), while those with levels in the highest tertile (>19.8 µmol/l) had an OR of 2.36 (95% CI: 1.01-5.52). Furthermore, each standard deviation (SD) increase in serum copper was found to be positively associated with the prevalence of stroke, with an OR of 1.44 (95% CI: 1.11-1.86). Dose‒response analysis showed a positive linear association between serum copper levels and stroke (Pnonlinearity=0.554). ConclusionsThis cross-sectional study suggested a positive association between serum copper levels and stroke among American adults.

Serum Copper Concentrations, Effect Modifiers and Blood Pressure: Insights from NHANES 2011-2014.

(1) Background: Epidemiological studies on the relationship between serum copper and hypertension are contradictory. We assessed the relationship between serum copper and blood pressure among adults in the United States. (2) Methods: We divided hypertension into two categories: treated hypertension and untreated hypertension. Linear or logistic regression analysis was applied to investigate the association between serum copper concentrations and blood pressure levels. (3) Results: As compared to quartile 1, the odds ratios (ORs) for untreated hypertension in quartiles 2, 3, and 4 were 1.02 (0.74-1.42), 1.23 (0.88-1.72), and 1.08 (0.74-1.58), respectively, in multivariable analysis (all p > 0.05). In non-hypertension, as compared with quartile 1, the β (95% CI) of systolic blood pressure for quartiles 2, 3, and 4 was -0.92 (-2.07-0.23), -0.05 (-1.30-1.20), and -0.48 (-1.83-0.88), respectively, in multivariable analysis (all p > 0.05). As compared to quartile 1, the ORs for treated hypertension in quartiles 2, 3, and 4 were 1.36 (0.88-2.10), 1.35 (0.87-2.09), and 1.56 (0.98-2.47), respectively, upon multivariable analysis including antihypertensive medication use as a covariate (all p > 0.05). Furthermore, 1SD increase in serum copper was non-significantly associated with 1.16 (0.97-1.37)-fold increased risk of hypertension in multivariable analysis (p = 0.096). (4) Conclusion: In the present study, we discovered that the serum copper concentration was not related with hypertension or blood pressure levels. Antihypertensive drug use may distort the correlation between copper and blood pressure levels. Information on antihypertensive drug use may be taken into account when identifying new risk factors for hypertension.

Circulating Serum Copper Is Associated with Atherosclerotic Cardiovascular Disease, but Not Venous Thromboembolism: A Prospective Cohort Study

Background and Objective: Serum copper has been linked to the risk of atherosclerotic cardiovascular disease (CVD). However, the potential association between serum copper and venous thromboembolism (VTE) is not known. The principal aim was to evaluate the potential prospective association between serum copper and VTE risk. A secondary aim was to confirm or refute previously reported associations between serum copper and atherosclerotic CVD. Methods: Serum copper was measured at baseline using atomic absorption spectrometry in 2,492 men aged 42–61 years without a history of VTE in the Kuopio Ischemic Heart Disease prospective cohort study. Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence interval (CI) for VTE. Results: During a median follow-up of 27.0 years, 166 VTE events occurred. The risk of VTE per 1 standard deviation increase in serum copper in age-adjusted analysis was HR: 1.02; 95% CI: 0.88–1.20, which was attenuated to HR: 0.99; 95% CI: 0.82–1.19, following further adjustment for several established and emerging risk factors. Comparing the top versus bottom tertiles of serum copper, the corresponding adjusted HRs were 1.16 (95% CI: 0.80–1.66) and 1.11 (95% CI: 0.74–1.68), respectively. In 1,901 men without a history of coronary heart disease (CHD), the multivariable-adjusted HR for CHD was 1.32 (95% CI: 1.10–1.59) comparing extreme tertiles of serum copper. Conclusion: In middle-aged Finnish men, we confirmed previously reported associations between high serum copper levels and increased risk of atherosclerotic CVD, but serum copper was not associated with future VTE risk. Other large-scale prospective studies conducted in women, other age-groups, and other populations are needed to confirm or refute these findings.

