Biomedical subjects

C M Townsend

Publications and source records attributed to C M Townsend.

At least 109 records · Page 6Linked to original sources

PubMed1993

Comparative effects of neurotensin and neuromedin N on growth of human pancreatic cancer, MIA PaCa-2.

Neurotensin (NT), an important regulatory hormone of the gut, stimulates growth of the human pancreatic cancer cell line MIA PaCa-2 in vitro. The purpose of our study was to compare the stimulatory effects of NT and neuromedin N (NMN), a structurally related hexapeptide, on the growth of MIA PaCa-2. In addition, the effects of NT on the growth of MIA PaCa-2 xenografts and normal GI tissues were assessed in athymic nude mice. MIA PaCa-2 cells, plated in serum-free media, were treated with either NT (10(-12)-10(-6) M) or NMN (10(-11)-10(-7) M) and cells were counted. For the in vivo study, MIA PaCa-2 cells were inoculated sc into 30 athymic nude mice and then randomized to two groups to receive either NT (600 micrograms kg-1, sc, tid) or vehicle. At sacrifice (day 35), the xenografted tumours, as well as normal host pancreas, jejunum and ileum were removed, weighed, and assayed for DNA, RNA and protein. Both NT and NMN stimulated the growth of MIA PaCa-2 cells in vitro with maximal (approximately 30%) increases occurring with dosages of 10(-9) M. In vivo, NT had a transient effect on xenografted MIA PaCa-2 tumour area with increases noted on days 21 and 25 of the study. Conversely, NT significantly stimulated the growth of jejunum and ileum, with a more pronounced effect noted in the jejunum. NT and NMN have similar growth-stimulatory effects on MIA PaCa-2 cells in vitro, which suggests an interaction through the same receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Neurotensin regulates growth of human pancreatic cancer.

OBJECTIVE: The effect of neurotensin (NT) on in vitro-growth of human pancreatic cancer cells (MIA PaCa-2) was examined. Furthermore, the intracellular signal-transduction pathways by which neurotensin regulates growth of MIA PaCa-2 cells were determined. SUMMARY BACKGROUND DATA: NT is trophic for normal rat pancreas, but the effect of NT on growth of human pancreatic cancer is not known. METHODS: Effects of NT (10(-12) to 10(-6) mol/l) on growth of MIA PaCa-2 cells were determined by both count of cell numbers and 3H-thymidine incorporation. Action of NT on phosphatidylinositol (PI) hydrolysis, cyclic AMP production, and intracellular calcium level were determined by conventional methods. The effects of 8-bromo-cyclic AMP and prostaglandin E2 on cell growth were determined. RESULTS: Low concentrations of NT (10(-12) to 10(-9) mol/l) stimulated growth in a dose-dependent manner, but higher concentrations of NT (10(-8) to 10(-6) mol/l) did not stimulate growth of MIA PaCa-2 cells. NT (10(-12) to 10(-6) mol/l) stimulated PI hydrolysis and increased intracellular calcium levels in a dose-dependent manner. High concentrations of NT (10(-8) to 10(-6) mol/l) stimulated production of cyclic AMP in a dose-dependent manner. 8-bromo-cyclic AMP inhibited growth of MIA PaCa-2 cells; prostaglandin E2 did not affect growth of MIA PaCa-2 cells. CONCLUSIONS: NT stimulates growth of MIA PaCa-2 cells through stimulation of PI hydrolysis and mobilization of calcium. Stimulation of the cyclic AMP pathway by high concentrations of NT abolishes the growth-stimulatory effect of NT that is mediated through PI hydrolysis or calcium mobilization.

Calcium↗

PubMed1993

Developmental expression of the neurotensin gene in the rat liver.

OBJECTIVE: This study determined whether the neurotensin gene is expressed during early development of the liver. SUMMARY BACKGROUND DATA: Neurotensin (NT), a gut tridecapeptide localized mainly to the distal small bowel and brain of adults, is an important hormone regulating gut motility, secretion and mucosal growth. Expression of NT peptide and the gene is found in fibrolamellar hepatocarcinomas, a variant of hepatocellular carcinoma, but not in the normal adult liver. METHODS: Northern and in situ hybridization techniques were used to determine expression of the neurotensin gene (NT/N) in the normal developing liver. RESULTS: NT/N is expressed in the fetal and early postnatal rat liver, but expression is repressed in the liver of the adult. In situ hybridization confirms the authors' Northern data and demonstrates a random distribution of NT/N expression in the fetal and 3-day postnatal liver. CONCLUSIONS: The authors conclude from this study that NT/N is expressed during early development of the rat liver with subsequent repression in the adult. NT/N may be reexpressed with malignant transformation of the liver.

