Higher Ceruloplasmin Levels Research Articles

Analysis of ATP7A Expression and Ceruloplasmin Levels as Biomarkers in Patients Undergoing Neoadjuvant Chemotherapy for Advanced High-Grade Serous Ovarian Carcinoma.

Ovarian cancer (OC), particularly high-grade serous carcinoma (HGSC), is a leading cause of gynecological cancer mortality due to late diagnosis and chemoresistance. While studies on OC cell lines have shown that overexpression of the ATP7A membrane transporter correlates with resistance to platinum-based drugs (PtBMs) and cross-resistance to copper (Cu), clinical evidence is lacking. The functionality of ceruloplasmin (CP), the main Cu-transporting protein in the blood, is dependent on, among other things, ATP7A activity. This study investigated ATP7A expression and CP levels as potential biomarkers for predicting responses to PtBMs. We included 28 HGSC patients who underwent neoadjuvant chemotherapy (NACT). ATP7A expression in ovarian and peritoneal tissues before NACT and in peritoneal and omental tissues after NACT was analyzed via qPCR, and CP levels in ascites and plasma were measured via ELISA before and after NACT. In total, 54% of patients exhibited ATP7A expression in pretreatment tissue (ovary and/or peritoneum), while 43% of patients exhibited ATP7A expression in tissue after treatment (peritoneum and/or omentum). A significant association was found between higher ATP7A expression in the peritoneum before NACT and an unfavorable CA-125 elimination rate constant k (KELIM) score. Patients with omental ATP7A expression had significantly higher plasma mean CP levels before NACT. Plasma CP levels decreased significantly after NACT, and higher CP levels after NACT were associated with a shorter platinum-free interval (PFI). These findings suggest that the ATP7A transporter and CP have the potential to serve as predictive markers of chemoresistance, but further research is needed to validate their clinical utility.

A role for ceruloplasmin in the control of human glioblastoma cell responses to radiation

BackgroundGlioblastoma (GB) is the most common and most aggressive malignant brain tumor. In understanding its resistance to conventional treatments, iron metabolism and related pathways may represent a novel avenue. As for many cancer cells, GB cell growth is dependent on iron, which is tightly involved in red-ox reactions related to radiotherapy effectiveness. From new observations indicating an impact of RX radiations on the expression of ceruloplasmin (CP), an important regulator of iron metabolism, the aim of the present work was to study the functional effects of constitutive expression of CP within GB lines in response to beam radiation depending on the oxygen status (21% O2 versus 3% O2).Methods and resultsAfter analysis of radiation responses (Hoechst staining, LDH release, Caspase 3 activation) in U251-MG and U87-MG human GB cell lines, described as radiosensitive and radioresistant respectively, the expression of 9 iron partners (TFR1, DMT1, FTH1, FTL, MFRN1, MFRN2, FXN, FPN1, CP) were tested by RTqPCR and western blots at 3 and 8 days following 4 Gy irradiation. Among those, only CP was significantly downregulated, both at transcript and protein levels in the two lines, with however, a weaker effect in the U87-MG, observable at 3% O2. To investigate specific role of CP in GB radioresistance, U251-MG and U87-MG cells were modified genetically to obtain CP depleted and overexpressing cells, respectively. Manipulation of CP expression in GB lines demonstrated impact both on cell survival and on activation of DNA repair/damage machinery (γH2AX); specifically high levels of CP led to increased production of reactive oxygen species, as shown by elevated levels of superoxide anion, SOD1 synthesis and cellular Fe2 + .ConclusionsTaken together, these in vitro results indicate for the first time that CP plays a positive role in the efficiency of radiotherapy on GB cells.

Serum proteomics analysis reveals the thermal fitness of crossbred dairy buffalo to chronic heat stress.

