Ceruloplasmin Research Articles

Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections.

Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected (n = 21) and control (n = 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1–679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections.

THE ROLE OF GUT INDIGENOUS MICROBIOTA IN THE DEVELOPMENT OF OXIDATIVE STRESS IN WOMEN WITH RECURRENT PYELONEPHRITIS

The aim of our study was to investigate the oxidative stress intensity depending on the content of Lactobacillus spp. in the colon of patients with recurrent pyelonephritis.
 Material and methods. The observational study involved 60 women with chronic kidney disease (CKD) stage I-II: uncomplicated pyelonephritis, aged 39.5 ± 3.2 years. According to the quantitative content ofLactobacillus spp. in the patients’ intestine, the women were allocated into two groups: the first group of the patients (n = 34) had a deficit ofLactobacillus spp. in the intestine, and the second one (n = 26) had a normal content of Lactobacillus spp. Along with the standard diagnostic methods, we defined the content of malondialdehyde levels in the serum (MDAs) and erythrocytes (MDAe) spectrophotometrically as an indicator of lipid peroxidation. Such parameters as the concentration of ceruloplasmin (CP), transferrin (TR) and sulfhydryl groups (SH-groups) in the blood and total peroxidase activity (TPA) in erythrocyte were studied as the indicators of antioxidant system. In addition, we calculated of oxidative stress index (OSI).
 Results. The analysis of lipid peroxidation defined a significant increase of MDA level in the serum (p = 0.008) and urine (p = 0.003) ofpatients with deficit of intestine lactobacillus spp. Moreover, in the patients ofGroup II we observed the high level of serum OSI (p = 0.03). By contrast, the TPA level was significantly reduced (p = 0.02).
 Conclusions. The results of our work confirm the experimental studies data, which demonstrate the leading role of gut indigenous microbiota in the development of oxidative stress.

Effects of paraoxonase, arylesterase, ceruloplasmin, catalase, and myeloperoxidase activities on prognosis in pediatric patients with sepsis

BackgroundThe present study aimed to investigate the levels of paraoxonase (PON), stimulated paraoxonase (SPON), arylesterase (ARE), ceruloplasmin (CLP), myeloperoxidase (MPO), and catalase (CAT) in pediatric sepsis and to explore their effects on the prognosis of sepsis. MethodsPatients diagnosed with sepsis (n=33) and healthy controls (n=30) were included. PON, SPON, ARE, CLP, MPO, and CAT activities were measured in the sepsis and control groups. Additionally, the parameters were compared between survivors and non-survivors in the sepsis group. The levels of hemoglobin, white blood cell, platelet, lactate, and C-reactive protein were measured in the blood samples drawn from the patients with sepsis at diagnosis, at the 48th hour, and on day 7. The pediatric risk of mortality and pediatric logistic organ dysfunction scores of the patients were used for the estimation of severity of disease. ResultsLower ARE (153.24 vs. 264.32U/L; p<0.001), lower CLP (80.58 vs. 97.98U/L; p=0.032), lower MPO (91.24 vs. 116.55U/L; p=0.023), and higher CAT levels (256.5 vs.145.5kU/L; p=0.003) were determined in the sepsis group as compared to the control group. There was no difference between the groups in terms of PON or SPON levels. No difference was determined between the survivors and non-survivors in terms of any of the parameters. ConclusionsThe present study determined that ARE, CLP, CAT, and MPO levels are different between the pediatric patients with sepsis and healthy controls. ARE level can be a potent biomarker for sepsis in critical patients in intensive care units. Further studies with larger samples are required to demonstrate the value of these parameters as prognostic biomarkers in pediatric sepsis.

Frequency-dependent changes in the amplitude of low-frequency fluctuations in patients with Wilson\u2019s disease: a resting-state fMRI study

