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Schumacher J.,University Mainz | Ramljak S.,IKFE Institute for Clinical Research and Development | Asif A.R.,University of Gottingen | Schaffrath M.,University Hospital | And 2 more authors.
Journal of Proteome Research

We investigated possible associations between sequence evolution of mammalian sperm proteins and their phosphorylation status in humans. As a reference, spermatozoa from three normozoospermic men were analyzed combining two-dimensional gel electrophoresis, immunoblotting, and mass spectrometry. We identified 99 sperm proteins (thereof 42 newly described) and determined the phosphorylation status for most of them. Sequence evolution was studied across six mammalian species using nonsynonymous/synonymous rate ratios (dN/dS) and amino acid distances. Site-specific purifying selection was assessed employing average ratios of evolutionary rates at phosphorylated versus nonphosphorylated amino acids (α). According to our data, mammalian sperm proteins do not show statistically significant sequence conservation difference, no matter if the human ortholog is a phosphoprotein with or without tyrosine (Y) phosphorylation. In contrast, overall phosphorylation of human sperm proteins, i.e., phosphorylation at serine (S), threonine (T), and/or Y residues, associates with above-average conservation of sequences. Complementary investigations suggest that numerous protein-protein interactants constrain sequence evolution of sperm phosphoproteins. Although our findings reject a special relevance of Y phosphorylation for sperm functioning, they still indicate that overall phosphorylation substantially contributes to proper functioning of sperm proteins. Hence, phosphorylated sperm proteins might be considered as prime candidates for diagnosis and treatment of reduced male fertility. © 2013 American Chemical Society. Source

Pfutzner A.,IKFE Institute for Clinical Research and Development
Journal of Diabetes Science and Technology

The article by Brzag and coauthors in this issue of Journal of Diabetes Science and Technology reports a competitive accuracy performance study for a branded meter in comparison with six low-cost meters currently available in the United States. It highlights several important topics: (1) the need for more stringent post-marketing requirements for blood glucose meters after launch and (2) low-cost meters use older technologies and their manufacturers do not usually seriously invest in new technology or constant quality assurance efforts. This may explain the study results, which show superior performance of the branded meter. Finally, the article pinpoints to the "quality versus price" dilemma faced by the prescribing physician and their patients in daily routine, which may be additionally aggravated by budget constraints and prescription rules in reimbursed markets. © Diabetes Technology Society. Source

Pfutzner A.,IKFE Institute for Clinical Research and Development | Klonoff D.C.,Mills Peninsula Health Services | Pardo S.,Bayer Diabetes Care | Parkes J.L.,Bayer Diabetes Care
Journal of Diabetes Science and Technology

Background: The Parkes error grid, which was developed in 1994, presented performance zones for blood glucose (BG) monitors with borders that were not mathematically specified at the time the grid was published. Methods: In this article, we (1) review the history of the Parkes error grid, (2) present the never-before-published exact coordinates and specifications of the grid so that others may produce an exact replica of the original grid, and (3) discuss our suggestions how this metric should be applied. Results: The new ISO15197:2013 guideline for system accuracy assessment of BG meters for patient self-measurement incorporates use of this metric for defining acceptable accuracy of BG monitors. It is expected that, for regulatory purposes, this document will stipulate that the error grid version for type 1 diabetes should be applied with the caveat that only the A zone represents acceptable accuracy. Conclusions: It remains to be seen by how much the new error grid, which is currently being developed by the Food and Drug Administration/Diabetes Technology Society/American Diabetes Association/The Endocrine Society/ Association for Advancement of Medical Instrumentation, will deviate from the Parkers error grid. © Diabetes Technology Society. Source

Forst T.,IKFE Institute for Clinical Research and Development | Forst T.,University Hospital | Hanefeld M.,Center for Clinical Studies | Pfutzner A.,IKFE Institute for Clinical Research and Development | Pfutzner A.,Bingen University of Applied Sciences
Expert Opinion on Pharmacotherapy

Introduction: Pioglitazone is approved in combination with several other blood-glucose-lowering drugs for the treatment of type 2 diabetes mellitus (T2DM). Beyond lowering blood glucose levels, each combination of different blood-glucose-lowering drugs for the treatment of T2DM evolves specific pleiotropic effects, which might be considered on an individual basis in a certain patient. Areas covered: The objective of this article is to provide a short review of the pathophysiology of T2DM and to provide a rationale for the combination of pioglitazone with other antidiabetic drugs, based on a pathophysiological understanding of T2DM. Therefore, a PubMed search was undertaken covering the search terms pioglitazone, antidiabetic drugs and combination therapy. Expert opinion: Treatment with pioglitazone in T2DM was shown to improve insulin resistance and blood glucose levels without increasing the risk of hypoglycemia. Beyond those metabolic activities, pioglitazone was shown to evolve anti-inflammatory and anti-atherogenic effects. It seems useful to combine different antidiabetic drugs based on the specific needs and contraindications in an individual patient. The treating of T2DM patients by addressing not only glucose control, but also the underlying pathophysiological etiology might help to improve patient prognosis in the long run, especially with regard to the vascular complications. © Informa UK, Ltd. Source

Ramljak S.,IKFE Institute for Clinical Research and Development | Lock J.P.,University of Massachusetts Medical School | Schipper C.,IKFE Institute for Clinical Research and Development | Musholt P.B.,IKFE Institute for Clinical Research and Development | And 3 more authors.
Journal of Diabetes Science and Technology

Background: Abnormal hematocrit levels may interfere with glucose readings of patient self-assessment blood glucose (BG) meters. The aim of this laboratory investigation was to assess the potential influence of hematocrit variations on a variety of BG meters applying diferent measurement technologies. Methods: Venous heparinized blood was manipulated to contain three diferent BG concentrations (50-90, 120-180, and 280-350 mg/dl) and five diferent hematocrit levels (25%, 35%, 45%, 55%, and 65%). After careful oxygenation to normal blood oxygen pressure (65-100 mmHg), each sample was measured (eight times) with the following devices: Accu-Chek® Aviva, Nano, and Active, Breeze ® 2 and Contour®, FreeStyle Freedom Lite®, GlucoDr. auto™, Glucofix® mio Plus, GlucoLab™, GlucoMen® L X Plus, Nova M ax® Link, Nova Max® P lus, OneTouch® Ultra® 2 and Verio®, On Call® Plus and Platinum, Optium Xceed®, Precision Xceed®, and TaiDoc Fora TD-4227. A YSI 2300 STAT Plus™ glucose analyzer served as reference method. Stability to hematocrit influence was assumed, with <10% mean glucose result bias between the highest and lowest hematocrit levels. Results: Six of the investigated meters showed a stable performance in this investigation: Accu-Chek Active (7%), Glucofix mio Plus (5%), GlucoMen LX Plus (4%), NovaMax Plus (4%), Nova Max Link (7%), and OneTouch Verio (3%). All other meters failed this hematocrit interference test, with FreeStyle Freedom Lite (11%), and On Call Platinum (12%) being the better devices and On Call Plus (68%), GlucoLab (51%), TaiDoc Fora TD-4227 (39%), and Breeze 2 (38%) showing the worst performance. Conclusions: Hematocrit may affect BG meter performance in daily routine. In case of interference, low hematocrit values (<35%) result in too high readings. Our results encourage use of meters that are not afected by hematocrit interference. © Diabetes Technology Society. Source

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