Effect of Chelation Therapy and Blood Transfusion on Trace Elements in Thalassemia Patients

Background: β-Thalassemia major is considered to be one of the most common inherited hemolytic anemia. Enhanced years of survival of thalassemia have led to unmasking related complications related to alterations in certain trace elements like magnesium, calcium, phosphorus, copper, zinc etc.&#x0D; Objective: Present study was conducted to evaluate the effect of iron chelation therapy and blood transfusion on certain trace elements (Magnesium, Calcium, Phosphorus, Copper, Zinc) in β-thalassemic patients on chelation therapy more than one year.&#x0D; Materials and Methods: In the present cross sectional study, 100 β-thalassemic patients receiving chelation therapy for atleast 1year were recruited from Civil Hospital Ahmedabad, Gujarat during February, 2017 to December, 2018 and equal number (n=100) of healthy subjects were taken as a control group in the age range of 8 to 15 years of both sexes (male &amp; female). The levels of serum magnesium, calcium, phosphorus, zinc, and copper in serum were analyzed and results were correlated with normal healthy subjects.&#x0D; Results: A significant increase in serum copper (P≤ 0.01) and phosphorus (P≤ 0.001) were observed levels while a significant (P≤ 0.05) fall in magnesium, calcium and zinc levels recorded in β-thalassemic patients in comparison to healthy control subjects.&#x0D; Conclusion: Aforementioned observations suggested that fluctuations in the trace elements levels in β- thalassemic children receiving blood transfusion and iron chelation therapy could leads to different complications like hemolyzed red cells, infections &amp; hemochromatosis renal damage, hypoparathyroidism etc. if remains untreated. Hence routine assessment of these elements is recommended for better management.

Copper Deficiency in Children With Intestinal Failure: Risk Factors and Influence on Hematological Cytopenias.

We investigated to what extent serum copper influences hemoglobin (Hb), neutrophil, and platelet counts and the factors associated with serum copper in children with intestinal failure (IF) who have their micronutrient status monitored according to a standard protocol. Children with IF admitted to a pediatric intestinal rehabilitation program and receiving home parenteral nutrition (PN) were followed up prospectively. Patients received vitamins and multi-trace elements (TEs) as part of the PN. Copper, iron, zinc, vitamin A, and cobalamin serum levels were routinely monitored at 3-month intervals or monthly when a deficiency was detected. Complete blood counts were performed biweekly. Repeated-measures analyses were used to estimate the effect of explanatory variables on the outcomes. Thirteen children with a median time receiving PN of 16.6 months were included. An average of 7 copper measurements per patient were performed; 53.8% of patients had a low serum level at least twice during the follow-up. Eight patients with cholestasis had TEs of PN discontinued. In the multivariable analysis, copper was not associated with Hb levels; an increase of 10µg/dL in serum copper resulted in an increase of 240/mm3 (95% confidence interval [CI], 18.0-30.1) neutrophils and of 8429/mm3 (95% CI, 466-1219) platelets (P < .001). Time of PN without copper, direct bilirubin levels, and ostomy were associated with lower serum copper. The increase in serum copper was associated with significant increases in neutrophil and platelet counts. Time without copper in PN, cholestasis, and having an ostomy negatively influenced copper status.

Abstract P2-08-63: The relationship between serum level of copper and ceruloplasmin and pathologic and clinical characteristics in early breast cancer patients