To investigate the frequency-dependent changes in the amplitude of low-frequency fluctuations (ALFF) in patients with Wilson’s disease (WD). Resting-state function magnetic resonance imaging (R-fMRI) were employed to measure the amplitude of ALFF in 28 patients with WD and 27 matched normal controls. Slow-5 (0.01–0.027 Hz) and slow-4 (0.027–0.073 Hz) frequency bands were analyzed. Apart from the observation of atrophy in the cerebellum, basal ganglia, occipital gyrus, frontal gyrus, precentral gyrus, and paracentral lobule, we also found widespread differences in ALFF of the two bands in the medial frontal gyrus, inferior temporal gyrus, insula, basal ganglia, hippocampus/parahippocampal gyrus, and thalamus bilaterally. Compared to normal controls, WD patients had increased ALFF in the posterior lobe of the cerebellum, inferior temporal gyrus, brain stem, basal ganglia, and decreased ALFF in the anterior lobe of the cerebellum and medial frontal gyrus. Specifically, we observed that the ALFF abnormalities in the cerebellum and middle frontal gyrus were greater in the slow-5 than in the slow-4 band. Correlation analysis showed consistently positive correlations between urinary copper excretion (Cu), serum ceruloplasmin (CP) and ALFFs in the cerebellum. Our study suggests the accumulation of copper profoundly impaired intrinsic brain activity and the impairments seem to be frequency-dependent. These results provide further insights into the understanding of the pathophysiology of WD.

Oestrus synchronisation and superovulation alter the cervicovaginal mucus proteome of the ewe

Although essential for artificial insemination (AI) and MOET (multiple ovulation and embryo transfer), oestrus synchronisation and superovulation are associated with increased female reproductive tract mucus production and altered sperm transport. The effects of such breeding practices on the ovine cervicovaginal (CV) mucus proteome have not been detailed. The aim of this study was to qualitatively and quantitatively investigate the Merino CV mucus proteome in naturally cycling (NAT) ewes at oestrus and mid-luteal phase, and quantitatively compare CV oestrus mucus proteomes of NAT, progesterone synchronised (P4) and superovulated (SOV) ewes. Quantitative analysis revealed 60 proteins were more abundant during oestrus and 127 were more abundant during the luteal phase, with 27 oestrus specific and 40 luteal specific proteins identified. The oestrus proteins most disparate in abundance compared to mid-luteal phase were ceruloplasmin (CP), chitinase-3-like protein 1 (CHI3L1), clusterin (CLU), alkaline phosphatase (ALPL) and mucin-16 (MUC16). Exogenous hormones greatly altered the proteome with 51 and 32 proteins more abundant and 98 and 53 proteins less abundant, in P4 and SOV mucus, respectively when compared to NAT mucus. Investigation of the impact of these proteomic changes on sperm motility and longevity within mucus may help improve sperm transport and fertility following cervical AI. SignificanceThis manuscript is the first to detail the proteome of ovine cervicovaginal mucus using qualitative and quantitative proteomic methods over the oestrous cycle in naturally cycling ewes, and also after application of common oestrus synchronisation and superovulation practices. The investigation of the mucus proteome throughout both the follicular and luteal periods of the oestrous cycle, and also after oestrous synchronisation and superovulation provides information about the endocrine control and the effects that exogenous hormones have on protein expression in the female reproductive tract. This information contributes to the field by providing important information on the changes that occur to the cervicovaginal mucus proteome after use of exogenous hormones in controlled breeding programs, which are commonly used on farm and also in a research setting.

Effect of oxidative stress on major plasma carotenoid content and composition in prepubertal children with growth hormone deficiency

Objective and hypotheses. This study aimed at examining the effect of oxidative stress on amount and composition of major plasma carotenoids in prepubertal children with growth hormone deficiency (GHD).Material and methods. Thirteen prepubertal treatment-naive children (2 girls, 11 boys; aged 3.5—12.0 yr, median 8.0 years; bone age 1.5—8.0 yr; median 6.0 years,) with GHD and 7 prepubertal health children (7 boys; aged 6—11 years; median 9.3 years) were included in the study. The levels and composition of carotenoids (lutein with zeaxanthin, lycopene isomers, β-cryptoxanthin, β- and α-carotene and ketocarotenoids) were measured using reverse phase HPLC. Activity of the antioxidant system was assayed via thiobarbituric acid reactive substances (TBARS), ceruloplasmin (CP) levels and total antioxidant capacity (TAC) of plasma. Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were also measured.Results. The levels of TBARS, TC and LDL-C in the GHD children were higher than in healthy children (median 5.6 vs 3.8 µM/L, 4.00 vs 4.37 and 2.40 vs 2.70 mM/L, respectively). Total carotenoid level did not significantly differ between control and the GHD groups. However, contents of lutein and β-cryptoxanthin were significantly lower in the GHD children in comparison with control group (21.34 vs 6.97 and 25.23 vs 10.08 mg/l, respectively). In contrast, levels of lycopene, α- and β-carotene did not significantly differ in the GHD and control groups. At the same time, the level of ketocarotenoids in the GHD children increases (35.67 vs 114.9 mg/l).Conclusions. We observed that the presence of mild oxidative stress leads to a changes in carotenoid profile of GHD children.

