Development of Cobalt-Binding Peptide Chelate from Human Serum Albumin: Cobalt-Binding Properties and Stability

Radioactive isotopes are used as drugs or contrast agents in the medical field after being conjugated with chelates such as DOTA, NOTA, DTPA, TETA, CyDTA, TRITA, and DPDP. The N-terminal sequence of human serum albumin (HSA) is known as a metal binding site, such as for Co2+, Cu2+, and Ni2+. For this study, we designed and synthesized wAlb12 peptide from the N-terminal region of HSA, which can bind to cobalt, to develop a peptide-based chelate. The wAlb12 with a random coil structure tightly binds to the Co(II) ion. Moreover, the binding property of wAlb12 toward Co(II) was confirmed using various spectroscopic experiments. To identify the binding site of wAlb12, the analogs were synthesized by alanine scanning mutagenesis. Among them, H3A and Ac-wAlb12 did not bind to Co(II). The analysis of the binding regions confirmed that the His3 and α-amino group of the N-terminal region are important for Co(II) binding. The wAlb12 bound to Co(II) with Kd of 75 μM determined by isothermal titration calorimetry when analyzed by a single-site binding model. For the use of wAlb12 as a chelate in humans, its cytotoxicity and stability were investigated. Trypsin stability showed that the wAlb12 − Co(II) complex was more stable than wAlb12 alone. Furthermore, the cell viability analysis showed wAlb12 and wAlb12 + Co(II) to be non-toxic to the Raw 264.7 and HEK 293T cell lines. Therefore, a hot radioactive isotope such as cobalt-57 will have the same effect as a stable isotope cobalt. Accordingly, we expect wAlb12 to be used as a peptide chelate that binds with radioactive isotopes.

Ischemia-Modified Albumin As A Marker For Acute Aortic Dissection: A Prospective Observational Study

Background: Delayed or misdiagnosed aortic dissection can lead to death and morbidity. Ischemia-modified albumin (IMA) measures the cobalt binding capability and has been associated with mortality in patients with acute aortic dissection (AAD). However, it is unknown whether IMA levels can differentiate AAD in patients with chest pains.Methods: A total of 100 suspected AAD patients were enrolled in this study. A cobalt-binding assay was used to determine the plasma IMA levels. In addition, the IMA levels of patients in different groups were compared based on the final diagnosis. Results: IMA levels were significantly higher in the AAD group than in the AMI, PE, and other groups (63.98 ± 14.38, 52.57 ± 9.54, 49.26 ± 10.99, 37.99 ± 6.59, respectively) within 24 hours after the onset of symptoms. The area under the curve (AUC) based on the IMA level was 0.810 (95% CI, 0.708–0.897), and the best threshold of IMA was 59.35 u/ml (specificity, 85.7% and sensitivity, 66%). The decision and clinical impact curves indicated that the IMA had an excellent standardized net benefit and could be suitable for patient diagnosis.Conclusion: IMA is elevated in AAD patients. The IMA levels have better performance for AAD than D-dimer and could be a potential biomarker with rapid and cost-effective diagnostic tests for early diagnosis of AAD. However, large-sample studies are needed to verify the findings.

Ischemia-Modified Albumin: Origins and Clinical Implications

Albumin is one of the most abundant proteins in the body of mammals: about 40% of its pool is located in the intravascular space and the remainder is found in the interstitial space. The content of this multifunctional protein in blood is about 60-65% of total plasma proteins. A decrease in its synthesis or changes of functional activity can destabilize oncotic blood pressure, cause a violation of transporting hormones, fatty acids, metals, and drugs. Albumin properties change under ischemic attacks associated with oxidative stress, production of reactive oxygen species, and acidosis. Under these conditions, ischemia-modified albumin (IMA) is generated that has a reduced metal-binding capacity, especially for transition metals, such as copper, nickel, and cobalt. The method of determining the cobalt-binding capability of HSA was initially proposed to evaluate IMA level and then licensed as an ACB test for routine clinical analysis for myocardial ischemia. Subsequent studies have shown the viability of the ACB test in diagnosing other diseases associated with the development of oxidative stress. This review examines recent data on IMA generation mechanisms, describes principles, advantages, and limitations of methods for evaluation of IMA levels, and provides detailed analysis of its use in diagnostic and monitoring therapeutic efficacy in different diseases.

