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  • Di Marco, Roberto  (39)
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  • 1
    Language: English
    In: International Journal of Molecular Medicine, September 2011, Vol.28(3), pp.437-442
    Description: Preclinical studies have shown that the anti-glucocorticoid drug mifepristone effectively inhibits HIV replication both in vitro and in vivo. However, the drug did not demonstrate anti-HIV activity in a previous phase I/II study when administered at the daily dose of 75-225 mg. The aim of this study was to assess whether mifepristone may exert antiretroviral activity or influence immunological parameters when administered orally at daily doses of 150 or 300 mg in highly active antiretroviral therapy (HAART)-naïve HIV-infected patients. We performed an open label non-randomized phase II study that included 26 patients who underwent 28 days of once daily oral administration of 150 (12 subjects) or 300 mg (14 subjects) of mifepristone. A total of 3 patients dropped out of the study, respectively 1 in the 150 mg dose group and 2 in the 300 mg dose group. The main hemato­chemical alterations reported were hypokalemia and increase in the blood levels of cortisol, especially in those patients that received mifepristone at the dose of 300 mg/day. Although we observed a trend of reduced viral load along the study in both groups, statistical significance was not achieved for either the primary nor the secondary endpoints. In summary, mifepristone treatment was well-tolerated but it failed to significantly influence viro-immunological parameters in HAART-naïve HIV-infected patients.
    Keywords: Surgical Stapler;
    ISSN: 1107-3756
    E-ISSN: 1791244X
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  • 2
    In: Nature Medicine, 2010, Vol.16(8), p.897
    Description: High amounts of glutamate are found in the brains of people with multiple sclerosis, an inflammatory disease marked by progressive demyelination. Glutamate might affect neuroinflammation via effects on immune cells. Knockout mice lacking metabotropic glutamate receptor-4 (mGluR4) were markedly vulnerable to experimental autoimmune encephalomyelitis (EAE, a mouse model of multiple sclerosis) and developed responses dominated by interleukin-17-producing T helper ([T.sub.H]17) cells. In dendritic cells (DCs) from those mice, defective mGluR4 signaling--which would normally decrease intracellular cAMP formation--biased [T.sub.H] cell commitment to the [T.sub.H]17 phenotype. In wild-type mice, mGluR4 was constitutively expressed in all peripheral DCs, and this expression increased after cell activation. Treatment of wild-type mice with a selective mGluR4 enhancer increased EAE resistance via regulatory T ([T.sub.reg]) cells. The high amounts of glutamate in neuroinflammation might reflect a counterregulatory mechanism that is protective in nature and might be harnessed therapeutically for restricting immunopathology in multiple sclerosis.
    Keywords: Multiple Sclerosis -- Risk Factors ; Multiple Sclerosis -- Care And Treatment ; Multiple Sclerosis -- Research ; Neurotransmitter Receptors -- Physiological Aspects ; Neurotransmitter Receptors -- Research ; T Cells -- Physiological Aspects ; T Cells -- Research;
    ISSN: 1078-8956
    E-ISSN: 1546170X
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  • 3
    Language: English
    In: Journal of Neuroimmunology, 15 January 2016, Vol.290, pp.66-69
    Description: Multiple sclerosis (MS) is an immunoinflammatory disease of the central nervous system that seems to be influenced by DNA methylation. We sought to explore the expression pattern of genes involved in the control of DNA methylation in Secondary Progressive (SP) MS patients' PBMCs. We have found that SP MS is characterized by a significant upregulation of two genes belonging to the family genes, and , and by a downregulation of and .
    Keywords: Multiple Sclerosis ; DNA Methylation ; Epigenetics ; Medicine ; Anatomy & Physiology
    ISSN: 0165-5728
    E-ISSN: 1872-8421
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  • 4
    Language: English
    In: Oncotarget, 03 April 2018, Vol.9(25), pp.17951-17970
    Description: Macrophage Migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine expressed by a variety of cell types. Although MIF has been primarily studied for its role in the pathogenesis of autoimmune diseases, it has also been shown to promote tumorigenesis and it is over expressed in various malignant tumors. MIF is able to induce angiogenesis, cell cycle progression, and to block apoptosis. As tailored therapeutic approaches for the inhibition of endogenous MIF are being developed, it is important to evaluate the role of MIF in individual neoplastic conditions that may benefit from specific MIF inhibitors. Along with this line, in this paper, we have reviewed the evidence of the involvement of MIF in the etiopathogenesis and progression of glioblastoma and the preclinical data suggesting the possible use of specific MIF inhibition as a potential novel therapeutic strategy for brain tumors.
