Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.26 (invertase)
 4,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incomplete intestinal metaplasia (IM) that is reported to be a risk factor for gastric carcinogenesis in man usually features sulfomucin production and thus is considered of colonic type. To cast light on the underlying mechanisms, we here examined the proportions of colonic and small intestinal phenotypes in IM by immunohistochemistry and real-time reverse transcription-polymerase chain reaction at the single isolated gland level. Carbonic anhydrase 1 (CA1) is a specific marker of colonic epithelial cells, whereas sucrase is specific to absorptive cells of the small intestine. Totals of 139 (23.5%) and 452 (76.5%) IM glands were judged to be CA1 positive and CA1 negative, respectively, in resected pyloric mucosa from cancer patients. The average score for MUC5AC in CA1-positive IMs was significantly lower than in CA1-negative counterpart tissue (P<0.0001), whereas the opposite was the case for sucrase (P<0.0001). High iron diamine-Alcian blue staining revealed CA1 expression to coincide with type I complete IM. The expression of CA1 mRNA strongly correlated with that of sucrase-isomaltase, and inversely with that of MUC5AC in isolated IM glands. In conclusion, CA1 could be colocalized with small intestinal proteins such as sucrase, but only rarely with the gastric mucin, MUC5AC. Its expression warrants further study, with the focus on stimulation and/or suppression mechanisms by gastric and intestinal transcription factors.
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PMID:Expression of small intestinal and colonic phenotypes in complete intestinal metaplasia of the human stomach. 1608 1

Mucositis is a debilitating side-effect of chemotherapy which affects the mucosa of the gastrointestinal tract, particularly the small intestine. Currently there are no simple, noninvasive methods to detect and monitor small intestinal function and the severity of mucosal damage. Activity of the brush-border enzyme sucrase provides an indicator of small intestinal absorptive function that remains relatively constant throughout life. Measuring 13CO2 levels in expired breath following ingestion of 13C-sucrose is a non-invasive marker of total intestinal sucrase activity. We evaluated the sucrose breath test (SBT) as an indicator of small intestinal injury and dysfunction, utilizing a rat model of chemotherapy-induced mucositis. SBT results reflected the time-course of damage and repair after methotrexate (MTX) treatment, with damage most severe 72 h after chemotherapy, and repair commencing after 96 h. SBT results correlated significantly with jejunal sucrase activity determined biochemically (r2= 0.89; p < 0.005). Moreover, calcium folinate ingested prior to chemotherapy totally prevented damage to the small intestinal mucosa induced by MTX, as assessed by the SBT in concert with structural, and biochemical indices. The SBT provides a simple, non-invasive, integrated measure of small intestinal damage and function. The SBT holds significant potential to monitor small intestinal function in cancer patients undergoing chemotherapy. This technique possesses further applicability to the screening of newly-developed agents for potential gastrointestinal toxicity including the development of new therapies targeted at minimising or preventing the onset of chemotherapy-induced mucositis.
Cancer Biol Ther 2006 Jan
PMID:Use of the 13C-sucrose breath test to assess chemotherapy-induced small intestinal mucositis in the rat. 1629 27

Research on cancer and other conditions has shown flavonoids and sphingolipids to be food components capable of exerting chemoprotective action. Nevertheless, little is known about their effects on healthy individuals and their potential usefulness as therapeutic agents. The present study examined the possible action of a dietary flavonoid, quercetin, and a sphingolipid, sphingomyelin, as functional foods in healthy animals. In particular, the effect on animal growth of supplementing a conventional diet with one or other of these substances (0.5 % quercetin and 0.05 % sphingomyelin) was considered. Possible action affecting intestinal physiology was also analysed by measuring the uptake of sugar and dipeptide, mediated by the Na(+)-dependent sugar transporter SGLT1 and the dipeptide Na(+)/H(+) exchanger PEPT1 respectively, and the activity of related intestinal enzymes such as sucrase, maltase and aminopeptidase N. Both substances seemed to modify small intestinal activity in healthy mice, altering intestinal enzymatic activity and nutrient uptake. These effects observed in the small intestine did not impair normal development of the animals, as no differences in serum biochemical parameters or in organ and body weights were found. The findings should help in elucidating the mechanisms of action of these food components with a view to their possible use in the prevention of certain pathological conditions.
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PMID:Effect of dietary quercetin and sphingomyelin on intestinal nutrient absorption and animal growth. 1651 30

