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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Human Movement Science 5 (1986), S. 359-371 
    ISSN: 0167-9457
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine , Sports Science
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 27 (1971), S. 173-186 
    ISSN: 1432-0738
    Keywords: Tetramethyl-thiuram Disulphide (Thiram TMTD) ; Mouse ; Skeletal Malformations ; Stage Specificity ; Cleft Palate ; Tetramethylthiuramdisulfid (Thiram, TMTD) ; Maus ; Skeletmißbildungen ; Stadienspezifität ; Gaumenspalten
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In den vorliegenden Untersuchungen wurden gravide Mäuseweibchen der Stämme NMRI und SW sowohl vom 6.–17. Trächtigkeitstag als auch während bestimmter Abschnitte der Gestation oral mit verschiedenen, für das Muttertier untoxischen Dosen (5–30 mg/Tier) von Tetramethylthiuramdisulfid (Thiram, TMTD) behandelt. Neben vermehrten Fruchtresorptionen und deutlichen Entwicklungsverzögerungen konnte bei beiden Stämmen in Abhängigkeit von der Konzentration ein für das Thiram charakteristisches Mißbildungssyndrom des Skelets (Gaumenspalten, gewellte Rippen, Verbiegungen der Extremitätenknochen, Mikrognathien) festgestellt werden. Außerdem war es anhand der unterschiedlichen Applikationszeitpunkte möglich, stadienspezifische Wirkungen zu ermitteln, wobei sich der 12. und 13. Tag der Keimesentwicklung als empfindlichster Abschnitt erwies. Hinsichtlich der Auslösung von Gaumenspalten zeigte sich der NMRI-Stamm wesentlich empfindlicher als der SW-Stamm. Als teratogen unwirksame Dosis sind für die Maus etwa 250 mg/kg anzusehen.
    Notes: Abstract In the studies described, pregnant female mice of the NMRI and SW strains were treated between the 6th and 17th day of pregnancy as well as during certain other periods of gestation with tetramethyl-thiuram disulphide (thiram, TMTD) in oral doses that were non-toxic 5–30 mg/animal) for adult animals. In addition to increased resorption of embryos and clearly retarded fetal development, a syndrome of skeletal malformations (cleft platae, “wavy” ribs, curved long bones of the extremities, and micrognathia) characteristic of thiram and related to concentration could be observed in both strains. Furthermore, varying times of application allowed for a determination of stage-specific effects. The 12th and 13th day of embryonic development proved to be the most susceptible phase. There was a considerably higher succeptibility of the NMRI than SW strain with regard to the induction of cleft palates. The teratogenically ineffective dose for mice is considered to be approx. 250 mg/kg.
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  • 3
    ISSN: 1432-1106
    Keywords: Body reference ; Extraocular proprioception ; Gaze direction ; Neck proprioception ; Vibration ; Visuomanual pointing ; Visual illusion ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The egocentric localization of objects in extrapersonal space requires that the retinal and extraretinal signals specifying the gaze direction be simultaneously processed. The question as to whether the extraretinal signal is of central or peripheral origin is still a matter of controversy, however. Three experiments were carried out to investigate the following hypotheses: 1) that the proprioceptive feedback originating in eye and neck muscles might provide the CNS with some indication about the gaze direction; and 2) that the retinal and proprioceptive extraretinal inputs might be jointly processed depending on whether they are of monocular or binocular origin. Application of low amplitude mechanical vibrations to either the extraocular or neck muscles (or both) of a subject looking monocularly at a small luminous target in darkness resulted in an illusory movement of the target, the direction of which depended on which muscle was stimulated. A slow upward target displacement occurred on vibrating the eye inferior rectus or the neck sterno-cleido-mastoidus muscles, whereas a downward shift was induced when the dorsal neck muscles (trapezius and splenius) were vibrated. The extent of the perceptual effects reported by subjects was measured in an open-loop pointing task in which they were asked to point at the perceived position of the target. These results extend to visually-oriented behavior the role of extraocular and neck proprioceptive inputs previously described in the case of postural regulation, since they clearly show that these messages contribute to specifying the gaze direction. This suggests that the extraretinal signal might include a proprioceptive component. The proposition that a directional body reference frame may be based on the common processing of various proprioceptive feedbacks is discussed.
