Therapy of aseptic nonunions with parathyroid hormone

European Journal of Orthopaedic Surgery & Traumatology - The absence of osseous consolidation of a fracture for 9 or more months with no potential to heal is defined as nonunion. Both for the...     

Safety assessment of newly marketed herbal medicines--methodological approach (Ginkgo biloba example in Bulgaria)

This study presents a proposal for the methodological approach for postmarketing safety profile assessment based on sales data and information for adverse drug reactions of newly introduced herbal medicinal products in the market. The study covers all herbal medicinal products containing dry extract of Ginkgo biloba leaves allowed for sale in Bulgaria. The methodological approach we create should be used for the establishment of the national herbal drugs policy complying with the recent European regulatory changes and specificity of the therapeutic practice in the country.     

PLLA-Based Block Copolymers via Raft Polymerization—Impact of the Synthetic Route and Activation Mechanism

Designing supramolecular structures with well-defined dimensions and diverse morphologies via the self-assembly of block copolymers is renowned. Specifically, the design of 1D fiber nanostructures is extensively emphasized, due to their unique properties in many areas, such as microelectronics, photonics, and particularly in the biomedical field. Herein, amphiphilic diblock copolymers of P(l -lactide)-b-P(N-t-butoxy-carbonyl-N´-acryloyl-1,2-diaminoethane)-co-P(N-isopropylacrylamide) PLLA_n-b-P(BocAEAm)_m-co- P(NiPAAm)_Ɩ are developed. Two synthetic strategies are investigated to equip PLLA with a chain transfer agent (CTA), either by Steglich esterification of PLLA-OH or via the ring-opening polymerization of l -lactide using a CTA containing a hydroxyl functional group. The second strategy proves to be superior in terms of degree of functionalization. The corona-forming blocks, with degrees of polymerization of 200 and above are achieved in good definition by photo-iniferter RAFT polymerization (Đ ≤ 1.25), while a Đ of 1.75 is obtained by conventional RAFT polymerization. The self-assembly of the developed system leads to the formation of nanofibers with a height of 11 nm and a length of ≈300 nm, which is determined by atomic force microscopy (AFM). These fibers are the basis for new antimicrobial nanomaterials after deprotection, as the subject of upcoming work.     

Reverse plasticity: TGF‐β and IL‐6 induce Th1‐to‐Th17‐cell transdifferentiation in the gut

Th17 cells are a heterogeneous population of pro‐inflammatory T cells that have been shown to mediate immune responses against intestinal bacteria. Th17 cells are highly plastic and can transdifferentiate to Th1/17 cells or unconventional Th1 cells, which are highly pathogenic in animal models of immune‐mediated diseases such as inflammatory bowel diseases. A recent European Journal of Immunology article by Liu et al. (Eur. J. Immunol. 2015. 45:1010–1018) showed, surprisingly, that Th1 cells have a similar plasticity, and could transdifferentiate to Th17 cells. Thus, IFN‐γ‐producing Th1 effector cells specific for an intestinal microbial antigen were shown to acquire IL‐17‐producing capacities in the gut in a mouse model of colitis, and in response to TGF‐β and IL‐6 in vitro. TGF‐β induced Runx1, and together with IL‐6 was shown to render the ROR‐γt and IL‐17 promoters in Th1 cells accessible for Runx1 binding. In this commentary, we discuss how this unexpected plasticity of Th1 cells challenges our view on the generation of Th1/17 cells with the capacity to co‐produce IL‐17 and IFN‐γ, and consider possible implications of this Th1‐to‐Th17‐cell conversion for therapies of inflammatory bowel diseases and protective immune responses against intracellular pathogens.     

Low power laser irradiation alters gene expression of olfactory ensheathing cells in vitro

BACKGROUND AND OBJECTIVES: Both photobiomodulation (PBM) and olfactory ensheathing cells (OECs) transplantation improve recovery following spinal cord injury. However, neither the combination of these two therapies nor the effect of light on OECs has been reported. The purpose of this study was to determine the effect of light on OEC activity in vitro. MATERIALS AND METHODS: OECs were purified from adult rat olfactory bulbs and exposed to 810 nm light (150 mW; 0, 0.2, or 68 J/cm(2)). After 7-21 days in vitro, cells underwent immunocytochemistry or RNA extraction and RT-PCR. RESULTS: Analysis of immunolabeling revealed a significant decrease in fibronectin expression in the cultures receiving 68 J/cm(2). Analysis of gene expression revealed a significant (P < 0.05) increase in brain derived neurotrophic factor (BDNF), glial derived neurotrophic factor (GDNF), and collagen expression in the 0.2 J/cm(2) group in comparison to the non-irradiated and 68 J/cm(2) groups. OEC proliferation was also found to significantly increase in both light treated groups in comparison to the control group (P < 0.001). CONCLUSIONS: These results demonstrate that low and high dosages of PBM alter OEC activity, including upregulation of a number of neurotrophic growth factors and extracellular matrix proteins known to support neurite outgrowth. Therefore, the application of PBM in conjunction with OEC transplantation warrants consideration as a potential combination therapy for spinal cord injury.     

Colony formation and colony size do not reflect the onset of replicative senescence in human fibroblasts

Replicative senescence of human fibroblasts in vitro has been used as a model for in vivo aging. The onset of replicative senescence varies between several months to years. A colony formation assay, critically dependent on growth speed, can be performed within weeks, and has been reported being an indicator for the onset of replicative senescence. Earlier we could not find a correlation between growth speed in mass cultures and onset of replicative senescence of human fibroblast strains. Therefore, we studied the colony formation assay in 23 fibroblast strains that varied widely in their replicative capacity. Neither the number nor the size of colonies was related to the onset of replicative senescence. The number of cells within the colonies was modestly correlated to the growth speed of the mass cultures. We conclude that the colony formation assay does not reflect the onset of replicative senescence in human fibroblasts.