Ischemia-modified albumin as a marker of vascular dysfunction and subclinical atherosclerosis in β-thalassemia major

Background: Ischemia-modified albumin (IMA) is an altered type of serum albumin that forms under conditions of oxidative stress and an independent predictor of major adverse cardiovascular events.

Objectives: To measure the levels of IMA in 45 children and adolescents with β-thalassemia major (β-TM) compared with 30 healthy controls and assess its relation to lipid peroxidation, vascular complications and subclinical atherosclerosis.

Methods: β-TM patients without symptoms of heart disease were studied focusing on transfusion history, chelation therapy, serum ferritin, malondialdehyde (MDA) and IMA levels. Echocardiography was performed and carotid intima media thickness (CIMT) was assessed.

Results: IMA and MDA levels were significantly higher in β-TM patients compared with controls (p?Conclusion: Our results highlight the role of oxidative stress in the pathophysiology of vascular complications in thalassemia. IMA could be useful for screening of β-TM patients at risk of cardiopulmonary complications and atherosclerosis because its alteration occurs in early subclinical disease.     

The relationships among the levels of oxidative and antioxidative parameters,FEV1 and prolidase activity in COPD

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by poorly reversible airflow limitations associated with an abnormal inflammatory response of the lung.

Methods: We investigated whether prolidase levels in serum, total antioxidant status, total oxidative status (TOS), and the oxidative stress index (OSI) were associated with the etiopathogenesis of COPD, and whether there is a relationship between prolidase activity and oxidative parameters and carotid artery intima-media thickness (CIMT) in patients with COPD. This study included 91 patients with COPD and 15 control cases. Routine haematological and biochemical parameters were determined in all patients. All subjects were fully informed about the study and provided consent.

Results: The mean age of the patients with COPD was 61.3?±?10.5 years and that of the control group was 56.2?±?12.1 years. The control group had a significantly higher plasma prolidase level than that in the COPD group. TOS and OSI levels in the control group were significantly lower than those in the COPD group. However, no significant differences were found in TALs or CIMT levels between the COPD and control groups. A negative correlation was detected between prolidase activity and age; however, no significant difference in age was observed between the two groups.

Conclusion: These results indicate that prolidase activity decreases in patients with COPD.     

Role of ceruloplasmin, transferrin and lipid peroxidation in bacterial infections of the CNS

Ceruloplasmin and transferrin blood serum levels were measured during bacterial infection of the CNS. A decrease in ceruloplasmin level and a gradual increase in transferrin level were observed on the 5th day of the disease. The minimum ceruloplasmin level was observed simultaneously with the maximum MDA and GOT levels. There was a close correlation between the time course of ceruloplasmin, transferrin, MDA and GOT changes and the clinical condition of the patient.     

The Ceruloplasmin Transferrin Ratio in the Blood of Patients at Different Stages of Parkinson’s Disease

The ratio of the concentrations of Cu²⁺-ceruloplasmin/Fe³⁺-transferrin in the blood plasma of 54 patients at different stages of Parkinson’s disease treated and not treated with L-DOPA was estimated by EPR-spectroscopy. It was established that in patients who suffer from Parkinson’s disease, the value of ceruloplasmin/ transferrin increased by 157% in comparison with the control group of clinically healthy people of the same age group. In patients with Parkinson’s disease, the ratio of ceruloplasmin/transferrin increased at stage 1 of the disease by 119%, at stage 2 by 117%, and at stage 3 by 135% in comparison with the control group. There was no statistically significant difference between the ratio of ceruloplasmin/transferrin in patients who received and did not recive L-DOPA replacement therapy. These data reveal changes in the functioning of the ceruloplasmin: transferrin system, which decreases the content of toxic ions of Fe²⁺ in the plasma of patients with Parkinson’s disease. These changes are a pathogenetically significant factor of Parkinson’s disease at all stages of the disease.     

Long-term stability of biomarkers of the iron status in human serum and plasma

Abstract

Context: In epidemiological research, it is very important to test the stability of biomarkers as function of both storage time and temperature.

