Caeruloplasmin Concentrations Research Articles

Undetectable caeruloplasmin values in a patient with autoimmune chronic active hepatitis.

Caeruloplasmin is an alpha 2 protein produced in the liver that is responsible for transporting copper in the blood. Caeruloplasmin values are usually high in patients with chronic liver diseases, including chronic active hepatitis: low values, however, are characteristic of Wilson's disease. The case of a 17 year old woman with very low caeruloplasmin values and chronic active hepatitis of the lupoid type is described. Steroid treatment resulted in an increase in the caeruloplasmin concentration and clinical improvement.

Carrageenan-induced granuloma and iron status in rats with dietary polyunsaturated fatty acid deficiency

Sprague-Dawley rats were fed for 4 months on a control diet or a polyunsaturated-fatty-acid (PUFA)-deficient diet. The combined effects of iron overload (Fe dextran) or Fe deficiency (desferrioxamine) on carrageenan-induced granuloma were studied. PUFA deficiency induced changes in Fe metabolism, but no alterations in lipid peroxidation variables were observed. Inflammation implied an increase in lipid peroxidation, Fe storage and caeruloplasmin concentration, together with symptoms of anaemia. PUFA deficiency in inflamed rats gave rise to a lower inflammatory response (granuloma weight and prostaglandin E2 concentration) and ethane exhalation. Fe overload potentiated inflammatory and lipid peroxidation processes, whereas Fe deficiency decreased them.

Copper distribution among serum proteins in paediatric liver disorders and malignancies

Fractionation of normal serum on Sephadex G-150, followed by determination of copper, caeruloplasmin and albumin concentrations, indicated that only approximately 71% of total serum copper was associated with caeruloplasmin; less than previously reported values. Seven per cent was associated with a high molecular weight protein, designated 'transcuprein', 19% with albumin and 2% with amino acids. Compared with adult serum the concentrations of caeruloplasmin and of copper associated with caeruloplasmin were low both in serum from neonates and in serum from patients with symptomatic Wilson's disease. However, in contrast to the neonate, Wilson's disease patients exhibited a raised total serum copper and raised non-caeruloplasmin-copper. In Indian Childhood Cirrhosis serum caeruloplasmin and caeruloplasmin-copper levels were normal, whilst the non-caeruloplasmin-copper was raised. Elevated non-caeruloplasmin-copper in Wilson's disease and Indian Childhood Cirrhosis may therefore represent an overspill into the serum from a copper-laden liver. Children with malignancy showed increased serum concentrations of copper and caeruloplasmin. Both caeruloplasmin-bound and non-caeruloplasmin-bound copper concentrations were elevated. It remains to be determined whether increased 'transcuprein'- and albumin-bound copper result from a sequestering of copper released from peripherally utilized caeruloplasmin, or are associated with increased rates of caeruloplasmin synthesis.

The effect of soluble-glass boluses containing copper, cobalt and selenium on the blood composition of ewes

An experiment was carried out on a site where herbage selenium content is known to be low, to examine the value of soluble-glass boluses as a means of providing supplementary copper, cobalt and selenium to ewes. Sixty-one Welsh half-bred ewes were divided into two groups. Thirty ewes were given a single glass bolus and 31 were left as untreated controls. Measurements of plasma copper and caerulo-plasmin concentrations, serum vitamin B 12 concentration and erythrocyte glutathione peroxidase activity all showed significant increases owing to treatment with soluble-glass boluses. These glass boluses also gave protection to the foetus and the young lamb in its early life.

An automated method for the kinetic measurement of ferroxidase activity.

The oxidase activity of caeruloplasmin towards Fe II (ferroxidase) appears to be of physiological significance both in iron metabolism and as a serum anti-oxidant. We have developed an automated assay for ferroxidase using a centrifugal analyser. The method is quick and precise, and is not subject to interference by haemolysis, jaundice or lipaemia. Ferroxidase activities correlate significantly with caeruloplasmin and copper concentrations. Normal reference ranges have been measured.

Caeruloplasmin concentration and oxidase activity in polyarthritis.

Caeruloplasmin (Cp) concentration and oxidase activity have been shown to be elevated in rheumatoid arthritis (RA) and psoriatic arthritis, but normal in Reiter's syndrome, Behcet's syndrome and juvenile seronegative polyarthritis. Synovial fluid Cp was significantly depressed in comparison with serum Cp in RA. During second-line therapy in RA, Cp concentration and activity fell significantly (P less than 0.001), but the change in Cp did not correlate with plasma viscosity.