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  • 4
    ISSN: 1432-1106
    Keywords: Key words Microgravity ; Muscle proprioception ; Posture ; Kinesthesia ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The ”illusions” experiment carried out on five astronauts during the last two French-Russian flights (Antarès in 1992 and Altaı˙˙r in 1993) and in the Russian Post-Antarès mission (1993) was designed to investigate the adaptive changes in human proprioceptive functions occurring in weightlessness at both the sensorimotor and cognitive levels, focusing on two kinds of responses: (1) whole-body postural reflexes, and (2) whole-body movement perception. These kinesthetic and motor responses were induced using the tendon-vibration method, which is known to selectively activate the proprioceptive muscular sensory channel and to elicit either motor reactions or illusory movement sensations. Vibration (70 Hz) was therefore applied to ankle (soleus or tibialis) and neck (splenii) muscles. The subject’s whole-body motor responses were analyzed from EMG and goniometric recordings. The perceived vibration-induced kinesthetic sensations were mimicked by the subjects with a joystick. The main results show that a parallel in-flight attenuation of the vibration-induced postural responses and kinesthetic illusions occurred, which seems to indicate that the proprioceptive system adapts to the microgravity context, where standing posture and conscious coding of anteroposterior body movements are no longer relevant. The same sensory messages are used at the same time in different sensory motor loops and in the coding of newly developed behavioral movements under microgravity. These results suggest that the human proprioceptive system has a high degree of adaptive functional plasticity, at least as far as the perceptualand motor aspects are concerned.
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  • 5
    ISSN: 1432-0738
    Keywords: Proposal ; New test guideline ; Skin sensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present EEC and OECD Guidelines for testing skin sensitization have been reviewed in light of scientific evidence demonstrating that those methods which use Freund's Complete Adjuvant (FCA) are likely to be more accurate in predicting a probable skin-sensitizing effect of a new substance in humans than those methods not employing Freund's Complete Adjuvant. In this new test guideline, therefore, the primary testing of a substance should be carried out using one of the recommended Adjuvant methods. In special cases a non-adjuvant method may be performed in addition. Not all of the seven methods in the EEC Guideline or eight methods in the OECD Guideline have been included, but in a proposal for an updated test protocol two Adjuvant tests (Maximization test by Magnusson and Kligman and Optimization test by Maurer), and two non-Adjuvant tests (Open Epicutaneous test by Klecak and Buehler test) are suggested. The criteria for selecting these methods are based on the fact that they are well validated and widely used on a broad basis by the scientific community. Furthermore, it is considered appropriate to permit the use of a lower number of animals than presently recommended for the testing of skin sensitization. This is also in agreement with aspects of animal welfare.
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  • 6
    ISSN: 1432-0738
    Keywords: Acute-toxic-class method ; Alternative ; LD50 test ; Animal welfare ; Classification ; Risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a national colloborative study an alternative to the classical LD50 test — the acute-toxic-class method — was validated. With this testing procedure mortality ranges are determined between defined dose levels that are used for classification and labelling in the European Community. The results were compared with LD50 data obtained from the literature which were categorized according to the defined dose levels. The results of this collaborative study have shown that the acute-toxic-class method allows allocation to the toxicity classes of very toxic, toxic, harmful and unclassified in the same manner as on the basis of the classical LD50 tests. The acute-toxic-class method uses fewer animals and subjects fewer animals to pain and distress than the LD50 test and yields the same information on toxic signs in the treated animals. Identical classifications were obtained by the six participating laboratories in 86% of the tests. This demonstrates that the acute-toxic-class method results in excellent reproducibility in comparison to the classical LD50 test and that this new method is a reliable alternative to the LD50 test.
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  • 7
    ISSN: 1432-0738
    Keywords: Trichloroethylene ; Dominant lethal assay ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Belastung von männlichen Mäusen mit TrichloräthylenDämpfen in Konzentrationen von 50, 202 und 450 ppm über 24 h zeigte keine mutagenen Wirkungen im Dominant-Letal-Test. Folgende Parameter wurden registriert und bewertet: Befruchtungsrate, postimplantativer Verlust, präimplantativer Verlust und dominante letale Mutationen.