Ischemia-Modified Albumin As a Marker for Acute Aortic Dissection: A Prospective Observational Study

Background: Delayed or misdiagnosed aortic dissection can lead to death and morbidity. Ischemia-modified albumin (IMA) measures the cobalt binding capability and has been associated with mortality in patients with acute aortic dissection (AAD). However, it is unknown whether IMA levels can differentiate AAD in patients with chest pains.Methods: A total of 100 suspected AAD patients were enrolled in this study. A cobalt-binding assay was used to determine the plasma IMA levels. In addition, the IMA levels of patients in different groups were compared based on the final diagnosis. Results: IMA levels were significantly higher in the AAD group than in the AMI, PE, and other groups (63.98 ± 14.38, 52.57 ± 9.54, 49.26 ± 10.99, 37.99 ± 6.59, respectively) within 24 hours after the onset of symptoms. The area under the curve (AUC) based on the IMA level was 0.810 (95% CI, 0.708–0.897), and the best threshold of IMA was 59.35 u/ml (specificity, 85.7% and sensitivity, 66%). The decision and clinical impact curves indicated that the IMA had an excellent standardized net benefit and could be suitable for patient diagnosis.Conclusion: IMA is elevated in AAD patients. The IMA levels have better performance for AAD than D-dimer and could be a potential biomarker with rapid and cost-effective diagnostic tests for early diagnosis of AAD. However, large-sample studies are needed to verify the findings.

Assessment of serum Ischemia Modified Albumin (IMA) Levels in Acute Rheumatic Fever

Introduction : Rheumatic fever (RF) is an autoimmune, multiorgan inflammatory disease. The patients develop carditis (50-78%), arthritis (35-88%), chorea (2-19%), erythema marginatum (< 6%) and subcutaneous nodules (< 1-13%). Ischemia modified albumin or cobalt binding albumin is one of new biomarker for inflammation and oxidative stress. Various previous studies indicate that acute rheumatic fever is associated with oxidative stress and inflammation. In the present study, we examined IMA, CRP, ESR and albumin levels in acute rheumatic fever.Material and method: This case control study was conductedbetween April 2017 to March 2018 in pediatrics department of Malda Medical College and Hospital. Study group composed of 42 children aged 5-18 years suffering from acute rheumatic fever diagnosed by modified jones criteria and they compared with 50 healthy age and sex match control. The IMA levels were compared among groups, and the association to acute phase reactants were investigated.Results: Values ofserumischemia modified albumin, ESR and C Reactive Protein were significantly higher in cases compared to control group (p value ≤0.001). But no significant differencewas found between values of serum albumin in cases compared to control group. Positive correlation was found between cases serum IMA and ESR, C-Reactive protein.Conclusion: Serumischemia modified albumin were significantly higher in children with acute rheumatic fever compared to control group, so IMA could be used as a biomarker in diagnosis of ARF. However, further multicenter and larger case studies are needed to provide stronger evidence.International Journal of Human and Health Sciences Vol. 05 No. 02 April’21 Page: 222-225

Ischemia-modified albumin (IMA) and dynamic thiol-disulfide homeostasis in patients with postherpetic neuralgia

Background Ischemia-modified albumin (IMA) is an isotype of albumin that increases under oxidative stress, and plasma thiols are main defense mechanisms against oxidative stress. The objective of this study was to investigate thiol-disulfide homeostasis and serum IMA levels in postherpetic neuralgia (PHN) patients. Methods A total of 29 PHN patients and 30 healthy controls were included in the study. Serum total and native thiol concentrations and serum disulfide concentration were measured using the method described by Erel and Neselioglu. The albumin cobalt binding test was used to measure serum IMA levels. Results Serum IMA levels were 1.21 ± 0.58 AU and 0.75 ± 0.09 AU in the PHN and control groups, respectively (p < 0.001). Serum total thiol concentrations were found to be 421.62 ± 90.28 μmol/L and 598.36 ± 73.63 μmol/L in the PHN and control groups, respectively (p < 0.001). Serum native thiol concentrations were found to be 365.75 ± 92.07 μmol/L and 531.90 ± 72.9 μmol/L in the PHN and control groups, respectively (p < 0.001). Serum disulfide concentrations were found to be 33.23 ± 5.33 μmol/L and 27.93 ± 7.81 μmol/L in the PHN and control groups, respectively (p = 0.003). The native thiol/total thiol ratio was significantly lower, and the disulfide/total thiol and disulfide/native thiol ratios were significantly higher in the PHN group compared to the controls. Conclusions IMA levels are high and dynamic thiol/disulfide homeostasis is disrupted in PHN patients.