Abstract Purpose: The increase of serum copper and ceruloplasmin has been reported to positively related with the progress of advanced breast cancers. However, the role of them in early breast cancer(EBC) is unknown. Methods: 209 female patients that been diagnosed as EBC within Xijing Hospital from Oct 2016 to Apr 2017 were included. The level of serum copper and ceruloplasmin were assayed using atomic absorption spectroscopy and immunoturbidimetry assay, respectively. The pathologic and clinical characteristics were analyzed by X test, t test and Pearson correlation analysis. p&amp;lt;0.05 is significant. Results: Table 1 show the primary characteristic of patients. After transforming copper and ceruloplasmin into binary variable (elevated and normal), age was both significant (p&amp;lt;0.01). The different expression level of ER, PR, Ki67 and molecular type, number and percent of metastatic lymph nodes were significant (p&amp;lt;0.01). After correlation analysis, negative relationship existed between age and copper or ceruloplasmin (coefficient = 0.265 or 0.233, p&amp;lt;0.01). And copper was positively related to the level of Ki67(coefficient = 0.169, p=0.018). While ceruloplasmin was negatively related to PR (coefficient = -0.273,p&amp;lt;0.01) and molecular type (coefficient = -0.217, p=0.05). Conclusions: This is the first study that revealed the abnormal escalation of serum copper and ceruloplasmin in Chinese EBC patients. The levels of both them were significantly higher in patients of young age, high Ki67 index and Luminal type. It is inferred that they might play an important role in early procedure of breast cancer, and it need more data in the future to validate. Table 1The primary characteristic of patientsCharacteristicResults(N=209)Median age, year(range)51.3(29-83)AJCC stage, N190*Stage 179Stage 281Stage 330Histological grade, N160*G119G2101G340Histopathologic characteristic, N206*DCIS13IDC-NOS151ILC7IDC-NOS + DCIS14Specific IDC21Primary tumor characteristic, N188*Median tumor size, cm(range)1.7(0.5-6.7)Median positive number of lymph nodes, N(range)2(1-23)Median percent of positive lymph nodes, %(range)13.3 (3.4-100)Molecular type, N(%)176*Luminal A (ER+/PR+/HER2-/Ki67&amp;lt;15%)29(16.5)Luminal B1 (ER+/PR+/HER2-/Ki67≥15%)85(48.3)Luminal B2 (ER+ and/or PR+/HER2+)19(10.8)HER2 (HER2+)12(6.8)Triple Negative (ER-/PR-/HER2-)31(17.6)Copper (Reference Value)11.8-21.28umol/LMedian of Copper (Range)17.7(12-32.9)Elevated cases, N (%)30(14.4)Normal cases, N (%)179(85.7)Ceruloplasmin (Reference Value)23-43mg/dLMedian of Ceruloplasmin (range)43.2(23.4-82.5)Elevated cases, N (%)88(42.3%)Normal cases, N (%)120(57.7)DCIS ductal carcinoma in situ;IDC-NOS invasive ductal carcinoma non special; ILC invasive lobular carcinoma; ER estrogen receptor; PR progesterone receptor; HER2 human epidermal growth factor receptor-2 * Excluding missing data Citation Format: Fan J, Wan Y, Zhao G, Wang T. The relationship between serum level of copper and ceruloplasmin and pathologic and clinical characteristics in early breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-63.

The relationship between serum level of copper and ceruloplasmin and pathologic and clinical characteristics in early breast cancer patients.

e13504Background: The increase in serum copper and ceruloplasmin has been reported to positively related with the progress of advanced breast cancers. However, the role of copper and ceruloplasmin ...

The Influence of Cigarette Smoke Exposure on the Copper Concentration in the Serum Depending on the Use of Menopausal Hormone Therapy.

This study evaluated the effect of menopausal hormone therapy (MHT) on serum concentration of copper in postmenopausal women depending on passive or active exposure to tobacco smoke or lack thereof. The study included healthy postmenopausal women aged 42–69 years, who used (n = 76) or did not use (n = 76) MHT. Salivary cotinine and serum copper concentrations were determined in all the study subjects. Salivary cotinine exceeded 14 ng/ml in 14 women from the MHT group (18.5%) and in 16 controls (21.1%). Up to 41 (27%) study subjects had serum copper above the upper normal limit (1.17 mg/l). No correlation was found between salivary cotinine and serum copper in women with cotinine concentrations <14 ng/ml, and these two parameters correlated weakly in subjects with cotinine >14 ng/ml. Salivary concentration of cotinine increased with serum copper level in the MHT group, but not in the controls; smokers using MHT presented with significantly higher serum copper than nonsmokers. These findings imply that MHT does not affect serum concentration of copper in women who are not exposed to tobacco smoke. However, MHT seems to contribute to unfavorable increase in serum copper in passive and active smokers.

Serum Zinc, Copper, Iron, and Magnesium Levels in Iranian Drug Users: A Case Control Study.

The changes in concentration of trace elements have effects on many organ systems, including the immune system. There have been conflicting reports on serum trace element levels in heroin users. This study was carried out to compare serum trace element concentrations in opium, heroin, and methamphetamine users. The study was done on 90 chronically illegal drug users (n = 30 per group) and 30 controls of the similar sex and age range (from 20 to 40 years). The control group was healthy subjects with no lifetime history of substance abuse or dependence. All of the substance users were selected from among those who had a history of substance use, for a minimum of 1 year. Serum zinc (Zn), copper (Cu), iron (Fe), and magnesium (Mg) were measured spectrophotometrically using chemistry analyzer. Serum Fe concentration was decreased in heroin (P = 0.026) and methamphetamine (P = 0.0001) users compared with healthy subjects, whereas serum Cu was higher in opium, heroin, and methamphetamine users (P < 0.01). Copper was negatively and significantly correlated with Fe in all groups (P < 0.05). There was no statistically significant difference between drug users and healthy subjects in serum concentrations of Zn and Mg. This study showed decreased in serum concentration of iron and increase in serum copper in drug users when compared with controls.

