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Berlin Brandenburg

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  • AGRIS (United Nations, Food and Agriculture Organization)  (16)
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  • 1
    Language: English
    In: Phytomedicine, 2011, Vol.18(5), pp.384-386
    Description: The extract EPs 7630 is an approved drug for the treatment of acute bronchitis in Germany. The postulated mechanisms underlying beneficial effects of EPs 7630 in bronchitis patients include immunomodulatory and cytoprotective effects, inhibition of interaction between bacteria and host cells, and increase of cilliary beat frequency on respiratory cells. Here, we investigated the influence of EPs 7630 on replication of a panel of respiratory viruses. Determination of virus-induced cytopathogenic effects and virus titres revealed that EPs 7630 at concentrations up to 100 μg/ml interfered with replication of seasonal influenza A virus strains (H1N1, H3N2), respiratory syncytial virus, human coronavirus, parainfluenza virus, and coxsackie virus but did not affect replication of highly pathogenic avian influenza A virus (H5N1), adenovirus, or rhinovirus. Therefore, antiviral effects may contribute to the beneficial effects exerted by EPs 7630 in acute bronchitis patients.
    Keywords: Pelargonium Sidoides ; Respiratory Viruses ; Acute Bronchitis ; Medicine ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0944-7113
    E-ISSN: 1618-095X
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  • 2
    Language: English
    In: Cellular and Molecular Life Sciences, 2011, Vol.68(6), pp.1079-1090
    Description: Human cytomegalovirus (HCMV) is a major pathogen in immunocompromised individuals. Here, non-toxic concentrations of the anti-cancer kinase inhibitor sorafenib were shown to inhibit replication of different HCMV strains (including a ganciclovir-resistant strain) in different cell types. In contrast to established anti-HCMV drugs, sorafenib inhibited HCMV major immediate early promoter activity and HCMV immediate early antigen (IEA) expression. Sorafenib is known to inhibit Raf. Comparison of sorafenib with the MEK inhibitor U0126 suggested that sorafenib inhibits HCMV IEA expression through inhibition of Raf but independently of signaling through the Raf downstream kinase MEK 1/2. In concordance, siRNA-mediated depletion of Raf but not of MEK-reduced IEA expression. In conclusion, sorafenib diminished HCMV replication in clinically relevant concentrations and inhibited HCMV IEA expression, a pathophysiologically relevant event that is not affected by established anti-HCMV drugs. Moreover, we demonstrated for the first time that Raf activation is involved in HCMV IEA expression.
    Keywords: Human cytomegalovirus ; Sorafenib ; Kinase inhibitor ; Raf ; Immediate early antigen ; Cancer chemotherapy ; Oncomodulation ; Antiviral therapy
    ISSN: 1420-682X
    E-ISSN: 1420-9071
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  • 3
    Language: English
    In: International Journal of Pharmaceutics, 2011, Vol.415(1), pp.244-251
    Description: Glioblastomas belong to the most devastating cancer diseases. For this reason, polysorbate 80 (Tween 80 )-coated poly(isohexyl cyanoacrylate) (PIHCA) (Monorex ) nanoparticles loaded with doxorubicin were developed and tested for their use for the treatment of glioblastomas. The preparation of the nanoparticles resulted in spherical particles with high doxorubicin loading. The physico-chemical properties and the release of doxorubicin from the PIHCA-nanoparticles were analysed, and the influence on cell viability of the rat glioblastoma 101/8-cell line was investigated. In vitro, the empty nanoparticles did not show any toxicity, and the anti-cancer effects of the drug-loaded nanoparticles were increased in comparison to doxorubicin solution, represented by IC values. The in vivo efficacy was then tested in intracranially glioblastoma 101/8-bearing rats. Rats were treated with 3 × 1.5 mg/kg doxorubicin and were sacrificed 18 days after tumour transplantation. Histological and immunohistochemical analyses were carried out to assess the efficacy of the nanoparticles. Tumour size, proliferation activity, vessel density, necrotic areas, and expression of glial fibrillary acidic protein demonstrated that doxorubicin-loaded PIHCA-nanoparticles were much more efficient than the free drug. The results suggest that poly(isohexyl cyanoacrylate) nanoparticles hold great promise for the non-invasive therapy of human glioblastomas.
