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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 349 (1994), S. 492-496 
    ISSN: 1432-1912
    Keywords: Kindling ; Pentylenetetrazol ; Learning ; Diazepam ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Repeated administration of pentylenetetrazol (PTZ) induces kindling and impairs shuttle-box learning. The available literature suggesting a close connection between seizure frequency and mental deficits in human epileptics allows us to hypothesize that seizure inhibition prevents the progressive mental retardation associated with kindling. In order to investigate the effect of motor seizure inhibition on mental impairment we administered diazepam (DZP) doses of 0.5 and 2.5 mg/kg, respectively 60 min prior to the 10 convulsant injections. After completion of kindling the learning performance of the rats was tested in the shuttle-box. PTZ kindling resulted in diminished shuttle-box learning. In control rats treated with DZP no significant changes in their learning ability occurred. Although DZP was found to suppress kindling development effectively a worsened shuttle-box learning could be observed in all PTZ groups treated with DZP.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1439-099X
    Keywords: Schlüsselwörter: p53-Überexpression ; Hypoxie ; Kopf-Hals-Karzinome ; Key Words: p53 ; Hypoxia ; Head and neck carcinomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Purpose: Clinical investigation of a potential relationship between the polarographically measured tumor oxygenation and the p53 status in patients with squamous cell carcinoma of the head and neck. Patients and Methods: In 99 patients with mostly advanced, histologically proven squamous cell carcinoma of the head and neck were estimated the classical tumor parameters (TNM stage, histological grading) the immunohistochemical p53-overexpression (DO-7) and the tumor oxygenation status (Eppendorf pO2 Histograph). The tumor volume and the hemoglobin concentration were evaluated simultaneously. Results: No statistically significant difference could be detected between immunohistological p53-positive (p53 ≥ 10% stained cells) and p53-negative tumors (p53 〈 10% stained cells) regarding both the median pO2 and the relative frequency of values ≤ 5 mm Hg. Moreover, no statistically relevant differences could be seen between both p53-groups considering the hemoglobin concentration, the TNM stag, the histological grading and the tumor volume. Conclusion: Our data imply that there is no association between p53-overexpression and tumor hypoxia in head and neck carcinomas. However, this is not necessarily in contradiction to experimental or clinical data that confirmed a relationship between hypoxia and p53-mediated increased malignancy of tumor cells in other tumor entities. The comparable oxygenation status of p53-positive and p53-negative tumors in our study is associated with an analogous clinical tumor aggressiveness of both groups. That could be caused by hypoxia related but p53-independent selection of tumor cells with a more malignant phenotype in head and neck carcinomas. However, further research is needed to prove this possible relationship.
    Notes: Ziel: Klinische Prüfung einer potentiellen Beziehung zwischen polarographisch gemesener Tumoroxygenierung und p53-Status bei Patienten mit Plattenepithelkarzinomen der Kopf-Hals-Region. Patienten und Methode: Bei 99 Patienten mit überwiegend fortgeschrittenen, histologisch gesicherten Plattenepithelkarzinomen der Kopf-Hals-Region wurden neben den klassischen Tumorparametern (TNM-Stadium, histologisches Grading) die immunhistochemische p53-Überexpression (DO-7) und der Tumoroxygenierungsstatus ermittelt (Eppendorf-pO2-Histograph). Simultan erfolgte die Bestimmung des Tumorvolumens und der Hämoglobinkonzentration. Ergebnisse: Zwischen immunhistochemisch p53-positiven (≥ 10% angefärbte Zellen) und p53-negativen (〈 10% angefärbte Zellen) Tumoren fand sich weder für den pO2-Median noch für die relative Anzahl von Werten ≤ 5 mm Hg ein statistisch signifikanter Unterschied. Auch bei der Betrachtung der Hämoglobinkonzentration, der TNM-Klassifikation, des histologischen Gradings und des Tumorvolumens fanden sich zwischen beiden p53-Gruppen keine statistisch relevanten Differenzen. Schlussfolgerung: Unsere Daten sprechen gegen eine Assoziation von p53-Überexpression und Tumorhypoxie bei Kopf-Hals-Karzinomen. Zu experimentellen und klinischen Ergebnissen, die bei anderen Tumorentitäten zeigen, dass Hypoxie zu einer p53-vermittelten Steigerung der Malignität führt, ergibt sich trotzdem kein prinzipieller Widerspruch. Die in unserer Studie adäquate Oxygenierung von p53-positiven und p53-negativen Tumoren reflektiert sich in einer vergleichbaren klinischen Tumoraggressivität beider Gruppen. Dies könnte dadurch bedingt sein, dass bei Kopf-Hals-Karzinomen hypoxieassoziierte, aber p53-unabhängiger Formen der Selektion von Tumorzellen mit malignerem Phänotyp zum Tragen kommen. Es bedarf jedoch weiterführender Untersuchungen, um einen solchen möglichen Zusammenhang zu belegen.
    Type of Medium: Electronic Resource
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