Objective: In this study, the stability of biomarkers of the iron status was tested up to 1 year of storage.

Materials and methods: The biomarkers include total iron, unsaturated iron binding capacity, ferritin, transferrin, soluble transferrin receptor, ceruloplasmin and haptoglobin.

Results: The concentrations of all biomarkers tested remain constant upon storage at ?20, ?70 and ?196?°C.

Conclusion: All biomarkers of the iron status were stable at the temperatures tested for 1 year.     

Plasma angiogenesis and oxidative stress markers in patients with diabetic retinopathy

Abstract

Background: Neovascularization in the retina and hyperglycaemia-induced oxidative stress are implicated in the pathogenesis of diabetic retinopathy (DR). In this study, we hypothesized that the plasma angiogenic and oxidative stress markers associated with these derangements could aid in the screening of diabetic patients who are at an increased risk of developing retinopathy.

Methods: This study included normal (n?=?148), type2 diabetes without retinopathy (DNR; n?=?148), proliferative DR (PDR; n?=?74) and non-PDR (NPDR; n?=?148) subjects. Plasma concentrations of vascular endothelial growth factor-A (VEGF-A), hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), pigment epithelium-derived factor (PEDF), nitric oxide (NO), soluble receptors for advanced glycation end products (sRAGE), malondialdehyde (MDA) and protein thiols were estimated.

Results: A statistically significant increase was observed in the plasma concentrations of pro-angiogenic factors and markers of oxidative stress in both retinopathy groups. By contrast, the concentrations of anti-angiogenic factors and antioxidants were decreased significantly in these groups. Receiver operating characteristic analysis indicated that the plasma thresholds of HIF-1α and PEDF can be suitable markers in case of NPDR. However, in PDR, HIF-1α, NO, MMP-9 and PEDF showed high sensitivity and specificity.

Conclusions: The factors associated with hypoxia, matrix degradation and angiogenic inhibition play a crucial role in predicting DR.     

Role of transferrin and ceruloplasmin in antioxidant activity of lung epithelial lining fluid

Lung epithelial lining fluid (ELF) is a thin layer of plasma ultrafiltrate and locally secreted substances that may provide antioxidant protection and serve as a "front-line" defense for the lower respiratory tract epithelium. To characterize the antioxidant properties of ELF, young, healthy, nonsmoking volunteers underwent bronchoalveolar lavage with determination of ELF volumes and ELF proteins. ELF (greater than 0.4 ml) is a potent inhibitor of lipid peroxidation as measured by malondialdehyde (MDA) production in an in vitro iron-dependent assay system. Two serum proteins, transferrin and ceruloplasmin, were quantitated in ELF and found to be potent inhibitors of lipid peroxidation. Other ELF components, including vitamin E, vitamin C, and albumin, did not function as antioxidants in this system. Several experimental observations suggest that ELF transferrin was more important than ceruloplasmin in inhibiting lipid peroxidation: 1) ELF concentrations of transferrin were 20-fold higher than those for ceruloplasmin; 2) ELF antioxidant activity was abolished by preincubation with Fe3+; 3) ELF antioxidant activity was minimally affected by sodium azide, which is known to inhibit ceruloplasmin ferroxidase activity; and 4) ELF ceruloplasmin ferroxidase activity was virtually nondetectable. ELF possesses a significant antioxidant activity that may be important in vivo in protecting the lung from oxidant injury.     

Plasma sE-cadherin and the plasma sE-cadherin/sVE-cadherin ratio are potential biomarkers for chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation with endothelial dysfunction. Cadherins are adhesion molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s) cadherin is released from the cell surface by the effects of proteases including matrix metalloproteinases (MMPs).

Objective: The aim of this study was to examine the associations of sE-/sVE-cadherin levels in plasma with the development of COPD.

Methods: Plasma sE-/VE-cadherin levels were measured by an enzyme-linked immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63 healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7 levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and 12 control).

Results: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios were significantly higher in COPD and SS than in HS and HN groups, while plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p?p?p?p?Conclusions: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.     