The effect of iron stores and liver disease on the serum concentration of transferrin, haemopexin and caeruloplasmin

AbstractSerum concentrations of transferrin, haemopexin and caeruloplasmin have been measured in patients with haemochromatosis and other liver disorders, and the levels compared with those in a control group. Patients with cirrhosis or extrahepatic portal hypertension had normal concentrations of the three proteins except when hepatic decompensation was evident. In decompensated cirrhosis serum albumin and haemopexin levels were reduced. Untreated haemochromatosis, characterized by excessive hepatic iron stores on biopsy, was associated with a significant reduction in the serum concentration of all three proteins. Reductions were documented in both cirrhotic and non‐cirrhotic haemochromatosis. The results document an effect of elevated hepatic iron stores on hepatic protein metabolism and suggest the need for further studies on the regulation of hepatic metalloprotein metabolism.

Caeruloplasmin, prealbumin and 6H2-macroglobulin as potential 0 indices of disease activity in different arthritides

Caeruloplasmin (Cp), prealbumin and alpha 2-macroglobulin (alpha 2-M) concentrations in serum were compared in rheumatoid arthritis (RA), osteoarthrosis, ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome, Behçet's syndrome, SLE and normal controls. Cp was significantly elevated (p less than 0.01) in all disease groups except for Reiter's syndrome and SLE. Prealbumin was only significantly depressed (p less than 0.01) in RA. The most notable elevation in alpha 2-macroglobulin occurred in Reiter's syndrome. However, these differences were generally still within the normal range, and hence these proteins are unlikely to offer alternative indices of disease activity suitable for monitoring the the progress of seronegative arthropathies.

Sub-cellular distribution of copper and caeruloplasmin in chemically induced tumour tissue

Copper and caeruloplasmin concentrations were determined in the subcellular fraction of tumour tissue from 15 Strain A mice bearing an induced fibrosarcoma. It was observed that copper concentration was higher in the mitochondrial fraction of tumour tissue when compared to that of tissues of similar site from normal controls. However, the caeruloplasmin concentration was lower in the various fractions of tumour tissue when compared to that of normal control tissue.

Serum protein pattern in normal pregnancy with special reference to acute-phase reactants.

The concentrations of acute-phase protein reactants, total protein, albumin and globulin fractions were measured throughout normal pregnancy in 27 women. alpha 1-Antitrypsin and caeruloplasmin concentrations increased gradually to reach their highest levels in the third trimester. Orosomucoid and haptoglobin showed similar patterns: higher levels in the first and third trimester with a decline around 24 weeks gestation. C-Reactive protein showed levels similar to those of non-pregnant healthy individuals (less than 5 mg/l) throughout pregnancy. alpha 1-, alpha 2- and beta-Globulin concentrations increased from the first trimester towards term. gamma-Globulin concentration changed little during gestation. The data obtained provide reference ranges for serum proteins in healthy pregnancy.

Increased plasma copper in patients with homocystinuria due to cystathionine beta-synthase deficiency.

We measured blood copper-containing proteins and plasma total copper in 15 patients with homocystinuria (14 with cystathionine beta-synthase deficiency and one with abnormal cobalamin metabolism), in 13 heterozygotes for cystathionine beta-synthase deficiency, and in 44 normal subjects. Plasma total copper was increased in patients with cystathionine beta-synthase deficiency compared with age- and sex-matched controls; the ratio was 1.41 +/- 0.14 for females and 1.39 +/- 0.15 for males (means +/- SD). This was due to corresponding increases in caeruloplasmin concentrations, but levels were unrelated to total plasma homocysteine. Erythrocyte superoxide dismutase levels were normal. The heterozygotes had normal plasma copper and caeruloplasmin levels. The increased copper and caeruloplasmin may contribute to the precocious atherogenesis occurring in homocystinuria by decreasing the adhesion of vascular endothelial cells to the intima. It is unlikely that decreased lysyl oxidase activity due to chelation of copper by homocysteine is important for the pathogenesis of the connective tissue defect in homocystinuria.

Copper deficiency in humans.

Copper deficiency of nutritional origin has been recognized as an important part of complex nutritional problems in Peru, as an occasional even in premature babies in Western countries, and as a real hazard of over-zealous zinc therapy or of prolonged parenteral alimentation in children or adults. Anaemia, osteoporosis and scurvy-like bone changes are recognized in the deficiency, and they respond to copper. Copper intake is falling in western countries as a result of prepackaging of foods, and low-grade chronic deficiency may become a problem. The features seen in Menkes' syndrome suggest that human beings may be rather susceptible to the vascular and neurological effects of copper deficiency; these effects may be encountered as a consequence of prolonged mild copper deficiency. Measurement of the serum concentrations of caeruloplasmin before and after moderate copper repletion is suggested as a method of detecting mild copper deficiency.

