[Designation of occupation and proper name--onomastical considerations on the early Christian inscription of Sarmanna medica from Gondorf on the River Mosel]. / Berufsbezeichnung und Eigenname--onomastische Erwägungen zur frühchristlichen Inschrift der Sarmanna medica aus Gondorf an der Untermosel.

Some time ago, the author published some hypotheses regarding the etymological roots of the name Sarmanna which appears in an early Christian epitaph, which may be as old as the 5th century A.D. In this paper, some of these hypotheses will be elaborated upon, based on additional evidence in support of its eastern germanic origin which suggests close semantic links to medica, Sarmanna's profession. This kind of semantic connection seems to be unique among known ancient epitaphs. It thus offers important sociological and historical evidence for processes of acculturation and assimilation also in the medical realm at the transition from late Antiquity to the early Middle Ages.

Loss of photoreceptor potential from retinal progenitor cell cultures, despite improvements in survival.

Retinal degeneration (RD) results from photoreceptor apoptosis. Cell transplantation, one potential therapeutic approach, requires expandable stem cells that can form mature photoreceptors when differentiated. Freshly dissociated primary retinal cells from postnatal day 2-6 (PN2-6) mouse retina can give rise, post-transplantation, to photoreceptors in adult recipients. Unfortunately, incorporation rates are low; moreover, photoreceptor potential is lost if the same PN2-6 cells are cultured prior to transplantation. We investigated the identity of the cells forming photoreceptors post-transplantation, using FACS sorted primary postnatal day (PN) 3-5 Rho-eGFP retinal cells. Higher integration rates were achieved for cells that were expressing Rho-eGFP at PN3-5, indicating that post-mitotic photoreceptor precursors already expressing rhodopsin form the majority of integrating rods. We then investigated improvement of cell culture protocols for retinal progenitor cells (RPCs) derived from PN3-5 retinal cells in vitro. We succeeded in improving RPC survival and growth rates 25-fold, by modifying retinal dissociation, replacing N2 supplement with B27 supplement minus retinoic acid (B27-RA) and coating flasks with fibronectin. However, levels of rhodopsin and similar photoreceptor-specific markers still diminished rapidly during growth in vitro, and did not re-appear after in vitro differentiation. Similarly, transplanted RPCs, whether proliferating or differentiated, did not form photoreceptors in vivo. Cultured RPCs upregulate genes such as Sox2 and nestin, markers of more primitive neural stem cells. Use of these cells for RD treatment will require identification of triggers that favour terminal photoreceptor differentiation and survival in vitro prior to transplantation.

[Vigantol--Adolf Windaus and the history of vitamin D]. / Vigantol--Adolf Windaus und die Geschichte des Vitamin D.

This publication shows the investigation of the chemistry and pharmacology, also the produce and the sale of vitamin D. Adolf Windaus was builded vitamin D by UV-irradiation from ergosterol of yeast. He gave his patents to Merck and Bayer, former I. G. Farbenindustrie, and they brang out the medical Vigantol in 1927. Also today you can buy Vigantol in the chemist's shop.

Retinal transplantation of photoreceptors results in donor-host cytoplasmic exchange.

Pre-clinical studies provided evidence for successful photoreceptor cell replacement therapy. Migration and integration of donor photoreceptors into the retina has been proposed as the underlying mechanism for restored visual function. Here we reveal that donor photoreceptors do not structurally integrate into the retinal tissue but instead reside between the photoreceptor layer and the retinal pigment epithelium, the so-called sub-retinal space, and exchange intracellular material with host photoreceptors. By combining single-cell analysis, Cre/lox technology and independent labelling of the cytoplasm and nucleus, we reliably track allogeneic transplants demonstrating cellular content transfer between graft and host photoreceptors without nuclear translocation. Our results contradict the common view that transplanted photoreceptors migrate and integrate into the photoreceptor layer of recipients and therefore imply a re-interpretation of previous photoreceptor transplantation studies. Furthermore, the observed interaction of donor with host photoreceptors may represent an unexpected mechanism for the treatment of blinding diseases in future cell therapy approaches.

Stem Cell-Derived Photoreceptor Transplants Differentially Integrate Into Mouse Models of Cone-Rod Dystrophy.