The interaction between nonalcoholic steatosis, anthropometric indicators and disturbance of lipid peroxidation and antioxidant defense in patients with signs of obesity.

Aim - to study charac­teristics of indicators of lipid peroxidation (LPO) and antioxidant system (AOS), depending on the body mass index (BMI) in patients with non-alcoholic steatosis (NASP) in combination with obesity (OB) and pathology of the biliary tract (BT). The study involved 100 patients with NASP in combination with OB and BT pathology, who at the time of sonographic and morphological study of liver biopsy presented signs of hepatic steatosis. Among the patients there were 19 men and 81 women. The average age of patients - (53,67 ± 1,11) years. The control group consisted of 20 practically healthy persons (PHP). BMI is determined by the formula Quetelet. Depending on the degree of BMI increase all patients with NASH and obe­sity were divided into three groups: 1 group – with BМI 25-29,9 kg/m 2 – ex­cessive body mass; 2 group – with BMI 30-34,9 kg/m 2 – obesity of I degree; 3 group – with BMI 35–39,9 kg/m 2 – obesity of ІІ degree. Status of LPO system was assessed by the concentration of malondialdehyde in plasma and red blood cells and the content of lipid peroxidation intermediates in the two phases of the lipid extract – isolated double bonds, diene conjugates, oksidien conjugates and the final LPO products – schiff bases. Factors of antioxidant defense activity were assessed by ceruloplasmin (CP), superoxide dismutase (SOD) and catalase in erythrocyte hemolysate. All LPO indicators have been activated in the two phases of lipid extract (from p<0,05 to p<0,001 when compared with a group of PHP and p<0,05 as compared to other groups of patients) and depended on increasing BMI. Indicators of AOS – SOD and catalase in all NASP groups practically did not differ from PHP parameters and did not depend on the increase of BMI. From the CP side a compensatory increase in its activity in response to the intensification of LPO was revealed. In NASP patients in combination with OB and comorbid disorders of BT the course of the disease was associated with significant violations of the oxidant-antioxidant balance, which depended on increasing BMI parameters.

Correlations between Copper Deficiency and Oxidative Stress in Dairy Cows

Copper (Cu) is an important microelement for the maintenance of normal metabolism of dairy cows and a variety of enzymic composition. When Cu deficiency is occurred in dairy cows, it’ll be accompanied by many diseases. The main objective of the present study was to explore the correlation between Cu deficiency and oxidative stress of lactating dairy cows and evaluate early-warning index for Cu deficiency. There were divided into two groups based on serum Cu levels: a Cu deficiency group and a control group. Serum levels of ceruloplasmin (CP), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), and Cu were analysed. The results showed that CP levels in the Cu deficiency group were significantly lower than in the control group, while T-AOC levels were significantly higher, but there were no significant differences between SOD and GSH-PX levels. Pearson correlation analysis showed that serum CP levels were very significantly positively correlated with Cu deficiency, while serum T-AOC levels were very significantly negatively correlated and SOD and GSH-PX serum levels showed no correlations. Logistic regression analysis showed that CP was a risk factor for Cu deficiency, ROC analysis showed that CP had diagnostic value for Cu deficiency, with a critical value of 13.7 U/l. Hence, CP and T-AOC levels in lactating cows showed strong correlations to Cu deficiency, indicating that serum CP can be used to predict Cu deficiency.

Oxidative stress and angiogenesis in primary hyperparathyroidism.