Although probiotics are beginning to enter mainstream medicine for disorders of the colon, their effects on the small bowel remain largely unexplored. We investigated the recently identified probiotic, Lactobacillus fermentum (L. fermentum) BR11 (BR11) and the prebiotic, fructo-oligosaccharide (FOS), both individually and in synbiotic combination, for their potential to alleviate intestinal mucositis. From Days 0-9, rats consumed skim milk (SM; saline + SM), low dose (LD-BR11; 1 x 10(6)cfu/ml), high dose (HD-BR11; 1 x 10(9)cfu/ml), LD-FOS (3%), HD-FOS (6%), or synbiotic (HD-BR11/FOS). On Day 7, rats were injected with 5-fluorouracil (5-FU; 150 mg/kg). All rats were sacrificed on Day 10. Intestinal tissues were collected for quantitative histology, sucrase, and myeloperoxidase (MPO) determinations. 5-FU decreased sucrase activity, villus height, crypt depth, and crypt cell proliferation compared to controls. Compared to 5-FU + SM, histological damage severity scores were increased for all treatments, although all were effective at reducing jejunal inflammation, indicated by reduced MPO activity (P < 0.05). The combination of BR11 and FOS did not provide additional protection. Moreover, HD-FOS and the synbiotic actually increased clinical mucositis severity (P < 0.05). We conclude that L. fermentum BR11 has the potential to reduce inflammation of the upper small intestine. However, its combination with FOS does not appear to confer any further therapeutic benefit for the alleviation of mucositis.
Nutr Cancer 2008
PMID:Lactobacillus fermentum BR11 and fructo-oligosaccharide partially reduce jejunal inflammation in a model of intestinal mucositis in rats. 1900 75

Sulforaphane (SF; 4-methylsulfinylbutyl isothiocyanate), a dietary compound derived from broccoli, may exhibit chemopreventive properties by inducing cell cycle arrest via induction of cyclin-dependent kinase inhibitor 1A (p21(waf1/cip1)), but the exact molecular mechanism has not been determined. Here we evaluate the role of the transcription factor Kruppel-like factor 4 (KLF4) in mediating the induction of p21(waf1/cip1) and cellular differentiation by SF and iberin (IB; 3-methylsulphinyl propyl isothiocyanate), also derived from broccoli. Exposure of Caco-2 and Caco-2/TC7 cells to SF and IB increased expression of both KLF4 and p21(waf1/cip1), whereas exposure of HT29 cells resulted only in induction of p21(waf1/cip1). In Caco-2 cells, small interfering RNA knock down of KLF4 expression attenuated induction of p21(waf1/cip1) in response to either SF or IB treatment. Contrary to expectation, prolonged exposure to SF reduced sucrase isomaltase activity, a marker of small intestinal differentiation in Caco-2 cells. Additional support for the SF-mediated induction of p21(waf1/cip1) by KLF4 was obtained from analyses of gastric tissue of Apc(Min/+) mice following acute intervention with SF but not from the analyses of other tissue of the intestinal tract. These results suggest that induction of p21(waf1/cip1) by SF or IB may be partly mediated by KLF4 in some colon cancer cells and tissues.
Nutr Cancer 2009
PMID:Involvement of KLF4 in sulforaphane- and iberin-mediated induction of p21(waf1/cip1). 1911 84

