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Berlin Brandenburg

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  • 1
    Language: English
    In: Medicinal Research Reviews, May 2005, Vol.25(3), pp.331-342
    Description: Systemically applied agents to modulate the Fas/FasL system, e.g., by stimulation of Fas on activated leukocytes or tumor cells failed as strategies in immune therapy due to severe toxic effects in the host. Recently, a novel strategy has been developed by using immobilized immune active biologicals in a medical device that may allow immune management without expensive systemic therapy. This review reports on the potential role of Fas/FasL in immune therapy and summarizes current experimental and clinical data with the leukocyte inhibition module (LIM), an immobilized anti‐Fas antibody containing device yet used in extracorporeal blood circulation. This proof of principal may stimulate the development of other devices based on the regulation of Fas/FasL or other targets relevant for immune disorders. © 2004 Wiley Periodicals, Inc.
    Keywords: Novel Therapeutic Strategies ; Immune Management ; Apoptosis
    ISSN: 0198-6325
    E-ISSN: 1098-1128
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  • 2
    Language: English
    In: Medicinal Research Reviews, May 2007, Vol.27(3), pp.401-416
    Description: Despite the fact that neutrophils are essential for the protection from invading pathogens, hyperactive neutrophils may elicit detrimental cerebral damage after severe trauma. The neutrophil interactions with the neurovascular unit entail endothelial dysfunction involving endothelial leakage, formation of edema, coagulation abnormalities, disturbed hemodynamics, tissue infiltration etc. These elements of the “whole body inflammation,” designated systemic inflammatory response syndrome (SIRS) in conjunction with intracerebral proinflammatory activities, are important triggers of post‐traumatic cerebral damage and mortality according to the “second hit” concept. From the immunologic point of view, the brain is an immune privileged site, known to resist autodestructive inflammatory activity much more efficiently than other organs because of the highly efficient diverse functions of the blood–brain barrier (BBB). However, both the underlying strategy of the BBB to maintain cerebral protecting functions against the post‐traumatic neutrophil‐mediated “second hit” and how activated neutrophils may overcome the BBB are currently unknown. Therefore, this review summarizes the current understanding of the “second hit,” the BBB physiology, and its role in the maintenance of cerebral immune privilege, and discusses recent findings that may explain the pathophysiologic neutrophil–BBB interactions occurring after severe trauma, thus offering novel therapeutic options to protect from post‐traumatic brain damage. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 3, 401–416, 2007
    Keywords: Blood–Brain Barrier ; Hyperactive Neutrophils ; Second Hit Concept ; Sirs ; Trauma
    ISSN: 0198-6325
    E-ISSN: 1098-1128
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  • 3
    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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