    Keywords: Doxorubicin ; Nanoparticles ; Poly(Isohexyl Cyanoacrylate) ; Glioblastoma ; Histology ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
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  • 4
    Language: English
    In: International Journal of Pharmaceutics, 2011, Vol.406(1), pp.128-134
    Description: Folic acid has been previously demonstrated to mediate intracellular nanoparticle uptake. Here, we investigated cellular uptake of folic acid-conjugated human serum albumin nanoparticles (HSA NPs). HSA NPs were prepared by desolvation and stabilised by chemical cross-linking with glutaraldehyde. Folic acid was covalently coupled to amino groups on the surface of HSA NPs by carbodiimide reaction. Preparation resulted in spherical HSA NPs with diameters of 239 ± 26 nm. As shown by size exclusion chromatography, 7.40 ± 0.90 μg folate was bound per mg HSA NPs. Cellular NP binding and uptake were studied in primary normal human foreskin fibroblasts (HFFs), the human neuroblastoma cell line UKF-NB-3, and the rat glioblastoma cell line 101/8 by fluorescence spectrophotometry, flow cytometry, and confocal laser scanning microscopy. Covalent conjugation of folic acid to HSA NPs increased NP uptake into cancer cells but not into HFFs. Free folic acid interfered with cancer cell uptake of folic acid-conjugated HSA NPs but not with uptake of folic acid-conjugated HSA NPs into HFFs. These data suggest that covalent linkage of folic acid can specifically increase cancer cell HSA NP uptake.
    Keywords: Nanoparticles ; Human Serum Albumin (HSA) ; Folic Acid ; Folate Receptor ; Cancer Targeting ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
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  • 5
    Language: English
    In: Medical Microbiology and Immunology, 2011, Vol.200(1), pp.53-60
    Description: Influenza A virus infection of macrophages and virus-induced pro-inflammatory gene expression are regarded to contribute to severity of influenza A virus-caused diseases. Although some data are available on cytokine production by influenza A virus-infected macrophages, systematic comparisons of the virus types are currently considered to be of high relevance in humans (pandemic H1N1/2009, seasonal H1N1, seasonal H3N2, highly pathogenic avian influenza H5N1) on pro-inflammatory potential, and relevant underlying cellular signalling events are missing. Here, we show that the infection of human monocyte-derived macrophages with pandemic H1N1/2009 (A/HH/01/2009), seasonal H1N1/1999 (A/New Caledonia/20/99), seasonal H3N2/2004 (A/California/7/2004) or highly pathogenic H5N1/2004 (A/Thailand/1(Kan-1)/04) results in similar infection rates. However, the investigated H1N1 strains caused delayed and decreased apoptosis in comparison with H3N2/2004 or H5N1/2004. Moreover, human macrophage infection with H3N2/2004 or H5N1/2004 but not with H1N1 viruses was associated with pronounced pro-inflammatory cytokine production and activation of relevant mitogen-activated protein kinase pathways as indicated by phosphorylation of p38, JNK and ERK 1/2. These findings are in line with clinical observations indicating enhanced disease severity in H3N2- or H5N1-infected patients compared to individuals infected with pandemic H1N1/2009 or seasonal H1N1.
    Keywords: Influenza A ; MAPK ; Cytokines ; Seasonal influenza ; H5N1 ; Pandemic H1N1/2009
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 6
    Language: English
    In: Medical Microbiology and Immunology, 2011, Vol.200(1), pp.1-5
    Description: The question whether human cytomegalovirus may affect cancer diseases has been discussed (very controversially) for decades. There are convinced believers and strict opponents of the idea that HCMV might be able to play a role in the course of cancer diseases. In parallel, the number of published reports on the topic is growing. Recently published and presented (Ranganathan P, Clark P, Kuo JS, Salamat S, Kalejta RF. A Survey of Human Cytomegalovirus Genomic Loci Present in Glioblastoma Multiforme Tissue Samples. 35th Annual International Herpes Workshop, Salt Lake City, 2010) data on HCMV detection in glioblastoma tissues and colocalisation of HCMV proteins with cellular proteins known to be relevant for glioblastoma progression motivated us to recapitulate the current state of evidence.
    Keywords: Cytomegalovirus ; Cancer ; Oncomodulation ; Tumour virus ; Glioblastoma ; Neuroblastoma
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 7
    Language: English
    In: Biochemical Pharmacology, 2011, Vol.81(2), pp.251-258
    Description: Enzastaurin is a selective protein kinase Cβ inhibitor which is shown to have direct antitumor effect as well as suppress glycogen synthase kinase-3β (GSK-3β) phosphorylation (resulting in its activation) in both tumor tissues and peripheral blood mononuclear cells (PBMC). It is currently used in phase II trials for the treatment of colon cancer, refractory glioblastoma and diffuse large B cell lymphoma. In this study, the direct effect of enzastaurin on effector function of human natural killer (NK) cells was investigated. The results obtained showed that enzastaurin suppressed both natural and antibody-dependent cellular cytotoxicity (ADCC) of NK cells against different tumor targets. This inhibition was associated with a specific down-regulation of surface expression of NK cell activating receptor NKG2D and CD16 involved in natural cytotoxicity and ADCC respectively, as well as the inhibition of perforin release. Analysis of signal transduction revealed that enzastaurin activated GSK-3β by inhibition of GSK-3β phosphorylation. Treatment of NK cells with GSK-3β-specific inhibitor TDZD-8 prevented enzastaurin-induced inhibition of NK cell cytotoxicity. Apart from the known antitumor and antiangiogenic effects, these results demonstrate that enzastaurin suppresses NK cell activity and may therefore interfere with NK cell-mediated tumor control in enzastaurin-treated cancer patients.