Serum protein degradation by hypochlorite

The structural integrity of serum proteins: albumin, immunoglobulin G, transferrin, ceruloplasmin and superoxide dismutase, and the functional activity of the latter two enzymes after their interaction with hypochlorite were studied. It was shown that the interaction between the proteins and hypochlorite resulted in protein injury and degradation of their native structure. In the case of ceruloplasmin and transferrin, a practically complete protein "dissipation" occurred, the albumin and superoxide dismutase structures being injured in a lesser degree. The inactivation of ceruloplasmin was slower than that of superoxide dismutase. The protein degradation by hypochlorite seems to be the main factor restricting the ability of the proteins to act as antiinflammatory drugs.     

Changes of urinary phospholipids in the chronic kidney disease patients

Abstract

Objective: To evaluate whether urinary phospholipids could be regarded as biomarkers of chronic kidney disease.

Materials and methods: Thirteen healthy volunteers and 26 consecutive chronic kidney disease patients were included. Urinary phospholipids were quantified by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

Results: Urinary phosphatidylcholines concentrations (PC 16:0/16:0, 16:0/22:3, 16:0/18:1 and 16:0/18:2) were significantly higher both in glomerulonephritis group (all p?<?0.001) and in tubulointerstitial injury group (all p?<?0.05) than in healthy control group. Meanwhile, sphingomyelin concentrations (SM 18:1/16:0 and 18:1/18:0) in glomerulonephritis group were significantly higher than those in healthy control group (all p?<?0.001). Urinary PCs and SMs were positively correlated with proteinuria but negatively correlated with serum albumin. Meanwhile, PCs were positively correlated with serum creatinine.

Conclusion: Our work first demonstrated that urinary phospholipids might be biomarkers for the chronic kidney disease patients. Increased urinary phospholipids in chronic kidney disease patients might result from proteinuria, damaged kidney function or proteinuria induced hypoalbuminemia or lipotoxicity.     

Plasma low-molecular-weight thiol/disulphide homeostasis as an early indicator of global and focal cerebral ischaemia

Objective: Recent studies have shown that cerebral ischaemia causes not only local, but also systemic oxidative stress. This leads to oxidation of thiol-containing compounds, including low-molecular-weight thiols (cysteine, glutathione, homocysteine and others). Therefore, the aim of this work was to verify the hypothesis that the thiol/disulphide homeostasis of low-molecular-weight thiols is disturbed in the early stages of cerebral ischaemia.

Methods: Two experimental rat models of ischaemia were used: a global model of vascular ischaemia (clamping the common carotid arteries?+?haemorrhage) and focal ischaemia (middle cerebral artery occlusion). The total levels of thiols and their reduced forms were measured before surgery and after 40 minutes of reperfusion (global) or 3?hours (focal) ischaemia.

Results: The global ischaemia model caused a marked (2.5–4 times, P?P?Discussion: These results suggest that plasma low-molecular-weight thiols are actively involved in oxidation reactions at early stages of cerebral ischaemia; therefore, their reduced forms or redox state may serve as a sensitive indicator of acute cerebrovascular insufficiency.     

慢性阻塞性肺疾病患者疾病认知水平调查及其影响因素分析

摘要 目的：调查慢性阻塞性肺疾病（COPD）患者疾病认知水平,分析COPD患者疾病认知水平的影响因素。方法：选择2018年10月至2020年11月我院收治的162例COPD患者,采用自行设计的一般资料调查问卷和COPD疾病认知问卷（BCKQ）收集患者信息和评估COPD疾病认知水平。采用单因素及多因素Logistic回归分析COPD患者疾病认知水平的影响因素。结果：共发放162份问卷,有效回收160份,有效回收率98.77%（160/162）。COPD患者BCKQ总分为（31.01±2.16）分,单因素分析结果显示不同年龄、职业、文化教育程度、居住地、家庭月收入、健康信息获得途径、每年急性发作次数、每年医疗支出的COPD患者BCKQ总分差异显著（P＜0.05）。进一步多因素Logistic回归分析结果显示职业、文化教育程度、家庭月收入、健康信息获得途径、每年急性发作次数是COPD患者疾病认知水平的影响因素（P＜0.05）。结论：COPD患者对疾病认知水平偏低,且受多种因素影响,临床工作者应结合相关因素进行针对性健康宣教,以提供患者对疾病的认知水平。     

