Interleukin-17 Promotes Autoimmunity by Triggering a Positive-Feedback Loop via Interleukin-6 Induction

Tensile deformation and failure behavior at room temperature of the open cell nickel and copper foams with high porosity (96%) fabricated with the slurry foaming process at Mitsubishi Materials Corporation, Japan, was studied. In-situ observation of the deformation and failure behavior was conducted with a digital microscope. Stress-strain curves were measured, in which a non-contact extensometer was employed to detect the strain of the samples accurately. Electric resistance was measured to monitor the damage evolution. Finite element stress analysis was conducted to calculate the morphological change of cells with applied strain and the stress distribution in cells. It was revealed that the deformation and failure progressed through the following four stages; stage I characterized by the elastic deformation, stage II by plastic deformation, stage III by the co-occurrence of plastic deformation and cumulative failure of struts and stage IV by the chain reaction of strut failure nearly in a limited cross-section, respectively. Also it was found that the distribution of failure strain of struts in stage III, measured from the serrations in the stress-strain curve, could be described by the Weibull distribution, with which the transition from stage II to III was identified. Also, the result of the statistical analysis suggested that the average failure strain of the struts in the foam is much higher than the strain at ultimate stress of the foam

Gamma-globulin Inhibits Superantigen-induced Lymphocyte Proliferation and Cytokine Production

Background: High-dose pooled human immunoglobulin (PHIG) treatment is sometimes effective in superantigen related inflammatory diseases, such as toxic shock syndrome and Kawasaki disease. Neutralizing antibody to superantigen might provide protection, but antigen independent immune regulation of PHIG is also a proposed mechanism. Methods: Staphylococcal enterotoxin B (SEB)-specific IgG antibody in PHIG products (Venoglobulin IH®) was detected by ELISA. The suppressive effect of PHIG or its fragments on proliferation and cytokine (IL-4 and IFN-γ) production from SEB-stimulated peripheral blood mononuclear cells was examined. Results: SEB-specific IgG was detected in PHIG products. PHIG (6.25-25 mg/ml) suppressed SEB-induced proliferation and cytokine production in a dose-dependent manner. Fab and F (ab’) 2 fractions of PHIG also suppressed the responses, but depletion of SEB-specific antibody from PHIG did not affect the inhibitory effects. The Fc fragment of PHIG also showed partial, but significant suppression. Conclusions: These data suggested the possibility that PHIG suppressed SEB-induced proliferation and cytokine production by some mechanisms independent of the presence of neutralizing antibody

Change of Young's Modulus with Increasing Applied Tensile Strain in Open Cell Nickel and Copper Foams

The change of Young's modulus with increasing applied tensile strain in the open cell nickel and copper foams, fabricated by the slurry foaming process at Mitsubishi Materials Corporation, Japan, was investigated experimentally and analytically. Stress-strain curves were measured at room temperature, in which the loading-unloading-reloading process was performed on the sample at various applied strains. For measurement of the strain of the sample itself accurately, the non-contact extensometer was employed. The Young's modulus values at various applied tensile strains were estimated from the slope of the elastic region in the stress-strain curve in the unloading process. It was revealed that two competitive factors affect on the Young’ modulus value. One is the irreversible morphology-change of cells arising from the plastic deformation of the metal as a results of which, the cells are elongated and struts are straight forwarded in the tensile direction. This factor acts to raise the Young’s modulus with increasing applied strain. Another factor is the failure of struts, which tends to reduce the Young's modulus with increasing applied strain, especially beyond the strain where the struts are failed successively. Accordingly, due to the competition of the former and latter factors, the Young's modulus increases, reaching maximum and then decreases with increasing applied strain in both of the foams. The increase in Young's modulus with increasing applied strain due to the change of geometry of struts was confirmed by the experimental test of micro-samples composed of several struts and nodes and by the simulation based on the finite element analysis using a model micro-sample

Tensile Deformation and Failure Behavior of Open Cell Nickel and Copper Foams

Tensile deformation and failure behavior at room temperature of the open cell nickel and copper foams with high porosity (96%) fabricated with the slurry foaming process at Mitsubishi Materials Corporation, Japan, was studied. In-situ observation of the deformation and failure behavior was conducted with a digital microscope. Stress-strain curves were measured, in which a non-contact extensometer was employed to detect the strain of the samples accurately. Electric resistance was measured to monitor the damage evolution. Finite element stress analysis was conducted to calculate the morphological change of cells with applied strain and the stress distribution in cells. It was revealed that the deformation and failure progressed through the following four stages; stage I characterized by the elastic deformation, stage II by plastic deformation, stage III by the co-occurrence of plastic deformation and cumulative failure of struts and stage IV by the chain reaction of strut failure nearly in a limited cross-section, respectively. Also it was found that the distribution of failure strain of struts in stage III, measured from the serrations in the stress-strain curve, could be described by the Weibull distribution, with which the transition from stage II to III was identified. Also, the result of the statistical analysis suggested that the average failure strain of the struts in the foam is much higher than the strain at ultimate stress of the foam

Intraocular tissue distribution of betamethasone after intrascleral administration using a nonbiodegradable sustained drug delivery device.

