Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Type of Medium
Language
Year
  • 1
    Language: English
    In: Science (New York, N.Y.), 12 March 2004, Vol.303(5664), pp.1681-3
    Description: Weak inhibition within visual cortex early in life prevents experience-dependent plasticity. Loss of responsiveness to an eye deprived of vision can be initiated prematurely by enhancing gamma-aminobutyric acid (GABA)-mediated transmission with benzodiazepines. Here, we use a mouse "knockin" mutation to alpha subunits that renders individual GABA type A (GABA(A)) receptors insensitive to diazepam to show that a particular inhibitory network controls expression of the critical period. Only alpha1-containing circuits were found to drive cortical plasticity, whereas alpha2-enriched connections separately regulated neuronal firing. This dissociation carries implications for models of brain development and the safe design of benzodiazepines for use in infants.
    Keywords: Neuronal Plasticity ; Dominance, Ocular -- Physiology ; Interneurons -- Physiology ; Neurons -- Physiology ; Receptors, Gaba-A -- Physiology ; Visual Cortex -- Physiology
    ISSN: 00368075
    E-ISSN: 1095-9203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Nanotechnology, 2011, Vol.22(24), p.245102 (12pp)
    Description: The second generation photosensitizer m THPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that m THPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free m THPC and m THPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost m THPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer m THPC.
    Keywords: Colonic Neoplasms -- Metabolism ; Intracellular Space -- Metabolism ; Lactic Acid -- Toxicity ; Mesoporphyrins -- Toxicity ; Nanoparticles -- Toxicity ; Polyglycolic Acid -- Toxicity;
    ISSN: 0957-4484
    E-ISSN: 1361-6528
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Neurobiology of Disease, November 2012, Vol.48(2), pp.189-201
    Description: Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. While sporadic in the majority of cases, PD-linked dominant mutations in the α-synuclein and LRRK-2 genes, and recessive mutations in the parkin, DJ-1 and PINK-1 genes have been identified in PD families in recent years. In this review we describe viral animal models for PD, i.e. models that are based on PD-associated mutations, and have been generated by viral delivery of the respective disease genes to the substantia nigra of rodents and non-human primates. To date, viral PD models comprise α-synuclein and LRRK-2-based overexpression models, as well as models that mimic parkin loss of function by overexpression of the parkin substrates Pael-R, CDCrel-1, p38/JTV or synphilin-1. These viral models provide valuable insights into Parkinson disease mechanisms, help to identify therapeutic targets and may contribute to the development of therapeutic approaches.
    Keywords: Medicine ; Anatomy & Physiology
    ISSN: 0969-9961
    E-ISSN: 1095-953X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Human gene therapy, June 2013, Vol.24(6), pp.613-29
    Description: Recombinant adeno-associated viral (AAV) vectors of serotypes 6, 8, and 9 were characterized as tools for gene delivery to dopaminergic neurons in the substantia nigra for future gene therapeutic applications in Parkinson's disease. While vectors of all three serotypes transduced nigral dopaminergic neurons with equal efficiency when directly injected to the substantia nigra, AAV6 was clearly superior to AAV8 and AAV9 for retrograde transduction of nigral neurons after striatal delivery. For sequential transduction of nigral dopaminergic neurons, the combination of AAV9 with AAV6 proved to be more powerful than AAV8 with AAV6 or repeated AAV6 administration. Surprisingly, single-stranded viral genomes persisted in nigral dopaminergic neurons within cell bodies and axon terminals in the striatum, and intact assembled AAV capsid was enriched in nuclei of nigral neurons, 4 weeks after virus injections to the substantia nigra. 6-Hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in the substantia nigra reduced the number of viral genomes in the striatum, in line with viral genome persistence in axon terminals. However, 6-OHDA-induced axonal degeneration did not induce any transsynaptic spread of AAV infection in the striatum. Therefore, the potential presence of viral particles in axons may not represent an important safety issue for AAV gene therapy applications in neurodegenerative diseases.