Chronic heat stress (CHS) reduces the production efficiency of the buffalo dairy industry. Relatively low-abundance proteins with particular functions in biological processes are changed by CHS. The present study aimed to quantify the differences in low-abundance proteins of crossbred dairy buffaloes under CHS and thermal-neutral (TN) conditions. With label-free quantification, 344 low-abundance proteins were identified in serum. Of these, 17 differentially expressed low-abundance proteins with known functions were detected, and six of the differentially expressed proteins related to heat stress were validated with parallel reaction monitoring. Lipase (LPL), glutathione peroxidase 3 (GPX3), cathelicidin-2 (CATHL2), ceruloplasmin (CP), and hemoglobin subunit alpha 1 (HBA1) cooperatively played roles in the thermal fitness of dairy buffalo by decreasing heat production and increasing blood oxygen delivery. Also, dairy buffaloes may adapt to CHS and hypoxia with high levels of RBCs, HBA1 and CP to increase blood oxygen delivery capacity.

Green colored plasma discovered in a male blood donor: A cause for concern?

The normal color of plasma is yellow, which is owing to the presence of factors such as bilirubin, hemoglobin, carotenoids, and iron transferrin. We recently came across an interesting case of greenish colored plasma in our blood bank. An extensive literature survey revealed that our conspicuous finding was not an isolated one and that similar such rare incidents have been reported in the past, on a sporadic basis. Several diverse reasons have been attributed to the peculiar greenish color like the presence of high ceruloplasmin levels, Pseudomonas aeruginosa infection and so on, but they were ruled out in our case. We thus, report our finding of greenish colored plasma in an otherwise healthy donor because of the rarity of its occurrence and also, to allay any sense of fear or alarm that an encounter may raise in the blood bank staff.

Urine exosomal ceruloplasmin: a potential early biomarker of underlying kidney disease.

Previously we found that kidney tissue and urinary exosomes from patients of diabetic kidney disease showed high levels of ceruloplasmin (CP). Because CP is an acute-phase protein of kidney origin, it could be an early marker of many other kidney diseases. To investigate this hypothesis, we first measured urine exosomal and kidney expression of CP in non-diabetic chronic kidney disease (CKD) patients (membranous nephropathy, focal segmental glomerulosclerosis, lupus nephritis and IgA nephropathy) followed by a longitudinal study in rat passive Heymann nephritis (PHN), a model of human membranous nephropathy. Urinary exosomes were isolated from urine of patients (and rats) by differential centrifugation. The exosomal extracts were used for measuring CP using ELISA. Kidney expression of CP was evaluated by immune-staining biopsy tissues. Similar techniques were applied in rat PHN model (produced by injection of anti-gp600 antiserum) to analyze urine exosomal and kidney CP. Urine exosomal CP levels were 10-20 times higher in CKD patients than in controls; consistent with this we found high immune-reactive CP localized in tubules and collecting ducts of biopsies of CKD patients. In the PHN model urinary exosomal CP level was significantly higher prior to the onset of proteinuria. Early rise of urine exosomal CP, which preceded proteinuria, correlated with high immunoreactive CP found in rat kidneys at this time. We propose that urine exosomal CP, observed to increase prior to proteinuria, makes it a potential urinary biomarker to diagnose early kidney disease.

Monensin controlled-release capsule administered in late-pregnancy differentially affects rumination patterns, metabolic status, and cheese-making properties of the milk in primiparous and multiparous cows

The increased resistance to disease observed after monensin treatment could reflect a reduction of inflammation and oxidative stress. We hypothesised that if monensin supplementation was given before calving, it would help in controlling inflammation, reduce the susceptibility to disease and increase the performance. Fourteen pregnant heifers (PR) and 24 multiparous cows (ML) were randomly assigned to a treated group (Mon) or a control group (Ctr). The Mon group received 32.4 g of monensin in a controlled-release capsule 21 days before calving (expected release rate, 335 mg/d for 95 days). Their health status, rumination activity, and plasma parameters were monitored from –28 to 56 days from calving. The milk yield (MY), milk composition, and cheese-making properties were also monitored. Rumen samples were collected at 30 days from calving to assess the volatile fatty acids composition and investigate immunological parameters. After calving, the Mon group had fewer clinical diseases, an increased rumination time, and a higher MY. Monensin reduced the infiltration of both T and B cells in rumen fluid. In ML, the Mon group had lower levels of β-hydroxybutyrate in the early postpartum period and a lower level of total reactive oxygen species. Of PR, the Mon group had a tendency for lower levels of nonesterified fatty acids, higher levels of ceruloplasmin after the first month of lactation, a tendency for lower levels of paraoxonase, higher levels of γ-glutamyl transferase and higher levels of total reactive oxygen species. Monensin treatment decreased the cheese-making properties in the milk of PR.HighlightsMonensin improved the performance of all the animals and decreased the disease incidence in all of them.Monensin heightened the inflammatory and oxidative stress status and reduced the cheese-making properties in pregnant heifers.Although different effects were seen in cows with different parity, dairy cows generally beneficed of monensin administration.

An electrochemical ceruloplasmin aptasensor using a glassy carbon electrode modified by diazonium-functionalized multiwalled carbon nanotubes

Fast and accurate determination of biological compounds in human fluids plays a crucial role in clinical analysis. Low levels and high levels of ceruloplasmin (Cp) in serum cause several diseases such as Wilson’s disease, therefore, its accurate determination in human fluids is important. A selective and sensitive electrochemical biosensor was developed for Cp detection using a Cp-specific recognition aptamer. The proposed aptasensor was based on a glassy carbon electrode modified with diazonium-functional multiwall carbon nanotubes. The aptamer was linked to the electrode surface using electrochemical approach, followed by chemical immobilization of aminated-aptamer. All fabrication steps were accompanied by changes to the electrochemical parameters. The binding of Cp to aptamer was monitored by cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy. The effective parameters were optimized. The calibration curve for Cp concentration was linear at 0.02–3.0 ng mL−1 and 3.0–80.0 ng mL−1 with a detection limit (signal-to-noise ratio of 3) of 3.7 pg mL−1. The fabricated aptasensor can serve as a powerful sensor for rapid diagnosis of Cp in the human serum sample and shows a great potential for practical bioapplication.

Prolonged Hypercupremia After Vertical Sleeve Gastrectomy Successfully Treated With an Excess of Oral Zinc

We have previously reported that hypercupremia occurs in up to 19% of individuals after bariatric surgery (Lee J, et al. Am J Gastroenterol, 2012). The national recommendation for two multivitamins with minerals daily for these patients (4 mg copper daily) may provide an excess of oral copper. A 30s-year-old female (BMI 49) underwent vertical sleeve gastrectomy with no immediate postoperative complication. When seen 5 months after surgery, she was taking two chewable multivitamins with minerals daily (4 mg elemental Cu and 24 mg elemental Zn daily). Hypercupremia was present, in association with elevated ceruloplasmin, noted in retrospect (see Table 1). Follow-up blood tests showed persistently normal levels of AST, ALT, alkaline phosphatase, and albumin. At 11 months after surgery, she was instructed to stop the multivitamins. At 12 months, when hypercupremia persisted, she started one Cu-free multivitamin daily. Despite this, high levels of serum Cu persisted at the 14-month visit. A search for underlying causes showed normal protein electrophoresis (no M-spike), negative celiac disease markers, and negative ANA. Of note, urinary copper excretion was normal at 15 mcg/24 hours (normal, < 35). She was instructed in a lowcopper diet. At the 2-year visit, she had realized a loss of 44% of her excess preoperative weight. Hypercupremia was still present. Slit lamp examination showed no Kayser-Fleischer rings. She was started on zinc sulfate 220 mg before meals twice daily (100 mg elemental Zn). On follow-up 2 months later, serum Cu and ceruloplasmin had essentially normalized. Hypercupemia after bariatric surgery may be related to ingestion of the high doses of Cu present in multivitamins with mineral supplements. In this case, the high levels of serum Cu correlated with high levels of ceruloplasmin. At the same time, the normal urinary Cu excretion and absence of K-F rings excluded a more general copper overload syndrome. It is unclear whether increased production of ceruloplasmin in this case was perhaps an independent response to significant weight loss, or was simply a reflection of an excess of available copper. Oral zinc can be an effective treatment to diminish copper overload in individuals with Wilson's disease. The mechanism of zinc's apparently beneficial effect in this patient is unclear, but may be related to suppression of ceruloplasmin secretion from the liver.2452 Figure 1 No Caption available.

