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  • 1
    Online Resource
    Online Resource
    New York, NY :Springer New York :
    UID:
    almahu_9949251670502882
    Format: 1 online resource (XXI, 583 p. 64 illus., 54 illus. in color.)
    Edition: 1st ed. 2014.
    ISBN: 1-4939-0521-X
    Series Statement: Methods in Pharmacology and Toxicology,
    Content: In Vitro Toxicology Systems brings together important issues and considerations needed in order to develop a workable, reliable, integrated testing strategy for the replacement of animals in toxicity testing regimes. This thorough volume includes sections on in vitro models for systemic organ toxicity, neurotoxicity, sensory organs, immunotoxicity and reproductive toxicity and addresses how stem cells may be used going forward. The book also tackles difficult areas of toxicology such as carcinogenicity and nanotoxicology, with additional chapters dedicated to kinetics, metabolism, and in vitro in vivo extrapolation. The book also addresses biological processes such as stress response pathways and mechanistic biomarkers and how these can be uncovered and measured using high content approaches. Reliable and authoritative, In Vitro Toxicology Systems will be of benefit not only to students, scientists, and regulators working in the field of chemical safety assessment but also to a wider scientific audience.
    Note: Bibliographic Level Mode of Issuance: Monograph , The Past, Present and Future of Chemical Risk Assessment.- In Vitro Systems for Hepatotoxicity Testing -- In Vitro Methods for Cardiotoxicity Testing -- Renal Cell Culture -- Cellular Models for In Vitro Lung Toxicology -- In Vitro Developmental Neurotoxicity Testing: Relevant Models and Endpoints -- Blood Brain Barrier In Vitro Models and Their Applications in Toxicology -- Ocular Toxicity -- In Vitro Models for Ototoxic Research -- Dermal Toxicity: Skin Sensitization -- Immunotoxicity -- Reproductive Toxicity -- Evaluating Endocrine Disruption In Vitro -- Current and Emerging In Vitro Methods for Genotoxicity and Carcinogenicity -- Use of Induced Pluripotent Stem Cells in Drug Toxicity Screening -- Human Stem/Progenitor Cell-Based Assays for Neurodevelopmental Toxicity Testing -- High Content Imaging Approaches for In Vitro Toxicology -- Application of Omics Technologies to In Vitro Toxicology -- Stress Response Pathways -- Translational Biomarkers, In Vitro and In Vivo -- Nanotoxicology -- Consideration of Metabolism in In Vitro Cellular Systems -- In Vitro Approaches to Predictive Biokinetics -- Extrapolating In Vitro Results to Predict Human Toxicity -- Considerations in the Development of In Vitro Toxicity Testing Methods Intended for Regulatory Use. , English
    Additional Edition: ISBN 1-4939-0520-1
    Language: English
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  • 2
    UID:
    almahu_9949251560102882
    Format: 1 online resource (XIV, 498 p. 84 illus.)
    Edition: 1.
    ISBN: 1-61779-077-X
    Series Statement: Neuromethods, 56
    Content: Societal, ethical, and cost-related issues, not to mention the need for sound scientific methods, have led to new and refined methods for the evaluation of health risks associated with neurotoxic compounds, relevant and predictive of exposure, relatively inexpensive, and ideally amenable to high throughput analysis and a reduction in animal use.  Cell Culture Techniques presents thorough traditional chapters, such as those on various cell culture methods that have evolved over the years, as well as innovative approaches to neurotoxicologic testing.  Accordingly, this detailed volume describes how stem cells, computational biology, and other novel powerful methods can now be applied to address the challenges of neurotoxic testing.  As part of the Neuromethods series, this work provides the kind of intensive description and implementation advice that is crucial for getting optimal results in the laboratory.   Practical and authoritative, Cell Culture Techniques serves both the novice and the experienced neurotoxicologist by inspiring the further development of mechanistically-driven, cost-effective, high throughput series of tests needed to meet the many contemporary challenges.