    Keywords: Transduction, Genetic ; Dependovirus -- Metabolism ; Neurons -- Metabolism ; Substantia Nigra -- Metabolism ; Virion -- Metabolism
    ISSN: 10430342
    E-ISSN: 1557-7422
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 28 April 2009, Vol.106(17), pp.7215-20
    Description: Several experimental manipulations of the CNS environment successfully elicit regeneration of sensory and bulbospinal motor axons but fail to elicit regeneration of corticospinal axons, suggesting that cell-intrinsic mechanisms limit the regeneration of this critical class of motor neurons. We hypothesized that enhancement of intrinsic neuronal growth mechanisms would enable adult corticospinal motor axon regeneration. Lentiviral vectors were used to overexpress the BDNF receptor trkB in layer V corticospinal motor neurons. After subcortical axotomy, trkB transduction induced corticospinal axon regeneration into subcortical lesion sites expressing BDNF. In the absence of trkB overexpression, no regeneration occurred. Selective deletion of canonical, trkB-mediated neurite outgrowth signaling by mutation of the Shc/FRS-2 activation domain prohibited Erk activation and eliminated regeneration. These findings support the hypothesis that the refractory regenerative state of adult corticospinal axons can be attributed at least in part to neuron-intrinsic mechanisms, and that activation of ERK signaling can elicit corticospinal tract regeneration.
    Keywords: Nerve Regeneration ; Extracellular Signal-Regulated MAP Kinases -- Metabolism ; Lentivirus -- Genetics ; Receptor, Trkb -- Metabolism ; Spinal Cord -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Nanomedicine: Nanotechnology, Biology, and Medicine, 2011, Vol.7(4), pp.454-463
    Description: The specific application and transport of drugs into malignant tissue is a critical point during diagnosis and therapy. Nanoparticles are known as excellent drug carrier systems and offer the possibility of surface modification with targeting ligands, leading to a specific accumulation in the targeted tissue. First, the specificity of such a carrier system has to be proven. In this study, cetuximab-modified nanoparticles based on biodegradable human serum albumin (HSA) are investigated regarding their cellular binding and intracellular accumulation. Different EGFR-expressing colon carcinoma cells were used to test possible cytotoxic potential, specific binding and intracellular accumulation. A specific accumulation targeting the EGFR could be shown. These results emphasize that cetuximab-modified HSA-nanoparticles are a promising carrier system for later drug transport. To our knowledge, this is the first study investigating the specific accumulation of HSA nanoparticles into different EGFR-expressing colon carcinoma cells. In this study, cetuximab-modified nanoparticles based on human serum albumin (HSA) are investigated regarding their cellular binding and intracellular accumulation. The results suggest that these nanoparticles are a promising carrier system for EGFR overexpressing colon carcinoma cells. Specific cellular accumulation of cetuximab-modified nanoparticles based on human serum albumin in different EGFR-expressing colon carcinoma cell lines. HSA-cetuximab nanoparticles show a cell specific accumulation depending the cellular EGFR-expression.
    Keywords: Nanoparticles ; Human Serum Albumin ; Colon Carcinoma ; Egfr ; Cetuximab ; Medicine
    ISSN: 1549-9634
    E-ISSN: 1549-9642
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Toxicology in Vitro, December 2011, Vol.25(8), pp.1557-1567
    Description: ► We compared the cytotoxicity of TP and TP-PM on Jurkat and HT29 cells. ► TP and TP-PM could induce an inhibition of cell growth and proliferation in both tumor cell lines. ► TP and TP-PM induced apoptosis and caused activation of caspase 3/7. ► TP-PM induced in tested cell lines stronger effects than TP. Triptolide (TP), a diterpenoid triepoxide purified from the Chinese herb Hook F is characterized by strong anti-tumor effects on various cancer cells. Except its anti-tumor effects, TP also shows multiple pharmacological side activities, such as anti-inflammatory, immune-suppressive and male anti-fertility. In order to reduce these side effects, especially the immuno-suppressive activity when used to cure cancer, a novel polymeric micelle system containing TP (TP-PM) was constructed. The immune-modulation effects of TP-PM have been evaluated by previous studies. In this study, we compared the cytotoxicity of TP and TP-PM on Jurkat and HT29 cells. Therefore, we determined the cell viability, membrane integrity, cell proliferation, apoptosis, and caspase 3/7 activity after exposure to TP and TP-PM. The results demonstrated that actually low concentrated TP and TP-PM could induce an inhibition of cell growth and proliferation as well as membrane damage in both tumor cell lines. TP and TP-PM induced apoptosis and caused activation of caspase 3/7 even at low concentrations. Both formulations destroyed the membrane of Jurkat cells, nevertheless, TP-PM showed stronger pernicious effects. In general, TP-PM induced in both tested cell lines stronger effects than TP. Therefore, polymeric micelles can be considered as promising carriers for TP in cancer therapy.
