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  • aging  (2)
  • α-difluoromethylornithine  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Effect of aging on gastric acid secretion, serum gastrin, and antral gastrin content in rats (1988)
    Springer
    Digestive diseases and sciences 33 (1988), S. 1544-1548 
    Details
    ISSN: 1573-2568
    Keywords: aging ; gastric secretion ; gastrin ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to characterize the effects of aging on gastric acid secretion and on serum and antral concentrations of gastrin in rats. Young and old Fischer 344 rats were prepared with gastric fistulas. Twenty-four hours after surgery, graded doses of human synthetic gastrin-17 (SHG-17) (2, 5, 10, 20, and 40 μg/kg) were given intravenously in random order. Gastric secretions were collected for gastric acid measurement before and at 15-min intervals after each dose of gastrin. In a separate study, blood was collected and the stomachs were removed for antral gastrin extraction from fed young and old rats. Serum and antral gastrin was measured by radioimmunoassay. The basal and gastrin-stimulated acid secretions were significantly decreased in aged rats compared to the young rats. The basal acid output was 0.4±0.2 μeq/15 min in the aged rats and 1.5±0.5 μeq/15 min in the young. The maximal acid output stimulated by gastrin was 11.1±1.8 μeq/15 min in the aged rats and 24.2±2.8 μeq/15 min in the young. Both serum and antral concentrations of gastrin were significantly decreased in aged rats. Serum gastrin concentration was 114.8±7.4 pg/ml in the aged rats and 192.0±14.4 pg/ml in the young. Antral gastrin concentration was 3.9±0.5 μg/g tissue in the aged rats, which was significantly less than the concentration in the young (6.5±0.4 μg/g tissue). Antral gastrin content did not change with aging. Gastric acid secretion in aged rats is significantly decreased compared to the young in both the basal condition and in response to fixed doses of exogenous gastrin. Diminished concentrations of circulating gastrin may well be responsible, at least in part, for the diminished acid secretion in the aged rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01535944
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Age-related changes in duodenal adaptation after distal small bowel resection in rat (1993)
    Springer
    Digestive diseases and sciences 38 (1993), S. 410-416 
    Details
    ISSN: 1573-2568
    Keywords: aging ; enterectomy ; disaccharidase ; proliferation ; differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two groups of male Fisher 344 rats (young: 4 months old; aged: 25 months old) underwent either 70% distal small bowel resection or sham operation (small bowel transection). Rats from each treatment group of each age were sacrificed on the 10th (N=15: young rats;N=13: aged rats) or 20th (N=15: young;N=13: aged) postoperative day (POD), and the duodenal mucosa was weighed and assayed for DNA, RNA, and protein contents, as well as for specific activities of the disaccharidase, sucrase, maltase, and lactase. Compared to the sham operation, distal small bowel resection significantly increased DNA by 48%, RNA by 122%, and protein by 75% in young rats and DNA by 40%, RNA by 92%, and protein by 71% in aged rats on the 20th POD. Both young and aged rats showed similar adaptive hyperplasia on the 10th POD. On the 20th POD after distal small bowel resection, specific activities of all tested enzymes were significantly increased in young rats (sucrase +86%, maltase +110% and lactase +64%), but showed no significant changes in aged rats. These findings suggest that the duodenum of aged rats may have sufficient proliferative potential to respond to distal small bowel resection, but that the mechanisms governing return of function in response to distal small bowel resection are inhibited in aged rats, compared to those mechanisms in the young.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01316492
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Cyclosporine and α-difluoromethylornithine exhibit differential effects on colon and pancreatic cancer in vitro (1987)
    Springer
    Investigational new drugs 5 (1987), S. 251-258 
    Details
    ISSN: 1573-0646
    Keywords: cancer ; cyclosporine ; pancreas ; colon ; polyamines ; α-difluoromethylornithine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract α-Difluoromethylornithine (DFMO) is a known irreversible inhibitor of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Cyclosporine (CsA) has been reported to inhibit ODC activity in vitro. In the present study, we compared the effects of DFMO and CsA on growth, survival, and polyamine levels in mouse colon cancer (MC-26) and hamster pancreatic cancer (H2T) cells in vitro. The growth and survival of MC-26 and H2T cells were inhibited by both DFMO and CsA. However, H2T cells were observed to be significantly more sensitive than MC-26 cells to both CsA and DFMO. The inhibitory effects of CsA were blocked by the addition of the polyamine, putrescine, in both MC-26 and H2T cells. Polyamine levels were altered significantly in both MC-26 and H2T cells treated with CsA and DFMO. However, the profile of these alterations differed between MC-26 and H2T cell lines. Putrescine and spermidine levels in MC-26 cells were more sensitive to DFMO inhibition than were H2T cells. Spermine levels were consistently elevated in MC-26 cells exposed to CsA or DFMO, while the level of spermine in H2T cells decreased significantly in response to the same drugs. These results suggest that CsA and DFMO exhibit different effects on colon and pancreatic cancer growth in vitro. In addition, the differences in the sensitivity of pancreatic and colon cancer to CsA and DFMO indicate potentially important differences in polyamine metabolism between the two cell lines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175295
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    2-deoxy-D-glucose inhibits the antitumor effects of α-difluoromethylornithine on the growth of colon cancer in vivo (1989)
    Springer
    Investigational new drugs 7 (1989), S. 131-138 
    Details
    ISSN: 1573-0646
    Keywords: polyamines ; cancer ; 2-deoxy-D-glucose ; α-difluoromethylornithine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has been shown to inhibit the growth of certain cancers. α-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the ratelimiting enzyme in polyamine biosynthesis. DFMO has been shown to inhibit cancer growth in a number of models. The present study was designed to investigate the effects of 2-DG alone and combined with DFMO on MC-26 mouse colon adenocarcinoma tumors growing in vivo. Twenty-eight male Balb/c mice were inoculated with 250,000 MC-26 cells, and then randomized into four groups of 7 each: group I served as control; group II received DFMO (3% in drinking water); group III received 2-DG (500 mg/kg/d IP); group IV received a combination of 2-DG and DFMO. Treatment began 5 days after tumor cell inoculation. MC-26 tumor area was reduced 73% by DFMO compared to a 24% reduction caused by 2-DG. The tumor weight was reduced 80% by DFMO and 52% by 2-DG. The tumor contents of DNA, RNA, and protein were significantly reduced by DFMO but not 2-DG. The tumor concentration of the polyamines putrescine and spermidine were reduced by DFMO alone or combined with 2-DG while spermine levels remained unchanged. 2-DG alone did not alter polyamine levels. These results indicate that both 2-DG and DFMO, when added as single agents, inhibit tumor growth. However, the addition of 2-DG to the DFMO regimen inhibited the antitumor effects of DFMO. Survival studies performed on MC-26 cells in vitro corroborated the antagonisms between DFMO and 2-DG that were shown in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00170849
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    Paper (German National Licenses)
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