    Note: Bibliographic Level Mode of Issuance: Monograph , Guidance on Good Cell Culture Practice (GCCP) -- Induced Pluripotent Stem Cells (iPSCs): An Emerging Model System for the Study of Human Neurotoxicology -- Neural Stem Cells -- Primary Cultures for Neurotoxicity Testing -- Preparation and Use of Serum-Free Aggregating Brain Cell Cultures for Routine Neurotoxicity Screening -- Cell Culture to Investigate Neurotoxicity and Neurodegeneration Utilizing Caenorhabditis elegans -- Modeling the Blood-Brain Barrier -- In vitro Models of the Blood-Cerebrospinal Fluid Barrier and Their Use in Neurotoxicological Research -- Introducing Cloned Genes into Cultured Neurons Providing Novel In vitro Models for Neuropathology and Neurotoxicity Studies -- P19 Embryonic Carcinoma Cell Line: A Model To Study Gene-Environment Interactions -- Signal Transduction and Neurotoxicity: What Can We Learn from Experimental Culture Systems? -- Neurite Degeneration in Human Neuronal SH-SY5Y Cells as an Indicator of Axonopathy -- The Use of Differentiating N2a and C6 Cell Lines for Studies of Organophosphate Toxicity -- Assessing Toxic Injuries of Experimental Therapeutics to the Crystalline Lens Using Lens Explant Culture -- Necrosis, Apoptosis, and Autophagy: Mechanisms of Neuronal and Glial Cell Death -- Inflammation and Reactive Oxygen/Nitrogen Species in Glial/Neuronal Cultures -- Neuronal Oxidative Injury and Biomarkers of Lipid Peroxidation -- Analysis of Protein Targets by Oxidative Stress Using the Oxyblot and Biotin-Avidin-Capture Methodology -- Catecholaminergic Cell Lines for the Study of Dopamine Metabolism and Neurotoxicity -- 13C NMR Spectroscopy and Mass Spectrometry Analysis of Intermediary Metabolism in Cultured Neural Cells -- Culture Models for the Study of Amino Acid Transport and Metabolism -- Neurotransmitter Transporters and Anticonvulsant Drug Development -- Ion Channel Electrophysiology in Cultured Neurons -- Neurotoxicity Assessment by Recording Electrical Activity from Neuronal Networks on Microelectrode Array Neurochips -- GABAA Receptor Binding and Ion Channel Function in Primary Neuronal Cultures for Neuropharmacology/Neurotoxicity Testing. , English
    Additional Edition: ISBN 1-61779-076-1
    Language: English
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  • 3
    UID:
    b3kat_BV047934453
    Format: 1 Online-Ressource (184 Seiten)
    Series Statement: OECD Series on Adverse Outcome Pathways
    Content: This AOP describes the linkage between inhibition of complex I (CI) of the mitochondrial respiratory chain and motor deficit as in parkinsonian disorders. Binding of an inhibitor to CI has been defined as the molecular initiating event (MIE) that triggers mitochondrial dysfunction, impaired proteostasis, which then cause degeneration of dopaminergic (DA) neurons. Neuroinflammation is triggered early in the neurodegenerative process and exacerbates it significantly. These causatively linked cellular key events result in motor deficit symptoms, typical for parkinsonian disorders, including Parkinson's disease (PD), described as the Adverse Outcome (AO). The weight-of-evidence supporting the relationship between the described key events is based mainly on effects observed after an exposure to the chemicals rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This AOP could apply for chemicals having structural similarities to the stressors, chemicals binding to CI and supports the mechanistic biological plausibility in the process of evaluation and integration of the epidemiological studies into the risk assessment
    Language: English
    URL: Volltext  (URL des Erstveröffentlichers)
    URL: Volltext  (URL des Erstveröffentlichers)
    Library Location Call Number Volume/Issue/Year Availability
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  • 4
    UID:
    gbv_1747666610
    Format: 1 Online-Ressource (184 p.)
    Series Statement: OECD Series on Adverse Outcome Pathways no.7
    Content: This AOP describes the linkage between inhibition of complex I (CI) of the mitochondrial respiratory chain and motor deficit as in parkinsonian disorders. Binding of an inhibitor to CI has been defined as the molecular initiating event (MIE) that triggers mitochondrial dysfunction, impaired proteostasis, which then cause degeneration of dopaminergic (DA) neurons. Neuroinflammation is triggered early in the neurodegenerative process and exacerbates it significantly. These causatively linked cellular key events result in motor deficit symptoms, typical for parkinsonian disorders, including Parkinson's disease (PD), described as the Adverse Outcome (AO). The weight-of-evidence supporting the relationship between the described key events is based mainly on effects observed after an exposure to the chemicals rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This AOP could apply for chemicals having structural similarities to the stressors, chemicals binding to CI and supports the mechanistic biological plausibility in the process of evaluation and integration of the epidemiological studies into the risk assessment.