Study of Serum Magnesium, Zinc and Copper in Alcoholic Liver Disease

Alcoholic liver disease is considered to be a major cause of morbidity and mortality, with increasing incidence day by day especially in developing countries like India. Alcohol intake remains the major cause of cirrhosis. This study is done to evaluate the serum magnesium, serum zinc and serum copper in alcoholic liver disease. This study shows a significant decrease in serum magnesium, serum zinc and increase in serum copper in patients with alcoholic liver disease. Nutritional abnormalities occur in alcoholic liver disease which might participate in progression of the disease. Malnutrition and malsupplementation of certain micronutrients can be observed in alcohol abusers. Malsupplementation or an excessive intake of special micronutrients may contribute to the development of hepatic damage in alcoholic liver disease. Routine biochemical assessment of trace elements in patients with alcoholic liver disease is an important step in the management protocol and to reduce the progression of disease.

Serum Zinc and Copper Changes in Male Infertility

Objective: The aim of this study to detect the correlation between trace elements such as zinc, copper andspermatogenesis, sperm viability and motility.Methodology: Serum and semen samples were collected from one hundred twenty patients with age ranged (20-50 years) attending the high institute for Embryo Research and Infertility Treatment/ Baghdad University, inaddition to thirty fertile males their age comparable to that of patients. The period of this study was from June2004 until the end of October 2004.Results: The result of routine seminal fluid analysis of all infertile males was divided according to WHO, (1999) limitinto four groups: Asthenospermia(A), Asthenoteratospermia(AT), Oligoasthenoteratospermia OAT andAzoospermia(Azoo), each group includes thirty patient. Results showed highly significant decrease in serum zincconcentration in different infertile groups compared to control group, and a slight increase in serum copperconcentration in different infertile group. With advancing age, all the infertile groups, as well as the control group,had a slight decrease in serum concentration of zinc, and a slight increase in serum copper concentration.Recommendations: Further studies are needed to evaluate the levels of different biochemical parameters inseminal plasma of different infertile groups.

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.

Serum antioxidant micromineral (Cu, Zn, Fe) status of drug dependent subjects: Influence of illicit drugs and lifestyle

BackgroundUse of illicit drugs induces multiple nutrient deficiencies. Drug habit, sexual practice and socioeconomic factors influence the nutrient profile of drug dependent subjects. The literature on this issue is still insufficient. This study has tested the hypothesis that illicit drug use and lifestyle impair mineral status. To test this hypothesis, 253 men multiple drug users of age 18–45 years were recruited to investigate their serum copper, zinc and iron levels. Influence of illicit drugs and their lifestyle on the mineral levels was also examined. The study subjects were drug dependent who had shared needles and had sexual activity with multiple partners. Serum concentrations of the minerals were estimated by atomic absorption flame spectrometry.ResultsResults showed a significant increase in serum copper and zinc concentrations, and decrease in iron level in drug dependent subjects. The increase of copper level was found to be much higher than that of zinc. Period of drug abuse had made a significant positive influence on the copper and iron levels, but it was apparently reversed for zinc concentration. Multiple sexual partnerships had significant influence on zinc status. There also were significant relationships observed between body mass index (BMI) as well as certain socioeconomic factors, and mineral status of drug dependent subjects and non-drug dependent controls. A series of multiple linear regression analysis predicted mineral values for education, age and BMI. The group (drug dependent subject = 1, non-drug dependent control = 2) had a significant influence on these parameters. However, after controlling these factors, it was shown that illicit drug use significantly contributed to influence the serum mineral levels.ConclusionIllicit drug use impairs serum mineral value causing an increase in copper and zinc and a decrease in iron. Lifestyle and nutritional status of drug dependent subjects influence serum mineral concentrations.