Mucositis is a common and debilitating side effect of chemotherapy that manifests due to the inability of chemotherapy agents to discriminate between normal and neoplastic cells. This results in ulcerating lesions lining the gastrointestinal tract. Moreover, the development of efficacious treatments for small intestinal mucositis has been hindered as the pathobiology of mucositis is still not fully understood. The small intestine is an extensive organ which is largely inaccessible by conventional means. Non-invasive biomarkers such as small intestinal permeability, H(2) breath tests, serum citrulline tests and the (13)C-sucrose breath test (SBT) have emerged as potential markers of small intestinal function. The SBT is emerging as the more appropriate biomarker to assess chemotherapy-induced mucositis in cancer patients and animal models, where it measures the decrease in sucrase activity associated with villus blunting and crypt disruption. The SBT has been successfully applied to detect mucositis induced by different classes of chemotherapy agents and has been used successfully to monitor small intestinal function with a range of candidate anti-mucositis treatments. We propose the SBT a superior biomarker of small intestinal function that could be successfully applied in clinical practice for monitoring the development of mucositis in cancer patients undergoing chemotherapy.
Cancer Biol Ther 2009 May
PMID:Mucositis and non-invasive markers of small intestinal function. 1927 75

There is an acute need for the development of effective therapies for mucositis, a debilitating side effect of cancer chemotherapy. Iberogast is a herbal extract reported to possess anti-inflammatory properties. We investigated Iberogast for its potential to reduce the severity of 5-Fluorouracil (FU)-induced mucositis in rats. Rats were allocated to three treatment groups (n = 8) and gavaged daily with a 10% solution of Iberogast or water from day 0 to day 8. Rats were injected intraperitoneally with 5-FU (150 mg/kg) or saline on day 6, and killed after 72 h. In vivo and in vitro sucrase activity was assessed by (13)C-sucrose breath test (SBT) and sucrase assay respectively. Intestinal disease severity was determined by histological assessment of villus height and crypt depth. Significant increases in villus height (277 +/- 9 microm) and crypt depth (67 +/- 3 microm) were observed in 5-FU + Iberogast-treated rats compared with 5-FU + Water (224 +/- 13 microm and 48 +/- 2 microm respectively; p < 0.05). Sucrase activity was significantly reduced in all 5-FU groups compared to control. Significant reductions in SBT and sucrase activity were observed in all 5-FU groups compared with Saline + Water controls (p < 0.05). We conclude that although Iberogast partially improved the histopathological features of 5-FU induced mucositis, it conferred no significant protection as indicated by the assessed endpoints.
Cancer Biol Ther 2009 May
PMID:The herbal extract, Iberogast, improves jejunal integrity in rats with 5-Fluorouracil (5-FU)-induced mucositis. 1927 79

Mucositis is a common side-effect of high-dose chemotherapy regimens. Grape seed extract (GSE) represents a rich source of proanthocyanidins with the potential to decrease oxidative damage and inflammation within the gastrointestinal tract. We evaluated GSE for its capacity to decrease the severity of chemotherapy-induced mucositis in vitro and in vivo. In vitro: GSE was administered to IEC-6 intestinal epithelial cells prior to damage induced by 5-Fluorouracil (5-FU). Cell viability was determined by neutral red assay. In vivo: Female Dark Agouti rats (130-180 g) were gavaged with 1 ml GSE (400 mg/kg) daily (day 3-11) and received 5-FU (150 mg/kg) by intraperitoneal (i.p.) injection on day nine to induce mucositis. Rats were sacrificed at day 12 and intestinal tissues collected for myeloperoxidase and sucrase activity assays and histological analyses. Statistical analysis was performed by one-way ANOVA. GSE prevented the decrease in IEC-6 cell viability induced by 5-FU (p < 0.01). Compared with 5-FU controls, GSE significantly reduced myeloperoxidase activity by 86% and 27% in the proximal jejunum (p < 0.001) and distal ileum (p < 0.05) respectively; decreased qualitative histological scores of damage (p < 0.05) in the proximal jejunum; increased villus height in the proximal jejunum (17%; p < 0.05) and distal ileum (50%; p < 0.01), and attenuated the 5-FU-induced reduction of mucosal thickness by 16% in the jejunum (p < 0.05) and 45% in the ileum (p < 0.01). GSE partially protected IEC-6 cells from 5-FU-induced cytotoxicity and ameliorated intestinal damage induced by 5-FU in rats. GSE may represent a promising prophylactic adjunct to conventional chemotherapy for preventing intestinal mucositis.
Cancer Biol Ther 2009 Feb
PMID:Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis. 1930 41

