The development of immunogenicity assays for clinical drug candidates targeting soluble proteins is challenging when the soluble target might produce either false-positive or false-negative signals in bridging anti-drug antibody screening assays. A generic soluble target removal protocol that uses a pH-dependent depletion was evaluated. An anti-drug antibody bridging assay with a pH-dependent soluble target depletion step was successfully developed.
View Article and Find Full Text PDFType 2 diabetes (T2D), alike Parkinson's disease (PD), belongs to the group of protein misfolding diseases (PMDs), which share aggregation of misfolded proteins as a hallmark. Although the major aggregating peptide in β-cells of T2D patients is Islet Amyloid Polypeptide (IAPP), alpha-synuclein (αSyn), the aggregating peptide in substantia nigra neurons of PD patients, is expressed also in β-cells. Here we show that αSyn, encoded by Snca, is a component of amyloid extracted from pancreas of transgenic mice overexpressing human IAPP (denoted hIAPPtg mice) and from islets of T2D individuals.
View Article and Find Full Text PDFBackground: Currently, there is a lack of knowledge, organisation and structure in modern health care systems to counter the global trend of obesity, which has become a major risk factor for noncommunicable diseases. Obesity increases the risk of diabetes, cardiovascular diseases, musculoskeletal disorders and cancer. There is a need to strengthen integrated care between primary and secondary health care and to enhance care delivery suited for patients with complex, long-term problems such as obesity.
View Article and Find Full Text PDFBackground: Overcrowding, reduced nurse to patient ratio, limited distance between incubators and absence of microbiological surveillance have been shown to promote spread of multidrug-resistant gram-negative organisms (MDRGN) in patients with birthweight < 1500 g. Patients > 1500 g treated on an intermediate care unit are unrepresented in recent literature. We therefore intended to present data obtained from a short-term overcrowded neonatal intermediate care unit (NIMCU) at a level III (international categorization) perinatal center at University Hospital Frankfurt, Germany.
View Article and Find Full Text PDFAMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced β cell stress, and promoted β cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin.
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