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  • English  (5)
  • Michaelis, Martin  (5)
  • Wiley Online Library  (5)
  • 1
    In: Acta Ophthalmologica, March 2012, Vol.90(2), pp.e98-e103
    Description: To compare cytokines in undiluted vitreous of treatment‐naïve patients with macular oedema without vitreomacular traction secondary to branch (BRVO), central (CRVO) and hemi‐central (H‐CRVO) retinal vein occlusion. Ninety‐four patients (median age 72 years, 42 men) underwent an intravitreal combination therapy, including a single‐site 23‐gauge core vitrectomy and the application of bevacizumab and dexamethasone due to vision‐decreasing macular oedema. Among these were 43 patients with BRVO, 35 with CRVO and 16 patients with hemi‐CRVO, which were distributed in a fresh or old retinal vein occlusion type (seven or more months after onset). Undiluted vitreous samples were analysed for interleukin 6 (IL‐6), monocyte chemoattractant protein‐1 (MCP‐1) and vascular endothelial growth factor (VEGF‐A) with cytometric BEAD assay. Vitreous samples from patients with idiopathic epiretinal membrane served as controls ( = 14). The mean cytokine values were highest in the CRVO group with IL‐6 = 64.7 pg/ml (SD ± 115.8), MCP‐1 = 1015.8 pg/ml (±970.1) and VEGF‐A = 278.4 pg/ml (±512.8), followed by the H‐CRVO group with IL‐6 = 59.9 pg/ml (SD ± 97.5), MCP‐1 = 938.8 pg/ml (±561.1) and VEGF‐A = 211.5 pg/ml (±232.4). The BRVO group had IL‐6 = 23.2 pg/ml (SD ± 48.8), MCP‐1 = 602.6 pg/ml (±490.3) and VEGF‐A = 161.8 pg/ml (±314.4). The values of MCP‐1 and VEGF‐A were significantly different for CRVO or H‐CRVO versus BRVO. All values were significantly higher than in the control samples, which had 6.2 ± 3.4 pg/ml (IL‐6), 253 ± 74 pg/ml (MCP‐1) and 7 ± 4.9 pg/ml (VEGF‐A). Within the old RVO type, only MCP‐1 was significantly different for CRVO or H‐CRVO versus BRVO. Both inflammatory markers and VEGF‐A were higher in CRVO and H‐CRVO than in BRVO undiluted vitreous samples. It seems that monocyte recruitment to the vessel wall, which might underlie the importance of eosinophils in tissue remodelling after RVO, is of special interest owing to the significant difference in MCP‐1 in the older RVO types.
    Keywords: Cytometric Bead Array ; Interleukin 6 ; Monocyte Chemoattractant Protein ; Retinal Vein Occlusion ; Vascular Endothelial Growth Factor ; Vitreous Samples
    ISSN: 1755-375X
    E-ISSN: 1755-3768
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  • 2
    Language: English
    In: FEBS Letters, 03 April 2007, Vol.581(7), pp.1317-1322
    Description: Treatment of transformed cells from leukemia or solid tumors with histone deacetylase inhibitors (HDACi) was shown to increase their sensitivity to NK cell lysis. In this study, treatment of IL-2-activated NK cells with HDACi including suberoylanilide hydroxamic acid and valproic acid was studied. Both drugs at therapeutic concentrations inhibited NK cell cytotoxicity on human leukemic cells. This inhibition was associated with decreased expression and function of NK cell activating receptors NKp46 and NKp30 as well as impaired granule exocytosis. NFκB activation in IL-2-activated NK cells was inhibited by both HDACi. Pharmacologic inhibition of NFκB activity resulted in similar effects on NK cell activity like those observed for HDACi. These results demonstrate for the first time that HDACi prevent NK cytotoxicity by downregulation of NK cell activating receptors probably through the inhibition of NFκB activation.
    Keywords: Cytotoxicity ; Nk Cells ; Histone Deacetylase Inhibitors ; Nk Cell Activating and Inhibitory Receptors ; Nuclear Factor Kappa B ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0014-5793
    E-ISSN: 1873-3468
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  • 3
    In: Wound Repair and Regeneration, September 2011, Vol.19(5), pp.597-607
    Description: The pathophysiology leading to delayed wound healing is complex and efficient therapeutic approaches for accelerated wound healing currently do not exist. We developed a novel drug‐eluting platform for the potential use in wound dressings. Here, we report on the potential of eluting ascorbic acid‐2‐phosphate (‐2), a highly stable variant of ascorbic acid, to induce angiogenesis and to promote collagen synthesis by fibroblasts. The drug‐eluting platform device () consists of biocompatible polymeric layers comprising polyethylene terephtalate, polyvinyl alcohol (), and polyurethane with as the solvent for ‐2. The angiogenic potential of ‐2 was evaluated in the endothelial cell tube formation assay () and in the chorion allantoic membrane () model. Collagen synthesis by ‐2‐stimulated fibroblasts was determined by irius ed staining. ‐2 significantly induced angiogenesis in five independent and assays and induced collagen synthesis in two different fibroblast cell lines. The eluting kinetics of ‐2 was determined by the ultraviolet anorop method and the functional 2,2′‐Azinobis‐(3‐ethylbenzthiazolin‐6‐sulfonic acid) method. Eluting profiles showed a continuous release in the range of biologically effective concentrations 〉10 days. This is the first report showing the proangiogenic‐ and collagen‐promoting features of ‐2. loaded with ‐2 ought to be further evaluated as wound dressings or as supplementary pads for topical treatment of delayed wound healing in preclinical studies.
    Keywords: Drug Delivery Systems ; Angiogenesis Inducing Agents -- Pharmacology ; Ascorbic Acid -- Analogs & Derivatives ; Neovascularization, Physiologic -- Drug Effects ; Wound Healing -- Drug Effects;
    ISSN: 1067-1927
    E-ISSN: 1524-475X
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  • 4
    Language: English
    In: Medicinal Research Reviews, July 2005, Vol.25(4), pp.383-397
    Description: The short chain fatty acid valproic acid (VPA) and VPA‐analogs modulate the biology of diverse tumor cell entities by inducing differentiation, inhibiting proliferation, increasing apoptosis, and immunogenicity and by decreasing metastatic and angiogenetic potential. This review updates an earlier one in 2002, reflecting the interest in VPA as a potent anticancer drug. A number of studies show that the types of known tumor cells susceptible to VPA is steadily increasing. Of special note is the strong antineoplastic activity of VPA in chemoresistant cancer cells. A novel and promising approach is combining VPA with other drugs to achieve a broad therapeutic index. Clinical studies are underway and the preliminary results indicate that VPA alone or in combination offers a promising avenue of treatment, both in solid and hematopoetic malignancies. © 2005 Wiley Periodicals, Inc.
    Keywords: Valproic Acid ; Hdac ; Differentiation ; Angiogenesis ; Combination Therapy ; Clinical Studies
    ISSN: 0198-6325
    E-ISSN: 1098-1128
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  • 5
    Language: English
    In: ChemInform, 11 October 2005, Vol.36(41), pp.no-no
    Description: For see ChemInform in Full Text.
    Keywords: Organic Chemistry ; Review ; Pharmacology ; Medicinal Chemistry ; Vaccines ; Serums
    ISSN: 0931-7597
    E-ISSN: 1522-2667
    Source: John Wiley & Sons, Inc.
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