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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Neuronal cell death as a result of apoptosis is associated with cerebrovascular stroke and various neurodegenerative disorders. Pharmacological agents that maintain normal intracellular Ca2+ levels and inhibit cellular oxidative stress may be effective in blocking abnormal neuronal apoptosis. In this study, a spontaneous (also referred to as age-induced) model of apoptosis consisting of rat cerebellar granule cells was used to evaluate the antiapoptotic activities of voltage-sensitive Ca2+ channel blockers and various antioxidants. The results of these experiments demonstrated that the charged, dihydropyridine Ca2+ channel blocker amlodipine had very potent neuroprotective activity in this system, compared with antioxidants and neutral Ca2+ channel blockers (nifedipine and nimodipine). Within its effective pharmacological range (10-100 nM), amlodipine attenuated intracellular neuronal Ca2+ increases elicited by KCl depolarization but did not affect Ca2+ changes triggered by N-methyl-D-aspartate receptor activation. Amlodipine also inhibited free radical-induced damage to lipid constituents of the membrane in a dose-dependent manner, independent of Ca2+ channel modulation. In parallel experiments, spontaneous neuronal apoptosis was inhibited in dose- and time-dependent manners by antioxidants (U-78439G, α-tocopherol, and melatonin), nitric oxide synthase inhibitors (N-nitro-L-arginine and N-nitro-D-arginine), and a nitric oxide chelator (hemoglobin) in the micromolar range. These results suggest that spontaneous neuronal apoptosis is associated with excessive Ca2+ influx, leading to further intracellular Ca2+ increases and the generation of reactive oxygen species. Agents such as amlodipine that block voltage-sensitive Ca2+ channels and inhibit cellular oxidative stress may be effective in the treatment of cerebrovascular stroke and neurodegenerative diseases associated with excessive apoptosis.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Soil use and management 15 (1999), S. 0 
    ISSN: 1475-2743
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract. Preferential flow has been increasingly recognised as a major component of water movement in many soils, particularly clays. This paper reviews problems in the measurement of solute fluxes in these soils, and discusses the solutions that have been adopted in UK studies of cracking clay soils. The estimation of solute fluxes is subject to many sources of error, which are best reduced by replicated measurements, such as those available in multi-plot experiments.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Soil use and management 11 (1995), S. 0 
    ISSN: 1475-2743
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract. Drainage hydrographs from mole-drained plots having different tillage treatments (tractor tined, gantry tined, tractor ploughed and gantry ploughed) were measured for different rain events over a growing season. In the autumn just after tillage, a large rainfall produced peaky drain flows on the tined plots but a rather flat response from the ploughed plots. In the winter, the drain response to a small rain event showed less differences in peak flows between the treatments. The recession time constant of the hydrographs was used as an index of the structural macropore development in the soil above the water table. Hydrographs from the gantry plots recessed more quickly than those on the tractor plots and those on the tined plots recessed more quickly than those on the ploughed plots. Lack of soil compaction on the gantry plots and continuous vertical fissuring created by the non-inverting tillage tines resulted in the gantry tined treatment having the fastest drainage response. In the ploughed plots compaction and smearing of the soil at the base of the plough layer restricted the rate of downward movemenl of water. The work indicates that soil management practices can play an important role in the drainage and leaching of aggregated soils.
