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  • drug metabolism  (2)
  • Adhesion molecules  (1)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Mund-, Kiefer- und Gesichtschirurgie 2 (1998), S. 131-135 
    ISSN: 1434-3940
    Schlagwort(e): Schlüsselwörter Mukositis ; Strahlentherapie ; Immunohistochemische Veränderungen ; Adhäsionsmoleküle ; Makrophagenmarker ; Key words Mucositis ; Radiotherapy ; Immunohistochemistry ; Adhesion molecules ; Macrophages
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: One of the most severe early side effects of radiation in head and neck cancer patients is mucositis. Inflammation of the oral mucose may lead to an extreme subjective burden, restricting the patients’ well-being and even leading to an interruption of radiotherapy. The aim of our prospective study was to investigate the pathological alterations of the oral mucosa during irradiation. Therefore, samples from head and neck cancer patients were taken before radiation and a 30-G and a 60-G radiation dose. Pathogenetic alterations were determined by immunohistochemical staining of various cell surface molecules known to be involved in the pathogenesis of inflammation. Staining was performed with antibodies against ICAM 1, VCAM 1, ELAM, 25F9, 27E10, and RM3-1. Our study demonstrates the expression rates of the various surface molecules during inflammation. Expression of RM3-1 and ICAM 1 showed a steep increase during the time of radiation, whereas expression of ELAM reached a low constant value. Therefore, we conclude that distinct cell surface molecules demonstrate a characteristic time-dependent expression during radiation. Better insight into the pathogenesis of radiation-induced mucositis may help to develop a pathological classification of mucositis and to improve therapeutic strategies.
    Notizen: Die strahleninduzierte orale Mukositis nimmt als die bedeutendste Frühreaktion der Radiatio einen of subjektiv stark belastenden Verlauf, der nicht selten zu einer äußerst unerwünschten Therapieunterbrechung oder sogar einem -abbruch führt. Leider liegen bisher keine longitudinalen Studien über differenziertere, quantifizierbare pathohistologische Veränderungen vor. Ziel dieser prospektiven Pilotstudie ist es, ein Verfahren zu etablieren, das es erlaubt, dem Verlauf der oralen Strahlenmukositis eine Zeitkinetik verschiedener Makrophagensubpopulationen und ausgewählter Adhäsionsmoleküle zuzuordnen. Dazu dokumentierten wir die immunhistochemischen Veränderungen der oralen Mukosa prä radiationem, bei 30 G und bei 60 G Energiedosis. Neben monoklonalen Antikörpern gegen 3 funktionell verschiedene Makrophagensubpopulationen (27E10, 25F9, RM3/1) kamen auch Marker für verschiedene endotheliale Adhäsionsmoleküle (VCAM-1, ICAM-1, Elam) zur Anwendung. Die Evaluierung der immunohistochemischen Befunde deutet auf eine signifikante Zunahme des antiinflammatorischen Makrophagen RM3/1 im Bindegewebe im Verlauf der Bestrahlung hin, während die Anzahl der inflammatorischen und reifen Makrophagen zu sistieren scheint. Das endotheliale Expressionsmuster der 3 Adhäsionsmoleküle VCAM-1, ICAM-1 und Elam ist durch einen signifikanten Anstieg von ICAM-1 bei nahezu gleichbleibender niedriger Expression von VCAM-1 und Elam gekennzeichnet. Unsere ersten Ergebnisse der Expressions- und Verteilungsmuster stellen Vergleichswerte dar, anhand derer in weiteren Studien die Pathogenese der oralen Strahlenmukositis genauer untersucht werden kann.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-1041
    Schlagwort(e): bufuralol ; hepatic oxidation ; debrisoquine/sparteine phenotype ; stereo- and regioselectivity ; metabolites ; healthy volunteers ; drug metabolism ; polymorphism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of the debrisoquine/sparteine-type of oxidation polymorphism on plasma bufuralol concentration and the pattern of urine metabolites was studied in extensive and poor metabolizer subjects. (+)- and (−)-bufuralol, and (+)- and (−)-OH-bufuralol in plasma were determined by enantioselective HPLC, and urinary bufuralol and its metabolites were assayed by gas chromatography-mass spectrometry. Three hours after administration of racemic bufuralol the plasma (−)/(+) isomeric ratio for unchanged bufuralol was 1.84 in extensive metabolizers, indicating preferential clearance of the (+)-isomer through aliphatic 1′-hydroxylation and glucuroconjugation, while the (−)-isomer was mainly eliminated by aromatic 4-hydroxylation. Poor metabolizers were characterized by impaired 1′- and 4-hydroxylation, with almost total abolition of the stereoselectivity of these reactions. The data strongly suggest that both 1′- and 4-hydroxylation are catalyzed by the same enzyme. These in vivo observations are in agreement with recent in vitro data obtained in human liver microsomes from phenotyped patients and support the concept of deficiency of a highly stereoselective cytochrome P-450 isozyme as the cause of this polymorphism.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-1041
    Schlagwort(e): Genetic polymorphism ; Cytochrome P450 ; drug metabolism ; codeine ; interethnic differences ; Chinese ; debrisoquine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The Far Eastern and Caucasian populations are strikingly different with respect to the debrisoquine/sparteine hydroxylation polymorphism. The number of poor metabolizers, as defined for Caucasians, is very low among Chinese and Japanese. We investigated the molecular basis for this difference by analysis of the CYP2D6 gene in 115 Chinese subjects, combined with phenotypic classification of codeine and debrisoquine metabolism. A correlation between the rates of metabolism of these two drugs and genotype, as analyzed by RFLP using XbaI, was observed among the Chinese. A high frequency (37%) of alleles indicative of gene insertions (reflected by Xba I 44kb fragments) was recorded in the Chinese, but was not associated with the poor metabolizer phenotype, as it is in Caucasians. PCR amplification of part of the CYP2D6 gene with mutation specific primers for CYP2D6A (29A) and CYP2D6B (29B) allelic variants revealed that the XbaI 44kb fragment in Chinese apparently contains a functional CYP2D6 gene, in contrast to the situation among Caucasians. The results provide a molecular explanation of the interethnic difference in the metabolism of drugs affected by the debrisoquine hydroxylation polymorphism.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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