SummaryBackgroundThe inappropriate elevation of parathormone (PTH), which regulates the process of angiogenesis in parathyroid tissue, causes the changes of activity of enzymes responsible for the removal of free radicals. Parathyroidectomy (PTX) in patients with primary hyperparathyroidism (PHPT) lowers the level of PTH and leads to the reduction of risk of cardiovascular and all-cause mortality by normalization of the antioxidant status. Therefore, the aims of the study were to assess the activity of antioxidant enzymes and free radical reaction products in patients after parathyroidectomy, and to evaluate the correlation between the systemic oxidative stress and angiogenic parameters.Materials and methodsPatients with PHPT treated surgically were enrolled into the study. Total antioxidant capacity (TAC), total oxidative status (TOS), oxidative stress index (OSI), superoxide dismutase (SOD), ceruloplasmin (CER), lipid hydroperoxides (LHP) and malondialdehyde (MDA) were measured before and after parathyroidectomy. The immunohistological expression of angiogenic factors in parathyroid specimens was assessed by the BrightVision method from ImmunoLogic using murine monoclonal anti-human: anti-VEGF, anti-CD31 and anti-CD106 antibodies.ResultsThe significant increase of TAC, CER, reduction of TOS, MDA, SOD, especially for cytoplasmic form, and significant decrease of OSI, LHP were observed after PTX. There was no significant correlation between changes of oxidative stress markers and angiogenic parameters: VEGF, CD-31, CD-106 in parathyroid tissue. The correlation level was low and medium.ConclusionsParathyroidectomy causes down-regulation of lipid peroxidation processes and leads to reduction of oxidative stress in patients with PHPT. The decrease in the OSI is the results of down-regulation of oxidative stress in the postoperative period. The change of the antioxidant status has no impact on angiogenesis processes in parathyroid tissue.

Quantification of ATP7B Protein in Dried Blood Spots by Peptide Immuno-SRM as a Potential Screen for Wilson's Disease.

Wilson's Disease (WD), a copper transport disorder caused by a genetic defect in the ATP7B gene, has been a long time strong candidate for newborn screening (NBS), since early interventions can give better results by preventing irreversible neurological disability or liver cirrhosis. Several previous pilot studies measuring ceruloplasmin (CP) in infants or children showed that this marker alone was insufficient to meet the universal screening for WD. WD results from mutations that cause absent or markedly diminished levels of ATP7B. Therefore, ATP7B could serve as a marker for the screening of WD, if the protein can be detected from dried blood spots (DBS). This study demonstrates that the immuno-SRM platform can quantify ATP7B in DBS in the picomolar range, and that the assay readily distinguishes affected cases from normal controls (p < 0.0001). The assay precision was <10% CV, and the protein was stable for a week in DBS at room temperature. These promising proof-of-concept data open up the possibility of screening WD in newborns and the potential for a multiplexed assay for screening a variety of congenital disorders using proteins as biomarkers in DBS.

Mechanism of action and effect of immune-modulating agents in the treatment of psoriasis

ObjectivesThe aim of this work is to study the possible mechanisms through which different immune-modulating agents can produce their beneficial effects on treatment of psoriasis and to determine whether the supplementation of these agents for psoriasis patients induces regression of psoriasis. Subjects and methodsOne hundred fifty participants were included in this study. The participants were divided into five groups: 1. Normal control group, 2. Psoriasis patients not taking any treatment, 3. Psoriasis patients treated with anti-psoriatic treatment (including coal tar, vitamin D3 analogues and corticosteroids). 4. Psoriasis patients treated with anti-psoriatic treatment and oral metformin (850mg twice daily) and 5. Psoriasis patients treated with anti-psoriatic treatment and oral pioglitazone (15mg once a day). Demographic characteristics, diabetic index, lipid profile and liver function tests were monitored. The CD4+ Tcells, CD8+ Tcells, CD4+/CD8+ ratio, interleukin-2 (IL-2), C-reactive protein (CRP) and ceruloplasmin (CP) were assayed. ResultsAfter treatment of psoriasis patients with a traditional anti-psoriatic drug in combination with metformin and peroxisome proliferator-activated receptor gamma (PPARɤ) agonist (pioglitazone), the CD4+ T cells, IL-2, CRP, CP, ALT and AST levels were statistically significantly decreased compared to psoriasis patients without treatment. Positive and significant correlations between CD4+ % and IL-2, CRP, CP, ALT and AST in psoriasis patients were recorded. ConclusionsThe activation of PPAR-γ receptors by pioglitazone results in reduced formation of the proinflammatory cytokines and infiltration by inflammatory cells. Additionally, metformin acts as a modulator of the immune system in psoriasis patients and has a remarkable effect on the early stages of psoriasis. Therefore, either pioglitazone or metformin in combination with traditional anti-psoriatic drugs provides better results in the treatment of psoriasis than does each alone.