Age Factors↗

PubMed1993

The effect of endogenous cholecystokinin released by bombesin and trypsin inhibitor on the regeneration of the pancreas.

OBJECTIVE: This study examined the effects of endogenous cholecystokinin (CCK) released by bombesin and FOY-305 (a synthetic inhibitor of trypsin on pancreatic regeneration in rats). SUMMARY BACKGROUND DATA: Trophic gut hormones (CCK and bombesin) stimulate the growth of the normal rat pancreas. However, the influence of endogenous gut hormones on pancreatic regeneration is unclear. METHODS: Male Fisher rats (n = 6 to 8 per group) were fed a protein-free diet and given ethionine (700 mg/kg intraperitoneally daily) for 8 to 9 days to induce degeneration of the pancreas. Regeneration was stimulated by giving the rats a regular chow diet. The effects of bombesin (10 micrograms/kg three times a day for 7 days) or FOY-305 (200 mg/kg daily for 8 days) on the process of regeneration were examined. RESULTS: At the end of the degeneration phase, there was near-total destruction of pancreatic acinar cells. Both bombesin and FOY-305 stimulated pancreatic regeneration. Growth measurements (weight and total content of DNA and protein) were significantly increased (p < 0.05) in the bombesin- and FOY-305-treated rats compared with controls. Histologic examination revealed widespread repopulation of the pancreas with acinar cells in the bombesin- and FOY-305-treated groups. The stimulating effects of both bombesin and FOY-305 on pancreatic regeneration were blocked completely by the CCK-receptor antagonist L-364,718. Growth measurements were not significantly increased in the groups of control rats or rats given L-364,718 alone. CONCLUSIONS: These results show that bombesin and FOY-305 significantly stimulated pancreatic regeneration. Because the stimulating effects of bombesin and FOY-305 on regeneration were blocked by the specific CCK-receptor antagonist L-364,718, it was concluded that this effect was mediated by endogenous CCK.

Animals↗

PubMed1993

Cortivazol increases glucocorticoid receptor expression and inhibits growth of hamster pancreatic cancer (H2T) in vivo.

Glucocorticoids are effective in the treatment of certain leukemias and lymphomas, but their effects on the growth of several solid tumors have not been determined. We report here that cortivazol (CVZ), a potent synthetic glucocorticoid, inhibits the growth of a hamster pancreatic adenocarcinoma, H2T, in vivo. CVZ regulation of glucocorticoid receptor (GR) expression was followed as a specific molecular correlate. H2T cells were injected into cheek pouches of male Syrian golden hamsters, where they formed readily measurable tumors. Two studies were performed. In the first, hamsters were randomized to three groups immediately after injection of tumor cells: control, CVZ (0.1 micrograms/g body wt), or CVZ (0.3 micrograms/g body wt). Injections of either CVZ or its vehicle were administered on a 14-day cycle of 5 treatment days, followed by 9 days off treatment. Tumors were measured and areas calculated weekly. On day 48, the hamsters were killed and the tumors excised, weighed, and analyzed for DNA, RNA, and protein content. In the second study, randomization and treatment schedule were as before, except that on day 33 the hamsters were killed, tumors were excised and weighed, and total RNA from the tumors was isolated. GR mRNA content was determined by filter hybridization with a 32P-labeled GR cDNA probe, and the signal normalized by reprobing for alpha-tubulin as an invariant, independent signal. At either dose, CVZ significantly inhibited H2T tumor area and weight and DNA, RNA, and protein content. Body weights of animals treated with CVZ were not significantly decreased as compared with controls. In addition, GR mRNA in H2T cells was increased approximately twofold by CVZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1993

Radioimmunoimaging of xenograft pancreatic cancer with 131I-monoclonal antibody P2.

