Wetenschap, werkelijkheid en onrustige eiwitten

Oratie uitgesproken door prof.dr. Marcellus Ubbink bij de aanvaarding van het ambt van hoogleraar op het gebied van Protein Chemistry aan de Universiteit Leiden op vrijdag 13 mei 2011Macromolecular Biochemistr

Design and development of a decision aid to enhance shared decision making by patients with an asymptomatic abdominal aortic aneurysm

Dirk T Ubbink1,2, Anouk M Knops1, Sjaak Molenaar1, Astrid Goossens11Department of Quality Assurance and Process Innovation and 2Department of Surgery, Academic Medical Center, Amsterdam, The NetherlandsObjective: To design, develop, and evaluate an evidence-based decision aid (DA) for patients with an asymptomatic abdominal aortic aneurysm (AAA) to inform them about the pros and cons of their treatment options (ie, surgery or watchful observation) and to help them make a shared decision.Methods: A multidisciplinary team defined criteria for the desired DA as to design, medical content and functionality, particularly for elderly users. Development was according to the international standard (IPDAS). Fifteen patients with an AAA, who were either treated or not yet treated, evaluated the tool.Results: A DA was developed to offer information about the disease, the risks and benefits of surgical treatment and watchful observation, and the individual possibilities and threats based on the patient’s aneurysm diameter and risk profile. The DA was improved and judged favorably by physicians and patients.Conclusion: This evidence-based DA for AAA patients, developed according to IPDAS criteria, is likely to be a simple, user-friendly tool to offer patients evidence-based information about the pros and cons of treatment options for AAA, to improve patients’ understanding of the disease and treatment options, and may support decision making based on individual values.Keywords: decision support techniques, research design, program development, abdominal aortic aneurysm, decision makin

Weak self-association of cytochrome c peroxidase molecules observed by paramagnetic NMR

Macromolecular Biochemistr

Creutzfeldt-Jakob disease and homocysteine levels in plasma and cerebrospinal fluid

Background: There is evidence that homocysteine contributes to various neurodegenerative disorders. Objective: To assess the values of homocysteine in patients with Creutzfeldt-Jakob disease (CJD) in both cerebrospinal fluid (CSF) and plasma. Methods: Study design: Case control study. Total homocysteine was quantified in CSF and plasma samples of CJD patients (n = 13) and healthy controls (n = 13). Results: Mean values in healthy controls: 0.15 mumol/l +/- 0.07 (CSF) and 9.10 mumol/l +/- 2.99 (plasma); mean values in CJD patients: 0.13 mumol/l +/- 0.03 (CSF) and 9.22 mumol/l +/- 1.81 (plasma). No significant differences between CJD patients and controls were observed (Mann-Whitney U, p > 0.05). Conclusions: The results indicate that the CSF and plasma of CJD patients showed no higher endogenous levels of homocysteine as compared to normal healthy controls. These findings provide no evidence for an additional role of homocysteine in the pathogenetic mechanisms underlying CJD neurodegeneration. Copyright (C) 2005 S. Karger AG, Basel

Hyperbaric Oxygen Therapy: Solution for Difficult to Heal Acute Wounds? Systematic Review

Hyperbaric oxygen therapy (HBOT) is used to treat various wound types. However, the possible beneficial and harmful effects of HBOT for acute wounds are unclear. We undertook a systematic review to evaluate the effectiveness of HBOT compared to other interventions on wound healing and adverse effects in patients with acute wounds. To detect all available randomized controlled trials (RCTs) we searched five relevant databases up to March 2010. Trial selection, quality assessment, data extraction, and data synthesis were conducted by two of the authors independently. We included five trials, totaling 360 patients. These trials, with some methodologic flaws, included different kinds of wound and focused on different outcome parameters, which prohibited meta-analysis. A French trial (n = 36 patients) reported that significantly more crush wounds healed with HBOT than with sham HBOT [relative risk (RR) 1.70, 95% confidence interval (CI) 1.11-2.61]. Moreover, there were significantly fewer additional surgical procedures required with HBOT (RR 1.60, 95% CI 1.03-2.50), and there was significantly less tissue necrosis (RR 1.70, 95% CI 1.11-2.61). In one of two American trials (n = 141) burn wounds healed significantly quicker with HBOT (P <0.005) than with routine burn care. A British trial (n = 48) compared HBOT with usual care. HBOT resulted in a significantly higher percentage of healthy graft area in split skin grafts (RR 3.50, 95% CI 1.35-9.11). In a Chinese trial (n = 145) HBOT did not significantly improve flap survival in patients with limb skin defects. HBOT, if readily available, appears effective for the management of acute, difficult to heal wound

Peroxidase Activity as a Tool for Studying the Folding of c-Type Cytochromes

The peroxidase activity of c-type cytochromes increases substantially by unfolding. This phenomenon was used to study the equilibrium unfolding of ferricytochrome c. The peroxidase activity is already enhanced at low denaturant concentrations. The lowest free energy folding intermediate is easily detected by this method, while it is invisible using fluorescence or optical spectroscopy. The free energy difference between this folding intermediate and the native state depends on the strength of the sixth ligand of the heme-iron and the increase in peroxidase activity upon unfolding is shown to be a sensitive indicator of the strength of this ligand. Under fully denaturing conditions, the peroxidase activity is inhibited by protein-based ligands. It is shown that at least three different ligand groups can be responsible for this inhibition, and that at neutral or alkaline pH, the predominant ligand is not histidine. The use of peroxidase activity assays as a method to study the unfolding of cytochrome c is evaluated.Macromolecular Biochemistr

The peroxidase activity of cytochrome c-550 from Paracoccus versutus

Macromolecular Biochemistr

Effect of the protein matrix of cytochrome c in supressing the inherent peroxidase activity of its heme group

Macromolecular Biochemistr