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  • 1
    Electronic Resource
    Electronic Resource
    Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: possible risk factors in the Alzheimer's-type neurodegenerative pathways (2001)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 76 (2001), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Oxidative stress may have an important role in the progression of neurodegenerative disorders such as Alzheimer's disease (AD) and prion diseases. Oxidative damage could result from interactions between highly reactive transition metals such as copper (Cu) and endogenous reducing and/or oxidizing molecules in the brain. One such molecule, homocysteine, a thiol-containing amino acid, has previously been shown to modulate Cu toxicity in HeLa and endothelial cells in vitro. Due to a possible link between hyperhomocysteinemia and AD, we examined whether interaction between homocysteine and Cu could potentiate Cu neurotoxicity. Primary mouse neuronal cultures were treated with homocysteine and either Cu (II), Fe (II or III) or Zn (II). Homocysteine was shown to selectively potentiate toxicity from low micromolar concentrations of Cu. The toxicity of homocysteine/Cu coincubation was dependent on the ability of homocysteine to reduce Cu (II) as reflected by the inhibition of toxicity with the Cu (I)-specific chelator, bathocuproine disulphonate. This was supported by data showing that homocysteine reduced Cu (II) more effectively than cysteine or methionine but did not reduce Fe (III) to Fe (II). Homocysteine also generated high levels of hydrogen peroxide in the presence of Cu (II) and promoted Aβ/Cu-mediated hydrogen peroxide production and neurotoxicity. The potentiation of metal toxicity did not involve excitotoxicity as ionotropic glutamate receptor antagonists had no effect on neurotoxicity. Homocysteine alone also had no effect on neuronal glutathione levels. These studies suggest that increased copper and/or homocysteine levels in the elderly could promote significant oxidant damage to neurons and may represent additional risk factor pathways which conspire to produce AD or related neurodegenerative conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2001.00178.x
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  • 2
    Electronic Resource
    Electronic Resource
    Substrate-Bound β-Amyloid Peptides Inhibit Cell Adhesion and Neurite Outgrowth in Primary Neuronal Cultures (2000)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 74 (2000), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Accumulation of theβ-amyloid protein (Aβ) in the brain is an important step in the pathogenesis of Alzheimer's disease. However, the mechanism of Aβ toxicity remains unclear. Aβ can bind to the extracellular matrix, a structure that regulates adhesive events such as neurite outgrowth and synaptogenesis. The binding of Aβ to the extracellular matrix suggests that Aβ may disrupt cell-substrate interactions. Therefore, the effect of substrate-bound Aβ on the growth of isolated chick sympathetic and mouse cortical neurons was examined. Aβ1-40 and Aβ1-42 had dose-dependent effects on cell morphology. When tissue culture plates were coated with 0.1-10 ng/well Aβ, neurite outgrowth increased. Higher amounts of Aβ peptides (≥μg/well) inhibited outgrowth. The inhibitory effect was related to aggregation of the peptide, as preincubation of Aβ1-40 for 24 h at 37 °C (a process known to increase amyloid fibril formation) was necessary for inhibition of neurite outgrowth. Aβ29-42, but not Aβ1-28, also inhibited neurite outgrowth at high concentrations, demonstrating that the inhibitory domain is located within the hydrophobic C-terminal region. Aβ1-40, Aβ1-42, and Aβ29-42 also inhibited cell-substrate adhesion, indicating that the effect on neurite outgrowth may have been due to inhibition of cell adhesion. The results suggest that accumulation of Aβ may disrupt cell-adhesion mechanisms in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2000.741122.x
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  • 3
    Electronic Resource
    Electronic Resource
    The Perturbation of the Ultraviolet Spectrum of Nitromethane in Mixed Solvents, with a Note on Complex Formation (1955)
    s.l. : American Chemical Society
    Journal of the American Chemical Society 77 (1955), S. 3959-3963 
    Details
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ja01620a005
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  • 4
    Electronic Resource
    Electronic Resource
    Non-exhaustive extraction techniques (NEETs) for the prediction of naphthalene mineralisation in soil (2004)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 241 (2004), S. 0 
    Details
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Non-exhaustive extraction techniques (NEETs) have been shown to measure the putatively bioavailable fraction of hydrophobic compounds in soil. To date, these studies have only considered bioavailability in a single soil type. In this study, naphthalene was amended into five different soil types and mineralisation, bacterial biosensor response and the number of indigenous microbial naphthalene degraders were determined. Two NEETs were used to extract the naphthalene from soil; hydroxypropyl-β-cyclodextrin (HPCD) and XAD-4. The HPCD extractable fraction correlated closely (R2= 0.917) with the portion that was mineralised, but the XAD-4 extract did not (R2= 0.044). HPCD may be ideal for the rapid assessment of the fraction of a hydrophobic organic contaminant that is available for biodegradation. A NEET that complements environmental microbial analysis will enhance our understanding of soil pollution interactions and equip us better in designing risk assessment models that integrate biological parameters. This application, although refined for soil samples, should be transferable to other environmental matrices.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/j.femsle.2004.10.023
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  • 5
    Electronic Resource
    Electronic Resource
    USE OF A PETHIDINE AND MIDAZOLAM COMBINATION FOR THE REVERSIBLE SEDATION OF CRABEATER SEALS (LOBODON CARCINOPHAGUS) (2003)
    Oxford, UK : Blackwell Publishing Ltd
    Marine mammal science 19 (2003), S. 0 
    Details
    ISSN: 1748-7692
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Between October and December of 1996–1999, off eastern Antarctica (60°-150°E), we darted 31 crabeater seals with midazolam and pethidine at estimated dose rates of 0.15–0.4 mg/kg and 1–3 mg/kg, respectively. Maximum sedation was reached at 23 ± 9 min (n = 18) and first signs of recovery were noted at 54 ± 24 min (n = 4). Seals greater than 250 kg body-mass were sedated by administration of approximately 90–100 mg midazolam and 600 mg pethidine, but the degree of sedation was unpredictable and did not permit invasive procedures in some cases. Behavior of the seal and adjacent conspecifics affected the success of procedures and our ability to monitor vital signs. Naloxone and flumazenil reversed sedation, making this combination attractive for use in animals adjacent to water. Additional ketamine was administered to two seals, resulting in improved restraint.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1748-7692.2003.tb01322.x
