A European focus on proteomics

A report on the First International Symposium of the Austrian Proteomics Platform, Seefeld, Austria, 26-29 January 2004

HemoCue®, an Accurate Bedside Method of Hemoglobin Measurement?

Objective. Evaluate the accuracy of this bedside method to determinehemoglobin (Hb) concentration in general surgery over a wide range of Hbvalues and to determine potential sources of error. Methods. Accuracy of Hbmeasurement using HemoCue® (AB Leo Diagnostics, Helsinborg, Sweden) wasassessed in 140 surgical blood samples using 7 HemoCue® devices incomparison with a CO-Oximeter (IL 482, Instrumentation Laboratory,Lexington, MA). To analyze potential sources of error, packed red cells andfresh frozen plasma were reconstituted to randomized Hb levels of 2-18g/dL. Results. In the surgical blood samples, the Hb concentrationdetermined by the CO-Oximeter (HbCOOX) ranged from 5.1 to 16.7 g/dL and theHb concentration measured by HemoCue® (HbHC) from 4.7 to 16.0 g/dL. Bias(HbCOOX - HbHC) between HbCOOX and HbHC was 0.6 ± 0.6 g/dL(mean ± SD) or 5.4 ± 5.0% (p < 0.001). Also in thereconstituted blood, the bias between HbCOOX and HbHC was significant (0.2± 0.3 g/dL or 2.1 ± 3.2%; p < 0.001). Themicrocuvette explained 68% of the variability between HbCOOX andHbHC. HemoCue® thus underestimates the Hb concentration by2-5% and exhibits a 8-10 times higher variability withonly 86.4% of HbHC being within ± 10% of HbCOOX.Conclusion. Although the mean bias between HbCOOX and HbHC was relativelylow, Hb measurement by HemoCue® exhibited a significant variability.Loading multiple microcuvettes and averaging the results may increase theaccuracy of Hb measurement by HemoCue

Iron Sucrose: A Wealth of Experience in Treating Iron Deficiency

Iron deficiency and iron-deficiency anemia are associated with increased morbidity and mortality in a wide range of conditions. In many patient populations, this can be treated effectively with oral iron supplementation; but in patients who are unable to take or who do not respond to oral iron therapy, intravenous iron administration is recommended. Furthermore, in certain conditions, such as end-stage kidney disease, chronic heart failure, and inflammatory bowel disease, intravenous iron administration has become first-line treatment. One of the first available intravenous iron preparations is iron sucrose (Venofer®), a nanomedicine that has been used clinically since 1949. Treatment with iron sucrose is particularly beneficial owing to its ability to rapidly increase hemoglobin, ferritin, and transferrin saturation levels, with an acceptable safety profile. Recently, important new data relating to the use of iron sucrose, including the findings from the landmark PIVOTAL trial in patients with end-stage kidney disease, have been reported. Several years ago, a number of iron sucrose similars became available, although there have been concerns about the clinical appropriateness of substituting the original iron sucrose with an iron sucrose similar because of differences in efficacy and safety. This is a result of the complex and unique physicochemical properties of nanomedicines such as iron sucrose, which make copying the molecule difficult and problematic. In this review, we summarize the evidence accumulated during 70 years of clinical experience with iron sucrose in terms of efficacy, safety, and cost-effectiveness

Parameters affecting baseline hip function in patients with cam-derived femoroacetabular impingement syndrome: data analysis from the German Cartilage Registry

Background Using the database of the German Cartilage Registry (KnorpelRegister DGOU), this study aims to present patient- and joint-related baseline data in a large cohort of patients with cam-derived femoroacetabular impingement syndrome (FAI) and to detect symptom-determining factors. Materials and methods Requiring cam morphology as the primary pathology, 362 patients were found to be eligible for inclusion in the study. The assessment of preoperative baseline data was performed using the patient-reported outcome measure—International Hip Outcome Tool (iHOT-33). Descriptive statistics were performed to present baseline data. Univariate and multiple regression with post hoc testing were used to identify patient- and joint-related factors that might affect the preoperative iHOT-33 and its subscores, respectively. Results The study collective’s mean age was 36.71 ± 10.89 years, with 246 (68%) of them being male. The preoperative mean iHOT-33 total was 46.31 ± 20.33 with the subsection “sports and recreational activities” presenting the strongest decline (26.49 ± 20.68). The parameters “age,” “sex,” “body mass index” (BMI), and the confirmation of “previous surgery on the affected hip” were identified to statistically affect the preoperative iHOT-33. In fact, a significantly lower mean baseline score was found in patients aged > 40 years (p < 0.001), female sex (p < 0.001), BMI ≥ 25 kg/m2 (p = 0.002) and in patients with previous surgery on the affected hip (p = 0.022). In contrast, the parameters defect grade and size, labral tears, and symptom duration delivered no significant results. Conclusions A distinct reduction in the baseline iHOT-33, with mean total scores being more than halved, was revealed. The parameters “age > 40 years,” “female sex,” “BMI ≥ 25,” and confirmation of “previous surgery on the affected hip” were detected as significantly associated with decreased preoperative iHOT-33 scores. These results help to identify symptom-defining baseline characteristics of cam-derived FAI syndrome. Trial registration: The German Cartilage Registry is conducted in accordance with the Declaration of Helsinki and registered at germanctr.de (DRKS00005617). Registered 3 January 2014—retrospectively registered. The registration of data was approved by the local ethics committees of every participating institution. Primary approval was given by the ethics committee at the University of Freiburg (No. 105/13). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS0000561

Divergent architecture of the heterotrimeric NatC complex explains N-terminal acetylation of cognate substrates

The heterotrimeric NatC complex, comprising the catalytic Naa30 and the two auxiliary subunits Naa35 and Naa38, co-translationally acetylates the N-termini of numerous eukaryotic target proteins. Despite its unique subunit composition, its essential role for many aspects of cellular function and its suggested involvement in disease, structure and mechanism of NatC have remained unknown. Here, we present the crystal structure of the Saccharomyces cerevisiae NatC complex, which exhibits a strikingly different architecture compared to previously described N-terminal acetyltransferase (NAT) complexes. Cofactor and ligand-bound structures reveal how the first four amino acids of cognate substrates are recognized at the Naa30–Naa35 interface. A sequence-specific, ligand-induced conformational change in Naa30 enables efficient acetylation. Based on detailed structure–function studies, we suggest a catalytic mechanism and identify a ribosome-binding patch in an elongated tip region of NatC. Our study reveals how NAT machineries have divergently evolved to N-terminally acetylate specific subsets of target proteins

Structural basis for the binding of IRES RNAs to the head of the ribosomal 40S subunit

Some viruses exploit internal initiation for their propagation in the host cell. This type of initiation is facilitated by structured elements (internal ribosome entry site, IRES) upstream of the initiator AUG and requires only a reduced number of canonical initiation factors. An important example are IRES of the virus family Dicistroviridae that bind to the inter-subunit side of the small ribosomal 40S subunit and lead to the formation of elongation-competent 80S ribosomes without the help of any initiation factor. Here, we present a comprehensive functional and structural analysis of eukaryotic-specific ribosomal protein rpS25 in the context of this type of initiation and propose a structural model explaining the essential involvement of rpS25 for hijacking the ribosome