Estimation of V-POSSUM and E-PASS Scores in Prediction of Acute Kidney Injury in Patients after Elective Open Abdominal Aortic Aneurysm Surgery.

BACKGROUND: V-POSSUM and E-PASS scoring systems are usually used to predict morbidity and early mortality in surgical patients. We conducted this study to assess the validity of the V-POSSUM and E-PASS scores in predicting risk of acute kidney injury (AKI) development in patients undergoing elective open abdominal aortic aneurysm (AAA) repair. METHODS: We studied a consecutive series of 171 patients with AAA, qualified for elective open infrarenal repair. Patients underwent a thorough examination, and the physiological and surgical stress components of the V-POSSUM and E-PASS scores were calculated. The classification of patients in terms of postoperative AKI was performed in accordance with KDIGO criteria. RESULTS: AKI was recognized in 62 patients. In these patients, we found significantly higher physiological and surgical stress components of V-POSSUM and E-PASS scores in relation to patients without AKI. ROC analysis showed that the E-PASS score with a cutoff point ≥0.796 and the V-POSSUM score (morbidity) with a cutoff point ≥77.2% with sensitivity of 75.8% and 74.2%, respectively, and with specificity of 83.5% for both, identified patients with postoperative AKI. CONCLUSIONS: V-POSSUM and E-PASS scores have similar good properties in predicting postoperative AKI in patients undergoing elective open AAA repair.

Ion mobility separation coupled with MS detects two structural states of Alzheimer's disease Aß1-40 peptide oligomers.

Mounting evidence points to the soluble oligomers of amyloid ß (Aß) peptide as important neurotoxic species in Alzheimer's disease, causing synaptic dysfunction and neuronal injury, and finally leading to neuronal death. The mechanism of the Aß peptide self-assembly is still under debate. Here, Aß1-40 peptide oligomers were studied using mass spectrometry combined with ion mobility spectrometry, which allowed separation of the signals of numerous oligomers and measurement of their collisional cross-section values (Ω). For several oligomers, at least two different species of different Ω values were detected, indicating the presence of at least two families of conformers: compact and extended. The obtained results are rationalized by a set of molecular models of Aß1-40 oligomer structure that provided a very good correlation between the experimental and theoretical Ω values, both for the compact and the extended forms. Our results indicate that mass spectrometry detects oligomeric species that are on-pathway in the process of fibril formation or decay, but also alternative structures which may represent off-pathway evolution of oligomers.

The Cu(II) complex of Abeta40 peptide in ammonium acetate solutions. Evidence for ternary species formation.

Fluorimetric Cu(ii) titrations of Alzheimer's disease (AD) Abeta40 peptide at various ammonium acetate concentrations demonstrated that ternary Cu(Abeta40)L complexes are formed with buffer components L, thereby providing a novel perspective on Cu(ii)-Abeta interactions.

[Natriuretic peptides--relevance in intensive care]. / Znaczenie pomiarów stezen peptydów natriuretycznych w intensywnej terapii.

The family of natriuretic peptides consists of the atria natriuretic peptide (ANP), the cerebral natriuretic peptide (BNP), the type C natriuretic peptide (CNP) and the peptide isolated from the dendroaspis snakes' poison (DNP), whose presence in humans has not been confirmed. The physiological function of ANP is in the control of arterial blood pressure by regulation of systemic vascular resistance of blood vessels. BNP is produced as one of the factors in the acute response to inflammatory tissue damage, mainly in coronary vessels. Increased serum concentrations of natriuretic peptides have been found in stress situations, such as trauma or major surgery, systemic hypotension, and in intrinsic myocardial dysfunction. High concentrations of natriuretic peptides were observed in severe sepsis, septic shock and in multiple organ failure, probably due to increased secretion by mediators of the inflammatory process.The highest concentrations of ANP and BNP were found in lethal conditions. On admission to ICU, the measurement of natriuretic peptide concentrations could be very helpful in differentiating the etiology of respiratory failure, and for assessment of the severity of ARDS. Quick tests for measurement of natriuretic peptides, so-called the "point of care testing (POCT)" are fast, easy to perform and, not requiring expensive equipment, are relatively cheap. Therefore, the assessment of natriuretic peptide may be used in scoring a patient's clinical status, for precise diagnosis in doubtful situations, and for determining appropriate treatment.

The binding constant for amyloid Abeta40 peptide interaction with human serum albumin.

Human serum albumin (HSA) is the major carrier of Abeta peptides in blood plasma. 1:1 interaction stoichiometries were established in previous indirect antibody-based studies for both Abeta40 and Abeta42, but corresponding binding constants were not provided. In this study we applied direct titrations of HSA with Abeta40 monitored using circular dichroism spectroscopy and obtained a dissociation constant (K(d)) of 5+/-1 microM for a HSA complex with Abeta40. The interaction resulted in an increase of the alpha-helical contents in the complex, compared to its components, which is quantitatively consistent with the known ability of Abeta40 to adopt a partially alpha-helical conformation in a hydrophobic environment. The relevance of these findings for the role of HSA in Abeta physiology is discussed.

Weak binding affinity of human 4EHP for mRNA cap analogs.

Ribosome recruitment to the majority of eukaryotic mRNAs is facilitated by the interaction of the cap binding protein, eIF4E, with the mRNA 5' cap structure. eIF4E stimulates translation through its interaction with a scaffolding protein, eIF4G, which helps to recruit the ribosome. Metazoans also contain a homolog of eIF4E, termed 4EHP, which binds the cap structure, but not eIF4G, and thus cannot stimulate translation, but it instead inhibits the translation of only one known, and possibly subset mRNAs. To understand why 4EHP does not inhibit general translation, we studied the binding affinity of 4EHP for cap analogs using two methods: fluorescence titration and stopped-flow measurements. We show that 4EHP binds cap analogs m(7)GpppG and m(7)GTP with 30 and 100 lower affinity than eIF4E. Thus, 4EHP cannot compete with eIF4E for binding to the cap structure of most mRNAs.

Alzheimer's disease Abeta peptide fragment 10-30 forms a spectrum of metastable oligomers with marked preference for N to N and C to C monomer termini proximity.

Oligomers of Abeta peptide have been indicated recently as a possible main causative agent of Alzheimer's disease. However, information concerning their structural properties is very limited. Here Abeta oligomers are studied by non-covalent complexes mass spectrometry and disulfide rearrangement. As a model molecule, an Abeta fragment spanning residues 10-30 (Abeta10-30) has been used. This model peptide is known to contain the core region responsible for Abeta aggregation to fibrils. Non-covalent complexes mass spectrometry indicates that, at neutral pH, monomers are accompanied by oligomers up to hexamers of gradually decreasing population. H-2H exchange studies and direct monomer exchange rate measurements with the use of 15N labeled peptides and mass spectrometry show a fast exchange of monomeric units between oligomers. Disulfide exchange studies of cysteine tagged Abeta10-30 and its mutant show proximity of N-N and C-C termini of monomers in oligomers. The presented data underscore a dynamic character for pre-nucleation forms of Abeta, however, with a marked tendency for parallel strand orientation in oligomers.

Influence of electric charge variation at residues 209 and 159 on the interaction of eIF4E with the mRNA 5' terminus.

Eukaryotic translation initiation factor 4E (eIF4E) is essential for efficient protein synthesis in cap-dependent translation. The protein specifically binds the cap structure at the mRNA 5' terminus and facilitates the assembly of the mRNA with other initiation factors and the 40S ribosomal subunit. Phosphorylation of eIF4E is implicated in the regulation of the initiation step of translation. However, the molecular mechanism of this regulation still remains unclear. To address this problem, we have determined the binding affinities of eIF4E specifically mutated at position 209 or 159 for a series of novel mono- and dinucleotide cap analogues by a fluorometric time-synchronized titration method. A 1.5-3-fold reduction in the affinity of cap for the S209E mutant and a 1-2-fold increase in the affinity of cap for the S209K mutant, depending on the negative charge of phosphate chains, indicate that phosphorylation at Ser209 creates electrostatic repulsion between the protein and the negatively charged cap structure. The inhibition of the ability to bind cap analogues by the K159A mutant and its phosphorylated counterpart shows significant participation of Lys159 in the binding of the capped mRNA. Both structural modifications, phosphorylation and the replacement of lysine with alanine, result in an increase in the negative Gibbs free energy of association that is proportional to the length of the cap phosphate chain and additive, i.e., equal to the sum of the individual destabilizing changes of DeltaG degrees. The possible implication of these results for the mechanism of control of eIF4E by phosphorylation, especially for the "clamping model", is discussed.