Genotoxicity of nitroso compounds and sodium dichromate in a model combining organ cultures of human nasal epithelia and the comet assay

Genotoxic effects of xenobiotics are a possible step in tumor initiation in the mucosa of the upper aerodigestive tract. Using the comet assay, detecting genotoxicity in human tissue has been restricted to single incubations in vitro, but in vivo most xenobiotics harm their target in a repetitive or chronic manner. Therefore, we propose a model, which provides repetitive incubations in human upper aerodigestive tract mucosa cultures. Samples of human inferior nasal turbinate mucosa (n = 25) were cultured according to a modified version of a technique originally described by Steinsvag. On day 1 fresh samples and on days 7, 9 and 11 organ cultures were incubated with N-nitrosodiethylamine (NDEA), sodium dichromate (Na2Cr2O7) and N'-methyl-N-nitro-N-nitrosoguanidine(MNNG). Mucosa samples and organ cultures, respectively, underwent a modified comet assay on days 1, 7 and 11. Genotoxicity could be shown for NDEA, Na2Cr2O7 and MNNG on days 1, 7 and 11. Duration of tissue culture and repetitive incubations did not significantly influence the results for NDEA. Nevertheless, Na2Cr2O7 and MNNG caused higher genotoxic effects on cultures subjected to the comet assay on day 11. This model may help to assess genotoxic hazards posed by environ mental pollutants that have a cumulative character in repetitive or chronic exposure in vivo. Copyright (C) 2001 S. Karger AG, Basel

Mesenchymal Stem Cells Promote Oligodendroglial Differentiation in Hippocampal Slice Cultures

We have previously shown that soluble factors derived from mesenchymal stem cells (MSCs) induce oligodendrogenic fate and differentiation in adult rat neural progenitors (NPCs) in vitro. Here, we investigated if this pro-oligodendrogenic effect is maintained after cells have been transplanted onto rat hippocampal slice cultures, a CNS-organotypic environment. We first tested whether NPCs, that were pre-differentiated in vitro by MSC-derived conditioned medium, would generate oligodendrocytes after transplantation. This approach resulted in the loss of grafted NPCs, suggesting that oligodendroglial pre-differentiated cells could not integrate in the tissue and therefore did not survive grafting. However, when NPCs together with MSCs were transplanted in situ into hippocampal slice cultures, the grafted NPCs survived and the majority of them differentiated into oligodendrocytes. In contrast to the prevalent oligodendroglial differentiation in case of the NPC/MSC co-transplantation, naive NPCs transplanted in the absence of MSCs differentiated predominantly into astrocytes. In summary, the pro-oligodendrogenic activity of MSCs was maintained only after co-transplantation into hippocampal slice cultures. Therefore, in the otherwise astrogenic milieu, MSCs established an oligodendrogenic niche for transplanted NPCs, and thus, co-transplantation of MSCs with NPCs might provide an attractive approach to re-myelinate the various regions of the diseased CNS. Copyright (C) 2009 S. Karger AG, Base

Intellectual Property and Indigenous Peoples: Adapting Copyright Law to the Needs of a Global Community

The definition and scope of intellectual property and associated laws are under intense debate in the emerging discourse surrounding intellectual property and human rights. These debates primarily arise within the context of indigenous peoples\u27 rights to protection and ownership of culturally specific properties. It is true that intellectual property laws are based on Western, developed markets, Western concepts of creation and invention, and Western concepts of ownership. But whatever their origins, those laws have been, and currently are, the primary vehicle for the protection of artistic, literary, and scientific works worldwide. To segregate indigenous interests from this international legal regime, particularly in light of the increasing globalization of markets, is to deny indigenous peoples both a powerful legal shield and a powerful legal sword. This Article argues that copyright laws can, and must, be expanded so as to maintain the vitality of, and protect, the creative artistic and literary works of indigenous cultures. The article proposes three major changes to international copyright law: the incorporation of collective and communal notions of authorship, the expansion of the originality requirement to reflect these forms of authorship, and the application of limits on the duration of copyright protection in a broader community context. The article further proposes that a variety of intellectual property mechanisms be drawn upon to provide special protection for “sacred” cultural works

Transforming Growth Factor Alpha Stimulation of Mucosal Tissue Cultures from Head and Neck Squamous Cell Carcinoma Patients Increases Chemoresistance to Cisplatin