Взаємозв'язок між дозою тривалого активатора рецепторів еритропоетину та оксидативним стресом у хворих, які лікуються методом гемодіалізу

Наукові дані щодо дозозалежного впливу тривалого активатора рецепторів еритропоетину (ТАРЕ) на показники оксидативного стресу та перекисного окислення ліпідів мембран еритроцитів у хворих на хронічну хворобу нирок V, які лікуються гемодіалізом (ГД), є обмеженими.&#x0D; Метою нашої роботи було оцінити взаємозв’язок між застосованою дозою ТАРЕ та інтенсивністю оксидативних процесів у ГД пацієнтів. &#x0D; Матеріал та методи. 38 ГД пацієнтів були включені до одномоментного обсерваційного дослідження. Протокол дослідження був схвалений локальною етичною комісією ДУ «Інститут нефрології НАМН України». Усі пацієнти надали письму інформовану згоду на участь у досліджені. Пацієнти були стратифіковані за квартилями (≤ 25% та ≥ 75%) відповідно до середньої дози ТАРЕ і розподілені наступним чином: I групу склали хворі, які отримували ТАРЕ більше 6 місяців у дозі ≤ 50 мкг/міс (n = 20), до II групи увійшли хворі, у яких доза ТАРЕ склала ≥ 125 мкг/міс (n = 18). Поряд із стандартними діагностичними методами досліджували концентрацію малонового діальдегіду у сироватці (МДА) й еритроцитах (MДAe), вміст у крові церулоплазміну (ЦП) та трансферину (ТР). Крім того, визначали загальну пероксидазну активність (ЗПА) у еритроцитах, проникність еритроцитарних мембран (ПЕМ), підрахували відсоток гемолізу.&#x0D; Результати. У ГД пацієнтів, які лікувались ТАРЕ у дозі ≥ 125 мкг/міс визначено підвищення концентрації ЦР (р = 0,007) та ТР (р = 0,0003), тоді як ЗПА була статистично значуще зниженою порівняно з ІІ групою (р = 0,02). Крім того, У пацієнтів І групи встановлено вищий відсоток гемолізу (р = 0,03) та ПЕМ (р ˂ 0,0001). Використовуючи модель пробіт-регресії, ми визначили дозозалежний вплив ТАРЕ на рівень ПЕМ: χ2 = 21; р ˂ 0,0001.&#x0D; Висновки. Таким чином, застосування ТАРЕ у дозі понад 125 мкг на місяць покращує антиоксидантний статус ГД хворих, але разом з тим, підвищує гемоліз еритроцитів та ПЕМ. Отримані нами дані потребують подальшого підтвердження.

Predictors of cognitive impairment in patients with chronic heart failure and reduced left ventricular ejection fraction