    Type of Medium: Electronic Resource
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  • 4
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    Minneapolis : Periodicals Archive Online (PAO)
    Philosophical Studies. 79:1 (1995:July) 1-36 
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  • 5
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    Oxford : Periodicals Archive Online (PAO)
    The British journal for the philosophy of science. 46:3 (1995:Sept.) 381 
    ISSN: 0007-0882
    Topics: Natural Sciences in General , Philosophy
    Notes: Discussions
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  • 6
    ISSN: 1573-904X
    Keywords: antisense phosphorothioate oligonucleotide ; stealth liposome ; pharmacokinetics ; monkey ; capillary gel electrophoresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study examined the pharmacokinetics and tissue distribution of an antisense oligonucleotide ISIS 2503, formulated in stealth (pegylated) liposomes (encapsulated) or in phosphate-buffered saline (unencapsulated). Methods. Encapsulated or unencapsulated ISIS 2503 was administered to rhesus monkeys by intravenous infusion. The concentrations of ISIS 2503 and metabolites in blood, plasma, and tissue samples were determined by capillary gel electrophoresis. Results. Plasma concentrations of encapsulated ISIS 2503 decreased mono-exponentially after infusion with a mean half-life of 57.8 hours. In contrast, the concentration of unencapsulated ISIS 2503 in plasma decreased rapidly with a mean half-life of 1.07 hours. Both encapsulated and unencapsulated ISIS 2503 distributed widely into tissues. Encapsulated ISIS 2503 distributed primarily to the reticulo-endothelial system and there were few metabolites observed. In contrast, unencapsulated ISIS 2503 distributed rapidly to tissue with highest concentration seen in kidney and liver. Nuclease-mediated metabolism was extensive for unencapsulated oligonucleotide in plasma and tissues. Conclusions. The data suggest that stealth liposomes protect ISIS 2503 from nucleases in blood and tissues, slow tissue uptake, and slow the rate of clearance from the systemic circulation. These attributes may make these formulations attractive for delivering oligonucleotides to sites with increased vasculature permeability such as tumors or sites of inflammation.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Philosophical studies 79 (1995), S. 1-36 
    ISSN: 1573-0883
    Source: Springer Online Journal Archives 1860-2000
    Topics: Philosophy
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-7373
    Keywords: edema ; enhancement ; glioblastoma multiforme ; MRI scan ; necrosis ; prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor necrosis, enhancement, and associated edema in patients with glioblastoma multiforme (GBM) represent biological variables that can be quantitated on preoperative MRI scans. We reviewed 48 highly selected patients, all of whom had supratentorial lesions, had undergone gross total tumor resection, and had received adjuvant treatments (radio- and chemotherapies). None of these patients had had surgery for recurrent tumor resection and none had harbored multifocal tumors. The median age was 50 years. The median Karnofsky performance score was 80. Multivariate analysis using the Cox regression model revealed that the strongest prognostic variable was the amount of tumor necrosis on preoperative scan (P 〈 0.001), with median survivals of 42, 24, 15, and 12 months for tumor necrosis grades of 0 (7 ‘pts’), I (11 ‘pts’),11 (9 ‘pts’), and III (21 ‘pts’), respectively. The intensity of enhancement of the tumor nodule was another prognostic factor (P = 0.003), with median survivals of 35, 18, and 13.5 months for enhancement grades of 0 (2 ‘pts’), I (22 ‘pts’), and II (24 ‘pts’), respectively. The extent of peritumoral edema had a quadratic effect (P = 0.001), with grades I (19 ‘pts’), II (22 ‘pts’), and III (7 ‘pts’) surviving for 24,12, and 20 months respectively. Location and volume of tumors were not statistically significant predictors of survival (P 〈 0.05). In conclusion, in this highly selected group, GBM patients with little or no necrosis and with less tumor nodule enhancement on preoperative MRI survive longer than patients with greater amounts of necrosis and greater degrees of tumor enhancement. In addition, a moderate degree of peritumoral edema is associated with worse prognosis.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-7373
    Keywords: adenoid cystic carcinoma ; brain metastasis ; magnetic resonance imaging ; parotid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A rare case of multiple hematogenous brain metastases from adenoid cystic carcinoma of the parotid gland is reported. The patient had a parotid tumor that was treated ten years prior to the appearance of the brain metastases. Magnetic resonance imaging (MRI) and histological findings, as well as the radiation therapy response, of this tumor are presented.
    Type of Medium: Electronic Resource
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