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The global prevalence of diabetes mellitus and other metabolic diseases is rapidly increasing. Animal models play pivotal roles in unravelling disease mechanisms and developing and testing therapeutic strategies. Rodents are the most widely used animal models but may have limitations in their resemblance to human disease mechanisms and phenotypes. Findings in rodent models are consequently often difficult to extrapolate to human clinical trials. To overcome this ‘translational gap’, we and other groups are developing porcine disease models. Pigs share many anatomical and physiological traits with humans and thus hold great promise as translational animal models. Importantly, the toolbox for genetic engineering of pigs is rapidly expanding. Human disease mechanisms and targets can therefore be reproduced in pigs on a molecular level, resulting in precise and predictive porcine (PPP) models. In this short review, we summarize our work on the development of genetically (pre)diabetic pig models and how they have been used to study disease mechanisms and test therapeutic strategies. This includes the generation of reporter pigs for studying beta-cell maturation and physiology. Furthermore, genetically engineered pigs are promising donors of pancreatic islets for xenotransplantation. In summary, genetically tailored pig models have become an important link in the chain of translational diabetes and metabolic research.

Diatoms are unicellular algae of enormous biodiversity that occur in all water habitats on earth. Their cell walls are composed of amorphous biosilica and exhibit species-specific nanoporous to microporous and macroporous patterning. Therefore, diatom biosilica is a promising renewable material for various applications, such as in catalysis, drug-delivery systems, and biophotonics. In this study, diatom biosilica of three different species (Stephanopyxis turris, Eucampia zodiacus, and Thalassiosira pseudonana) was used as support material for gold nanoparticles using a covalent coupling method. The resulting catalysts were applied for the oxidation of d-glucose to d-gluconic acid. Because of its high specific surface area, well-established transport pores, and the presence of small, homogeneously distributed gold nanoparticles on the surface, diatom biosilica provides a highly catalytically active surface and advanced accessibility to the active sites. In comparison to those of the used reference supports, higher catalytic activities (up to 3.28 × 10–4 mmolGlc s–1 mgAu–1 for T. pseudonana biosilica) and slower deactivation were observed for two of the diatom biosilica materials. In addition, diatom biosilica showed very high gold-loading capacities (up to 45 wt %), with a homogeneous nanoparticle distribution.

In the presence of the chiral amide AMX the quinolones (Ia)—(Ic) and (IVa) undergo photocyclization with good to high regio- and enantioselectivity.

The aim of this study was to compare the mucoadhesive properties of thiolated chitosans with regard to their molecular mass and type of immobilized thiol ligand. Mediated by a carbodiimide, aromatic- and aliphatic-thiol-bearing compounds were covalently attached to low- and medium-molecular-mass chitosan. All synthesized conjugates displayed on average 320 ± 50 μmol of immobilized free thiol groups per gram of polymer. The rheological synergy was observed by the mixture of equal volumes of polymer with mucin solution. Because of the increase in viscosity of the conjugate/mucin mixture, the self-crosslinking properties and the interaction of thiomers with the mucus layer could be confirmed. Further mucoadhesion of the chitosan conjugates was evaluated in vitro with the rotating cylinder method and tensile studies on excised porcine intestinal mucosa. The results show a significantly enhanced residence time (p Chitosan–4-mercaptobenzoic acid > Chitosan–glutathione > Chitosan–6-mercaptonicotinic acid > Chitosan–N-acetyl cysteine > Chitosan–thioglycolic acid > Unmodified chitosan. The charge, pKa, and reactivity of the attached compounds were found to be important factors influencing the mucoadhesive potential of the polymer. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Topical application of lidocaine is an effective approach for treatment of post-herpetic neuralgia and other painful neuropathies. Lidocaine inhibits voltage-gated Na(+) channels and it most likely reduces excitability of cutaneous sensory neurons which can be hyperexcitable or spontaneously active in states of neuropathic pain. However, lidocaine and other local anesthetics also exert a pronounced neurotoxicity and they activate the irritant receptors TRPV1 and TRPA1. In this randomized and double-blinded study, we explored the ability of lidocaine patches (5%) to alter sensory function and epidermal nerve fiber density in skin of healthy volunteers. As assessed by quantitative sensory testing, significantly elevated thresholds for touch, pin prick pain and mechanically induced wind-up were observed in skin treated with lidocaine patches. These effects reversed to baseline values within 2days after termination of the treatment. Pressure pain and thresholds for heat and cold-induced pain were not affected by the lidocaine patch. A moderate but significant decrease in epidermal nerve fiber density was observed in skin blister roofs obtained after 42days of treatment with lidocaine patches. The placebo patch did not induce any changes in sensory thresholds or nerve fiber density. In conclusion, lidocaine patches seem to have differential effects on sensory modalities in healthy skin. A degeneration of epidermal nerve fibers has previously been demonstrated for patches containing the TRPV1-agonist capsaicin and our findings suggest that this effect might also be relevant for lidocaine patches. These data warrant further studies on molecular mechanisms mediating a relief of neuropathic pain by topical lidocaine.