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West Chester, PA, United States

Kim J.-S.,Rush University Medical Center | Ellman M.B.,Rush University Medical Center | Yan D.,Rush University Medical Center | An H.S.,Rush University Medical Center | And 10 more authors.
Journal of Cellular Physiology | Year: 2013

The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production, and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. © 2013 Wiley Periodicals, Inc. Source


Green J.,Synthes INC.
Injury | Year: 2010

Excessive intramedullary pressure coincident to surgical procedures requiring entrance and surgical manipulation within the intramedullary canal is a problem that was recognized by Gerhard Küntscher, the godfather of intramedullary nailing. He expressed concern about this phenomenon in his early writings during the 1940's. Although he suggested certain technical methods to moderate the event while doing the surgical procedure he had no solution for absolutely preventing its occurrence. This became more of an issue after he introduced motorized reaming in the mid 1950's to improve the strength of intramedullary fixation. The first to demonstrate that pressure could be avoided during intramedullary surgeries were Lorenzi, Olerud and Dankwardt- Lillieström in the late 1960's. Using a method that employed suction evacuation of intramedullary content prior to reaming, and by introducing irrigation while reaming, they were able to achieve negative pressures during their intramedullary work. They proved that if an IM technique did not inject fat throughout the bone and into the organism there were significant benefits both locally and systemically. With impeccable methodology, they showed fat destroyed the vascularity of the bone and inhibited its revascularization. Systemically, its presence was associated with death and morbidity. K.M. Stürmer, using sheep in studies done in the 1980's, further validated the effectiveness of negative pressure reaming to prevent adverse effects associated with reaming. The attempt to create a device to provide these benefits clinically, however, has been challenging. The group in Muenster did work with a rinsing-suction-reamer (RSR) that showed fat introduction with reaming need not be significantly greater than when using an external fixator. In the US, the effort has focused on developing a reamer that integrated suction and irrigation into its design. This instrument has been given the acronym of RIA (reamer/irrigator/aspirator). The rationale and development of this system is detailed in this paper. Now that the intramedullary canal can be reamed using a negative pressure method this domain, as a unique source of biological material, is being increasingly investigated. The cells and tissue harvested from this space have tremendous therapeutic promise. © 2010 Elsevier Ltd. All rights reserved. Source


Villasmil M.L.,The Institute of Metabolic Disorders | Villasmil M.L.,Cato Research Ltd. | Francisco J.,The Institute of Metabolic Disorders | Gallo-Ebert C.,The Institute of Metabolic Disorders | And 5 more authors.
Cell Cycle | Year: 2016

Sphingolipids are major constituents of membranes. A number of S. cerevisiae sphingolipid intermediates such as long chains sphingoid bases (LCBs) and ceramides act as signaling molecules regulating cell cycle progression, adaptability to heat stress, and survival in response to starvation. Here we show that S. cerevisiae haploid cells must synthesize ceramide in order to induce mating specific cell cycle arrest. Cells devoid of sphingolipid biosynthesis or defective in ceramide synthesis are sterile and harbor defects in pheromone-induced MAP kinase-dependent transcription. Analyses of G1/S cyclin levels indicate that mutant cells cannot reduce Cln1/2 levels in response to pheromone. FACS analysis indicates a lack of ability to arrest. The addition of LCBs to sphingolipid deficient cells restores MAP kinase-dependent transcription, reduces cyclin levels, and allows for mating, as does the addition of a cell permeable ceramide to cells blocked at ceramide synthesis. Pharmacological studies using the inositolphosphorylceramide synthase inhibitor aureobasidin A indicate that the ability to synthesize and accumulate ceramide alone is sufficient for cell cycle arrest and mating. Studies indicate that ceramide also has a role in PI(4,5)P2 polarization during mating, an event necessary for initiating cell cycle arrest and mating itself. Moreover, our studies suggest a third role for ceramide in localizing the mating-specific Ste5 scaffold to the plasma membrane. Thus, ceramide plays a role 1) in pheromone-induced cell cycle arrest, 2) in activation of MAP kinase-dependent transcription, and 3) in PtdIns(4,5)P2 polarization. All three events are required for differentiation during yeast mating. © 2016 Taylor & Francis. Source


Klein C.,University Hospital of Tuebingen | Sprecher C.,AO Research Institute Davos | Rahn B.A.,AO Research Institute Davos | Green J.,Synthes INC. | Muller C.A.,Stadtisches Klinikum Karlsruhe
Injury | Year: 2010

The purpose of the present study was to evaluate the Reamer/Irrigator/ Aspirator (RIA), a reaming system designed to incorporate the advantages of irrigation and suction for every day clinical use. The evaluation process was focused on the displacement of the medullary content and its impact on cortical perfusion. The results of the RIA reamed nailing were compared to conventional non-reamed nailing (NRN). The tibia of the sheep was used as an acute fracture model. The fracture and nailing procedure was followed by intravital staining with Procion red. The effects on cortical perfusion (Procion red staining) were addressed in polymer embedded sections and cryosections. Sudan III stained cryosections were evaluated with respect to the cortical fat distribution. After irrigation and suction minute amounts of fat were observed in the cortex, whereas after non-reamed nailing the endosteal third of the cortical bone was penetrated with fat. Non-reamed nailing acutely showed better perfusion in the endosteal tenth and periosteal third of the cortical bone, after irrigation and suction reaming perfusion was preserved to a lesser degree. Irrigation and suction significantly reduces fat intravasation, and thus the danger of system-wide damage. Therefore, the Reamer/Irrigator/Aspirator is as efficient as its experimental predecessors. © 2010 Elsevier Ltd. All rights reserved. Source


Tschegg E.K.,Vienna University of Technology | Lindtner R.A.,Innsbruck Medical University | Doblhoff-Dier V.,University of Natural Resources and Life Sciences, Vienna | Stanzl-Tschegg S.E.,University of Natural Resources and Life Sciences, Vienna | And 4 more authors.
Journal of the Mechanical Behavior of Biomedical Materials | Year: 2011

Bioresorbable materials for implants have become increasingly researched over the last years. The bone-implant-interfaces of three different implant materials, namely a new bioresorbable magnesium alloy, a new self-reinforced polymer implant and a conventional titanium alloy, were tested using various methods: push-out tests, SEM and EDX analyses as well as surface analyses based on stereoscopic 3D pictures were conducted. The fracture energy is proposed as a very significant reference value for characterizing the mechanical performance of a bone-implant system. By using a video-extensometer system instead of, as is commonly done, tracking the movement of the crosshead in the push-out tests, the accuracy of measurement could be increased. © 2010 Elsevier Ltd. Source

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