Objective — to investigate the predictors of cognitive impairment (CI) in patients with CHF and reduced left ventricular ejection fraction of (rLVEF). Materials and methods. The examinations involved 124 patients with CHF aged 18 to 75 years, NYHA II—IV. Cognitive function was evaluated with the use of Mini-Mental State Examination (MMSE), Schulte рrobe, HADS scale. CI counted as MMSE ≤ 26 points. In addition to the standard general clinical examination, the quality of life was assessed with the use of The Minnesota Living with Heart Failure Questionnaire (MLHFQ); physical activity of patients was evaluated by Duke Activity Status Index (DASI) and the 6-minute walking test; immunoenzymometric (determination of interleukin 6, NT-proBNP, insulin), ultrasound diagnostic of endothelium-mediated vasodilatory response of the brachial artery. Statistical methods: descriptive statistics (median, upper and lower quartile), univariant logistic regression, multivariate logistic regression. Results and discussion. CI was observed in 68.5 % of patients and was associated with age (OR 1.07, 95 % CI: 1.03—1.11), duration of CHF symptoms (OR 1.02, 95 % CI: 1.001—1.03), and with the presence and duration of such co-morbidities as AH and IHD (OR 3.46, 95 % CI: 1.44—8.30 and OR 2.60, 95 % CI: 1.14—5.90 respectively). According to the univariate regression analysis, high risk of CI was defined in patients NYHA III—IV (OR 2.68, 95 % CI: 1.22—5.87) with worse quality of life assessed by MLHFQ (OR 1.02, 95 % CI: 1.002—1.04) and with the high ceruloplasmin levels (OR 1.02, 95 % CI: 1.01—1.03). At the same time, lower risk of CD was associated with better functional status (the 6-minute walking test, DASI (OR 0.996, 95 % CI: 0.99—0.999 and OR 0.96, 95 % CI: 0.94—0.99 respectively) and adherence to therapy (OR 0.77, 95 % CI: 0.60—0.98), and also with better endothelium-mediated vasodilatory response (OR 0.9, 95 % CI: 0.83—0.98). According to multivariate analysis, the independent CI predictors in patients with CHF and rLVEF were age, duration of AH, low adherence to therapy and high ceruloplasmin level of blood plasma. Conclusions. Cognitive dysfunction was observed in the majority of patients with CHF and associated with age, duration of CHF symptoms, presence and duration of AH and IHD. High risk of CI have patients with NYHA III—IV functional class, worse quality of life and high ceruloplasmin level. At the same time, the risk of CI developing was lower in the individuals with better functional status (6-minute walking test, DASI), better adherence to the treatment, and better endothelium-mediated vasodilatory response. According to the results of multivariate analysis, independent predictors of CI in patients with CHF were age, duration of AH, poor adherence to treatment and high serum ceruloplasmin level.

Effects of dry period length and dietary energy source on inflammatory biomarkers and oxidative stress in dairy cows

Negative energy balance in dairy cows in early lactation has been associated with increased inflammation and oxidative stress in these cows. The objective of this study was to evaluate the effects of dry period (DP) length and dietary energy source on inflammatory biomarkers and oxidative stress in dairy cows. Holstein-Friesian dairy cows (60 primiparous and 107 multiparous) were assigned randomly to a 3 × 2 factorial design with 3 DP length (0, 30, or 60 d) and 2 early lactation rations (glucogenic or lipogenic). Cows were fed a glucogenic or lipogenic ration from 10 d before the expected calving date. Blood was collected in wk -3, -2, -1, 1, 2, and 4 relative to calving. Dry period length affected inflammatory biomarkers and oxidative stress, especially in wk 1 and 2 after calving. Cows with a 0-d DP had higher levels of ceruloplasmin, cholesterol, and reactive oxygen metabolites, and they tended to have higher haptoglobin levels compared with cows with a 30- or 60-d DP. Cows with a 0-d DP had a lower plasma paraoxonase and bilirubin in the first 2 wk after calving and a lower liver functionality index compared with cows with a 60-d DP. Cows of parity >3 fed a glucogenic ration had higher cholesterol levels compared with cows of parity >3 fed a lipogenic ration. No interaction between DP length and ration was present for inflammatory biomarkers or oxidative stress variables. Plasma bilirubin levels for cows with a 0-d DP were negatively related to energy balance and metabolic status in these cows. Moreover, occurrence of clinical health problems (fever, mastitis, metritis, and retained placenta) was 41, 27, and 30% for cows with 0-, 30-, and 60-d DP, respectively. High levels of ceruloplasmin, cholesterol, and reactive oxygen metabolites in cows with 0-d DP were related to the occurrence of health problems in these cows. In conclusion, omitting the DP increased levels of ceruloplasmin, cholesterol, and reactive oxygen metabolites, and decreased levels of bilirubin and paraoxonase in plasma, independent of ration, compared with cows with a 60-d DP. These contrasting effects of DP length on inflammatory status could be explained in part by the improved energy balance and occurrence of health problems in these cows, but was not related to increased somatic cell count in cows with a 0-d DP. Cows with a 0-d DP had better energy balance, but also had higher levels of oxidative stress compared with cows with a 60-d DP. Moreover, occurrence of health problems did not differ between cows with different DP lengths.