Monoclonal antibodies (McAbs) to pancreatic cancer were developed by fusing SP2/0 cells and splenocytes from Balb/c mice immunized with CH-2 cells. The specific binding rates of McAb P1 and P2 were 40.1 and 43.8%, respectively, shown by binding radioreactivity assay in vitro, which were in sharp contrast with those of control groups (p < 0.05). The biodistribution of radioiodinated McAb P2 was studied by measuring parameters of tumor-specific radioreactivity in nude mice bearing CH-2 tumors. The ratios of tumors to nontumors were all > 2 at 48 h. The localization index of cancer and the ratio of tumor to pancreas were 4.05 and 4.16, respectively, at 72 h. Therefore, 131I-McAbs may be useful for radioimmunoimaging (RII) of pancreatic cancer. After intraperitoneal injection of 131I-McAb P2 into tumor-bearing nude mice, imaging of xenograft pancreatic cancer became increasingly distinct with the nonspecific background fading, especially in the period of 72-96 h. Examination of pancreatic cancer tissues by immunohistochemical methods revealed that McAb P2 was strongly positive (86%) in comparison with other tumors and normal tissues. The results demonstrated that clinical RII of pancreatic cancer was feasible with McAb P2.

Animals↗

PubMed1993

Successful intracerebroventricular allotransplantation of parathyroid tissue in rats without immunosuppression.

The lateral ventricle of the brain may be an immunoprivileged site for viable allografts. Allotransplanted parathyroid tissue from histoincompatible ACI rats survived and remained functional for more than 3 months in the cerebroventricles of recipient F344 rats. Microscopic examination proved that the allotransplanted parathyroid tissues retained normal histological features. In sharp contrast, when the parathyroid was placed beneath the renal capsule the allografted parathyroid tissue uniformly lost its capacity to liberate parathyroid hormone within one month, and only residual scar tissue remained at the transplantation site. After allotransplantation of parathyroid tissue into the cerebroventricle, the serum concentrations of both Ca++ and parathyroid hormone were maintained at levels similar to those before parathyroidectomy, until the time of sacrifice. During the 3-month period of post-transplantation observation, no neurological symptoms were noted in any of the F344 rats.

Animals↗

PubMed1993

Effects of FK506 and cyclosporine on dynamic insulin secretion from isolated dog pancreatic islets.

Pancreatic islet transplantation may be the most ideal treatment for patients with insulin-dependent diabetes mellitus. However, immunosuppressive agents such as cyclosporine A(CsA) and FK506, used for these transplanted patients have been reported to cause glucose intolerance. In the present study, we have compared the effects of CsA and FK506 on glucose-stimulated insulin release from the isolated dog pancreatic islets, which have been maintained in culture for 3 days after isolation. The isolated dog pancreatic islets, pretreated for 24 hr with either CsA or FK506 (1, 10, and 100 nM), were perifused with 16.7 mM glucose. Pretreatment with both drugs suppressed glucose-stimulated insulin secretion in a dose-dependent fashion. CsA (100 nM), which is a therapeutically relevant concentration, significantly suppressed both the first and second phases of glucose-stimulated insulin release compared with 100 nM FK506. These findings suggest that, with a therapeutically relevant concentration, FK506 may be less toxic than CsA against pancreatic islets in patients with organ or cell transplantation.

Animals↗

PubMed1993

Differential expression of the neurotensin gene in the developing rat and human gastrointestinal tract.

Neurotensin (NT) is an important hormone regulating gut motility, secretion, and growth. The purpose of this study was to determine the developmental expression of the NT/neuromedin N gene (NT/N) in the gut and pancreas of rats and humans. We found that NT/N expression, initially low in the fetal rat jejunum and ileum, is increased by postnatal day 3. This increase is independent of contact with luminal nutrients as demonstrated by elevated NT/N expression in rat jejunoileal grafts implanted in nude mice. NT/N expression reaches maximal levels in the small bowel by postnatal day 14. After postnatal day 28, NT/N mRNA levels remain constant in the ileum but decrease in the jejunum. Transient NT/N expression is found in the colon of fetal and postnatal rats. Similar to the rat, NT/N expression is low in the human fetal ileum but increases in the adult. In the human colon, NT/N is transiently expressed in the fetus at midgestation but disappears by birth and, similarly, is not apparent in the adult. We conclude the following. 1) The NT/N gene demonstrates a complex pattern of tissue-specific expression; the jejunum and ileum show a similar pattern of expression until the end of the fourth postnatal week, when NT/N levels decrease in the jejunum to assume the distinctive adult topographical distribution with NT/N increasing along the jejunoileal axis. 2) NT/N is transiently expressed in the colon of rats and humans during a developmental stage characterized by morphological and functional similarities to the small bowel; therefore, NT/N may provide a useful endocrine marker to further define the complex differentiation pathway leading to small bowel and colonic phenotypes.