Assessment of copper status in pregnancy by means of determining the specific oxidase activity of ceruloplasmin

Background: Conditions not directly related to copper nutriture, such as pregnancy, infections and inflammation, which increase serum copper concentration even during copper deprivation, may be expected to conceal changes in copper status. It has been suggested that the specific enzymatic activity of ceruloplasmin (activity per unit mass of enzyme protein) may be a sensitive indicator of copper status and is not affected by factors such as hormones or sex. In this study, we investigated the behaviour of specific oxidase activity of ceruloplasmin and the copper/ceruloplasmin ratio in pregnant women. Methods: Copper, immunoreactive ceruloplasmin and its oxidase activity were determined in serum from 52 women in the last trimester of normal pregnancy, and in 50 control women of similar age living in the same area and who were not taking oral contraceptives. The results are expressed as mean±S.E.M. Results: In the group of pregnant women, significantly higher serum levels of copper, ceruloplasmin and its oxidase activity were found than in the control group ( p<0.001). In both groups, a high correlation was found between these biochemical variables ( r≥0.905, p<0.001). However, in the group of pregnant women the specific oxidase activity for ceruloplasmin (364.4±3.3 vs. 407.5±3.8 U/g) and the copper/ceruloplasmin ratio (2.82±0.03 vs. 3.19±0.04 μg/mg) were significantly lower than in the control group ( p<0.001). Conclusions: Although pregnancy accelerates the rate of ceruloplasmin protein synthesis and release with an increase of serum copper, the decrease in specific oxidase activity of circulating ceruloplasmin would be an indicator of the degree of depletion of the mother's copper deposits in order to deal with the foetus' needs.

Predicting copper status in beef cattle using serum copper concentrations

Abstract Copper deficiency is common in pasture-fed cattle in New Zealand(1). In general, the diagnosis of copper deficiency in a herd of cattle is based on a combination of history, examination of animals, examination of the environment, chemical analysis of blood, liver or pasture, and treatment response trials. The laboratory diagnosis of copper deficiency is currently based on liver and either plasma or serum concentrations of copper. Ellison(2) reviewed the copper reference range for cattle used by the animal health laboratories in New Zealand and concluded that there is strong agreement in the literature that serum copper concentrations greater than 7.9 &#x1d6cd;mol/l and liver copper concentrations greater than 95 &#x1d6cd;mol/kg are adequate for young cattle. Furthermore, it has been reported that if copper concentrations in the liver are greater than 150–200 &#x1d6cd;mol/kg wet weight, there is a negligible increase in serum copper as liver concentrations increase further(2), with individual animal variation accounting ...

Effect of copper sulfate on experimental atherosclerosis.

Serum copper concentration increases significantly (p < 0.01) in rats with experimental atherosclerosis compared to a control group. The serum zinc, the zinc, and copper concentration in abdominal aorta and in liver decreases significantly (p < 0.05) compared to the control group. Administration of copper sulfate for 100 d in these animals induces a significant increase of serum copper (p < 0.01), decrease of serum cholesterol (p < 0.05) and increase of liver copper concentration as compared with the group fed only a high cholesterol diet. In the aorta of these animals the copper concentration increases and edema and lipid infiltration are considerably less than in the group of animals fed only a high lipid diet.

Effects of dietary excess amino acids on the concentrations of cholesterol, .ALPHA.-tocopherol, ascorbic acid, and copper in serum and tissues of rats.

An experiment was conducted with growing rats to investigate the effects of feeding excessive specific L-amino acids for 8 days on serum and tissue cholesterol, alpha-tocopherol, ascorbic acid, and copper, and on liver microsomal cytochrome P-450. To a 10% casein diet were added 4% L-methionine, 5% L-cystine, 5% L-histidine, 5% L-threonine, 5% L-tryptophan, 5% L-phenylalanine, 5% L-tyrosine, 6% L-valine, 7% L-isoleucine, 7% L-lysine, or 8% L-leucine. Excessive cystine and histidine increased serum cholesterol and alpha-tocopherol. Excessive cystine and methionine increased liver and kidney alpha-tocopherol and ascorbic acid. Excessive tyrosine and phenylalanine caused a marked increase in serum copper and ceruloplasmin activity, whereas excessive cystine, methionine, and histidine caused a decrease in the ceruloplasmin activity. Excessive histidine increased liver cytochrome P-450, whereas excessive tyrosine markedly decreased liver cytochrome P-450.

Serum copper concentration as an index of clinical lung injury.

