High‐Pressure‐Mediated Thiourea‐Organocatalyzed Asymmetric Michael Addition to (Hetero)aromatic Nitroolefins: Prediction of Reaction Parameters by PCP‐SAFT Modelling

Thiourea-organocatalyzed Michael additions of diethyl malonate to various heteroaromatic nitroolefins (13 examples) have been studied under high-pressure (up to 800 MPa) and ambient pressure conditions. High pressure was conducive to enhanced product yields by a factor of 2-12 at a given reaction time, high reaction rates (reaction times were decreased from 72-24 h down to 4-24 h) and high enantioselectivity. Elucidating the effects of solvents for maximizing reaction rates and yields has been carried out using the Perturbed-Chain Polar Statistical Associating Fluid Theory (PCP-SAFT), allowing for the first time a prediction of the kinetic profiles under high-hydrostatic-pressure conditions

Evaluation of Functional Erythropoietin Receptor Status in Skeletal Muscle In Vivo: Acute and Prolonged Studies in Healthy Human Subjects

BACKGROUND: Erythropoietin receptors have been identified in human skeletal muscle tissue, but downstream signal transduction has not been investigated. We therefore studied in vivo effects of systemic erythropoietin exposure in human skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: The protocols involved 1) acute effects of a single bolus injection of erythropoietin followed by consecutive muscle biopsies for 1-10 hours, and 2) a separate study with prolonged administration for 16 days with biopsies obtained before and after. The presence of erythropoietin receptors in muscle tissue as well as activation of Epo signalling pathways (STAT5, MAPK, Akt, IKK) were analysed by western blotting. Changes in muscle protein profiles after prolonged erythropoietin treatment were evaluated by 2D gel-electrophoresis and mass spectrometry. The presence of the erythropoietin receptor in skeletal muscle was confirmed, by the M20 but not the C20 antibody. However, no significant changes in phosphorylation of the Epo-R, STAT5, MAPK, Akt, Lyn, IKK, and p70S6K after erythropoietin administration were detected. The level of 8 protein spots were significantly altered after 16 days of rHuEpo treatment; one isoform of myosin light chain 3 and one of desmin/actin were decreased, while three isoforms of creatine kinase and two of glyceraldehyd-3-phosphate dehydrogenase were increased. CONCLUSIONS/SIGNIFICANCE: Acute exposure to recombinant human erythropoietin is not associated by detectable activation of the Epo-R or downstream signalling targets in human skeletal muscle in the resting situation, whereas more prolonged exposure induces significant changes in the skeletal muscle proteome. The absence of functional Epo receptor activity in human skeletal muscle indicates that the long-term effects are indirect and probably related to an increased oxidative capacity in this tissue

Erythropoietin protects against diabetes through direct effects on pancreatic β cells

In mouse models of type 1 and type 2 diabetes, administration of human erythropoietin protects against disease by acting directly on pancreatic β cells

Evaluation of a Network Based Learning Environment for Dermatology

The importance of computer networks in a non technical environment is steadily increasing. Especially medicine is becoming a major user with its high demand in current information. We show here, how dermatology education can win by new network based applications. Because visual information is very important in dermatology, we have done in depth examinations for image quality considering compression, resolution, colour display, and transfer times. The basis layer for all our teaching resources is an image database, that is used to offer dynamic lecture scripts, case reports, an atlas and a quiz system. For evaluation purposes a generic user survey was used. The result of our evaluation and access statistics are very encouraging. I. Introduction Dermatology is a visually oriented discipline because diagnosis and differential diagnosis is mainly based on the recognition of the clinical and histopathological features. Therefore, images of diseases are extraordinary important in education ..

From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product

Advanced Therapy Medicinal Products (ATMP) provide promising treatment options particularly for unmet clinical needs, such as progressive and chronic diseases where currently no satisfying treatment exists. Especially from the ATMP subclass of Tissue Engineered Products (TEPs), only a few have yet been translated from an academic setting to clinic and beyond. A reason for low numbers of TEPs in current clinical trials and one main key hurdle for TEPs is the cost and labor-intensive manufacturing process. Manual production steps require experienced personnel, are challenging to standardize and to scale up. Automated manufacturing has the potential to overcome these challenges, toward an increasing cost-effectiveness. One major obstacle for automation is the control and risk prevention of cross contaminations, especially when handling parallel production lines of different patient material. These critical steps necessitate validated effective and efficient cleaning procedures in an automated system. In this perspective, possible technologies, concepts and solutions to existing ATMP manufacturing hurdles are discussed on the example of a late clinical phase II trial TEP. In compliance to Good Manufacturing Practice (GMP) guidelines, we propose a dual arm robot based isolator approach. Our novel concept enables complete process automation for adherent cell culture, and the translation of all manual process steps with standard laboratory equipment. Moreover, we discuss novel solutions for automated cleaning, without the need for human intervention. Consequently, our automation concept offers the unique chance to scale up production while becoming more cost-effective, which will ultimately increase TEP availability to a broader number of patients