Biomedical subjects

Diane M Harris

Publications and source records attributed to Diane M Harris.

5 recordsLinked to original sources

PubMed2003

Intestinal polyp formation in the Apcmin mouse: effects of levels of dietary calcium and altered vitamin D homeostasis.

This study evaluated the effects of various levels of dietary calcium on polyp formation, vitamin D homeostasis, and fecal bile acids in the Apcmin mouse. Female Apcmin mice were randomized to three groups and fed a purified diet with either half or double the level of calcium in control AIN-93G. Serum 25-OH-D and fecal bile acids were measured at weeks 0 and 12 of treatment. Mice were killed for polyp scoring by two observers blinded to treatment after 12 weeks. Results show there was no difference in polyp number or tumor load with dietary calcium in any treatment group. Serum 25-OH-D was reduced and total fecal bile acids were increased in animals that received the high calcium diet. We have previously shown that vitamin D supplementation diminishes polyp load; the lack of effect of an altered calcium diet seen here may be due to a disturbance in vitamin D homeostasis.

Animals↗

PubMed2003

Antidiabetic actions of arachidonic acid and zinc in genetically diabetic Goto-Kakizaki rats.

In previous studies, we showed that feeding arachidonic acid (AA) supplemented with a fixed amount of zinc lowered blood glucose concentrations in the fed state and water intake in rats with streptozotocin-induced diabetes. The present study was designed to determine dose-dependent effects of AA supplemented with a fixed amount of zinc on fed blood glucose levels, water intake, and glucose tolerance in genetically type 2 diabetic Goto-Kakizaki (G-K) Wistar rats. In an acute study, 20 mg/kg AA plus 10 mg/kg zinc administered via gastric gavage significantly improved oral glucose tolerance in G-K rats when compared to rats given distilled water (DW) only. When rats were treated chronically (2 weeks) with increasing doses of AA in drinking water, fed blood glucose concentrations and water intake were maximally decreased with diets containing 20 or 30 mg/L AA plus 10 mg/L zinc. Three-hour average area-above-fasting glucose concentrations (TAFGC; index of oral glucose tolerance) in diabetic G-K rats treated with 10, 20, or 30 mg/L AA plus 10 mg/L zinc for 2 weeks were significantly decreased relative to DW-treated rats. The effect on TAFGC values was maintained for an additional 2 weeks after cessation of treatment. Plasma insulin levels significantly increased in rats treated with 20 mg/L AA only or 10 mg/L AA plus 10 mg/L zinc, but not in rats treated with 20 or 30 mg/L AA plus 10 mg/L zinc, which are the most effective doses for the improvement of clinical signs of diabetes in G-K rats. In in vitro assays, 0.2 mg/mL AA in the incubation media was optimal for glucose uptake in isolated soleus muscle slices. These results suggest that treatment of genetically diabetic G-K rats with AA plus zinc lowers blood glucose levels via improvement of insulin sensitivity.

Animals↗

PubMed2003

Anti-hyperglycemic activity of zinc plus cyclo (his-pro) in genetically diabetic Goto-Kakizaki and aged rats.

We previously reported that treatment of streptozotocin-induced diabetic rats with zinc plus cyclo (his-pro) (CHP) decreased fed blood glucose levels and water intake. The present study was conducted to examine the dose-dependent, acute, and chronic treatment effects of CHP on oral glucose tolerance (OGT), fed blood glucose levels, water intake, and plasma insulin levels in young and aged Sprague-Dawley (S-D) rats, nondiabetic Wistar rats, and genetically diabetic Goto-Kakizaki (G-K) rats. Acute gastric gavage of 10 mg zinc plus 1.0 mg CHP/kg body weight significantly improved OGT in 4- and 13-month-old nondiabetic S-D rats and in 2-month-old diabetic G-K rats. Young S-D and G-K rats returned to pretreatment OGT values 1 week after acute gavage of zinc plus CHP (ZC), but improved OGT values persisted for at least 1 week after gavage in aged S-D rats. OGT values and fed blood glucose decreased to the greatest extent among other treatments when G-K rats were given free access to drinking water containing 1.0 to 1.5 mg CHP/L plus 10 mg zinc/L for 2 weeks. Although food and water intake showed a tendency to decrease, no statistically significant differences were observed in young G-K rats. Plasma insulin levels and blood glucose levels in both normal and diabetic G-K rats decreased with 2-week treatment with ZC. To test the direct effects of ZC on muscle tissue, we observed the effect of various doses of ZC on normal and G-K rat muscle slices. The optimal level of CHP alone for maximal muscle glucose uptake in muscle slices from normal rats was 10 microg/mL and 5.0 microg/mL in G-K rats, and ZC stimulated glucose uptake. However, no statistically significant difference was demonstrated between normal and G-K rat tissues in this study. These results indicate that oral intake of an optimal dose of ZC stimulates blood glucose metabolism, probably by stimulating muscle glucose utilization.

Aging↗

PubMed2003

Gene expression profile of metastatic colon cancer cells resistant to cisplatin-induced apoptosis.

The current chemotherapeutic modalities for advanced colorectal cancer are limited. DNA-platinating drugs such as cisplatin have poor efficacy against this malignancy. The aim of this study was to identify genes that render survival advantage after cisplatin treatment in metastatic colon cancer. Cell lines SW480 (primary colon cancer) and SW620 (metastatic lesion from the same patient) were obtained from ATCC. Apoptosis was measured by FACS analysis of cisplatin-treated (0.01-10 micro g/ml) and untreated cells. Simultaneous analysis of approximately 1200 cDNAs was performed by microarray technique on untreated and treated cells from lines. Microarray results were confirmed by RT-PCR. The SW620 cell line was more resistant to apoptosis induced by cisplatin. Western blot analysis revealed equal expression of pro-caspases 3, 8, and 9 in both cell lines. Microarray analysis identified 15 genes and 9 expressed sequence tags (ESTs) significantly altered both by cell type (metastatic vs. non-metastatic) and treatment vs. non-treatment. Several of these transcripts are well-characterized genes including MCT, GAD67, P19, GSTM3, Cyclin D1, ATM, and CO-029 that have been implicated in various malignancies. In the present study, we have identified a set of genes responsible for apoptosis resistance following treatment with cisplatin in the late stages of carcinogenesis. Targeting these genes may increase chemotherapy effectiveness in advanced colon cancer and reduce toxicity in normal tissue.

Adenocarcinoma↗

PubMed2002

1alpha,25-(OH)(2)-D(3) and its synthetic analogue decrease tumor load in the Apc(min) Mouse.

Both calcium and vitamin D are thought to be able to inhibit colon carcinogenesis. To better define the effects of vitamin D, we studied 1alpha,25-(OH)(2)-D(3) and a noncalcemic synthetic analogue of vitamin D(3) (VD(3)) in the Apc(min) mouse. Female Apc(min) mice 4-5 weeks old were randomized to four groups: a VD(3)-treated group (n = 11) were given injections of 0.01 microg of 1alpha,25-(OH)(2)-D(3) i.p. three times per week; an analogue-treated group (n = 10) received 5 microg of 1alpha,25-(OH)(2)-16-ene-19-nor-24-oxo-D(3) i.p. three times per week; and a control group (n = 12) received sham injections of PBS. A sulindac-treated group (n = 10) was used as a positive control. Doses of these compounds were chosen based on previous toxicity studies in mice and rats. After 10 weeks of treatment, mice were killed and two observers (S. H., R. W. I.), blinded to treatment, scored polyp number and size. Tumor number was not affected with 1alpha,25-(OH)(2)-D(3) or vitamin D analogue administration. A significant decrease in total tumor load (sum of all polyp areas) over the entire gastrointestinal tract was seen in the analogue (36% decrease; P < 0.05) and the VD(3) groups (46%; P < 0.001). There was a significant decrease in polyp number (49%; P < 0.001) and polyp area (70%; P < 0.001) in the sulindac group. Reverse transcription-PCR of the total RNA derived from intestinal tissue revealed expression of the vitamin D receptor throughout the small intestine and the colon. Serum calcium levels in the analogue group were not elevated at week 4 of treatment and only moderately elevated (22%) by week 8 (P < or =0.001). In contrast, serum calcium in the VD(3) group was significantly elevated (P < or =0.001) at weeks 4 (23%) and 8 (45%). Food intake and growth rate were significantly lower in the VD(3) group (26%, P < 0.001, and 27%, P < 0.001, respectively) at week 10. In contrast, food intake and growth rate were similar for the control, sulindac, and analogue groups. Our results indicate that a noncalcemic analogue of vitamin D can significantly decrease intestinal tumor load in Apc(min) mice without severe toxic side effects and suggest that these compounds may have utility as chemopreventive agents in groups at high-risk for colon cancer.

Adenomatous Polyposis Coli↗