    Notes: Abstract Exposure of male mice to trichloroethylene vapours during 24 h at levels of 50,202 and 450 ppm did not reveal mutagenic effects in the dominant lethal assay. The following parameters were registered and evaluated: Fertilization rate, post-implantation loss, preemplantation loss and dominant lethal mutations.
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  • 8
    ISSN: 1432-0738
    Keywords: Hydroxyurea ; Skeletal malformations ; Stage specificity ; Organotropism ; Schlüsselwörter ; Hydroxyharnstoff ; Skeletmißbildungen ; Stadienspezifität ; Organotropie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In den vorliegenden Untersuchungen wurden gravide Mäuseweibchen vom Stamm NMRI sowohl chronisch vom 6.–17. Trächtigkeitstag als auch während bestimmter Abschnitte der frühen und embryonalen Entwicklung oral mit verschiedenen, für das Muttertier untoxischen Dosen von Hydroxyharnstoff (HHS) behandelt. Es konnten neben vermehrter Fruchtresorption und deutlichen Entwicklungsverzögerungen für den Hydroxyharnstoff und verwandte Verbindungen charakteristische Skeletmißbildungen (Kyematopathien und Embryopathien) induziert werden. An Hand der unterschiedlichen Applikationszeitpunkte war es ferner möglich, eine gewisse Stadienspezifität sowie Organotropie des Wirkstoffes festzustellen.
    Notes: Summary In the studies presented pregnant female mice of the NMRI strain were treated chronically from the 6th to 17th day of pregnancy as well as during certain periods of early and embryonic development with different oral doses of hydroxyurea (HU) which were non-toxic for the maternal animals. In addition to increased incidence of embryo resorption and definite delay in development, characteristic skeletal malformations (cyematopathies and embryopathies) for hydroxyurea could be induced. On the basis of different times of application, it was further possible to establish a certain stage specificity as well as organotropism of the substance.
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  • 9
    ISSN: 1432-0738
    Keywords: Monolinuron ; Buturon ; Mouse ; Embryotoxicity ; Cleftpalate ; Monolinuron ; Buturon ; Maus ; Embryotoxizität ; Gaumenspalten
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die akute orale LD50 für virginelle NMRI-Mäuseweibchen betrug 2528 mg/kg für Monolinuron und 1791 mg/kg für Buturon. In den vorliegenden Untersuchungen zur Embryotoxizität wurden gravide Mäuseweibchen des Stammes NMRI sowohl vom 6.–15. Tag der Trächtigkeit oral mit 25–1000 mg Monolinuron/kg (I) und mit 100–400 mg Buturon/kg (II) als auch während bestimmter Abschnitte der Fetogenese (10.–13. Tag p. c.) mit 500 mg I/kg und mit 350 mg Il/kg behandelt. Nach zehnmaliger Verabreichung konnte neben einer Erhöhung des postimplantativen Verlustes und deutlichen Entwicklungsverzögerungen im höheren Dosisbereich ab 100 mg I/kg und ab 300 mg II/kg eine dosisabhängige Vermehrung der Rate an Gaumenspalten festgestellt werden. Bei den höheren Dosen waren außerdem bei beiden Substanzen in geringerem Umfang gewellte und verwachsene Rippen zu beobachten. Bei Monolinuron traten außerdem hypoplastische Oberkiefer und bei Buturon Exenterien und Exencephalien auf. Die Verabreichung der Substanzen zwischen dem 10. und 13. Trächtigkeitstag führte zu einer Erhöhung der Zahl an Gaumenspalten, wobei der Effekt nach Gabe von Buturon deutlicher war. In einem Aufzuchtversuch zur Beurteilung der Postnatalentwicklung wurden 200 und 500 mg I/kg sowie 200 und 350 mg II/kg vom 6.–15. Tag der Gestation oral verabreicht. Beide Substanzen führten bei der jeweils höheren Dosierung sowohl zu einer erhöhten Sterblichkeit der Jungtiere bis 3 Wochen post partum als auch zu einer deutlichen Steigerung der Rate an Gaumenspalten.