慢阻肺伴左心衰竭临床特征与影响因素分析

摘要 目的：探讨慢阻肺伴左心衰竭临床特征与影响因素。方法：回顾性选择2019年1月至2020年12月来我院诊治的慢性阻塞性肺疾病患者150例。根据是否合并心衰,将150例患者分为慢阻肺伴左心衰竭组（A组）与慢阻肺未伴左心衰竭组（B组）。分析150例患者中慢阻肺伴左心衰竭的占比,分析对比两组一般资料、习惯和疾病病史、肺功能、心脏彩超、心电图结果、血液指标水平与动脉血气指标,采用Logistic回归分析慢阻肺伴左心衰竭的影响因素。结果：（1）150例患者中,慢阻肺伴左心衰竭者占比为32.00 %,慢性阻塞性肺疾病未合并左心衰竭者占比为68.00 %。（2）两组性别、年龄、患病时间、糖尿病史、吸烟史、高血压史、冠心病史、FEV1/FVC、左房内径、左心室舒张末内径、左室重量分数、左室后壁厚度、肺动脉压、血小板计数、C反应蛋白、降钙素原、凝血酶原时间、D-二聚体、白蛋白、肌酸激酶同工酶、N末端脑钠肽前体、PaCO₂、PaO₂、SaO₂对比有差异（P<0.05）。（3）Logistic回归分析结果表明、性别、年龄、糖尿病史、吸烟史、高血压史、冠心病史、左心室舒张末内径、肺动脉压是影响慢阻肺合并左心衰竭患者的影响因素（P<0.05）。结论：慢阻肺伴左心衰竭的占比较高,其与性别为男性、年龄偏大、有糖尿病史、吸烟史、高血压史、冠心病史、左心室舒张末内径升高、肺动脉压升高相关,需对以上因素给予积极干预及治疗。     

Circulating microparticles in severe pulmonary arterial hypertension increase intercellular adhesion molecule-1 expression selectively in pulmonary artery endothelium

Background

Management guidelines of chronic obstructive pulmonary disease (COPD) are mainly based on results of randomised controlled trials (RCTs), but some authors have suggested limited representativeness of patients included in these trials. No previous studies have applied the full range of selection criteria to a broad COPD patient population in a real-life setting.

Methods

We identified all RCTs of inhaled long-acting bronchodilator therapy, during 1999–2013, at ClinicalTrials.gov and translated trial selection criteria into definitions compatible with electronic medical records. Eligibility was calculated for each RCT by applying these criteria to a uniquely representative, well-characterised population of patients with COPD from the Optimum Patient Care Research Database (OPCRD).

Results

Median eligibility of 36 893 patients with COPD for participation in 31 RCTs was 23 % (interquartile range 12–38). Two studies of olodaterol showed the highest eligibility of 55 and 58 %. Conversely, the lowest eligibility was observed in two studies that required a history of exacerbations in the past year (3.5 and 3.9 %). For the patient subgroup with modified Medical Research Council score ≥2, the overall median eligibility was 27 %.

Conclusions

By applying an extensive range of RCT selection criteria to a large, representative COPD patient population, this study highlights that the interpretation of results from RCTs must take into account that RCT participants are variably, but generally more representative of patients in the community than previously believed.

     

Blood and sputum protein biomarkers for chronic obstructive pulmonary disease (COPD)

ABSTRACT

Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous set of disorders, characterized by airflow limitation, and reduced lung function. Despite increasing knowledge regarding its pathophysiology, there has been limited advancement in therapeutics and the current treatment strategy is symptom management and prevention of exacerbations.