Acute phase responses to experimental salmonellosis in calves and colibacillosis in chickens: Serum iron and caeruloplasmin

Calves and chickens were artificially infected with virulent strains of S. dublin or E. coli and changes in serum iron and caeruloplasmin concentration were studied in order to investigate whether the changes in these constituents described in laboratory animals after the injection of endotoxins also occurred in response to induced bacterial infection in farm animals. Salmonella infection in calves resulted in an acute and significant hypoferraemia, which correlated closely with the onset and severity of clinical signs but was not influenced by the immune status of the calf. Colibacillosis in chickens also resulted in an acute and significant hypoferraemia, which differed from that seen in infected calves in the duration of the response (over 7 days and approx. 2 days respectively). The unbound iron-binding capacity of the serum in calves showed a moderate increase 24 h after infection and then decreased rapidly in unison with the restoration of serum iron concentration, whereas in chickens there was a progressive increase from 6 h after infection extending beyond 4 days after infection. It is suggested that the demonstrated differences between calves and chickens reflect true variation in this antibacterial defence mechanism between host species. Changes in serum caeruloplasmin concentration after infection were slower in onset than the hypoferraemic response in both species. The concentration increased from about 2 days after infection, was maximal at 4 days and showed a sharp decline in calves and a moderate decrease in chickens at 7 days. The demonstrated difference in duration of the response between host species may indicate that caeruloplasmin is associated with restoration of serum iron concentration at the end of the hypoferraemic response. Conversely the increase in caeruloplasmin concentration may be a change mediated by pathogenic bacteria to overcome the host hypoferraemic response.

A Study of the Caeruloplasmin Concentrations found in 75 Patients with Wilson's disease, their Kinships and Various Control Groups

We have studied the concentration of the blue copper protein caeruloplasmin in the serum of 195 young, normal adults, 147 patients with neurological diseases and 78 patients with subacute or chronic liver disease. These have served as controls for 75 patients with Wilson's disease before treatment was started and during follow up for periods extending up to 20 years. We have also studied 444 members of the kinships. Caeruloplasmin has been estimated by an enzyme assay using dimethyl pphenylenediamine as substrate and, when necessary, we have checked the values so obtained by a new immunoenzymatic method and also by determining serum copper. The mean caeruloplasmin concentration in 83 normal males was 333.3 mg/l (S.D. 60·7). In 112 females it was 410·1 mg/l (S.D. 130·2). These 112 females were shown to comprise two populations, the larger ( n 82) had a mean of 365·6 mg/l (S.D. 92·8) and the smaller a mean of 606·6 mg/l (S.D. 157·5). The former figure is taken as the normal. The mean value for 75 patients with Wilson's disease was 63·3 mg/l (S.D. 87·6) before treatment; after treatment it fell to 45·0 mg/l (S.D. 79·8). However in 11 of these patients the mean caeruloplasmin concentration rose, after treatment, from 108·5 mg/l (S.D. 27·7) to 168·7 mg/l (S.D. 33·6). The mean values for the hepatic and neurological control cases closely approximated to the mean values for the sex matched normals. However both these groups showed a wide range of variation with many patients falling outside the normal 95 per cent confidence limits. Low caeruloplasmin values in patients with either hepatic or neurological disease may lead to considerable diagnostic confusion. The mean caeruloplasmin concentration for the obligate heterozygotes was significantly depressed in bath males and females but only 36 out of 160 fell below the normal 95 per cent confidence limit. The percentage of detectable heterozygotes fell, as did the calculated gene frequency, in more distant relatives. When there was a marked and unexpected discrepancy between the serum caeruloplasmin concentration as estimated by the enzymatic assay and the serum copper concentration the caeruloplasmin value was checked by the immunoenzymatic method. In patients with liver disease and in those with treated Wilson's disease the immunoenzymatic method was found to be in good agreement with the serum copper concentration. This suggests that there is, in some patients, an inhibitor present which interferes with the enzymatic assay. The finding of a low caeruloplasmin level in the serum of a patient with undiagnosed hepatic or neurological disease by an enzymatic method cannot be taken as evidence of absence of this protein unless it is confirmed by an immunological technique.

Serum antioxidant activity in normal and abnormal subjects.