    Keywords: Antibody-Dependent Cellular Cytotoxicity ; Natural Cytotoxicity ; Nkg2d ; Protein Kinase Cβ ; Glycogen Synthase Kinase-3β ; Pharmacy, Therapeutics, & Pharmacology ; Chemistry
    ISSN: 0006-2952
    E-ISSN: 1873-2968
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  • 8
    Language: English
    In: Medical Microbiology and Immunology, 2010, Vol.199(4), pp.291-297
    Description: Hypercytokinaemia is thought to contribute to highly pathogenic H5N1 influenza A virus disease. Glycyrrhizin is known to exert immunomodulatory and anti-inflammatory effects and therefore a candidate drug for the control of H5N1-induced pro-inflammatory gene expression. Here, the effects of an approved parenteral glycyrrhizin preparation were investigated on H5N1 virus replication, H5N1-induced pro-inflammatory responses, and H5N1-induced apoptosis in human monocyte-derived macrophages. Glycyrrhizin 100 μg/ml, a therapeutically achievable concentration, impaired H5N1-induced production of CXCL10, interleukin 6, and CCL5 and inhibited H5N1-induced apoptosis but did not interfere with H5N1 replication. Global inhibition of immune responses may result in the loss of control of virus replication by cytotoxic immune cells including natural killer cells and cytotoxic CD8 + T-lymphocytes. Notably, glycyrrhizin concentrations that inhibited H5N1-induced pro-inflammatory gene expression did not affect cytolytic activity of natural killer cells. Since H5N1-induced hypercytokinaemia is considered to play an important role within H5N1 pathogenesis, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.
    Keywords: Glycyrrhizin ; H5N1 ; Cytokines ; Monocyte-derived macrophages
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 9
    Language: English
    In: Medical Microbiology and Immunology, 2010, Vol.199(2), pp.93-101
    Description: Tumor resistance to lysis by resting natural killer (NK) cells may be overcome by priming of NK cells with cytokines or by binding of NK activating receptors to ligands expressed on target cells. In this study, major histocompatibility complex class I (MHC-I)-negative LNCaP and MHC-I-positive DU145 cells were infected with genetically modified influenza A virus lacking the non-structural gene 1 (∆NS1 IAV). The cells were used to investigate the influence of ∆NS1 IAV infection on NK cell lysis of tumor cells as well as to prime NK cells for lysis of LNCaP and DU145 cells. While LNCaP cells infected with ΔNS1 IAV showed enhanced lysis when compared with mock-infected cells (93% ± 1.47 vs. 52% ± 0.74), both mock-infected and ΔNS1 IAV-infected DU145 cells were resistant to NK cell lysis. Moreover, NK cells primed with ΔNS1 IAV-infected LNCaP/DU145 cells effectively lysed resistant DU145 and sensitive LNCaP cells to a greater extent than NK cells primed with mock-infected LNCaP/DU145 or non-primed NK cells. Also, NK cell priming with ΔNS1 IAV-infected tumor cells enhanced extracellular signal-regulated kinase phosphorylation and increased granule release in NK cells. The increased granule release was specifically mediated by NKp46, which eventually potentiated NK cells primed with ΔNS1 IAV-infected tumor cells to overcome the inhibitory effects posed by MHC-I expression on DU145 cells. These findings show that in addition to direct lytic activity of NK cells, ΔNS1 IAV may influence anti-tumoral responses by priming NK cells.
    Keywords: Cytotoxicity ; NK cell priming ; Major histocompatibility complex class I ; Degranulation ; Oncolytic influenza A virus
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 10
    In: Journal of Clinical Microbiology, 2008, Vol. 46(6), p.2122
    Description: Here we describe for the first time the productive in vitro infection of human retinal pigment epithelial cells by varicella-zoster virus (VZV), resulting in a typical cytopathic effect (CPE) that is characterized by enlarged cells with increased granularity. Depending on the CPE dissemination, high titers of up to 1.6 x 10 super(6) PFU of cell-free and cryostable VZV/ml can be recovered.
    Keywords: Retinal Pigment Epithelium ; Retina ; Replication ; Pigments ; Infection ; Varicella-Zoster Virus ; Replication;
    ISSN: 0095-1137
    ISSN: 00951137
    E-ISSN: 1098660X
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