    Keywords: D-Dt ; Brain Tumors ; Glioblastoma ; Macrophage Migration Inhibitory Factor ; Neuro-Oncology
    E-ISSN: 1949-2553
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  • 5
    Language: English
    In: Experimental and Therapeutic Medicine, 09/2017, Vol.14(3), pp.2439-2444
    Description: P40 is a particulate fraction or fragment isolated from Corynebacterium granulosum , which exhibits a wide spectrum of pharmacological functions including antitumor, antibacterial, phagocytic, antiviral and cytokine induction effects. In the present study, the immunomodulatory potential of P40-conjugated with hyaluronic acid was assessed in a mouse model of dermatitis induced by oxazolone. Oxazolone-induced allergic contact dermatitis is a T cell-mediated Th2-like hypersensitivity reaction, which mimics the corresponding reaction in humans. Female cluster of differentiation-1 mice were sensitized on days 0 and 1 by the application of 2% oxazolone onto a shaved back. The disease was induced by re-challenge on day 7 using 15% oxazolone in the inner and outer of the left ears of the mice. Mice were topically treated with hyaluronic acid-P40 conjugate cream or with placebo to the inner and outer surface of the left ear for 7 consecutive days starting from 1 h after the sensitization. A significant reduction in ear thickness and weight and in edema and leukocyte recruitment were observed in the mice treated with hyaluronic-P40 conjugate cream compared with mice treated with the cream base alone (P〈0.05). Thus, P40-conjugated with hyaluronic acid may constitute an innovative dermatitis treatment.
    Keywords: Dermatitis ; Oxazolone ; Immunomodulation ; P40 Fraction
    ISSN: 1792-0981
    E-ISSN: 1792-1015
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  • 6
    Language: English
    In: Clinical Immunology, April 2015, Vol.157(2), pp.198-204
    Description: Uveitis is a sight-threatening inflammatory disease of the eye which represents the third leading cause of blindness in the developed countries. The conventional pharmacological treatment includes corticosteroids and immunosuppressive agents, which are limited by their side effects. New therapeutic strategies are thus strongly needed. Exogenously-administered carbon monoxide (CO) may represent an effective treatment for conditions characterized by a dysregulated inflammatory response. Carbon monoxide-releasing molecules (CORMs) are a novel group of compounds capable of carrying and liberating controlled quantities of CO. Among CORMs, CORM-A1 represents the first example of water soluble CO releaser. We show here that CORM-A1 under a late prophylactic regime is able to significantly ameliorate the natural course of experimental autoimmune uveoretinitis, a rodent model of immunoinflammatory posterior uveitis. The present study strongly supports the development of CORM-A1 as a potential new drug for treatment of patients with non-infectious posterior uveitis.
    Keywords: Carbon Monoxide ; Corm-A1 ; Non-Infectious Uveitis ; Eau ; Medicine
    ISSN: 1521-6616
    E-ISSN: 1521-7035
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  • 7
    Language: English
    In: Journal of Neuroimmunology, 15 August 2013, Vol.261(1-2), pp.82-86
    Description: Multiple sclerosis (MS) is an immunoinflammatory disease that affects the central nervous system. Heme oxygenase-1 (HO-1) is one of the three isoforms of the heme oxygenase enzyme that catabolyzes the degradation of heme into biliverdin with the production of free iron and CO. We show in this study that HO-1 expression is reduced in PBMCs of MS patients and that during exacerbation of the disease there is a significant downregulation of this enzyme. We conclude that HO-1 may play a significant role in the maintenance of immune homeostasis which is disrupted in autoimmune disorders, such as MS.
    Keywords: Multiple Sclerosis ; Ho-1 ; Autoimmunity ; IFN-Beta ; Medicine ; Anatomy & Physiology
    ISSN: 0165-5728
    E-ISSN: 1872-8421
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  • 8
    In: Journal of Cellular Physiology, December 2014, Vol.229(12), pp.1918-1925
    Description: Increasing evidence supports the role of epigenetics in the development of autoimmune disorders and the possibility of using epigenetic modifying drugs in the context of MS has not yet been investigated. We have explored the effect of the hypomethylating agent 5-aza-2'-deoxycytidine (DAC) in two murine models of experimental allergic encephalomyelitis (EAE). DAC treatment was associated with a significant amelioration of the clinical and histological hallmarks of EAE in both models. These effects were observed both in prophylactic and therapeutic regimens. The milder course of the disease was associated with a reduction in the number of spinal cord infiltrating lymphocytes and amelioration of the histopathological signs associated with EAE. In addition, increased transcript levels of anti-inflammatory cytokines and decreased mRNA expression of pro-inflammatory mediators were also observed. Finally, DAC treatment increased the percentage of circulating regulatory T cells by inducing Foxp3 expression via demethylation of a CpG island in Foxp3. J. Cell. Physiol. 229: 1918-1925, 2014. © 2014 Wiley Periodicals, Inc.