Adult↗

PubMed1993

Parathyroid hormone-related peptide production and action in a myoepithelial cell line derived from normal human breast.

Physiological roles for PTH-related peptide (PTHrP) appear varied, but remain to be clarified. The peptide is present in large amounts in milk, and PTHrP mRNA has been shown to be present in high amounts in lactating mammary gland. Because PTHrP can cause smooth muscle relaxation, we hypothesized that the peptide might affect the contractility of the breast myoepithelial cell and thereby affect milk ejection. To test this idea, we asked whether PTHrP might affect second messenger responses in a human mammary gland myoepithelial-cell line (Hs578Bst) derived originally from normal breast tissue. To verify the presumed origin of these cells, we also examined the effects of oxytocin. Cells were grown in culture in multiwell plates and exposed to test peptides for 15 min in buffer containing 1 mM isobutylmethylxanthine, and intracellular cAMP was measured by RIA. Both PTHrP-(1-34) and PTH-(1-34) increased cAMP in a dose-related fashion (ED50, 5 nM), with a maximal effect (3-fold) occurring at 100 nM. The ability of PTHrP to stimulate cAMP was inhibited by a 10- to 100-fold molar excess of the specific inhibitors, PTH-(3-34) or PTHrP-(7-34). Inhibitors alone did not alter cAMP. Oxytocin also produced an increase in cAMP, but the effect was inconsistent and occurred only with high doses (0.1-1 microM). Using cells grown on coverslips and loaded with fura-2AM, intracellular Ca2+ was monitored in cells exposed to test peptides. Oxytocin (0.2-20 nM) produced rapid dose-related increases in intracellular Ca2+, with a peak and plateau characteristic of initial mobilization of intracellular Ca2+, followed by entry of extracellular Ca. The plateau was eliminated by the Ca channel antagonist La3+ or by perfusion of cells with Ca-free medium. PTHrP (10-100 nM) altered the intracellular Ca2+ response to oxytocin in 66% of 39 preparations tested. PTHrP inhibited the Ca2+ response when given before oxytocin or transiently decreased the plateau phase of the Ca2+ response when given after oxytocin. Analysis of cellular mRNA using reverse transcription polymerase chain reaction indicated that these cells express the gene for PTHrP, and immunohistochemistry using antiserum to PTHrP revealed positive staining of cells. Measurement of immunoreactive PTHrP in conditioned medium confirmed that these cells can synthesize and secrete the peptide. The finding of a response of this cell line to oxytocin provides functional evidence of their myoepithelial derivation.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗

PubMed1993

Studies of growth regulation in a neuroendocrine cell line.

Studies of growth-regulation of neuroendocrine cells have been hampered by a lack of suitable in vitro models. We established and have maintained a functioning human pancreatic carcinoid cell (BON) line. BON cells synthesize and secrete several growth factors. Among those, we have found that serotonin stimulates growth of BON cells through specific receptors linked to cyclic AMP pathway. In this study, effects of other growth factors on growth and serotonin release, and the effects of serotonin and TGF-beta 1 on the polyamine biosynthetic pathway, were examined. TGF-beta 1 inhibited both growth and serotonin release in a dose-dependent fashion. Basic FGF stimulated growth, but failed to affect serotonin release. Other peptide growth factors had no effect on either growth or serotonin release. Serotonin stimulated ODC enzyme activity, but TGF-beta 1 failed to affect ODC enzyme activity. These findings suggest that growth of neuroendocrine cells can be delicately regulated by their own products in an autocrine fashion.

Adult↗

PubMed1993

Persistence of the circadian variation and altered response to hepatectomy of hepatic ornithine decarboxylase activity with malignant tumor burden.

We measured the effect of MC-26 mouse colon cancers (of different sizes) on the circadian rhythm of hepatic ornithine decarboxylase (ODC) activity and hepatic ODC activity during the 24 hr after 60% hepatectomy. Tumor-free control mice showed a normal circadian rhythm of ODC activity with the highest levels at 1100 hr and the lowest levels at 2300 hr. The amplitude of the rhythm was diminished significantly in mice with a large tumor burden (3% of their body weight), and hepatic ODC activity was significantly less than in the tumor-free mice at every point during the 24 hr of the study. In mice with "early" tumors (0.3% of body weight), basal activity of ODC was normal and there was no reactive increase in activity following hepatectomy. In contrast, mice with "late" (3% of body weight) tumors had significantly lower basal ODC activities and the increase in ODC activity following hepatectomy was prolonged and exaggerated. We concluded that tumor burden is associated with abnormal ODC activity and that these differences are exaggerated after hepatectomy. Furthermore, although average ODC concentrations in tumor-bearing mice fell precipitously, the circadian rhythm in hepatic ODC persisted. This finding indicates early recognition by the host of tumor presence, which has a profound negative regulatory effect on hepatic ODC. Apparently, this effect does not impinge on circadian control mechanisms, indicating that these signals act independently.