Levels of heavy and essential trace metals and their correlation with antioxidant and health status in individuals occupationally exposed to municipal solid wastes.

Recent studies have indicated an increased incidence of toxic neuropathies among waste management workers (WMW) possibly linked to increased detection of heavy metals in municipal solid wastes. The present study evaluated serum levels of some heavy and essential trace metals in relation to oxidant/antioxidant status of WMW. One hundred and twenty-six WMW and 84 non-WMW (control) were recruited. Metal/element concentration was measured by atomic absorption spectrophotometry and oxidant/antioxidant markers were determined using standard procedures. The WMW exhibited significantly ( p < 0.001) decreased ferric reducing ability of plasma (FRAP) and higher levels of ceruloplasmin (Cp) and malondialdehyde. Iron (Fe) and copper (Cu) levels were significantly lower ( p < 0.05) and higher ( p < 0.001), respectively in WMW when compared with control while levels of other trace elements were not significantly different between these groups. Lead (Pb) and chromium levels were significantly higher ( p < 0.001 and p < 0.05, respectively) in WMW while mercury levels were comparable with those of control subjects. In WMW, Cp ( r = -0.182; p > 0.05) and FRAP ( r = 0.277; p < 0.05) negatively and positively correlated with Pb, respectively, while a positive correlation was observed between zinc ( r = 0.230; p < 0.05) and Pb and between Cu ( r = 0.541; p > 0.001) and Fe. Overall, the decreased antioxidant capacity and increased oxidative stress observed in WMW in this study may be related to their blood levels of heavy and essential trace metals. Conscious efforts are required, therefore, to reduce risk and protect WMW from toxic neuropathies and other adverse health consequences of occupational exposure.

Increased circulating cell-free hemoglobin levels reduce nitric oxide bioavailability in preeclampsia

Contrasting with increased nitric oxide (NO) formation during healthy pregnancy, reduced NO bioavailability plays a role in preeclampsia. However, no study has examined whether increased NO consumption by enhanced circulating levels of cell-free hemoglobin plays a role in preeclampsia. We studied 82 pregnant women (38 healthy pregnant and 44 with preeclampsia). To assess NO bioavailability, we measured plasma and whole blood nitrite concentrations using an ozone-based chemiluminescence assay. Plasma ceruloplasmin concentrations and plasma NO consumption (pNOc) were assessed and plasma hemoglobin (pHb) concentrations were measured with a commercial immunoassay. We found lower whole blood and plasma nitrite concentrations in preeclamptic patients (-48 and -39%, respectively; both P < 0.05) compared with healthy pregnant women. Plasma samples from preeclamptic women consumed 63% more NO ( P = 0.003) and had 53% higher pHb and 10% higher ceruloplasmin levels than those found in healthy pregnant women ( P < 0.01). We found significant positive correlations between pHb and pNOc ( r = 0.61; P < 0.0001), negative correlations between pNOc and whole blood or plasma nitrite concentrations ( P = 0.02; r = -0.32 and P = 0.01; r = -0.34, respectively), and negative correlations between pHb and whole blood or plasma nitrite concentrations ( P = 0.03; r = -0.36 and P = 0.01; r = -0.38, respectively). These findings suggest that increased pHb levels lead to increased NO consumption and lower NO bioavailability in preeclamptic compared with healthy pregnant women.