    Keywords: Animals–Administration & Dosage ; Anti-Inflammatory Agents–Adverse Effects ; Anti-Inflammatory Agents–Administration & Dosage ; Azacitidine–Analogs & Derivatives ; Azacitidine–Metabolism ; Cytokines–Drug Therapy ; Disease Models, Animal–Genetics ; Encephalomyelitis, Autoimmune, Experimental–Pathology ; Encephalomyelitis, Autoimmune, Experimental–Genetics ; Encephalomyelitis, Autoimmune, Experimental–Pathology ; Mice–Pathology ; Multiple Sclerosis–Pathology ; Multiple Sclerosis–Pathology ; T-Lymphocytes, Regulatory–Pathology ; Anti-Inflammatory Agents ; Cytokines ; Decitabine ; Azacitidine;
    ISSN: 0021-9541
    E-ISSN: 1097-4652
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  • 9
    In: Antimicrobial Agents and Chemotherapy, 2001, Vol. 45(5), p.1591
    Description: Multifunctional protein 14 (MFP-14) is a ubiquitous protein that inhibits the production of tumor necrosis factor alpha (TNF- alpha ) and gamma interferon (IFN- gamma ), which are involved in the pathogenesis of sepsis. Here, lipopolysaccharide (LPS)-induced lethality in mice was markedly reduced by MFP-14. The treatment also lowered LPS-induced levels of TNF- alpha and IFN- gamma in the blood.
    Keywords: Lipopolysaccharides ; Endotoxins ; Endotoxemia ; Immunomodulation ; Lipopolysaccharides ; Endotoxins ; Endotoxemia ; Immunomodulation ; Mfp-14 ; Mfp-14 ; Microbial ; In Vitro and in Vivo Effects ; Mice ; Treatment ; Prevention ; Mice ; Treatment ; Prevention ; Mfp-14 ; Mice ; Prevention ; Treatment;
    ISSN: 0066-4804
    ISSN: 00664804
    E-ISSN: 10986596
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  • 10
    Language: English
    In: The Journal of Neuroscience, 07/01/2002, Vol.22(13), pp.5403-5411
    Description: The chemokine RANTES is critically involved in neuroinflammation and has been implicated in the pathophysiology of multiple sclerosis. We examined the possibility that activation of G-protein-coupled metabotropic glutamate (mGlu) receptors regulates the formation of RANTES in glial cells. A 15 hr exposure of cultured astrocytes to tumor necrosis factor-alpha and interferon-gamma induced a substantial increase in both RANTES mRNA and extracellular RANTES levels. These increases were markedly reduced when astrocytes were coincubated with l-2-amino-4-phosphonobutanoate (l-AP-4), 4-phosphonophenylglycine, or l-serine-O-phosphate, which selectively activate group III mGlu receptor subtypes (i.e., mGlu4, -6, -7, and -8 receptors). Agonists of mGlu1/5 or mGlu2/3 receptors were virtually inactive. Inhibition of RANTES release produced by l-AP-4 was attenuated by the selective group III mGlu receptor antagonist (R,S)-alpha-methylserine-O-phosphate or by pretreatment of the cultures with pertussis toxin. Cultured astrocytes expressed mGlu4 receptors, and the ability of l-AP-4 to inhibit RANTES release was markedly reduced in cultures prepared from mGlu4 knock-out mice. This suggests that activation of mGlu4 receptors negatively modulates the production of RANTES in glial cells. We also examined the effect of l-AP-4 on the development of experimental allergic encephalomyelitis (EAE) in Lewis rats. l-AP-4 was subcutaneously infused for 28 d by an osmotic minipump that released 250 nl/hr of a solution of 250 mm of the drug. Detectable levels of l-AP-4 ( approximately 100 nm) were found in the brain dialysate of EAE rats. Infusion of l-AP-4 did not affect the time at onset and the severity of neurological symptoms but significantly increased the rate of recovery from EAE. In addition, lower levels of RANTES mRNA were found in the cerebellum and spinal cord of EAE rats infused with l-AP-4. These results suggest that pharmacological activation of group III mGlu receptors may be useful in the experimental treatment of neuroinflammatory CNS disorders.
    Keywords: Anatomy & Physiology;
    ISSN: 0270-6474
    E-ISSN: 1529-2401
    Source: CrossRef
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