Areas covered: Biomarkers represent important tools for the implementation of precision medicine. As fundamental molecules of all living processes, proteins could provide crucial information about how genes interact with the environment. Proteomics studies could act as important tools in identifying reliable biomarkers to enable a more precise therapeutic approach. In this review, we will explore the most promising blood and sputum protein biomarkers in COPD that have been consistently reported in the literature.

Expert commentary: Given the complexity of COPD, no single protein biomarker has been able to improve the outcomes of COPD patients. According to preliminary studies, precision medicine in COPD will likely require a combination of different proteins in a biomarker panel for clinical translation. With advancements in current mass spectrometry techniques, an enhancement in the identification of new biomarkers will be observed, and improvements in sequence database search can fill in potential gaps between biomarker discovery and patient care.     

Trace elements and some extracellular antioxidant protein levels in serum of patients with laryngeal cancer

In this study, we investigated the levels of serum Zn, Cu, Mg, Mn, Fe, ceruloplasmin (Cp), transferrin (Trf), and albumin in laryngeal carcinoma and correlated their levels with the cancer stage. The sera from 35 patients with laryngeal cancer (10 at stage II, 12 at stage III, and 13 at stage IV) were extracted before treatment and compared with those from the healthy control group (n=15). Although serum Fe and Mn concentrations were lower in the laryngeal cancer groups (for all stages) than in the control group, the difference was not statistically significant (p>0.05). The higher Cu (p<0.001) and Cp (p<0.01) and lower Zn (p<0.01), Mg (p<0.001), and Trf (p<0.01) concentrations were found in laryngeal cancer groups (for each stage) when compared to the control group. In the comparison of stages II, III, and IV (with each other), all parameters were found to be statistically not significant (p>0.05). On the other hand, no meaningful difference was found in terms of the serum albumin level. In our opinion, alterations in the level of trace elements and antioxidant proteins, important for many metabolic processes, in laryngeal cancer may not be a reason for but is, in fact, a consequence of the disease itself.     

The influence of radiotherapy on ceruloplasmin and transferrin in whole blood of breast cancer patients

Ceruloplasmin and transferrin are proteins which play a potential role in the process of breast cancer development. These molecules contain Cu²⁺ (ceruloplasmin) or Fe³⁺ ions (transferrin) and thus constitute paramagnetic centers, which can be studied using electron paramagnetic resonance method. The aim of the study was to determine how paramagnetic centers in whole blood of breast cancer patients change under the influence of radiation therapy. Samples of whole blood were taken from 17 women with breast cancer treated with radiotherapy. The measurements were carried out at 170 K using X-band electron paramagnetic resonance (EPR) spectrometer Bruker EMX-10. Two distinct EPR lines, derived from high-spin Fe³⁺ in transferrin and Cu²⁺ from ceruloplasmin, were revealed in all frozen samples. The amplitude and integrated intensity of the EPR signal from Cu²⁺ in ceruloplasmin significantly decreased in all patients after the delivery of the radiation fraction. When comparing the integral intensity of the signal from Fe³⁺ in transferrin, three different situations were identified which are patient specific: a significant increase, an insignificant change, or a significant decrease after the irradiation. A decreased level of Cu²⁺ from ceruloplasmin in patients after radiotherapy means a low level of ceruloplasmin in the plasma or an increased content of reduced Cu⁺ ions. Differences in the integrated intensity of the EPR signal from transferrin translate directly into the amount of bound iron. The observed changes could indicate how well the organism fights against cancer and how easily it adapts to the situation of biochemical stress.     

The effect of albumin,ceruloplasmin, and other serum constitutents on Fe(II) oxidation