Beneficial bacteria (probiotics) and probiotic-derived factors have the potential to ameliorate disorders of the intestine. The aim of this study was to compare live Streptococcus thermophilus TH-4 (TH-4), dead TH-4 and TH-4 supernatant in rats treated with 5-Fluorouracil. Rats were randomly allocated to five treatment groups (n=8-10): Saline+Water; 5-FU+Skim Milk; 5-FU+Live TH-4; 5-FU+Supernatant TH-4; and 5-FU+Dead TH-4. 5-FU (150mg.kg(-1)) was administered by a single intraperitoneal injection on day 0; animals were killed on day 4. Treatments were administered daily from days -2 to 3 via oro-gastric gavage. Metabolic parameters were measured daily. Blood was obtained by cardiac puncture, and intestinal tissues removed for quantitative and qualitative histological assessment, including: villous height and area; crypt depth and area, mitotic count and crypt fission; biochemical determination of sucrase and myeloperoxidase (MPO) activity; and disease severity scoring. One-way ANOVA statistical analyses were conducted for the majority of outcome measures. Live TH-4 significantly reduced disease severity score by 13% (p< 0.05), and partially normalised mitotic counts compared with 5-FU+Skim milk controls. Live and supernatant TH-4 reduced crypt fission by 69% and 48% (p< 0.05), respectively, compared to 5-FU+Skim Milk controls. No significant differences (p> 0.05) in the occurrence of bacteraemia were evident across all groups. Live TH-4 partially normalised mitotic count and histological severity score in 5-FU treated rats. The inhibitory effect of live TH-4 and TH-4 supernatant on crypt fission suggests therapeutic utility in the prevention of disorders characterised by increased crypt fission, such as colorectal carcinoma.
Cancer Biol Ther 2009 Mar 15
PMID:Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent, 5-Fluorouracil (5-FU). 1930 60

Mucositis resulting from cancer chemotherapy is a serious disorder of the alimentary tract. Emu oil has demonstrated anti-inflammatory properties in animal models of arthritis and wound healing; however, its effects on the intestine remain unknown. We investigated emu oil for its potential to decrease the severity of mucositis in a rat model. Female Dark Agouti rats (110-150 g) were orogastrically gavaged with emu oil (0.5 or 1 ml) or water (1 ml) for 5 d before intraperitoneal injection of 5-fluorouracil (5-FU, 150 mg/kg) or saline (control), and this was continued up to the day of sacrifice (48, 72 and 96 h post 5-FU administration). Histological (villus height, crypt depth (CD) and disease severity score) and biochemical (myeloperoxidase (MPO) activity) parameters were determined in intestinal tissues collected at sacrifice. Sucrase activity in vivo was quantified by the sucrose breath test. Activated neutrophil activity (MPO) in the ileum was significantly decreased by emu oil (0.5 ml, 451 (sem 168) U/g and 1 ml, 503 (sem 213) U/g) compared with 5-FU-treated controls (1724 (sem 431) U/g) 96 h post 5-FU administration. There were also significant increases in CD (152 (sem 8) microm) in the ileum of rats that received 1 ml emu oil at 96 h compared with 5-FU-treated controls (CD (106 (sem 12) microm)). Emu oil did not affect sucrase activity. Emu oil decreased acute ileal inflammation, and improved mucosal architecture in the intestine during recovery from chemotherapy in rats. Further studies investigating the potential benefits of emu oil as a nutritional supplement for the treatment of intestinal disorders are indicated.
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PMID:Orally administered emu oil decreases acute inflammation and alters selected small intestinal parameters in a rat model of mucositis. 2037 26


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