    Language: English
    Library Location Call Number Volume/Issue/Year Availability
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  • 5
    UID:
    gbv_1747662224
    Format: 1 Online-Ressource (212 p.)
    Series Statement: OECD Series on Adverse Outcome Pathways no.14
    Content: The thyroid hormones (TH) are essential for brain development, maturation, and function as they regulate the early key developmental processes. Normal human brain development and cognitive function relays on sufficient production of TH during the perinatal period. The function of Na+/I- symporter (NIS) is critical for the physiological production of TH levels in the serum. The present AOP describes causative links between inhibition of NIS function leading to the decreased levels of TH in the blood and consequently in the brain, causing learning and memory deficit in children. Learning and memory depend upon the coordinated action of different brain regions and neurotransmitter systems creating functionally integrated neural networks. Hippocampus and cortex are the most critical brain structures involved in the process of cognitive functions. The function of NIS and its essentiality for TH synthesis is well known across species, however, quantitative information of KERs is limited.
    Language: English
    Library Location Call Number Volume/Issue/Year Availability
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  • 6
    UID:
    b3kat_BV047936416
    Format: 1 Online-Ressource (99 Seiten) , 21 x 29.7cm
    Series Statement: OECD Series on Adverse Outcome Pathways
    Content: It is well documented and accepted that learning and memory processes rely on physiological functioning of the glutamate receptor N-methyl-D-aspartate (NMDAR). Both animal and human studies investigating NMDA itself, experiments with NMDAR antagonists and mutant mice lacking NMDAR subunits strongly support this statement (Rezvani, 2006). Activation of NMDARs results in long-term potentiation (LTP), which is related to increased synaptic strength, plasticity and memory formation in the hippocampus (Johnston et al., 2009). LTP induced by activation of NMDA receptors has been found to be elevated in the developing rodent brain compared to the mature brain, partially due to 'developmental switch' of the NMDAR 2A and 2B subunits (Johnston et al., 2009). Activation of the NMDAR also enhances brain derived neurotrophic factor (BDNF) release, which promotes neuronal survival, differentiation and synaptogenesis (Tyler et al., 2002; Johnston et al., 2009). Consequently, the blockage of NMDAR by chemical substances during synaptogenesis disrupts neuronal network formation resulting in the impairment of learning and memory processes (Toscano and Guilarte, 2005). This AOP is relevant to developmental neurotoxicity (DNT). The molecular initiating event (MIE) is described as the chronic binding of antagonist to NMDAR in neurons during synaptogenesis (development) in hippocampus (one of the critical brain structures for learning and memory formation). One of the chemicals that blocks NMDAR after chronic exposure is lead (Pb2+), a well-known developmental neurotoxicant
    Language: English
    URL: Volltext  (URL des Erstveröffentlichers)
    URL: Volltext  (URL des Erstveröffentlichers)
    Library Location Call Number Volume/Issue/Year Availability
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  • 7
    UID:
    b3kat_BV047937117
    Format: 1 Online-Ressource (118 Seiten) , 21 x 29.7cm
    Series Statement: OECD Series on Adverse Outcome Pathways
    Content: Under physiological conditions activation of glutamate ionotropic receptors such as N-methyl-D-aspartate (NMDARs), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPARs) and kainate (KARs) is responsible for basal excitatory synaptic transmission and synaptic plasticity. However, sustained over-activation of these receptors can induce excitotoxic neuronal cell death. Increased Ca2+ influx through NMDARs promotes many pathways of toxicity due to generation of free radical species, reduced ATP production, endoplasmic reticulum (ER) stress and protein aggregation. Neuronal injury induced by over-activation of these receptors and the excessive Ca2+ influx is considered an early key event of excitotoxicity. The proposed AOP is relevant to adult neurotoxicity. The MIE has been defined as a direct binding of agonists to NMDARs or indirect, through prior activation of AMPARs and/or KARs resulting in sustained NMDARs over-activation causing excitotoxic neuronal cell death, mainly in hippocampus and cortex, two brain structures fundamental for learning and memory processes
    Language: English
    URL: Volltext  (URL des Erstveröffentlichers)
    URL: Volltext  (URL des Erstveröffentlichers)