This study has analyzed the role of several serum constituents, that have been proposed to effect the following reactionin situ: {fx1-1} {fx1-2} These reactions were monitored by measuring the rate of Fe(II) oxidation in the presence of apo-transferrin (reaction A) and Fe(III)-transferrin formation (reaction B) at 465 nm. Reactions A and B were found to be kinetically equivalent. The results show that, singly or in combination, bicarbonate, orthophosphate, citrate, apo-transferrin, and/or albumin have less than one-tenth of the ability to enhance the oxidation of Fe(II) compared to the serum enzyme, ceruloplasmin. It was also found that the rate of Fe(II) oxidation by serum Fe-ligands was influenced by the efficiency of oxygen utilization. Whereas ceruloplasmin produces a 4∶1 ratio of Fe(II) oxidized to oxygen utilized, the non-enzymic components yield a 2∶1 or 3.09∶1 ratio. These data support the role of ceruloplasmin as an antioxidant that prevents the formation of the intermediate active oxygen species O ₂ ⁻ · and H₂O ₂ ^· through the Fe(II) auto-oxidation reaction. A hitherto unrecognized factor in the control of nonenzymic oxidation of Fe(II) was serum albumin. This protein, at >25 μM, was found to sharply dampen the rate of Fe(II) oxidation in the presence of a physiological concentration of bicarbonate, citrate, and transferrin Albumin did not appear to affect the ceruloplasmin catalyzed oxidation of Fe(II) at pH 7.0. The addition of ceruloplasmin effected up to a 44 × increase in the rate of Fe(II) oxidation and Fe(III)-transferrin formation even in the presence of 0.60 mM albumin.     

Increased Oxidative Stress and Altered Levels of Nitric Oxide and Peroxynitrite in Tunisian Patients with Chronic Obstructive Pulmonary Disease: Correlation with Disease Severity and Airflow Obstruction

This study was aimed to evaluate the oxidant–antioxidant imbalance in the pathogenesis of chronic obstructive pulmonary disease (COPD) in Tunisians. We assessed 16 parameters related to the oxidative status that include malondialdehyde (MDA), total protein carbonyls (PCs), and advanced oxidation protein products (AOPP). We also examined the activity of glutathione peroxydase (GSH-Px), catalase, and superoxide dismutase (SOD) in the plasma and erythrocytes. Levels of total thiols, reduced glutathione (GSH), total antioxidant status (TAS), hydrogen peroxide, ascorbic acid, iron, and protein sulfhydryls were determined using spectrophotometry. We also evaluated the level of nitric oxide (NO) and peroxynitrite in plasma from COPD patients and healthy controls. Estimation of DNA damage was determined using the comet assay. Pulmonary functional tests were performed by body plethysmography. Levels of MDA, PC, DNA damage, and AOPP were significantly increased while total thiols, GSH, and TAS were decreased in COPD patients. GSH-Px activity was higher in COPD patients while no difference was found for catalase and SOD. We also observed a lower level of NO and peroxynitrite in COPD patients. Decreased levels of peroxynitrite were found to correlate with disease progression, as well as with forced expiratory volume in 1 s/forced vital capacity among COPD patients. Multivariate analysis revealed that NO is associated with pathological pathways that help to predict patient outcome independently of the degree of airflow obstruction. These results indicate the presence of a systemic oxidative stress and highlight the importance of NO and peroxynitrite as major effectors in COPD development and airflow obstruction.     

Fibrinogen is an efficient antioxidant

Fibrinogen has been included among the risk factors for vascular disease. Fibrinogen belongs with albumin, ceruloplasmin and transferrin to an acute phase protein group in the plasma. Albumin, ceruloplasmin and transferrin are already recognized as natural antioxidants. In the present study we used three different oxygen generating systems in order to test whether fibrinogen is able to act as an antioxidant in an in vitro system. We used 1) pyrogallol auto-oxidation, 2) the reaction catalysed by xanthine oxidase coupled with the reduction of ferricytochrome c and 3) chemiluminescence. We found that in a dose-dependent manner fibrinogen inhibited superoxide generation (pyrogallol and xanthine-xanthine oxidase reactions), ferrous ion oxidation and hydroxyl radical dependent degradation (of deoxyribose). Fibrinogen also inhibited LDL oxidation (copper and azo compound-induced), hydrogen peroxide oxidation and chemiluminescence produced by polymorphonuclear leukocytes. Fibrinogen, albumin, ceruloplasmin and transferrin act as a supplementary antioxidant defense mechanism against oxidative stress arising from inflammatory conditions.