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  • 6
    Electronic Resource
    Electronic Resource
    200 Years of British Hydrogeology (2005)
    Oxford, UK; Malden, USA : Blackwell Science Inc
    Ground water 43 (2005), S. 0 
    Details
    ISSN: 1745-6584
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Geosciences
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1745-6584.2005.0111.x
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  • 7
    Electronic Resource
    Electronic Resource
    Issues in Meta-Regression Analysis: An Overview (2005)
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Journal of economic surveys 19 (2005), S. 0 
    Details
    ISSN: 1467-6419
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Economics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0950-0804.2005.00248.x
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  • 8
    Electronic Resource
    Electronic Resource
    NATURAL HEALTH PRODUCTS AND DRUG DISPOSITION * (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 203-226 
    Details
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Botanicals such as herbal products (HPs) and nutraceuticals (NCs) are often regarded as low risk because of their long history of human use. Anecdotal and literature reports of adverse drug events (ADEs) and clinical studies with HPs are increasing, but many of the reports are incomplete and contradictory. These reports need to identify confounding factors and explain contradictory findings if they are to help health care professionals or patients understand what risks are involved. HPs are complex botanicals, not single-active ingredient (SAI) products. Studies can be confounded by different manufacturing processes and formulations, including cosmetics and food supplements; environment; chemotypes; misidentification or adulteration; and factors associated with the patient or user population such as use, total drug load, and genetics. Future studies need to be conducted with characterized product that includes all commercially available related products. Clinical trials should be relevant to the user population and take into account the confounding factors that may influence the interpretation of the findings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.095950
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  • 9
    Electronic Resource
    Electronic Resource
    An investigation of the role of auditory cortex in sound localization using muscimol-releasing Elvax (2004)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 19 (2004), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Lesion studies suggest that primary auditory cortex (A1) is required for accurate sound localization by carnivores and primates. In order to elucidate further its role in spatial hearing, we examined the behavioural consequences of reversibly inactivating ferret A1 over long periods, using Elvax implants releasing the GABAA receptor agonist muscimol. Sub-dural polymer placements were shown to deliver relatively constant levels of muscimol to underlying cortex for 〉5 months. The measured diffusion of muscimol beneath and around the implant was limited to 1 mm. Cortical silencing was assessed electrophysiologically in both auditory and visual cortices. This exhibited rapid onset and was reversed within a few hours of implant removal. Inactivation of cortical neurons extended to all layers for implants lasting up to 6 weeks and throughout at least layers I–IV for longer placements, whereas thalamic activity in layer IV appeared to be unaffected. Blockade of cortical neurons in the deeper layers was restricted to ≤ 500 µm from the edge of the implant, but was usually more widespread in the superficial layers. In contrast, drug-free Elvax implants had little discernible effect on the responses of the underlying cortical neurons. Bilateral implants of muscimol–Elvax over A1 produced significant deficits in the localization of brief sounds in horizontal space and particularly a reduced ability to discriminate between anterior and posterior sound sources. The performance of these ferrets gradually improved over the period in which the Elvax was in place and attained that of control animals following its removal. Although similar in nature, these deficits were less pronounced than those caused by cortical lesions and suggest a specific role for A1 in resolving the spatial ambiguities inherent in auditory localization cues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0953-816X.2004.03379.x
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  • 10
    Electronic Resource
    Electronic Resource
    Cholesterol is necessary both for the toxic effect of Aβ peptides on vascular smooth muscle cells and for Aβ binding to vascular smooth muscle cell membranes (2003)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 84 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Accumulation of beta amyloid (Aβ) in the brain is central to the pathogenesis of Alzheimer's disease. Aβ can bind to membrane lipids and this binding may have detrimental effects on cell function. In this study, surface plasmon resonance technology was used to study Aβ binding to membranes. Aβ peptides bound to synthetic lipid mixtures and to an intact plasma membrane preparation isolated from vascular smooth muscle cells. Aβ peptides were also toxic to vascular smooth muscle cells. There was a good correlation between the toxic effect of Aβ peptides and their membrane binding. ‘Ageing’ the Aβ peptides by incubation for 5 days increased the proportion of oligomeric species, and also increased toxicity and the amount of binding to lipids. The toxicities of various Aβ analogs correlated with their lipid binding. Significantly, binding was influenced by the concentration of cholesterol in the lipid mixture. Reduction of cholesterol in vascular smooth muscle cells not only reduced the binding of Aβ to purified plasma membrane preparations but also reduced Aβ toxicity. The results support the view that Aβ toxicity is a direct consequence of binding to lipids in the membrane. Reduction of membrane cholesterol using cholesterol-lowering drugs may be of therapeutic benefit because it reduces Aβ-membrane binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.01552.x
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