The purpose of this ongoing study is to determine whether thoracic radiotherapy for lung cancer produces an early increase in serum copper (Cu) concentration, an increase which might predict clinical outcome. Copper and iron concentrations were measured in serum obtained from nonsmall cell lung cancer patients at 0, 1, 2, 4, and 6 weeks after the start of radiotherapy. Control groups included patients irradiated for breast cancer (low dose of radiation to the lung), for endometrial, cervical or prostatic cancer (no dose to lung), and patients with congestive heart failure, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and cutaneous burns with or without smoke inhalation (no irradiation). Serum Cu concentration increased at least 10 micrograms/dl from the pretreatment level in approximately 75% of the adenocarcinoma and squamous cell lung cancer patients, but in only 1 of 4 undifferentiated lung cancer cases. In virtually all of these responders, serum Cu increased to a maximum at 2 weeks after the start of therapy, then plateaued or decreased slightly despite continuing irradiation. Within the subset of squamous cell lung cancers, there was a direct correlation between the degree of histologic differentiation and both baseline serum Cu concentration and the probability of an early increase therein. In contrast, only 33% of breast cancer patients and 15% of endometrial, cervical and prostate cancer patients exhibited an increase in serum Cu concentration at 2 weeks after the start of radiotherapy. Serum Cu concentration was within normal limits in virtually all patients with congestive heart failure, pulmonary hypertension, and COPD. Burn patients exhibited a significant reduction in serum Cu, although concomitant smoke inhalation increased serum Cu back to low-normal levels. Serum iron concentration did not change significantly in any category of patients. These data suggest that thoracic radiotherapy for well differentiated non-small cell lung cancer is accompanied by an early increase in serum Cu concentration. This increase is partly but not wholly related to lung dose in particular rather than tissue dose in general, and specifically reflects radiation-induced lung injury rather than pneumopathy in general. In lung cancer patients, the change in serum Cu concentration during the first 2 weeks of radiotherapy exhibits a sufficiently broad range (+60 to -13 micrograms/dl) to permit testing this parameter as a predictor of tumor response and pulmonary complications.

Role of interleukin-1 in augmenting serum neutralization of bacterial lipopolysaccharide.

We have previously described an assay to quantify the serum neutralization of bacterial lipopolysaccharide which is based on a spectrophotometric Limulus amoebocyte lysate test (T.J. Novitsky, P.F. Roslansky, G.R. Siber, and H.S. Warren, J. Clin. Microbiol. 21:211-216, 1985). Studies since have shown that serum samples drawn from patients with leukemia and fever, gram-negative or gram-positive bacterial infections, or shock caused by gram-negative bacteria neutralize approximately 10-fold more lipopolysaccharide than do samples from normal controls. These findings suggested that the increased neutralization might reflect an acute-phase response and raised the question of whether it might be under the control of interleukin-1. To answer this question, we studied the neutralization of lipopolysaccharide in serum samples drawn from rabbits before and after the administration of crude interleukin-1, prepared from activated macrophage supernatants, and recombinant human interleukin-1. Crude interleukin-1 induced a 5.7-fold increase in serum neutralization 24 h after intravenous injection, and cloned interleukin-1 induced a 3.0-fold increase (P less than or equal to 0.01 and 0.05, respectively). In individual rabbits given identical doses of crude interleukin-1 on a weight basis, the serum-neutralizing ability correlated significantly with three activities of interleukin-1: rise in temperature (r2 = 0.558; P less than or equal to 0.01), decrease in serum iron (r2 = 0.534; P less than or equal to 0.01), and increase in serum copper (r2 = 0.323; P less than or equal to 0.05). We conclude that the increase in neutralization of bacterial lipopolysaccharide by serum samples drawn from patients with inflammatory states is mediated, at least in part, by interleukin-1, presumably through the induction of acute-phase serum proteins.

Serum copper concentration changes in chronic hemodialyzed patients.

We studied the behavior of copper during hemodialysis and the relationship between serum copper levels and hematologic parameters such as red blood cell count (RBC), hematocrit (Hct), hemoglobin (Hb), and serum iron in 48 hemodialyzed patients. To study diffusion, we measured copper in the arterial blood and in the dialysate at the inflow and outflow sites of the dialyzer. To study hemoconcentration, the change in hematocrit values and total serum protein values were examined. To study liberation of copper from the dialyzer membrane, copper concentrations in normal saline were measured before and after the saline was used to wash dialyzers of various kinds. We found that changes in serum copper concentration were due mainly to hemoconcentration and liberation, but partly also to diffusion, and that the net result of changes was a significant increase in serum copper. We observed no correlation between serum copper levels and RBC, Hct, Hb, and serum iron levels.