Biomarkers Predicting Acute GvHD and Transplant Outcomes in 120 Consecutive Allogeneic HSCT Recipients

Background: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for many haematological diseases. Despite advances in supportive therapies, acute Graft-versus-Host Disease (aGvHD) remains the leading cause of early morbidity and mortality. There are shortcomings in the prediction of aGVHD, indicating the urgent need for non-invasive and reliable laboratory tests to allow a precision-medicine tailored prophylactic approach.Aims: We conducted a prospective observational study to ascertain the potential usefulness of the levels of eleven biomarkers, measured pre- and at +7 days post-alloHSCT, in predicting the development and severity of aGvHD in allo-HSCT patients. These time-points were chosen as early risk stratification may provide a window for additional prophylactic measures.Methods: We collected data from 120 consecutive patients (41 female and 79 male; median age 52, range 19-77 years) who underwent allo-HSCT at our institute between 2014 and 2015. Most patients were affected by myeloid malignancies (AML=52%, MDS=11%, MPN=5%) while 32% were of lymphoid origin (ALL, MM and lymphomas). Revised disease-risk index (DRI, Armand et al.) was low or intermediate for 41% of pts, high for 44% and very high for 15% of them. Most patients (n=101) received peripheral blood stem cells (PBSC). Stem cell donors were unrelated (n=39, HLA matching 9/10 in 14 and 10/10 in 25), family haploidentical (n=56), HLA-identical sibling (n=21), or cord blood (n=4). Post-transplant GvHD prophylaxis was PT-Cy-bases in 65 patients, ATG-bases in 28 patients, both agents in 18 cases whilst 9 patients received neither. Additionally, sirolimus and MMF were used as additional GvHD prophylaxis according to institutional guidelines. The following biomarkers were measured 7 days pre- and post-transplant: interleukin-6 (IL6), Ceruloplasmin(CER), Cholinesterase (CHE), Albumin, Immunoglobulin A, Gammaglutamyl-transferase (GGT), White Blood Cells, Neutrophils, Haemoglobin,Platelets and Glycaemia. ROC curves were used to define optimal cut-offs of the biochemical variables to predict 100-day severe aGvHD and 100-days TRM by logistic regression. Then cumulative incidences curves (CI) for aGvHD and TRM and overall-survival (OS) curves were computed comparing patients under and over the identified cut offs for the variables with the best reported sensitivity and specificity. Multivariate Cox proportional hazard regression was finally applied.Results: The 100-days CI of grade III-IV aGvHD was 13.5%, with a 100-days CI of TRM of 12%. The 1-year OS was 64%. Death was reported in 49 of the total 120 patients: 5/49 deaths were attributable to aGvHD. At baseline, IL6 threshold value of 2.5 pg/ml was significantly associated with the prediction of 100-days severe aGVHD (sens 65%, spec 61%) and TRM (sens 75%, spec 61%). Patients with IL-6 concentration equal or superior to 2.5 pg/ml had higher 100-days CI of severe aGvHD (16% Vs 6%, p 0,03) and TRM (12% Vs 3%, p 0,06). Interestingly, higher IL6 concentrations were associated to worse 1-year OS (42% Vs 82%, p<0,001) and were able to better stratify OS also in patients with the same DRI class (OS in low-intermediate risk: 58% vs 85%; high-risk 39% vs 78%; very high-risk 21% vs 49%; p 0,01). At 7 days after HSCT, GGT values were raised in patients who later developed grade III-IV GvHD (cut-off 129 U/l by ROC analysis, sens 69%, spec 67%). Indeed, patients with GGT>= 129 U/l levels had higher 100-days CI of severe aGVHD (15% vs 7%, p 0,16) and TRM (13% vs 4%, p 0,01), in addition to worse OS (53% vs 71% at 1y, p 0,03). By multivariate analysis (adjusting for age, DRI, Sorror comorbidity index, type of donor, source of stem cells, and backbone of GvHD prophylaxis) pre-transplant IL6 concentrations were significantly associated to severe aGvHD (HR 3, p 0.04), TRM (HR 3, p 0.06), and OS (HR 2.6, p 0,004).Conclusion: In our series, baseline IL6 levels are predictors of aGvHD, especially with regards to grade III/IV aGvHD and translate in a higher risk of TRM and worse OS. This biomarker could be incorporated in a treatment algorithm to increase primary GvHD prophylaxis in patients at risk of severe aGVHD, potentially improving the final outcome of allo-HSCT. DisclosuresCiceri:MolMed SpA: Consultancy.