High ceruloplasmin levels are associated with obsessive compulsive disorder: a case control study

BackgroundAlterations in ceruloplasmin are currently assumed as one of the mechanisms underlying the development of a number of neurodegenerative disorders. Several studies indicate that elevated serum ceruloplasmin levels may play a role in schizophrenia by exacerbating or perpetuating dopaminergic dysregulation. No study investigating the relationship between ceruloplasmin and obsessive-compulsive disorder (OCD) has been published to date. Nowadays OCD is increasingly speculated to be a different disorder than other anxiety disorders, and rather is considered to be more similar to psychotic disorders. The objective of this study to explore whether there is an association of ceruloplasmin with OCD as in schizophrenia.Method26 pure OCD and 9 co-morbid OCD patients from Gaziantep University Sahinbey Research Hospital, Psychiatry Clinics, diagnosed according to the DSM IV and 40 healthy controls were included in the study. Blood samples were collected; ceruloplasmin levels were measured.ResultsThe mean ceruloplasmin level in pure OCD patients, co-morbid OCD patients, and control group persons were 544.46 ± 26.53, 424.43 ± 31.50 and 222.35 ± 8.88 U/L respectively. Results of all 3 groups differ significantly. Positive predictive value of ceruloplasmin for that cut-off point is 31/31 (100%) and negative predictive value is 40/44 (91%) in our group.ConclusionAlthough the nature of relationship is not clear there was an association between ceruloplasmin levels and OCD in our study.

Is elevated serum ceruloplasmin level associated with increased risk of coronary artery disease?

An imbalance between the lipid peroxidation process and antioxidative protection is associated with the pathophysiology of coronary artery disease (CAD). The authors aimed to determine the relationship between the contributors of antioxidant protection, such as paraoxonase-1 (PON1) activity, albumin, vitamin C and ceruloplasmin (CP) levels, and lipid peroxidation indicators. In the present study, the activity of PON1 was measured, together with serum concentrations of a variety of lipid constituents, albumin, vitamin C and CP levels, and lipid peroxidation indicators (conjugated dienes [CDs] and thiobarbituric acid-reactive substances [TBARS]). Data were gathered from 26 nondiabetic, angiographically proven, Turkish CAD patients and 26 healthy controls living in the Antalya region (Turkey). CAD patients had significantly lower PON1 activity, high-density lipoprotein cholesterol, vitamin C and albumin concentrations, and higher CP, CD and TBARS concentrations than the controls. In the entire study population (n=52), serum CP levels were positively correlated with TBARS and CD levels, and negatively correlated with albumin and vitamin C levels, as well as with PON1 activity. On multiple logistic regression analysis, risk factors associated with CAD included high CP and low albumin levels. CAD patients and controls were matched for age and sex, and high CP and low albumin levels were found to be independent risk factors for CAD. The present data gathered from the study group living in the Antalya region verifies that in CAD patients, CP impairs the oxidant-antioxidant balance in favour of the oxidants.

High levels of ceruloplasmin in the serum of transgenic mice developing hepatocellular carcinoma

Transgenic mice expressing the Simian virus 40 large T antigen under the control of the liver-specific human antithrombin-III promoter all develop well-differentiated hepatocellular carcinoma. During tumour development serum ceruloplasmin (Cp) increases gradually until it reaches 30 times control levels in all transgenic mice at 6 months of age. The accumulation of Cp in the serum is due to the increased transcription of the Cp gene as well as to the increase in Cp mRNA stability in the livers of the transgenic mice. One-half of the overproduced Cp is charged with copper and Cp-associated serum oxidase activity increases in parallel with the holo-Cp concentration. Through its ferroxidase activity Cp is involved prominently in iron metabolism. Analysis of copper and iron in serum and liver revealed increased copper levels in the serum of tumour-bearing animals and which increased in parallel with Cp concentration; the amounts of copper in the liver were unchanged. In contrast, serum iron remained constant during tumour development whereas the iron concentration in the livers of the transgenic mice decreased.

Specific oxidase activity of cord serum ceruloplasmin in the newborn.