PURPOSE. To evaluate the tissue distribution of betamethasone (BM) after implantation of a nonbiodegradable intrascleral implant as a new, controlled intraocular delivery system. METHODS. Nonbiodegradable intrascleral implants designed to release BM for at least 1 month were placed in the sclera of pigmented rabbits. The BM concentrations in the aqueous humor, vitreous, and retina-choroid were determined by highperformance liquid chromatography (HPLC) at 3, 7, 14, and 28 days after implantation. The BM concentrations in three sections of retina-choroid were also investigated. Retinal toxicity was evaluated by electroretinography and histology. RESULT. The BM released from the intrascleral implant in vitro and in vivo showed zero-ordered release profiles for 4 weeks. The BM concentrations in the retina-choroid after placement of the intrascleral implants remained higher than effective concentrations for suppressing various inflammatory processes for at least 28 days. The BM concentrations in the retina-choroid around the implantation site were more than 10 times higher than in the opposite side throughout the study. No substantial toxic reactions were observed by electroretinography or histology. CONCLUSIONS. These findings suggested that the nonbiodegradable intrascleral implant could be a useful drug carrier for intraocular delivery of BM without producing severe retinal toxicity. The intrascleral site may be considered for effective intraocular drug distribution after implantation. (Invest Ophthalmol Vis Sci

Effects of Functional Groups and Sugar Composition of Quercetin Derivatives on Their Radical Scavenging Properties

Quercetin derivatives are widespread in the plant kingdom and exhibit various biological actions. The aim of this study was to investigate the structure–activity relationships of quercetin derivatives, with a focus on the influence of functional groups and sugar composition on their antioxidant capacity. A series of quercetin derivatives were therefore prepared and assessed for their DPPH radical scavenging properties. Isoquercetin <i>O</i>-gallates were more potent radical scavengers than quercetin. The systematic analysis highlights the importance of the distribution of hydroxy substituents in isoquercetin <i>O</i>-gallates to their potency

Effect of benzalkonium chloride on transscleral drug delivery. Invest Ophthalmol Vis Sci 46: 703–8

PURPOSE. To investigate the effect and safety of benzalkonium chloride on transscleral drug delivery in the rabbit after continuous intrascleral administration. METHODS. Betamethasone 21-phosphate (BP) aqueous solutions, with or without benzalkonium chloride (BAK), were continuously administered to albino rabbit sclera with an osmotic pump for 1 week. The BP concentrations in the aqueous humor, vitreous, and retina-choroid were measured by highperformance liquid chromatography (HPLC). To investigate the effect of BAK on scleral permeability of BP in vitro, penetration of BP aqueous solution with or without BAK across the rabbit sclera was evaluated using a two-chamber Ussing apparatus. To determine the effects of BAK on transscleral delivery of large molecules, 20-and 70-kDa fluorescein isothiocyanate (FITC)-dextran (FD-20 and -70, respectively) aqueous solutions, with or without BAK, were continuously administered to the sclera by an osmotic pump. The intensity of fluorescence in the aqueous humor, vitreous, and retina-choroid was measured by fluorescence spectrophotometry at 1 week after implantation of the pump. The retinal toxicity of BAK was evaluated electrophysiologically and histologically. RESULTS. BAK increased concentrations of BP in the vitreous and retina-choroid compared with the control. BP was not detected in the aqueous humor. In the in vitro study, BAK did not increase the scleral permeability of BP. In the retina-choroid, BAK significantly increased concentrations of FD-20 but did not increase those of FD-70. The addition of BAK did not increase concentrations of FD-20 or -70 in the vitreous. No substantial toxic reactions were observed in the retina in electrophysiological or histologic examinations after the addition of BAK. CONCLUSIONS. The results of this study demonstrate that BAK may improve the ocular penetration of a drug in a transscleral drug delivery system without producing toxic reactions. (Invest Ophthalmol Vis Sci. 2005;46:703-708