Dietary supplementation of L-glutamine and L-glutamate in broiler chicks subjected to delayed placement

This study was conducted to investigate the effect of dietary glutamine (Gln) + glutamic acid (Glu) supplementation on growth performance and physiological stress response in broiler chickens subjected to 24 h delay in placement. Equal number of day-old broiler chicks were assigned to either immediate placement or with 24 h delay in placement with no access to feed and water. Chicks from each placement group were fed either standard starter diet (control) or standard starter diet +1% AminoGut (AG; mixture of 10% Gln and 10% Glu) from 1 to 21 d. Blood and duodenal samples were collected at 21 d for analysis of serum levels of ceruloplasmin (CER), ovotransferin (OVT) and α-1 acid glycoprotein (AGP), duodenal heat shock protein (HSP) 70 expression, and villi length and crypt depth. Results showed that delayed placement for 24 h was detrimental to weight gain during the starter phase (1 to 21 d) but not thereafter. AG supplementation was not able to eliminate that reduction in weight gain and feed intake during the starter stage. However, the observed enhancement in villi length and crypt depth at d 21 resulted in improvement of FCR and weight gain during the finisher stage (22 to 42 d) and consequently the overall period (1 to 42 d). Broiler chickens supplemented with AG also showed lower mortality rate, and higher AGP, OVT, CER, and HSP 70 expression compared to their control counterparts. Based on AGP, OVT, CER, and HSP 70 expression, there is no indication that delayed placement was physiologically stressful to the broiler chickens at 21 d of age.

Acute phase protein mRNA expressions and enhancement of antioxidant defense system in Black-meated Silkie Fowls supplemented with clove (Eugenia caryophyllus) extracts under the influence of chronic heat stress.

BackgroundThe current study investigates the anti-stress effects of clove (Eugenia caryophyllus) extracts (0, 200, 400, and 600 mg/kg) on serum antioxidant biomarkers, immune response, immunological organ growth index, and expression levels of acute phase proteins (APPs); ovotransferrin (OVT), ceruloplasmin (CP), ceruloplasmin (AGP), C-reactive protein (CRP), and serum amyloid-A (SAA) mRNA in the immunological organs of 63-d-old male black-meated Silkie fowls subjected to 21 d chronic heat stress at 35 ± 2 °C.ResultsThe results demonstrated that clove extract supplementation in the diet of Silkie fowls subjected to elevated temperature (ET) improve growth performance, immune responses, and suppressed the activities of glutathion peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and thioredoxin reductase (TXNRD); reduced serum malonaldehyde (MDA) and glutathione (GSH) concentrations when compared with fowls raised under thermoneutral condition (TC). Upon chronic heat stress and supplementation of clove extracts, the Silkie fowls showed a linear increase in GSH-Px, SOD, CAT, and TXNRD activities (P = 0.01) compared with fowls fed diets without clove extract. ET decreased (P < 0.05) the growth index of the liver, spleen, bursa of Fabricius and thymus. However, the growth index of the liver, spleen, bursa of Fabricius and thymus increased significantly (P < 0.05) which corresponded to an increase in clove supplemented levels. The expression of OVT, CP, AGP, CRP, and SAA mRNA in the liver, spleen, bursa of Fabricius and thymus were elevated (P < 0.01) by ET compared with those maintained at TC. Nevertheless, clove mitigates heat stress-induced overexpression of OVT, CP, AGP, CRP and SAA mRNA in the immune organs of fowls fed 400 mg clove/kg compared to other groups.ConclusionsThe results showed that clove extracts supplementation decreased oxidative stress in the heat-stressed black-meated fowls by alleviating negative effects of heat stress via improvement in growth performance, antioxidant defense mechanisms, immunity, and regulate the expression of acute phase genes in the liver and immunological organs.Electronic supplementary materialThe online version of this article (doi:10.1186/s40781-016-0122-4) contains supplementary material, which is available to authorized users.

Correlations between ceruloplasmin, lactoferrin and myeloperoxidase in meconium.

