GLORIA

GEOMAR Library Ocean Research Information Access

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Apoptosis  (1)
  • Calcium channels  (1)
  • 1
    ISSN: 1432-0843
    Keywords: Etoposide ; Topoisomerase II ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A number of clinically important drugs such as the epipodophyllotoxins etoposide (VP-16) and teniposide (VM-26), the anthracyclines daunorubicin and doxorubicin (Adriamycin), and the aminoacridine amsacrine exert their cytotoxic action by stabilizing the cleavable complex formed between DNA and the nuclear enzyme topoisomerase II. We have previously demonstrated in several in vitro assays that the anthracycline aclarubicin (aclacinomycin A) inhibits cleavable-complex formation and thus antagonizes the action of drugs such as VP-16 and daunorubicin. The present study was performed to validate these in vitro data in an in vivo model. At nontoxic doses of 6 and 9 mg/kg, aclarubicin yielded a marked increase in the survival of non-tumor-bearing mice given high doses of VP-16 (80–90 mg/kg) in six separate experiments. In therapy experiments on mice inoculated with Ehrlich ascites tumor cells, aclarubicin given at 6 mg/kg roughly halved the increase in median life span induced by VP-16 at doses ranging from 22 to 33 mg/kg. An attempt to determine a more favorable combination of VP-16 and aclarubicin by increasing VP-16 doses failed, as the two drugs were always less effective than VP-16 alone. The way in which VP-16-induced DNA strand breaks lead to cell death remains unknown. However, VP-16 has been reported to cause apoptosis (programmed cell death) in several cell lines. To ascertain whether the protection given by aclarubicin could have a disruptive effect on the apoptotic process, we used the small intestine as an in vivo model. Whereas VP-16-induced apoptosis in crypt stem cells was detectable at a dose as low as 1.25 mg/kg, aclarubicin given at up to 20 mg/kg did not cause apoptosis. Indeed, aclarubicin caused a statistically significant reduction in the number of cells rendered apoptotic by VP-16. The present study thus confirms the previous in vitro experiments and indicates the value of including an in vivo model in a preclinical evaluation of drug combinations.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 425 (1993), S. 187-189 
    ISSN: 1432-2013
    Keywords: Mesenteric artery ; Resting membrane potential ; Outer cell ; Junctional potential ; Spike ; Calcium channels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Membrane electrical properties of smooth muscle cells at different loci in the vessel wall of rat small mesenteric arteries were studied using glass microelectrodes. Isometric force was measured simultaneously. Penetrations of smooth muscle cells on the adventitial side (outer cells) showed an average resting potential, −43.1±0.8 mV (n=24). In outer cells, numerous depolarizing junctional potentials and, to a lesser degree, hyperpolarizing junctional potentials were observed. When current was injected, electrotonic potentials were recorded. Input resistance was 2.2±0. 1×109 Ω (n=15), suggesting that the low resistance pathways commonly observed in smooth muscle tissue are absent among these cells. Transmural electrical stimulation of nerves elicited spikes and summation of junctional potentials, accompanied by force. TTX virtually abolished these effects of the transmural stimulation. In contrast, cells near the intima (inner cells) had an average resting potential of −65.8±0.9 mV (n=37). No spontaneous electrical activity was observed; nor could electrotonic potentials be recorded. Thus, the smooth muscle cells from the outer layer of rat small resistance arteries differ from the inner cells in their lower membrane potentials, generation of spikes, higher input resistance and innervation. Results also suggest that the influence of nerves may be to facilitate opening of voltagegated Ca2+ channels in innervated cells.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...