Animals↗

PubMed1993

Glutamine is essential for epidermal growth factor-stimulated intestinal cell proliferation.

BACKGROUND: Glutamine stimulates growth of intestinal mucosa in vivo, but the mechanisms involved are unknown. The purpose of this study was to determine whether glutamine is essential for proliferation of enterocytes stimulated by epidermal growth factor (EGF). In addition, we determined which specific mitogenic actions of EGF require glutamine. METHODS: A nontransformed rat intestinal mucosal cell line (IEC-6) was stimulated with EGF (20 ng/ml) without and with glutamine (0.1 to 10 mmol/L). DNA, RNA, and protein synthesis were quantitated by determining incorporation of tritiated thymidine, tritiated uridine, and 14C-leucine, respectively. Cell numbers and messenger RNA levels of early growth response genes (zif268, jun-B, c-myc) were also determined. RESULTS: Glutamine was required for EGF stimulation of DNA, RNA, and protein synthesis and cell replication; however, EGF-stimulated expression of zif268, jun-B, and c-myc occurred in the absence of glutamine. CONCLUSIONS: This study showed that glutamine is essential for EGF-stimulated intestinal mucosal cell proliferation. The mitogenic effects of EGF can be divided into the glutamine-independent, such as the signal transduction pathway leading to the induction of early growth response genes, and the glutamine-dependent, including DNA, RNA, and protein synthesis.

Animals↗

PubMed1993

New experimental model of proximal and distal colon transposition in rats.

The proximal and distal portions of the colon have different morphologic and histochemical features. To ascertain whether these features are genetically or environmentally determined, we attempted to develop a transposition model of the proximal and distal portions of the colon in rats. Four-month-old male Fisher 344 rats were used. Four centimeters of the proximal colon segment circulated by the right colonic artery and 4 cm of the distal colon segment circulated by the middle colic artery were interchanged isoperistaltically. In the control group, the colon was transected and reanastomosed. All rats tolerated the surgery and maintained good condition for 4 weeks, when they were euthanized. No differences in body weight and food intake were observed between the transposition and control groups. Macroscopic appearance of the stomach and small intestine was normal in both the transposition and control groups, but the cecum was dilated and the new proximal portion of the colon was slightly dilated in the transposition group. This new experimental model will be helpful in examining the mechanism by which different features of the proximal and distal portions of the colon are derived. It will also assist in the research of carcinogenesis in the colon, in determining why the distal portion of the colon is more susceptible to carcinogens, compared with the proximal portion of the colon.

Animals↗

PubMed1992

Unexpected growth-stimulatory effect of somatostatin analogue on cultured human pancreatic carcinoid cells.

Therapeutic efficacy of a synthetic somatostatin analogue for the treatment of carcinoid tumors is still controversial. In vivo studies performed in our laboratory showed that a somatostatin analogue, SMS 201-995, significantly inhibited growth of human pancreatic carcinoid (BON) tumors xenotransplanted into athymic nude mice. In the present study, however, SMS 201-995 did not inhibit in vitro growth of BON cells, but rather SMS 201-995 stimulated growth in a dose-dependent fashion. The growth-stimulatory effect was likely mediated through the reduction of cyclic AMP production. Unsuccessful treatment of certain types of carcinoid tumor with SMS 201-995 may be partly due to the direct growth-stimulatory effect of SMS 201-995 on carcinoid cells.

Carcinoid Tumor↗

PubMed1992

Receptor-mediated autocrine growth-stimulatory effect of 5-hydroxytryptamine on cultured human pancreatic carcinoid cells.