Oxidative stress and the generation of reactive oxygen/nitrogen species has a known significant impact on intrauterine fetal growth and the risk of metabolic diseases in adulthood. Compounds accumulated in fetal meconium may be a source of information about the oxidoreductive status during the intrauterine development. Three metal-containing proteins ceruloplasmin (CP), lactoferrin (LF) and myeloperoxidase (MPO) constitute the complementary panel modulating oxidative stress. The aim of this study was to assess the concentrations of these proteins and their correlations in meconium from healthy neonates. The CP, LF and MPO concentrations were determined using ELISA Kits. All serial meconium portions (n=80) were collected from healthy full-term neonates (n=19). The mean±SD concentrations [μg/g] in meconium samples were as follows: CP 312.4±229.7 (range 52.2-1076), LF 45.6±78.9 (range 1.7-511.4), MPO 1.8±1.7 (range 0.02-8.8) with statistically significant correlations between CP vs. LF (R=0.459, p=0.00009) and LF vs. MPO (R=0.354, p=0.0013). A statistically significant increase in the concentrations (p<0.05) between the first and the last meconium portions was found for LF (p=0.027) and for MPO (p=0.0006). Strong correlations between the meconium concentrations of CP, LF and MPO indicate a possible role of these complementary proteins in maintaining homeostasis of the intrauterine environment of the fetus. CP, LF and MPO measured in meconium may serve as biomarkers for assessment of impairment of oxidative balance during intrauterine life with its potential impact on disease development in adulthood.

ІНТЕНСИВНІСТЬ ОКИСНЮВАЛЬНИХ ПРОЦЕСІВ В ОРГАНІЗМІ ЩУРІВ, УРАЖЕНИХ ТЕТРАХЛОРМЕТАНОМ, ПІСЛЯ ВИКОРИСТАННЯ НАСТОЙКИ З ХОСТИ ЛАНЦЕТОЛИСТОЇ

В експерименті на тваринах, уражених тетрахлорметаном, доведено антиоксидантні властивості настойки з листя хости ланцетолистої, що проявляється зниженням інтенсифікації процесів перекисного окиснення ліпідів та окиснювальної модифікації білків у сироватці крові та печінці щурів. Під її впливом відбувається зниження вмісту ТБК-активних продуктів та 2,4-динітрофенілгідразонів, підвищення активності каталази, вмісту відновленого глутатіону та зниження вмісту церулоплазміну в ураженому організмі.

ПРОАТЕРОГЕННІ МЕТАБОЛІЧНІ РОЗЛАДИ ТА ОЦІНКА СИСТЕМИ ПЕРОКСИДАЦІЇ ЛІПІДІВ У КУРЦІВ, ХВОРИХ НА НЕСТАБІЛЬНУ СТЕНОКАРДІЮ

&lt;p&gt;РЕЗЮМЕ. Обстежено 68 хворих на нестабільну стенокардію (НС), з яких 23 жінки курці, 24 жінки, які не курили і не зазнавали пасивного впливу куріння та 21 чоловік-курець. У жінок-курців, порівняно з жінками, які не курили та чоловіками-курцями, спостерігалось зростання показників загального холестерину (ЗХС), холестерину ліпопротеїдів низької густини (ХС ЛПНГ), холестерину ліпопротеїдів дуже низької густини (ХС ЛПДНГ), тригліцеридів (ТГ) та активності ПОЛ, а вміст ХС ЛПВГ був нижчим, ніж у жінок-некурців та чоловіків-курців. Рівень церулоплазміну (ЦП) був вищим у чоловіків-курців, ніж у жінок-курців і некурців, в яких рівень ЦП був практично однаковий.&lt;/p&gt;