PURPOSE: Preclinical studies on photoreceptor transplantation provided evidence for restoration of visual function with pluripotent stem cells considered as a potential source for sufficient amounts of donor material. Adequate preclinical models representing retinal disease conditions of potential future patients are needed for translation research. Here we compared transplant integration in mouse models with mild (prominin1-deficient; Prom1-/-) or severe (cone photoreceptor function loss 1/rhodopsin-deficient double-mutant; Cpfl1/Rho-/-) cone-rod degeneration. METHODS: For photoreceptor transplant production, we combined the mouse embryonic stem cell retinal organoid system with rhodopsin-driven GFP cell labeling by recombinant adeno-associated virus (AAV). Organoid-derived photoreceptors were enriched by CD73-based magnetic-activated cell sorting (MACS) and transplanted subretinally into wild-type, Prom1-/- and Cpfl1/Rho-/- hosts. The survival, maturation, and synapse formation of donor cells was analyzed by immunohistochemistry. RESULTS: Retinal organoids yielded high photoreceptor numbers that were further MACS-enriched to 85% purity. Grafted photoreceptors survived in the subretinal space of all mouse models. Some cells integrated into wild-type as well as Prom1-/- mouse retinas and acquired a mature morphology, expressing rod and synaptic markers in close proximity to second-order neurons. In contrast, in the novel Cpfl1/Rho-/- model with complete photoreceptor degeneration, transplants remained confined to the subretinal space, expressed rod-specific but only reduced synaptic markers, and did not acquire mature morphology. CONCLUSIONS: Comparison of photoreceptor grafts in preclinical models with incomplete or complete photoreceptor loss, showed differential transplant success with effective and impaired integration, respectively. Thus, Cpfl1/Rho-/- mice represent a potential benchmark model resembling patients with severe retinal degeneration to optimize photoreceptor replacement therapies.

Preparation and characterization of chitosan and trimethyl-chitosan-modified poly-(epsilon-caprolactone) nanoparticles as DNA carriers.

The purpose of this research was to prepare poly-(epsilon-caprolactone) (PCL) particles by an emulsion-diffusion-evaporation method using a blend of poly-(vinyl alcohol) and chitosan derivatives as stabilizers. The chitosan derivatives used were chitosan hydrochloride and trimethyl chitosans (TMC) with varying degrees of quaternization. Particle characteristics-size, zeta potential, surface morphology, cytotoxicity, and transfection efficiency-were investigated. The developed method yields PCL nanoparticles in the size range of 250 to 300 nm with a positive surface charge (2.5 to 6.8 mV). The cytotoxicity was found to be moderate and virtually independent of the stabilizers' concentration with the exception of the highly quaternized TMC (degree of substitution 66%) being significantly more toxic. In immobilization experiments with gel electrophoresis, it could be shown that these cationic nanoparticles (NP) form stable complexes with DNA at a NP:DNA ratio of 3:1. These nanoplexes showed a significantly higher transfection efficiency on COS-1 cells than naked DNA.

Developments in the area of bioadhesive drug delivery systems.

This paper aims to review the current progress in bioadhesion for drug delivery applications as well as new techniques related to this field. Research started with mucoadhesive polymers that had already been in use as excipients and were rapidly used in new formulations. Their major drawback was found in their unspecific binding, as they adhere to almost any mucosal surface. As some of the polymers showed additional properties such as enzyme inhibition and permeation enhancement, however, they remain interesting as multifunctional excipients. In contrast to mucoadhesion, the concept of specific bioadhesion by use of lectins and other adhesion molecules is now gaining increasing attention as these substances bind directly to receptors on the cell surface rather than to the mucus gel layer. Since specific binding to the cell surface is often followed by uptake and intracellular transport, new chances for drug delivery evolved. Bioadhesion may, thus, enable researchers to deliver macromolecular drugs directly to specific target cells and has implications also relevant to other fields of science, such as tissue engineering, gene delivery and nanotechnology.

In vitro expanded stem cells from the developing retina fail to generate photoreceptors but differentiate into myelinating oligodendrocytes.

Cell transplantation to treat retinal degenerative diseases represents an option for the replacement of lost photoreceptor cells. In vitro expandable cells isolated from the developing mammalian retina have been suggested as a potential source for the generation of high numbers of donor photoreceptors. In this study we used standardized culture conditions based on the presence of the mitogens FGF-2 and EGF to generate high numbers of cells in vitro from the developing mouse retina. These presumptive 'retinal stem cells' ('RSCs') can be propagated as monolayer cultures over multiple passages, express markers of undifferentiated neural cells, and generate neuronal and glial cell types upon withdrawal of mitogens in vitro or following transplantation into the adult mouse retina. The proportion of neuronal differentiation can be significantly increased by stepwise removal of mitogens and inhibition of the notch signaling pathway. However, 'RSCs', by contrast to their primary counterparts in vivo, i.e. retinal progenitor cells, loose the expression of retina-specific progenitor markers like Rax and Chx10 after passaging and fail to differentiate into photoreceptors both in vitro or after intraretinal transplantation. Notably, 'RSCs' can be induced to differentiate into myelinating oligodendrocytes, a cell type not generated by primary retinal progenitor cells. Based on these findings we conclude that 'RSCs' expanded in high concentrations of FGF-2 and EGF loose their retinal identity and acquire features of in vitro expandable neural stem-like cells making them an inappropriate cell source for strategies aimed at replacing photoreceptor cells in the degenerated retina.