    Keywords: Cytotoxicity ; Triptolide ; Polymeric Micelles ; In Vitro ; Pharmacy, Therapeutics, & Pharmacology ; Chemistry ; Public Health
    ISSN: 0887-2333
    E-ISSN: 1879-3177
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Journal of Materials Science: Materials in Medicine, 2012, Vol.23(10), pp.2399-2412
    Description: The use of an “over 1000-nm near-infrared (NIR) in vivo fluorescence bioimaging” system based on lanthanide containing inorganic nanostructures emitting in the visible and NIR range under 980-nm excitation is proposed. It may overcome problems of currently used biomarkers including color fading, phototoxicity and scattering. Gd 2 O 3 :Er 3+ ,Yb 3+ nanoparticles and nanorods showing upconversion and NIR emission are synthesized and their cytotoxic behavior is investigated by incubation with B-cell hybridomas and macrophages. Surface modification with PEG- b -PAAc provides the necessary chemical durability reducing the release of toxic Gd 3+ ions. NIR fluorescence microscopy is used to investigate the suitability of the nanostructures as NIR–NIR biomarkers. The in vitro uptake of bare and modified nanostructures by macrophages is investigated by confocal laser scanning microscopy. In vivo investigations revealed nanostructures in liver, lung, kidneys and spleen a few hours after injection into mice, while most of the nanostructures have been removed from the body after 24 h.
    Keywords: Animals–Chemistry ; Biocompatible Materials–Pharmacokinetics ; Cell Line–Chemistry ; Cell Survival–Pharmacokinetics ; Erbium–Methods ; Erbium–Chemistry ; Gadolinium–Pharmacokinetics ; Gadolinium–Pharmacokinetics ; Mice–Pharmacokinetics ; Microscopy, Electron, Scanning–Pharmacokinetics ; Nanostructures–Pharmacokinetics ; Powder Diffraction–Pharmacokinetics ; Spectroscopy, Near-Infrared–Pharmacokinetics ; Surface Properties–Pharmacokinetics ; Tissue Distribution–Pharmacokinetics ; Ytterbium–Pharmacokinetics ; Ytterbium–Pharmacokinetics ; Biomedical Materials ; Nanostructured Materials ; Microscopy ; Cytotoxicity ; Biocompatible Materials ; Gadolinium Oxide ; Erbium ; Gadolinium ; Ytterbium;
    ISSN: 0957-4530
    E-ISSN: 1573-4838
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Science, 06 October 2000, Vol.290(5489), pp.131-134
    Description: Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and analyzed two mouse lines in which the α2 or α3 GABA A (γ-aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the α2(H101R) point mutation but present in mice with the α3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by α2 GABA A receptors, which are largely expressed in the limbic system, but not by α3 GABA A receptors, which predominate in the reticular activating system.
    Keywords: Physical sciences -- Chemistry -- Chemical compounds -- Lymphocytes ; Biological sciences -- Biology -- Physiology -- Tranquilizers ; Biological sciences -- Biology -- Genetics -- Tranquilizers ; Applied sciences -- Engineering -- Transportation -- Tranquilizers ; Biological sciences -- Biology -- Zoology -- Tranquilizers ; Health sciences -- Medical sciences -- Immunology -- Tranquilizers ; Physical sciences -- Chemistry -- Chemical compounds -- Tranquilizers ; Health sciences -- Medical sciences -- Pharmaceutics -- Tranquilizers ; Biological sciences -- Biology -- Genetics -- Tranquilizers ; Biological sciences -- Biology -- Cytology -- Tranquilizers
    ISSN: 00368075
    E-ISSN: 10959203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: FEBS Letters, 1998, Vol.431(3), pp.400-404
    Description: Amino acids in the alpha- and gamma-subunits contribute to the benzodiazepine binding site of GABA(A)-receptors. We show that the mutation of a conserved histidine residue in the N-terminal extracellular segment (alpha1H101R, alpha2H101R, alpha3H126R, and alpha5H105R) results not only in diazepam-insensitivity of the respective alphaxbeta2,3gamma2-receptors but also in an increased potentiation of the GABA-induced currents by the partial agonist bretazenil. Furthermore, Ro 15-4513, an inverse agonist at wild-type receptors, acts as an agonist at all mutant receptors. This conserved molecular switch can be exploited to identify the pharmacological significance of specific GABA(A)-receptor subtypes in vivo.
    Keywords: Neurotransmitter ; Receptor ; Γ-Aminobutyric Acid ; Benzodiazepine ; Recombinant ; Central Nervous System ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0014-5793
    E-ISSN: 1873-3468
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages