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  • 1
    Description / Table of Contents: The first book of its kind, devoted exclusively to the assessment of DNA damage by the Comet assay in modern toxicology, The vast number of chemicals existing or being added into the environment, have globally aroused great concern regarding their adverse effects in human population. Development and validation of sensitive and better test systems which can assess the adverse effects of chemicals at an early stage for intervention strategies to be implemented in time is currently in progress. This book documents the latest research and showcases the versatile, state-of-the-art technique - the Comet assay - in the field of modern toxicology. The assay is a simple, sensitive rapid and visual technique for the quantitative and qualitative assessment of DNA damage in single cells. The Comet Assay in Toxicology is the first book of its kind to be devoted exclusively to the Comet assay and its applications as an important tool in modern toxicology. This multi-author book will serve as both a reference and a guide to investigations in the biomedical, biochemical and pharmaceutical sciences. Written by investigators from the fields of genetic toxicology and human epidemiology, the authors have first-hand knowledge from their chosen sub-specialities and are active contributors to the peer-reviewed scientific literature. The book is divided into five major sections, reflecting the range of interest in the exploitation of this assay. The book's scope begins with an introduction section reviewing its genesis for those new to the technique and the current knowledge of the various fields in which it finds wide acceptance. This section sets the scene by explaining why the assay has become the most sensitive and sought after assay in modern toxicology. Next is a whole section that considers various procedures being followed to assess different types of DNA damage in various cell types and is contributed by experts in the respective fields. The third section puts together the specific applications of the assay in the diverse fields ranging from genetic toxicity testing to human monitoring, and environmental toxicology. The fourth section consists of the guidelines and recommendations for the conduct of the assay in in vitro and in vivo systems, based on the recommendations of the International Workgroups on genotoxicity test procedures. Finally, the book draws to a close with an assessment of the statistics used for the understanding of the data generated by the assay. This is a unique reference book as it provides the scientific community with the advances in Comet assay as well as its applications. It also incorporates a detailed section with instant and comprehensive information on the procedure of the assay and the latest protocols being used worldwide as well as statistical analyses to be followed. The book is aimed at students as well as scientists in the area of molecular epidemiology and genetic toxicology
    Type of Medium: Online Resource
    Pages: 374 p , Online-Ressource , 43 b&w, ill
    Edition: RSC eBook Collection 1968-2009
    Series Statement: Issues in toxicology v. 5
    Language: English
    Note: Ebook , Preface-- Part I: Genesis of Comet assay-- Part II: Various procedures for the Comet assay-- Oxidative damage-- Water disinfection by-products-- Comet assay in Plants-- Double Strand-- Breaks in bacteria-- Comet - FISH-- Double strand breaks (DSBs) - radiation/challenge assay - Radiation-- Apoptosis-- Multiple mouse organs-- Part III: Applications of Comet assay-- Dietary intervention studies-- Comet assay in Mussels-- Exercise-- Arsenic-- DSBs - radiation/challenge assay - Radiation-- In vivo Comet assay-- In vitro parallelogram approaches-- Photobiology-- Comet assay in sperm-- Comet assay in Human monitoring-- Part IV: Guidelines for comet assay-- In Vitro And In Vivo Guidelines for the Comet Assay-- In vivo Guidelines for Comet-- Part V: Image analysis and Statistics-- Models for image analysis-- Statistics in comet assay.
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  • 2
    Online Resource
    Online Resource
    [Hamburg] : Marine Training Center Hamburg
    Keywords: Forschungsbericht ; Hafenschlepper ; Fernsteuerung ; Manöver ; Voith-Schneider-Propeller ; Simulation
    Type of Medium: Online Resource
    Pages: 1 Online-Ressource (96 Seiten, 7,11 MB) , Illustrationen, Diagramme
    Language: German
    Note: Förderkennzeichen BMWi 03SX443C , Verbundnummer 01180304 , Autoren dem Berichtsblatt entnommen , Unterschiede zwischen dem gedruckten Dokument und der elektronischen Ressource können nicht ausgeschlossen werden , Sprache der Zusammenfassungen: Deutsch, Englisch
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  • 3
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  • 4
    Publication Date: 2023-06-16
    Description: Comprehensive management of karst water resources requires sufficient understanding of their dynamics and karst-specific modeling tools. However, the limited availability of observations of karstic groundwater dynamics has been prohibiting the assessment of karst water resources at regional to global scales. This paper presents the first global effort to integrate experimental approaches and large-scale modeling. Using a global soil-moisture monitoring program and a global database of karst spring discharges, the simulations of a preliminary global karstic-groundwater-recharge model are evaluated. It is shown that soil moisture is a crucial variable that better distinguishes recharge dynamics in different climates and for different land cover types. The newly developed dataset of karst spring discharges provides first insights into the wide variability of discharge volumes and recharge areas of different karst springs around the globe. Comparing the model simulations with the newly collected soil-moisture and spring-discharge observations, indicates that (1) improvements of the recharge model are still necessary to obtain a better representation of different land cover types and snow processes, and (2) there is a need to incorporate groundwater dynamics. Applying and strictly evaluating these improvements in the model will finally provide a tool to identify hot spots of current or future water scarcity in the karst regions around the globe, thus supporting national and international water governance.
    Description: Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659
    Keywords: ddc:551.49 ; Karst ; Soil moisture ; Spring discharge analysis ; Groundwater recharge ; Global simulation model
    Language: English
    Type: doc-type:article
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: There is evidence that an inflammatory microglial reaction participates in the pathophysiology of dopaminergic neuronal death in Parkinson's disease and in animal models of the disease. However, this phenomenon remains incompletely characterized. Using an in vitro model of neuronal/glial mesencephalic cultures, we show that the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) stimulates the proliferation of microglial cells at concentrations that selectively reduce the survival of DA neurones. The mitogenic action of MPP+ was not the mere consequence of neuronal cell demise as the toxin produced the same effect in a model system of neuronal/glial cortical cultures, where target DA neurones are absent. Consistent with this observation, the proliferative effect of MPP+ was also detectable in neurone-free microglial/astroglial cultures. It disappeared, however, when MPP+ was added to pure microglial cell cultures suggesting that astrocytes played a key role in the mitogenic mechanism. Accordingly, the proliferation of microglial cells in response to MPP+ treatment was mimicked by granulocyte macrophage colony-stimulating factor (GM-CSF), a proinflammatory cytokine produced by astrocytes and was blocked by a neutralizing antibody to GM-CSF. Thus, we conclude that the microglial reaction observed following MPP+ exposure depends on astrocytic factors, e.g. GM-CSF, a finding that may have therapeutic implications.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To better understand the neurotrophic function of the neurotransmitter noradrenaline, we have developed a model of mesencephalic cultures in which we find low concentrations (0.3–10 µm) of noradrenaline to be remarkably effective in promoting long-term survival and function of dopaminergic neurons. This protective action reproduced the effect of caspase inhibition. It was atypical in that it occurred independently of adrenoceptor activation and was mimicked by some antioxidants, redox metal chelators and the hydroxyl radical detoxifying enzyme catalase. Interestingly, intracellular reactive oxygen species (ROS) were drastically reduced by treatment with noradrenaline, indicating that the neurotransmitter itself acted as an antioxidant. Prevention of oxidative stress was, however, independent of the glutathione antioxidant defense system. Chemical analogues of noradrenaline bearing two free hydroxyl groups in the ortho position of the aromatic ring (o-catechols), as well as o-catechol itself, mimicked the survival promoting effects of the neurotransmitter, suggesting that this diphenolic structure was critical for both neuroprotection and reduction of ROS production. Paradoxically, the autoxidation of noradrenaline and the ensuing production of quinone metabolites may be required for both effects, as the neurotransmitter was spontaneously and rapidly degraded over time in the culture medium. These results support the concept that central noradrenergic mechanisms have a neuroprotective role, perhaps in part by reducing oxidative stress.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Bax is a proapoptotic member of the Bcl-2 family of proteins. It is believed to exert its action primarily by facilitating the release of cytochrome c from the mitochondrial intermembrane space into the cytosol, leading to caspase activation and cell death. Because alterations in mitochondrial respiratory function, caspase activation and cell death with morphologic features compatible with apoptosis have been observed post mortem in the brain of patients with Parkinson's disease, we tried to clarify the potential role of Bax in this process in an immunohistochemical study on normal and Parkinson's disease post-mortem brain and primary mesencephalic cell cultures treated with MPP+. We found that Bax is expressed ubiquitously by dopaminergic (DA) neurons in post-mortem brain of normal and Parkinson's disease subjects as well as in vitro. Using an antibody to Bax inserted into the outer mitochondrial membrane as an index of Bax activation, no significant differences were observed between control and Parkinson's disease subjects, regardless of the mesencephalic subregion analysed. However, in Parkinson's disease subjects, the percentage of Bax-positive melanized SNpc neurons containing Lewy bodies, suggestive of DA neuronal suffering, was significantly higher than the overall percentage of Bax-positive neurons among melanized neurons. Furthermore, all melanized SNpc neurons in Parkinson's disease subjects with activated caspase-3 were also immunoreactive for Bax, suggesting that Bax anchored in the outer mitochondrial membrane of melanized SNpc neurons showing signs of neuronal suffering or apoptosis is increased compared with DA neurons that are apparently unaltered. Surprisingly, MPP+ treatment of tyrosine hydroxylase (TH)-positive neurons in primary mesencephalic cultures did not cause redistribution of Bax, although cytochrome c was released from the mitochondria and nuclear condensation/fragmentation was induced. Taken together, these findings suggest that in the human pathology, Bax may be a cofactor in caspase activation, but our in vitro data fail to indicate a central role for Bax in apoptotic death of DA neurons in an experimental Parkinson's disease paradigm.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1540-8183
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sixteen balloon expandable Medtronic Wiktor tantalum stents were implanted in the major coronary arteries of six minipigs, which were maintained on a normal diet and given 500 mg aspirin per day. Angiographic and histologic examinations were performed 6 and 26 weeks after implantation. Angiographically reviewed, stenting increased the inner diameter of the coronary arteries from 2.61 ± 0.44 to 3.02 ± 0.34 mm (n = 16, P ≤ 0.001). Six weeks later, this value was reduced from 2.98 ± 0.35 to 2.33 ± 0.46 mm (n = 9, P ≤ 0.05), and between 6 and 26 weeks, an increase from 2.17 ± 0.44 to 2.93 ± 0.40 mm occurred (n = 6, P ≤ 0.05). Histologic evaluation at 26 weeks after stent implantation revealed an increase of the cross-sectional area of the total vessel from 4.30 ± 1.09 to 5.50 ± 1.67 mm2 (n = 9; P ≤ 0.01). This was due to widening of the total vessel and intimal proliferation, which amounted to 1.19 ± 0.46 mm2 within the stented segment, as compared to 0.03 ± 0.03 mm2 in control sections (P ≤ 0.01). The areas of free vessel lumen, media muscularis, and adventitia remained unchanged. In 15 of the 16 hislologically examined coronary arteries, the internal elastica was fractured at the site of stent implantation. Twelve stents had also penetrated through the external elastica without evidence of wall hemorrhage. Thirteen out of 16 stents were angiographically followed, of which 12 were patent at the final reangiography. In one animal, acute thrombosis of the stented vessel after guidewire induced coronary artery spasm caused chronic right heart failure due to right ventricular myocardial infarction. Sudden death occurred in another pig 2 hours after successful implantation of three grossly oversized stents (inner vessel diameter: 2.4 ± 0.2 mm, stent diameter 3.2 ± 0.5 mm). Autopsy revealed extensive dissections of the media with subsequent vessel occlusion. It is concluded that Medtronic Wiktor stents can be placed easily, even in more distal or curved coronary arteries. Despite antiaggregational medication, intimal proliferation is observed early after implantation, reaches a maximum at about 6 weeks, and is followed by a regression 26 weeks poststenting. At 26 weeks follow-up, the free vessel lumen at the stent site was not significantly reduced as compared to control segments. Proper adjustment of internal vessel diameter and stent diameter is necessary to prevent major dissections and thrombotic occlusions.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1540-8183
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We report about the 6-month follow-up of 28 consecutive patients treated with a new tantalum stent (Wiktor™ stent, Medtronic, Inc.). Indication for stenting was the prevention of restenosis in eight patients (restenosis group), and threatening or acute closure after PTCA in 20 patients (acute closure group). Twenty-eight of 30 stents were successfully positioned in 27 of 28 patients (96%), whereas implantation failed twice in one patient. Immediate stent occlusion developed in two patients in the acute closure group (7.4%). Subacute stent occlusion was observed in three patients (11%), one in the restenosis group, two in the acute closure group, between 3 and 5 days after implantation. Coronary bypass surgery had to be performed in four patients (15%): one patient after failed stent placement, two after acute, and one after subacute stent thrombosis. Major bleeding complications related to the anticoagulative drug regimen occurred in nine patients (33%). Three patients (11%) died for reasons most probably not related to stent implantation. A 6-month angiographic follow-up revealed restenosis in two of 19 patients (11%), one patient in each group. Sixteen of the 27 stented patients (59%) reached 6-month follow-up without death, acute or subacute stent thrombosis, or restenosis. It is concluded that the Wiktor stent can be placed with a high rate of success. It may also reduce the risk of restenosis. The stent also offers the possibility to circumvent emergency bypass surgery in case of PTCA related vessel occlusion. Acute and subacute stent occlusion still remains an unsolved topic.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of interventional cardiology 4 (1991), S. 0 
    ISSN: 1540-8183
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: From 1988 to 1990 chronic coronary occlusions were treated with a newly developed slowly rotating angioplasty system (ROTACS), which is designed for atraumatic passage of arterial obstructions. In all 152 patients (mean age 55 years, ranging from 29 to 78 years) attempts to recanalize the coronary occlusion with conventional guidewire systems had failed. In 74/152 patients the age of the occlusion could be estimated because of a previous angiogram or clinical event. It ranged from 1–192 months (median 6 months, mean value 14 months; in 20% of patients it was 1–3, in 37% 4–6, in 28% 7–12, and in 15% 〉 12 months). The occlusion was localized in the right coronary artery (RCA) in 86 cases, in the left anterior descending coronary artery (LAD) in 37 cases, and in the circumflex branch of the left coronary artery in 17 cases. Eleven bypass occlusions were treated. One patient had a LAD and RCA occlusion. Out of 152 patients 84 could be recanalized. The success rate rose with experience from 30% to 60%. It was 55% in the LAD, 52% in the RCA, 70% in the circumflex branch, and 63% in bypass grafts. The success rate in relation to the age of the occlusion was 93% in occlusions of 1–3 month duration, 74% in occlusions of 4–6 months duration, 52% in occlusions of 6–12 months duration, and 8% in occlusions older than 12 months. Seventy-six of the successfully treated patients underwent follow-up angiography after 4 months. In 56/76 (74%) the vessel remained open. Twenty-two patients (29%) had restenosis that was successfully dilated in 21 patients. Twenty patients (26%) had reocclusion. Thus, the angiographically determined long-term success rate was 72%. Emergency operation was necessary in two patients in whom reopening of the LAD was attempted although the occlusion was located directly at the take-off of the LAD from the left main. Since this type of occlusion was consequently considered a contraindication, no further serious complications occurred. There was one myocardial infarction, no death, no vessel wall perforation or other complications in the 152 patients. It is concluded that low speed ROTACS is a safe technique that can be applied in chronic coronary occlusions even if the duration of occlusion exceeds 6 months. (J Interven Cardiol 1991; 4:15–165)
    Type of Medium: Electronic Resource
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