The monoclonal epidermal growth factor receptor ( EGFR) antibody cetuximab (Erbitux(TM)) was recently approved by the European Medicines Agency for the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) in combination with a platinum-based chemotherapy. Since the antibody has only a limited effect as a monotherapy, possible explanations for the synergistic effect with cisplatin are enhanced antibody-dependent cytoxicity and increased sensitivity to the drug. Most of our knowledge of EGFR biology in HNSCC is based on studies using EGFR inhibitors and/or antibodies. Our study was designed to evaluate the impact of EGFR stimulation on cisplatin-induced DNA damage. Therefore, tissue cultures were produced of tumor-free oropharyngeal mucosa biopsies of HNSCC patients and controls. In a previous study, overexpression of EGFR in tissue cultures from tumor patients compared to controls was confirmed by immunohistochemical staining. Twenty-four-hour stimulation of tissue cultures with transforming growth factor alpha (TGF-alpha), a specific EGFR ligand, resulted in a reduction of cisplatin-induced DNA damage by 35% in cases, whereas in controls TGF-alpha had no effect. This reflects a statistically significant increase in cellular chemoresistance to cisplatin following TGF-alpha stimulation and helps to further understand effects of EGFR antisense therapy in combination with chemotherapy. Copyright (C) 2010 S. Karger AG, Base

Pesantren and the Preservation of Islam Nusantara

This article describes the background of the rise of an Indonesian moderate Islamic understanding in the midst of a trans-national Islamic movement with the scriptural-puritanical in it's character which spread out pervasively in the country; and this new Islamic model is intolerant to local traditions. Meanwhile, historically, Islam Nusantara has been deeply rooted among the Moslems in archipelago, and this traditional-moderate Islam has been developed by Wali-songo. Islam Nusantara is accommodative to the local cultures and traditions. It produces a moderate and tolerant model of Islam. This article also describes the role of pesantren in protecting the heritages of Islam Nusantara. Copyright (c) 2015 by KARSA. All right reservedDOI: 10.19105/karsa.v23i2.71

Studies on mechanisms of augmentation of liver regeneration by cyclosporine and FK 506

Evidence could not be found of immune modulation of liver regeneration. The powerful immunosuppressive drug FK 506, which augments the response after partial hepatectomy in normal rats, had the same effect in T cell—deficient nude rats. The cytotoxicity of natural killer cells in treated nude rats was not significantly changed by FK 506 therapy. However, the serum of FK 506—treated nude rats increased hepatocyte proliferation when added to third‐party hepatocyte cultures, suggesting that FK 506 had induced a serum growth factor in the nude rats or had suppressed an inhibitory factor. A hypothesis was advanced that FK 506 (and cyclosporine) affects hepatic growth by nonimmunological pathways. (HEPATOLOGY 1991;14:140–143.) Copyright © 1991 American Association for the Study of Liver Disease

Kinetics of 5-aminolevulinic acid-induced fluorescence in organ cultures of bronchial epithelium and tumor

Background: 5-Aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence improves the differentiation of tumor and normal tissue in the bladder, skin and brain. Objective: The kinetics of 5-ALA-induced protoporphyrin IX (PPIX) fluorescence in organ cultures of normal human bronchial epithelium and cocultures of bronchial epithelium and tumor have been studied. Methods: Cultured biopsies of bronchial epithelium were exposed for 5 or 15 min, or continuously to 5-ALA. PPIX fluorescence was quantified for up to 300 min by spectroscopy. Cocultures of normal bronchial epithelium and a non-small-cell lung cancer cell line (EPLC-32M1) were incubated with 5-ALA. Space-resolved fluorescence microscopy was used to quantify PPIX fluorescence kinetics in the tumor and normal epithelium. Results: In cultures of normal epithelium, PPIX fluorescence kinetics were shown to depend on the duration of exposure to 5-ALA. There was a trend to higher fluorescence intensities with longer exposure times. In cocultures of bronchial epithelium and tumor, increases of fluorescence intensity were significantly greater in the tumor. Best tumor/normal tissue fluorescence ratios were found between 110 and 160 min after exposure to 5-ALA. Conclusion: Data obtained in this coculture system of bronchial epithelium and tumor is valuable to optimize modalities of fluorescence bronchoscopy for the diagnosis of early bronchial carcinoma. Copyright (C) 2002 S. Karger AG, Basel

Intercultural frames of Bible translation ownership in DR Congo

This paper offers an intercultural approach to Bible translation ownership in the Democratic Republic of Congo (DR Congo). It examines Bible translation ownership models in the current culture in this country, past church cultures, and original or early biblical cultures. After showing the similarities and differences in ownership models between the chosen frames of reference, it suggests a way forward for effective ownership of the Bible translation process in DR Congo, including the holding and protection of copyright by an organisation frame of the target linguistic community