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Linda Bergander Niklas Wahlstr?m Tomas Alsberg Jan Bergman Agneta Rannug Ulf Rannug 《Drug metabolism and disposition》2003,31(2):233-241
The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) exhibits the highest aryl hydrocarbon receptor (AhR) binding affinity reported so far. In different cells, in vitro, both extracts of UV-irradiated tryptophan and the synthesized pure compound FICZ induce a rapid and transient expression of AhR-regulated genes. The transient induction suggests that the biotransformation gene battery induced by AhR activation takes part in a metabolic degradation of the ligand, whereby a low steady-state level is regained. The down-regulation of AhR-regulated gene expression was previously shown to be dependent on cytochrome P450 1A1 (CYP1A1). Metabolism of FICZ generates five major metabolites, which appeared as three peaks (M1-M3) in the high performance liquid chromatography. The aim of the present study was to use rat liver S9 from Aroclor-pretreated rats to produce large enough quantities of FICZ metabolites for structure characterization and to determine their product precursor relationship. NMR analysis of large combined fractions of the metabolites indicated that M3 and M2 contained 2 isomers, respectively. By means of liquid chromatography-mass spectrometry (negative ion electrospray mode) and NMR spectroscopy (by (1)H-NMR, correlation spectroscopy, and nuclear Overhauser effect spectroscopy techniques) five metabolites of FICZ were identified, and their structures were elucidated. The molecular weights of the two M3 isomers were 300 and both M2 and M1 compounds demonstrated molecular weights of 316, corresponding to addition of one (M3) and of two oxygen (M2 and M1), respectively. The structures were assigned as 2- and 8-hydroxy (M3), 2,10- and 4,8-dihydroxy (M2) and 2,8-dihydroxy derivatives of indolo[3,2-b]carbazole-6-carboxaldehyde (6-formylindolo[3,2-b]carbazole). 相似文献
23.
U. Tnne A. J. Hiltunen B. Vikander K. Engelbrektsson H. Bergman I. Bergman H. Leifman S. Borg 《Acta psychiatrica Scandinavica》1995,91(5):299-304
Impairment on neuropsychological tests during steady-state drug use and withdrawal, and after discontinuation of benzodiazepines, was studied in primary benzodiazepine-dependent patients. One group of patients was tested before and the other group after the initiation of a gradual tapering-off of the drug, and both groups were tested approximately 1 year later. At the initial assessment, both groups of patients showed impairment on most of the tests of general intelligence and on several of the tests in the Halstead-Reitan battery, as well as on a test of nonverbal memory, in comparison with healthy controls. At follow-up the patient groups had reached the level of the control group. This study confirmed earlier observations of neuropsychological deficits in long-term benzodiazepine-using patients and demonstrated that these changes are at least partly reversible by discontinuing drug intake. 相似文献
24.
In this article, we will discuss prophylactic submental skin incision-performed after tight mucosal closure-in total laryngectomy; we will suggest means of avoiding incisional breakdown and pharyngocutaneous fistula. 相似文献
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The influence of seven disinfectants on the dimensional stability of a base plate wax, Tenax, was studied. Two methods for treatment were tested - immersion for one hour and spraying respectively. After spraying no significant influence on the wax could be established and after immersion four of the seven disinfectants, including Cidex and K-644, likewise had no significant influence on the dimensional stability. The wax specimens did not show any significant weight increase (less than one per cent) after immersion for four days but in four disinfectant solutions the surface properties of the wax specimens had changed showing that active components of the disinfectants were absorbed into or adsorbed on the wax surface. 相似文献
28.
Consumption of false morel (Gyromitra esculenta Fr.) has been associated not only with acute poisoning, but also with a carcinogenic risk. The hydrolysis of acetaldehyde-N-methyl-N-formylhydrazone (gyromitrin, the main toxic component of false morel) results in the formation of the methylating agents N-methyl-N-formylhydrazine (MFH) and N-methylhydrazine (MMH) (by further hydrolysis of MFH). This study reports traces of N-7-methylguanine (N7MeGu) in liver DNA from mice and a rat treated with gyromitrin. After repeated administration of MMH, N7MeGu was identified in rat liver DNA. In mice exposed to MMH according to a dosing scheme identical to that reported to induce tumours in this species, O6-methylguanine was present in liver and kidney DNA. The results indicate that a relatively low carcinogenic risk is associated with false morel consumption. The risk may be greater in individuals with a decreased detoxification rate (acetylation) of MFH, in whom larger amounts of MMH are formed from gyromitrin. 相似文献
29.
Low urethral pressure and stress urinary incontinence in women: risk factor for failed retropubic surgical procedure 总被引:2,自引:0,他引:2
Nineteen women with stress urinary incontinence (SUI) and low urethral pressure were compared with 106 patients with SUI and normal urethral pressure. All underwent either a revised Pereyra procedure or Burch retropubic urethropexy, and all had detailed clinical and urodynamic evaluations before their operation and one year postoperatively. Surgical procedures effectively stabilized the bladder base and enabled adequate abdominal pressure transmission to the urethra in both groups of women. In spite of these urodynamic findings, the failure rate in women with stress urinary incontinence and low urethral pressure was significantly higher compared with women with good urethral pressure (50% vs 23% for the Pereyra procedure and 33% vs 12% for the Burch procedure [p less than 0.05]), indicating an etiology for their incontinence other than poor support to the urethrovesical junction; therefore, the need for another approach to cure stress incontinence. 相似文献
30.
Interactions of rutaecarpine alkaloids with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver 总被引:1,自引:0,他引:1
Gillner Mikael; Bergman Jan; Cambillau Christian; Gustafsson Jan-Ake 《Carcinogenesis》1989,10(4):651-654
Rutaecarpine alkaloids have the capacity to inhibit specific2,3,7,8-[1,6-3H]tetrachlorodibenzo-p-dioxin (TCDD) binding inrat liver cytosol, as analysed by electrofocusing in polyacrylamidegel. The IC50 value for binding of 7,8-dehydrorutaecarpine wasestimated to 7 nM indicating a high-affinity interaction, whereasrutaecarpine appeared less active (IC50 110 nM). These findingsare of interest in view of the fact that analogues to thesecompounds may be formed following UV-irradiation of tryptophanand that such photo-products have been suggested to constitute(the) endogenous ligand(s) for the TCDD receptor. As furthersupport of this notion, the rutaecarpine alkaloids investigatedcould be fitted into a rectangle of 6.8x13.7 A, a characteristiccommon for most high affinity ligands of the TCDD receptor hithertostudied. In view of their structural similarity to dehydrorutaecarpineand the agreement of their mol. wt with that of the photoproductwith the highest affinity for the TCDD receptor, we suggestdeaza-analogues of dehydrorutaecarpine to represent possiblecandidates for the endogenous TCDD receptor ligand. 相似文献