5-hydroxytryptamine (5-HT) is a mitogen for fibroblasts, vascular smooth muscle cells, renal mesangial cells, and jejunal crypt cells. The human carcinoid cell line (termed BON) that we established in our laboratory from a pancreatic carcinoid tumor produces and secretes 5-HT. In this study, therefore, we examined the effect of 5-HT on growth of BON cells. Furthermore, by use of selective 5-HT receptor antagonists, we examined receptor and post-receptor mechanisms by which 5-HT-induced responses were produced. 5-HT stimulated growth of BON cells. 5-HT stimulated phosphatidylinositol (PI) hydrolysis in a dose-dependent fashion and inhibited cyclic AMP production in a dose-dependent fashion. The 5-HT1A/1B receptor antagonist, SDZ 21-009, prevented the reduction of cyclic AMP production evoked by 5-HT and inhibited the mitogenic action of 5-HT. The 5-HT1C/2 receptor antagonist, mesulergine, competitively inhibited PI hydrolysis, but did not affect the mitogenic action of 5-HT. The mitogenic action of 5-HT and the reduction of cyclic AMP production evoked by 5-HT were also inhibited by pertussis toxin. These results suggest that 5-HT is an autocrine growth factor for BON cells and that mitogenic mechanism of 5-HT involves receptor-mediated inhibition of the production of cyclic AMP which may be linked to pertussis toxin-sensitive GTP binding protein. 8-bromo-cyclic AMP inhibited growth of BON cells whereas 8-bromo-cyclic GMP had no effect on cell growth. Involvement of protein kinase A in BON cell growth regulation was confirmed by the observation that a cAMP-dependent protein kinase antagonist (Rp-cAMPS) could stimulate BON cell growth.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1992

Neurotensin prevents intestinal mucosal hypoplasia in rats fed an elemental diet.

Liquid elemental diets are associated with mucosal hypoplasia of both the small intestine and colon. Neurotensin, a tridecapeptide widely distributed in the gut, is trophic for the small intestine of rats fed a normal chow diet. The purpose of this study was to determine whether neurotensin could reverse the hypoplasia of intestinal mucosa that is associated with feeding a liquid elemental diet. Forty male Sprague-Dawley rats were randomized into five groups. Four groups were fed (for seven days) a glutamine-free liquid elemental diet. Subcutaneous injection of saline (control) or neurotensin (33, 100 or 300 micrograms/kg) were given to the groups of rats every 8 hr for seven days. Group five (Chow) received rat chow ad libitum for seven days. Rats were killed on day 8, and the proximal jejunum, distal ileum, and proximal colon removed. Mucosal weight, DNA, RNA, and protein contents were determined. Neurotensin (300 micrograms/kg) increased the cellularity of the small intestinal mucosa and reversed mucosal hypoplasia due to an elemental diet; a more pronounced effect was noted in the jejunum compared to the ileum. Neurotensin (33 and 100 micrograms/kg) increased mucosal DNA content in the jejunum but was not effective in reversing the hypoplasia. Neurotensin had no effect on growth of colonic mucosa. These results suggest that neurotensin may be an important trophic hormone for the small intestine. Administration of neurotensin may alleviate hypoplasia of the small bowel mucosa and maintain functional integrity of the gut during prolonged feeding of an elemental diet.

Animals↗

PubMed1992

Burn-induced transcriptional regulation of small intestinal ornithine decarboxylase.

The mechanisms responsible for gut repair after burn injury have not been established. Polyamines are required for eukaryotic cell growth and differentiation. The enzyme ornithine decarboxylase (ODC) catalyzes the rate-limiting step in polyamine biosynthesis. The role of ODC activity in repair of injured small bowel mucosa after burns has not been investigated. This study examined the effects of burn injury on gut mucosal mass and regulation of ODC gene expression and ODC activity in small bowel mucosa. After an overnight fast, 18 male Sprague-Dawley rats (250 to 300 g) were randomized into sham, 20% burn, or 60% burn groups. We measured ODC activity, mucosal weight, deoxyribonucleic acid (DNA) content, and protein content in proximal and distal small bowel mucosa at postburn intervals of 0, 3, 12, 24, and 48 hours. Gut mucosal ODC messenger ribonucleic acid (mRNA) levels were determined. Burn injury caused significant atrophy of the gut mucosa by 12 hours postburn; restoration was evident by 48 hours after burn. ODC activity was increased in the proximal small bowel at 12 and 24 hours after burn in the rats in both the 20% burn and 60% burn groups; by contrast, only rats in the 60% burn group had increased ODC activity in the distal small bowel. ODC mRNA levels increased in the proximal gut mucosa as early as 3 hours after the burn and returned to control values after 24 hours. These data show that mucosal restoration begins soon after burn injury and that the induction of ODC mRNA and ODC activity are important events.

Animals↗