Serum oxidant activity (AOA) was correlated with the serum caeruloplasmin and serum copper concentration and with the total and available serum iron-binding capacity in 313 normal and abnormal subjects. In all groups except in patients with Wilson's disease (hepatolenticular degeneration) there was a highly significant direct correlation between serum AOA and serum caeruloplasmin concentration. A statistically significant direct correlation between serum AOA and the available iron-binding capacity of serum was found only in normal subjects and in children with thalassemia major and iron overload. There was no correlation between serum AOA and the serum tocopherol concentration in any of the groups studied.

Impairment of acute protein reactivity in chronic renal failure.

The acute phase protein response was studied after elective surgery in 13 normal subjects and 9 patients with severe chronic renal failure. Total haemolytic complement reactivity (CH50) and serum concentrations of C1q, C1s, C4, C3, factor B, properdin, C5, C9, C-reactive protein (CRP), caeruloplasmin, alpha1-acid glycoprotein and haptoglobin were measured preoperatively and on days 2, 4 and 6 after operation. Abnormalities were seen in the group with chronic renal failure. Firstly, there was no significant acute phase response of C1s, C3, C5, C9 and CH50 and a significant reduction in the response of factor B. Secondly, CRP showed prolonged elevation in the post-operative period in contrast to the transient rise seen in the control group. With the possible exception of alpha1-acid glycoprotein, the behaviour of the non-complement proteins (caeruloplasmin and haptoglobin) was comparable for the two groups. These defects could impair the physiological response to infection in patients with severe chronic renal failure.

Two Cases of Choreatic Syndrome Caused by Polycythemia vera

Two patients with choreatic syndromes caused by polycythemia vera recovered after treatment of the polycythemia by only two venesections: this proves that the syndrome is due to reversible alterations. Investigations of the cerebral circulation in one of the patients showed that blood flow was lowest in the grey matter at the basal region of the brain: this suggests that the alterations might mainly occur there. However, investigation of erythrocyte rheology, glucose-6-phosphate dehydrogenase, serum concentrations of caeruloplasmin and serotonin, and urinary excretion of epinephrine, norepinephrine and vanillylmandelic acid gave normal results in both patients. There are therefore no indications as to the possible pathophysiology of these alterations. There are now 24 cases reported, including our 2 patients, which suggests that the association of these two diseases may not be so rare as supposed.

ESR study of development of RFM/Un murine myeloid leukaemia

The blood, spleen and liver of RFM/Un mice were examined by means of electron spin resonance (ESR) throughout the course of myeloid leukaemia induced by i.v. injection of leukaemic spleen cells. Marked changes in the concentration of iron transferrin and caeruloplasmin were observed in the blood 1 day after injection. As the disease progressed, changes occurred in the concentrations of the ascorbyl radical and of paramagnetic metal complexes in both spleen and liver. These changes are compared with those induced in RF/J mice injected with normal and leukaemic spleen cells from RFM/Un mice.

Changes in the concentration of copper in serum of sheep during halothane anaesthesia

Concentrations of serum copper and caeruloplasmin were measured in jugular blood samples of sheep before, during and after halothane anaesthesia. Significant decreases were recorded in the concentration of serum copper during anaesthesia, but caeruloplasmin activity did not change significantly. The serum copper concentration increased when the sheep were allowed to recover, and returned to pre-anaesthetic values after 3 h.

Plasma protein concentrations in hypertriglyceridaemic subjects. Effect of clofibrate and comparison with normal subjects

Clofibrate, a widely used hypolipidaemic agent was given for twelve weeks to ten subjects with hypertriglyceridaemia. Its effect on lipoprotein-lipids and caeruloplasmin, IgA, IgM, α 2-macroglobulin and transferrin was assessed by comparing analyses at 4, 8 and 12 weeks on therapy with the means of values at two weeks before and at the start of treatment. The normal variation in plasma proteins was assessed in six healthy volunteers during the same period of time. On clofibrate, very low density lipoprotein (VLDL) cholesterol and triglyceride concentrations fell, but the concentrations of cholesterol in low density (LDL) and high density (HDL) lipoproteins showed no consistent change. Caeruloplasmin and IgM concentrations decreased significantly, IgA showed a limited fall (significant only at 8 weeks) and α 2-macroglobulin did not change. The concentration of transferrin increased on therapy. No relationships were found between the falls in VLDL-lipid concentrations and the alterations in other plasma proteins. No significant variation occurred in the concentrations of lipids or proteins in the normal subjects during the period of study. The results indicate that clofibrate exerts general effects on protein metabolism.