    Library Location Call Number Volume/Issue/Year Availability
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  • 8
    UID:
    b3kat_BV047931939
    Format: 1 Online-Ressource (212 Seiten)
    Series Statement: OECD Series on Adverse Outcome Pathways
    Content: The thyroid hormones (TH) are essential for brain development, maturation, and function as they regulate the early key developmental processes. Normal human brain development and cognitive function relays on sufficient production of TH during the perinatal period. The function of Na+/I- symporter (NIS) is critical for the physiological production of TH levels in the serum. The present AOP describes causative links between inhibition of NIS function leading to the decreased levels of TH in the blood and consequently in the brain, causing learning and memory deficit in children. Learning and memory depend upon the coordinated action of different brain regions and neurotransmitter systems creating functionally integrated neural networks. Hippocampus and cortex are the most critical brain structures involved in the process of cognitive functions. The function of NIS and its essentiality for TH synthesis is well known across species, however, quantitative information of KERs is limited
    Language: English
    URL: Volltext  (URL des Erstveröffentlichers)
    URL: Volltext  (URL des Erstveröffentlichers)
    Library Location Call Number Volume/Issue/Year Availability
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  • 9
    UID:
    gbv_1747694827
    Format: 1 Online-Ressource (99 p.) , 21 x 29.7cm.
    Series Statement: OECD Series on Adverse Outcome Pathways no.5
    Content: It is well documented and accepted that learning and memory processes rely on physiological functioning of the glutamate receptor N-methyl-D-aspartate (NMDAR). Both animal and human studies investigating NMDA itself, experiments with NMDAR antagonists and mutant mice lacking NMDAR subunits strongly support this statement (Rezvani, 2006). Activation of NMDARs results in long-term potentiation (LTP), which is related to increased synaptic strength, plasticity and memory formation in the hippocampus (Johnston et al., 2009). LTP induced by activation of NMDA receptors has been found to be elevated in the developing rodent brain compared to the mature brain, partially due to 'developmental switch' of the NMDAR 2A and 2B subunits (Johnston et al., 2009). Activation of the NMDAR also enhances brain derived neurotrophic factor (BDNF) release, which promotes neuronal survival, differentiation and synaptogenesis (Tyler et al., 2002; Johnston et al., 2009). Consequently, the blockage of NMDAR by chemical substances during synaptogenesis disrupts neuronal network formation resulting in the impairment of learning and memory processes (Toscano and Guilarte, 2005). This AOP is relevant to developmental neurotoxicity (DNT). The molecular initiating event (MIE) is described as the chronic binding of antagonist to NMDAR in neurons during synaptogenesis (development) in hippocampus (one of the critical brain structures for learning and memory formation). One of the chemicals that blocks NMDAR after chronic exposure is lead (Pb2+), a well-known developmental neurotoxicant.
    Language: English
    Library Location Call Number Volume/Issue/Year Availability
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  • 10
    UID:
    gbv_1747696145
    Format: 1 Online-Ressource (118 p.) , 21 x 29.7cm.
    Series Statement: OECD Series on Adverse Outcome Pathways no.6
    Content: Under physiological conditions activation of glutamate ionotropic receptors such as N-methyl-D-aspartate (NMDARs), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPARs) and kainate (KARs) is responsible for basal excitatory synaptic transmission and synaptic plasticity. However, sustained over-activation of these receptors can induce excitotoxic neuronal cell death. Increased Ca2+ influx through NMDARs promotes many pathways of toxicity due to generation of free radical species, reduced ATP production, endoplasmic reticulum (ER) stress and protein aggregation. Neuronal injury induced by over-activation of these receptors and the excessive Ca2+ influx is considered an early key event of excitotoxicity. The proposed AOP is relevant to adult neurotoxicity. The MIE has been defined as a direct binding of agonists to NMDARs or indirect, through prior activation of AMPARs and/or KARs resulting in sustained NMDARs over-activation causing excitotoxic neuronal cell death, mainly in hippocampus and cortex, two brain structures fundamental for learning and memory processes.
    Language: English
    Library Location Call Number Volume/Issue/Year Availability
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