In a study of 50 full-term newborns, we found serum levels of ceruloplasmin, its oxidase activity and specific oxidase activity (activity per unit mass of enzyme protein) which were significantly lower than in adult subjects (p<0.001). A significant correlation was obtained between the specific oxidase activity of the neonatal ceruloplasmin and the transferrin/alpha-fetoprotein ratio (p<0.01), which reflects the maturity of the fetal hepatocyte through its ability to synthesise fetal- and non-fetal-associated proteins. The lower specific oxidase activity of the ceruloplasmin in newborns would be due to a higher relative proportion of apoprotein, and/or other molecular forms with a poor copper content in the oxidase sites. This could be due to an inability to transfer copper into a common intracellular pool for holoceruloplasmin synthesis and biliary copper excretion. A high interindividual variability was found for the specific oxidase activity of the neonatal ceruloplasmin, and in the newborns with higher levels of ceruloplasmin this, from a catalytic point of view, is more similar to the adult form.

High ceruloplasmin levels in rats without high lipoprotein oxidation rates

The serum copper protein ceruloplasmin, though sometimes considered an antioxidant, can promote lipoprotein oxidation in vitro under certain conditions. However, an inflammation-induced, two week elevation of rat serum ceruloplasmin levels did not render low plus very low density lipoproteins more prone to oxidation in vitro. Thus, high ceruloplasmin levels in vivo are not necessarily associated with high lipoprotein oxidation rates.

Dietary Copper Level Affects Copper Metabolism During Lipopolysaccharide-Induced Immunological Stress in Chicks

Two experiments were conducted to examine the effect of dietary Cu level on Cu metabolism during the acute phase response in broiler chicks with adequate (Experiment 1) or deficient (Experiment 2) Cu. Diets based on cornstarch and isolated soybean protein were used to formulate a basal diet, and basal diet plus either 5, 10, or 15 mg/kg additional Cu as either CuO or CuSO4. Each diet was fed to six pens of five chicks per pen (Experiment 1) or eight pens of five chicks (Experiment 2). Half of the chicks on each diet were injected with Salmonella typhymurium lipopolysaccharide (LPS) on alternate days. In Experiment 1, LPS significantly decreased daily gain, feed intake, and feed efficiency (P < 0.01) and increased the concentration of Cu in blood plasma (P < 0.01). In the uninjected birds, adding 5, 10, or 15 mg/kg Cu as CuO or 15 mg/kg Cu as CuSO4 increased the rate of gain over that of chicks fed the basal diet. In the birds challenged with LPS, 10 mg/kg Cu as CuO increased the rate of gain and efficiency compared to those of chicks fed the basal diet. Addition of CuSO4 to the diet of chicks challenged with LPS did not affect gain, intake, or feed efficiency compared to those of chicks fed the basal diet. Ceruloplasmin levels were higher in chicks challenged with LPS than in control chicks (P = 0.03), and this difference tended to be greater in chickens fed CuO than in chickens fed CuSO4 (P = 0.07). In chicks challenged with LPS, feeding CuO at all levels and feeding CuSO4 to give 10 or 15 mg/kg Cu increased ceruloplasmin levels above that of chicks fed the basal diet. Hepatic Mn superoxide dismutase (SOD) and Cu/Zn SOD were not influenced by dietary Cu level or source or LPS. Results of Experiment 2 were similar to those of Experiment 1 except that supplemental CuSO4 and CuO gave similar increases in gain and CuSO4 was more effective at increasing ceruloplasmin levels. Chicks given supplemental Cu had higher ceruloplasmin levels following challenge with LPS than Cu-deficient chicks fed the basal diet. Apparently, Cu requirements are higher for chicks experiencing an acute phase response than for healthy chicks.

Carrageenan-induced acute inflammation in magnesium deficient rats

Magnesium (Mg) deficient rats show biochemical signs of mild inflammation. Conceivably, this could prime rats for enhanced stress-induced inflammation, or inhibit such injury by raising body contents of protective proteins such as the acute phase reactants. Mg deficient rats showed normal acute paw inflammation due to carrageenan treatment, despite high levels of ceruloplasmin, an acute phase protein. Thus, Mg deficiency, though it produced a moderate acute phase response, did not exert a general effect on susceptibility to inflammation.