Biomedical subjects
Publications and source records attributed to E Seidl.
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The disadvantages of high flexible endoureteral stents (DJ) in case of tumorinduced extrinsic ureteral compression are due to an insufficient vertical stability of the used stents leading to stent-compression and consecutive hydro- or pyonephrosis. The new developed tumor-stent used in case of tumor-induced ureteral compression is available from 6 to 8 French in diameter and 24 to 32 cm in length. The corpus consists of a combination of high-stability plastics but is of sufficient elasticity in length. Both ends consist of extremely elastic J-parts guaranteeing an exact fixation. As against common DJ's with the same outside-diameter the new stent has a comparable interior diameter and compared to used "old" tumor stents promises a higher interior flow in case of extrinsic diseases. The application can be undertaken in well-known technique, needs no special instrumentation and no learning-curve. To date 52 stents at our urologic departments were placed without any problems, the latest remaining for 15 months. Tumor-induced compression or a higher rate of encrustation could not be seen. All patients tolerated these stents well. In our opinion the new stabilized endoureteral stent can be seen as a better solution instead of percutaneous nephrostomy or frequent stent changing in patients with tumor induced extrinsic ureteral compression.
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A number of methoxy-substituted 7,11b,12,13-tetrahydro-6H-dibenzo-[a,f]quinolizines with short alkyl groups in position 6 or 12 were synthesized by the Bischler-Napieralski reaction using the appropriate starting material followed by a second ring closure reaction involving a base-generated benzyne intermediate. The methoxy functions in positions 2 or 3 and 9 were cleaved with BBr3 and the free hydroxy groups converted into the acetates. The enantiomers of two of these derivatives were separated by liquid chromatography on triacetylcellulose. Compounds with alkyl substituents bind strongly to the estrogen receptor except those with a cis-orientation at the central ring connection. The RBA values ranged from 2.2-10.8 (17 beta-estradiol: RBA = 100). There was no major difference in binding between the (+) and (-)-enantiomers. The 3,9-diacetoxy-6-alkyl derivatives also showed binding affinity for the progesterone receptor (RBA: 1.2-3.1). The 2,9-diacetoxydibenzoquinolizines trans-61 and -6m with ethyl and propyl respectively in position 12 strongly inhibited the growth of hormone-sensitive MCF-7 breast cancer cells at concentrations of 10(-6) M and higher but were inactive in hormone-independent MDA-MB 231 breast cancer cells. Preliminary tests with hormone-dependent MXT mouse mammary tumors as model showed that these compounds have also antineoplastic activity in vivo. Derivative trans-61 at a dose of 20 mg/kg body weight, administered 3 times/week, inhibited the growth of these tumors by 78% (tamoxifen: 76% inhibition). Studies on the estrogenic and antiestrogenic properties of these agents in mice revealed that they are mixed agonists/antagonists with strong antiestrogenic activity at low doses but significant estrogenic effects at higher doses.
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Fourteen (2.5 per cent) of 568 chromosome preparations after CVS showed discrepancies between the placental and fetal karyotype, mainly due to placental mosaicism. The presence of a second cell line within the placenta was confirmed in all but one case, in which cytogenetic reinvestigations were carried out. Our clinical data indicate that severe developmental retardation in the newborn is not to be expected if only the placenta carries the chromosomally abnormal cell line.
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The experiments concerned the association of opioid dependence with specific opioid receptors. Previous investigations have demonstrated that tolerance may be confined to only one type of opioid receptor. These findings could suggest that dependence develops invariably only with receptors which have been rendered tolerant. We report here that in the guinea-pig isolated ileum, which has been made selectively tolerant to a mu-receptor agonist, naloxone may precipitate a sign of dependence at mu-receptors chronically activated and at naive kappa-receptors. Furthermore, suppression of the withdrawal contracture in preparations rendered dependent on a mu-receptor agonist can be achieved by very low concentrations of a kappa-agonist, e.g. dynorphin A. These findings challenge the current concept that confines drug dependence only to that opioid receptor type which has been activated chronically.
Opiate dependence attributable to specific types of opiate receptors was studied in the isolated guinea-pig ileum made tolerant/dependent in vivo to a specific narcotic agonist. Apparently, induction of dependence of mu-receptors was associated with dependence of kappa-receptors and vice versa. These investigations involved the use of the irreversible mu-receptor antagonist beta-funaltrexamine to provide preparations with functional kappa-receptors only. The documented cross-dependence between different opiate receptor types suggests a common system with which these opiate receptors interact.
The development of opioid dependence and tolerance attributed to selective types of opiate receptors was studied in the isolated ileum of guinea pigs chronically exposed to specific opioids. These investigations were based on reports that in this preparation highly tolerant opiate receptors may coexist with opiate receptors of almost unchanged sensitivity. Thus, the ilea were set up in vitro and tested for tolerance and dependence. Apparently precipitation of the withdrawal contracture, indicating dependence, proved a more sensitive parameter than the phenomenon of tolerance. Maximal dependence was determined at rather low degrees of tolerance (5 to 10 fold). The intensity of the withdrawal contracture failed to increase as opiate tolerance did. Furthermore, the experiments failed to present evidence for the existence of selective dependence at specific opiate receptor types. These findings may suggest multiple adaptational mechanisms upon chronic activation of opiate receptors. One mechanism may be responsible for the development of dependence and a low degree of tolerance, whilst a further increase of tolerance may be associated with changes at the opiate binding site level.
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In the specific tissue of the rabbit carotid body as well as in the connective tissue surrounding the organ, pO2 distribution was measured with membrane-covered needle electrodes (tip diameter 1-2 microns). The histograms resulting from measurements in the specific tissue were shifted to low pO2 values as compared to other tissues. The oxygen blowing test, i.e. exposure of the carotid body to humidified 100% oxygen was employed to decide upon the site of measurement: pO2 increased when the electrode measured in the surrounding tissue (type 1 response); pO2 remained stable or slightly decreased when the electrode sampled in the specific carotid body tissue (type 2 response). After the experiment, the electrode track was reconstructed from histological serial sections and the type of reaction was related to the type of tissue. Low pO2 values were found to prevail in the specific carotid body tissue, which leads to the conclusion that the amount of low pO2 values determines the degree of chemoreceptor activity.