The Analysis Proteome Dominant Species of Microorganisms in Agrobiocenosis the Volgograd Region for the Presence of Nickel and Cobalt-Dependent Proteins

The use of modern bioinformatic approaches for the solution of environmentally oriented tasks provides new data that can be used for spot control anthropogenic ecosystems and ecosystem rebuilding of their violation obtained from adverse factors of natural and antropogenical genesis. This work aims at demonstrating and identifying nickel and cobalt binding proteins in dominant species of microorganisms of agrocenosis that allows you to create an information database for accumulating and processing information about the regularities of the functioning of agro-ecosystem in arid conditions, leading to the growth of economic efficiency of the farming system and increase the success of environmental management. The main purpose of the work was to study the presence of nickel and cobalt binding proteins included in the proteome, the dominant species of microorganisms from three typical agrocenoses of the Volgograd region. Nickel and cobalt binding proteins were distributed not only in their functional features, participation in metabolism, proteolytic activity, transport and regulation of gene expression and proteins, The results of virtual screening proteome the dominant microorganisms of the genus Bacillus and Actinomyces in the Uniprot database showed that the soil microbiota of the considered agrocenosis is also characterized by a sufficiently large number of metal – dependent proteins: 264 – for representatives of the Genus Actinomyces and 564 – for Bacillus subtilis, of of which about 35–40 % are annotated. According to the results, the concentration of metals in the soil of agrocenosis, namely in the arid zone, has a very strong impact on the livelihoods of crops and microorganisms in the soil. The use of the obtained results can be used as a basis for the implementation of targeted high-precision management of biocenoses in order to improve the sustainability of natural communities and the economic efficiency of agrocenoses.

Albumin Cobalt Binding or Ischaemia Modified Albumin: A test of great prognostic value in malaria

Background : We evaluated albumin cobalt binding (ACB) assay as a prognostic marker for severe malaria in a medical college setting .Methods :Consecutive adult patients admitted with both vivax and falciparum malaria were evaluated with ACB assay at the time of admission. Detailed work up and individual patient directed management were instituted in addition to immediate artemisin based antimalarial therapy.Results :100 consecutive patient ( 50 with vivax and 50 with falciparum malaria ) were evaluated . Reference range for ACB assay was established using 50 adult healthy ( 25 male and 25 female ) individuals . 16 out of 50 p. falciparum infected developed complicated malaria. All malaria infected patients had high ACB levels ( P<0.0001). There was step wise increase in ACB levels from healthy volunteers to different category of malaria( P<0.0001 ) without any overlap. Conclusion: ACB can be used as a robust simple and cheap prognostic marker for organ dysfunction in severe malaria.

Ischemia-Modified Albumin as a Marker of Acute Coronary Syndrome: The Case for Revising the Concept of “N-Terminal Modification” to “Fatty Acid Occupation” of Albumin

Ischemia-modified albumin (IMA) is assumed “N-terminal modified” albumin which is generated immediately following myocardial ischemia. The diagnosis of IMA is based on reduced cobalt binding affinity to albumin which is attributed mainly to incapability of cobalt to bind at albumin’s modified N-terminus. Although the albumin cobalt binding test was accepted as a potentially powerful marker for discriminating acute coronary syndrome from nonischemic chest pain, its usefulness has been brought into question in recent years. Patients with acutely ischemic myocardium exhibit a rapid increase in serum levels of fatty acids (FAs). Almost all released FAs are strongly bound to albumin which create conformational changes in the protein with resultant reduced cobalt binding affinity. There is a clear metabolic and temporal relationship between IMA measured via albumin cobalt binding testing and serum levels of FAs. In line with what has been suggested recently in the literature, we conclude that a shift from the concept of “N-terminal modified” to “FA-occupied” albumin is required, as this better describes IMA in patients with acute coronary syndrome. We also offer “oxidation modified albumin, OMA,” which is conceptually different from the “FA-occupied” IMA, to describe modification of albumin in chronic disease associated with increased oxidative stress.