Acute Acalculous Cholecystitis as Initial Presentation of Amyloidosis

Amyloidosis is a relatively rare disease characterized by deposition of abnormal protein on any tissue or organ. It can present with a wide range of clinical manifestations depending on organ system involvement. We present here a 47-year-old Asian woman with history of hypothyroidism who came to emergency room with intermittent right upper quadrant abdominal pain for a month with worsening of symptoms for the last 3 - 4 days. Physical examination revealed mild abdomen distension, right upper quadrant tenderness, hepatomegaly and bipedal pitting edema. Her pertinent laboratory findings were serum albumin of 1.6, total bilirubin of 3.5, direct of 2.1, AST/ALT of 151/81 and alkaline phosphatase of 1,339. Her blood urea nitrogen/Cr was 20/1.6 and urinalysis was positive for proteinuria of 300 mg/dL. Ultrasound (US) of gallbladder revealed hepatomegaly, thickened gallbladder wall with 4 mm gall bladder polyps vs. non-shadowing stones concerning for acute cholecystitis. Her viral serologies were suggestive of past hepatitis B infection. Antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, alpha-1 antitrypsin, ceruloplasmin and iron profile were within normal limits. Liver biopsy was positive for amyloidosis. There are very few cases reported in the literature of amyloidosis initially presenting with features of acute cholecystitis and cholestatic pattern of liver function tests along with ascites. Our patient presented clinically as acute cholecystitis. The clinical dilemma was more when US commented on the findings as non-shadowing stones vs. polyps. Diffuse wall thickening of gall bladder as seen in US in this case might just be amyloid deposition rather than actual inflammation and the non-shadowing stones could as well be the amyloid deposition. Cholecystitis secondary to gallbladder localization of amyloidosis is very unusual. In conclusion, amyloidosis can rarely present as acute cholecystitis and there could be diagnostic dilemma because of inconclusive US findings. J Med Cases. 2016;7(10):459-460 doi: http://dx.doi.org/10.14740/jmc2159w

Expression of Iron Transporters and Pathological Hallmarks of Parkinson's and Alzheimer's Diseases in the Brain of Young, Adult, and Aged Rats.

Iron accumulates progressively in the brain with age; however, the cause is unknown. We hypothesized that iron accumulation may be associated with the age-induced changes in the expression of iron metabolism proteins in the brain. Here, we systematically investigated iron content and the expression of two major iron importers, transferrin receptor 1 (TfR1) and divalent metal transporter (DMT1), two iron exporters, ferroportin 1 (Fpn1) and ceruloplasmin (CP), and hepcidin, along with the pathological hallmarks of Parkinson's (PD) and Alzheimer's diseases (AD) in the brain of young (3months), adult (12months), and aged (24months) rats. We demonstrated that age has a region-specific effect on iron transport proteins along with iron content in the cortex, striatum, hippocampus, and substantia nigra. We also found an age-dependent increase in hyperphosphorylated tau, total beta-amyloid, and neurotoxic oligomeric aggregates in the cortex and hippocampus as well as an increase in α-synuclein and a decrease in tyrosine hydroxylase positive neurons in the substantia nigra. Our findings suggest that the age-dependent increase in brain iron may be partly due to the age-induced increase in DMT1 expression, rather than TfR1 and Fpn1 expression, and also imply that the increased brain iron is associated with expression of the pathological hallmarks of AD and PD.

A Study on Antioxidants and Iron nutritional status in Type 2 Diabetes Mellitus with and without Coronary Heart Disease

Background: Diabetes mellitus is an endocrinal disorder. Patients with type 2 diabetes are at high risk for several cardiovascular disorders: coronary heart disease, stroke, peripheral arterial disease, cardiomyopathy and congestive heart failure. Materials & Methods: This, case control study was conducted on 60 subjects. Among them 20 were controls, 20 were known Type 2 Diabetes Mellitus patients and 20 were Type 2 Diabetes Mellitus patients with coronary heart disease. A laboratory investigations consisting of glucose, total cholesterol, triglycerides, HDLC, LDLC, Vitamin E, MDA, Ceruloplasmin, Ferritin, Iron, TIBC and Transferrin were carried out on fasting blood sample of subjects selected for this study. Results: In the present study, FBS, PPBS, total cholesterol, LDL-Cholesterol, VLDL-Cholesterol and antioxidant parameters such as MDA, Ceruloplasmin and ferritin were significantly increased in T2DM patients and T2DM patients with coronary heart disease when compared to controls. Vitamin E and HDL cholesterol was significantly decreased. Iron, TIBC and Transferrin did not show significant difference. ( p value <0.05). Conclusion: The findings of this study is in accordance to earlier studies, that there is dyslipidemia, increased lipid peroxidation, inflammation and oxidative stress in diabetics compared to non diabetics; and the oxidative stress further increases as diabetes to cardiovascular diseases. These observations suggest that supportive therapy aimed at the reduction of dyslipidemia and oxidative stress may prevent the development and progression of vascular complications, responsible for the increased mortality and morbidity associated with type 2 diabetes mellitus. Future large prospective studies are recommended.