    Notes: Abstract The acute LD50 in virginal NMRI-Mice was found to be 2528 mg/kg for monolinuron and 1791 mg/kg for buturon. Pregnant female mice of the NMRI strain were administered orally 25–1000 mg monolinuron/kg (I) and 100–400 mg buturon/kg (II) on days 6–15 of gestation and, during defined phases of fetal development (days 10–13 after conception), 500 mg I/kg and 350 mg II/kg. Following administration of 10 doses, an increase of postimplantative losses and clear retardation of development in the upper dose range from 100 mg I/kg and 300 mg Il/kg as well as a dose-dependent increase of the rate of cleft palates could be observed. High doses of both substances given from day 6–15 of pregnancy produced minor numbers of wavy and fused ribs as well as hypoplasia of the upper jaw after application of monolinuron and exenteria and exencephaly after buturon. Administration of monolinuron between days 10 and 13 of gestation resulted a minor and that of buturon a clear increase of the number of cleft palates. To evaluate postnatal development 200 and 500 mg I/kg, and 200 and 300 mg II/kg were administered orally on days 6–15 of gestation. In the higher doses, both substances produced an increased mortality among the offspring up to 3 weeks after birth, and a clear increase of the rate of cleft palates.
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  • 10
    ISSN: 1432-0738
    Keywords: Mutagenicity testing ; Standard protocol ; Dominant lethal assay ; Male mice ; Collaborative study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The members of the work group “Dominant Lethal Mutations of the ad hoc Committee Chemogenetics” jointly carried out experimental studies in the period from November 1972 until February 1976. On the basis of the results obtained and the experience gained, they worked out on February 27, 1976, a standard protocol for the dominant lethal test (DLT) on male mice. The recommendations are: 1. The mating period should preferentially be as short as possible to obtain information about germ cell-stage specific actions of chemical mutagens. Its selection should be based on the objectives of individual investigators. For screening purposes, and with respect to a high fertilization rate, a 4-day mating period is recommended. 2. The total test period should cover at least 12 mating periods, i.e. the whole spermatogenic cycle. A limitation of the DLT to certain “critical” mating periods of high sensitivity is only permissible in repeat tests, or if the parts of gametogenesis concerned, e.g. spermatogoniogenesis or spermatocytogenesis, are studied by cytogenetical tests. 3. The mode of mating should preferentially be 1∶1. 4. The number of test animals to be used depends on various biological and statistical factors; no generally valid statement can be made concerning the number of test animals. By rule of thumb in the order of 50 fertilized females per group per mating interval is recommended. 5. The individual dosing of the substance in terms of mg/kg body weight is to be preferred. Otherwise, the weights of the animals should not deviate more than 5% from the mean value. 6. Results obtained from ill animals or those that died in the course of the trial should not be included in the evaluation. 7. The sensitivity of the mouse strain used against a standard dose of a known mutagen should be regularly checked; this evidence should be presented in publications. 8. For the following test conditions each investigator should make an optimal choice: animal strain, animal age and housing conditions. The investigator has also to decide whether a preliminary mating, in order to check the fertility of the animals to be used, and vaginal-plug evidence are useful in a given case. 9. The autopsy of the dams is best carried out a fortnight from the middle of the mating interval. 10. The results should be documented as completely as possible in the investigational report. The following data were also considered as essential, serving a direct comparison of the test groups: number of mated females (absolute), number of females with implantation (absolute and in %), number of implantations and of live and dead implants (absolute and per female). If the corpora lutea graviditates were counted, their number as well as the pre-implantation loss (absolute and per female) are to be stated. These data are also desirable for publications. 11. For the biological evaluation the following formula can be used for the calculation of dominant lethal factors: FL% = [1-live implants per female of the test group/live implants per female of the control group]×100 12. Statistical evaluation is an essential part of the DLT and various methods are known. For the statistical evaluation it is decisive which biological model and which statistical criteria are most important for the investigator. The DLT must be carried out according to the requirement of the model chosen.
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