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  • cervical dysplasia  (2)
  • 5-lipoxygenase inhibitor  (1)
  • Glutathione  (1)
  • Olfactory epithelium  (1)
  • Springer  (4)
  • American Institute of Physics (AIP)
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  • Springer  (4)
  • American Institute of Physics (AIP)
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  • 1
    ISSN: 1432-0878
    Schlagwort(e): Thiols ; Glutathione ; γ-Glutamyl transpeptidase ; Olfactory epithelium ; Respiratory epithelium ; Perireceptor events ; Rat (Sprague Dawley)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Components of the γ-glutamyl cycle, including thiols, glutathione (GSH) and γ-glutamyl transpeptidase (γ-GT), were localized in the nasal mucosae of rats using histochemical and immunohistochemical methods. In olfactory mucosa, thiols were widely distributed, with intense staining in the mucociliary complex (MC), basal cells, acinar cells of Bowman's glands (BG), and olfactory nerve bundles, and with moderate staining in olfactory receptor neurons (ORNs). GSH was localized in MC, BG acinar cells, nerve bundles and, to a lesser extent, in ORNs. γ-GT immunoreactivity was restricted to the MC and to basolateral and apical membranes of BG acinar and duct cells. The basolateral membrane of BG acinar cells, located in close association with blood vessels and connective tissue, showed granule-like immunoreactivity. Inrespiratory mucosa, all three compounds were localized in the MC and acinar cells of respiratory glands (RG). In the MC, γ-GT immunoreactivity was associated primarily with brush borders of ciliated cells. Granular immunoreactivity was also apparent in the supranuclear region of RG acinar cells. These results demonstrate that components of the γ-glutamyl cycle are localized in olfactory and respiratory glands, and that they are secreted into the mucus, where they may mediate perireceptor events such as detoxification and/or solubilization of air-borne xenobiotics, toxicants and odorants.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    ISSN: 1573-0646
    Schlagwort(e): trans-retinoic acid ; cervical dysplasia ; chemoprevention
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Forty-two patients were entered into a phase I trial to evaluate the vitamin A derivative, trans-retinoic acid, in cervical intraepithelial neoplasia. Treatment consisted of four consecutive 24-h applications of retinoids via an inert collagen sponge in a cervical cap. Patients were followed for response at 3-month intervals using cytology, colposcopy, and selected biopsies. Thirty-six patients were evaluable (mild dysplasia, 13; moderate dysplasia, 17; severe dysplasia, 6) with follow-up from 5 to 18 months. Complete regression was seen in 2/14 (14%) patients treated with concentrations of 0.05% → 0.1167% and in 10/22 (45%) patients treated with concentrations of 0.1583% → 0.484% (p 〈 0.05). One patient with negative biopsies at 12 months has subsequently recurred at 18 months.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    ISSN: 1573-0646
    Schlagwort(e): cervical dysplasia ; all-trans-retinoic acid ; tissue uptake of anticancer drug ; collagen sponge-cervical cap
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract The present study was undertaken to evaluate the systemic absorption and cervical tissue uptake of all-transretinoic acid (TRA), delivered via a collagen spongecervical cap delivery device in patients with intraepithelial cervical dysplasia. Ten patients with histologically proven mild or moderate cervical dysplasia were included in this pharmacologic study. The two TRA concentrations (0.05% and 0.372%) selected for study represent the starting and maximally tolerated doses used in phase I clinical trial. All-trans-retinoic-11-3H acid (3H-TRA, 500 μCi) was used to facilitate cervical tissue uptake studies. Cervical biopsies and post-treatment blood samples were obtained from each patient after TRA exposure. The uptake of TRA into cervical tissues four hours after drug administration was significantly increased at the maximally tolerated TRA dose. There was a rapid decrease in cervical tissue concentration of TRA at the 0.372% dose between 4 and 24 h after drug exposure, suggesting a relatively short elimination half-life of TRA in cervical tissues. HPLC analysis of post-treatment blood samples indicate that there was no systemic absorption of TRA after local cervical administration.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    ISSN: 1573-904X
    Schlagwort(e): drug design ; pharmacokinetic screening ; 5-lipoxygenase inhibitor ; o-quinone analogues
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The o-naphthoquinone derivative, CGS 8515 (I), is a potent inhibitor (IC50, 0.1 µM) of 5-lipoxygenase, but its therapeutic potential is compromised by a short plasma half-life (22 min) and extremely poor oral bioavailability (〈2%). Poor biopharmaceutical properties of CGS 8515 were attributed to poor aqueous solubility and rapid in vivo hydrolysis of its methyl ester function to an inactive metabolite (IC50, 100 µM). An active amide analogue (II) was synthesized to prevent rapid hydrolysis. While analogue II appeared to be stable in vivo, its plasma half-life was also short (10 min), possibly because of rapid tissue distribution rather than metabolic elimination. Therefore, three potent analogues with increased aqueous solubilities were synthesized and compared with respect to their pharmacokinetic properties. The analogue with the highest aqueous solubility (V) demonstrated a plasma concentration vs time profile with the largest area under the curve (AUC) and the smallest distribution (α) phase of all the analogues studied. The percentage AUC of the terminal phase (β) for three analogs paralleled their aqueous solubilities. The oral bioavailability of V was improved to 27%, compared to 2% for the parent compound, CGS 8515.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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