Myenteric Denervation Downregulates Galectin-1 and-3 Expression in Gastric Carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Endogenous carotenoid concentrations in cancerous and non-cancerous tissues of gastric cancer patients in Korea

Carotenoid concentrations were measured in serum and in both non-cancerous and cancerous gastric mucosal tissues of Korean patients with gastric cancer (n = 18). Carotenoids in serum and gastric tissue were extracted with chloroform/methanol (2:1), and measured using reverse-phase high-performance liquid chromatography with a C30 column. Cryptoxanthin and β-carotene were the major carotenoids in the Korean blood and they had a median ratio of non-cancerous tissue/serum levels which was less than 1.0. No significant differences of Cryptoxanthin and β-carotene levels were found between non-cancerous and cancerous tissues. After incubation of β-carotene with gastric tissue, significantly higher levels of β-carotene breakdown products were produced in the homogenates of cancerous tissue when compared with non-cancerous tissue. Lutein, zeaxanthin and α-carotene were the minor carotenoid constituents in the blood and their median ratio of non-cancerous tissue/serum levels was greater than 1.0. Cancerous tissue had significantly lower levels of lutein, zeaxanthin and α-carotene than did non-cancerous tissue. It appears that the increased breakdown of β-carotene and cryptoxanthin in cancerous tissue can be compensated for by an increased uptake of circulating carotenoids by cancerous tissue, whereas lutein, zeaxanthin and α-carotene levels in cancerous tissue are not able to be maintained.

Anti-ulcerogenic and analgesic activities of the leaves of Wilbrandia ebracteata in mice

Wilbrandia ebracteata (Cogn.) Cogn. is a medicinal plant belonging to the Cucurbitaceae family used popularly as an antiulcer and analgesic medicine. The hydromethanol extract of leaves was investigated to determine its anti-ulcerogenic (ethanol and indomethacin induced gastric damage) and analgesic (writhing and tail-flick tests) activities in mice (efficacy), its acute toxicity (safety), and its phytochemistry (quality control). Oral administration of leaf extract at a dose of 1000 mg/kg body wt. significantly reduced 73.3% of the total area of lesion in ethanol-induced gastric damage, but was inactive in an indomethacin-induced gastric damage test. The hydromethanol extract was also inactive in both analgesic tests. Oral administration of the leaf extract did not produce mortality in mice, while the LD50 value of the roots was 22.10 mg/kg body wt. in female mice and 58.31 mg/kg body wt. in male mice. Leaves of W. ebracteata reacted positively for steroids, flavonols, flavanones, saponins, tannins and xanthones and negative for other compounds, including cucurbitacins. Leaf extract of W. ebracteata was active as an anti-ulcerogenic, probably through increasing gastric defensive factors, and flavonoids might be the main constituent responsible for this activity.

GSTT1, GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Evaluation of Strychnos pseudoquina St. Hil. leaves extract on gastrointestinal activity in mice

Strychnos pseudoquina St. Hil. (Loganiaceae) was investigated for its ability to protect the gastric mucosa against injuries caused by non-steroidal anti-inflammatory drugs (piroxicam) and a necrotizing agent (HCl/EtOH) in mice. The MeOH extract and enriched alkaloidic fraction (EAF) provided significant protection in experimental models wheer used at doses of 250 and 1000 mg/kg. In vivo tests were carried out to evaluate for possible toxic effects and no mortality was observed up to the 5 g/kg dose level. Phytochemical investigation led to the isolation of a new indole alkaloid, which elucidated the observed pharmacological effects. © 2005 Pharmaceutical Society of Japan.

Genetic alterations in benign lesions: Chronic gastritis and gastric ulcer

Aim: To investigate the occurrence of chromosome 3, 7, 8, 9, and 17 aneuploidies, TP53 gene deletion and p53 protein expression in chronic gastritis, atrophic gastritis and gastric ulcer, and their association with H pylori infection. Methods: Gastric biopsies from normal mucosa (NM, n = 10), chronic gastritis (CG, n = 38), atrophic gastritis (CAG, n = 13) and gastric ulcer (GU, n = 21) were studied using fluorescence in situ hybridization (FISH) and immunohistochemical assay. A modified Giemsa staining technique and PCR were used to detect H pylori. An association of the gastric pathologies and aneuploidies with H pylori infection was assessed. Results: Aneuploidies were increasingly found from CG (21%) to CAG (31%) and to GU (62%), involving mainly monosomy and trisomy 7, trisomies 7 and 8, and trisomies 7, 8 and 17, respectively. A significant association was found between H pylori infection and aneuploidies in CAG (P = 0.0143) and GU (P = 0.0498). No TP53 deletion was found in these gastric lesions, but p53-positive immunoreactivity was detected in 45% (5/11) and 12% (2/17) of CG and GU cases, respectively. However, there was no significant association between p53 expression and H pylori infection. Conclusion: The occurrence of aneuploidies in benign lesions evidences chromosomal instability in early stages of gastric carcinogenesis associated with H pylori infection, which may confer proliferative advantage. The increase of p53 protein expression in CG and GU may be due to overproduction of the wild-type protein related to an inflammatory response in mucosa. © 2006 The WJG Press. All rights reserved.

Does troncular vagotomy modify the proliferative gastric lesions induced in rats by duodenogastric reflux?

Purpose: to investigate if combining VT to DGR through the pylorus can modulate the biological behavior of PL induced by DGR and to verify if TV alone can induce morphologic lesions in the gastric mucosa. Methods: 62 male Wistar rats were assigned to four groups: 1 - Control (CT) gastrotomy; 2 - Troncular Vagotomy (TV) plus gastrotomy; 3 - Duodenogastric reflux through the pylorus (R) and 4 - Troncular vagotomy plus DGR (RTV). The animals were killed at the 54 week of the experiment. DGR was obtained by anastomosing a proximal jejunal loop to the anterior gastric wall. TV was performed through isolation and division of the vagal trunks. Gastrotomy consisted of 1 cm incision at the anterior gastric wall. PL were analyzed gross and histologically in the antral mucosa, at the gastrojejunal stoma and at the squamous portion of the gastric mucosa. Results: Groups R and RTV developed exophytic lesions in the antral mucosa (R=90.9%; RTV=100%) and at the gastrojejunal stoma (R=54.54%; RTV=63.63%). Histologically they consisted of proliferative benign lesions, without cellular atypias, diagnosed as adenomatous hyperplasia. Both groups exposed to DGR presented squamous hyperplasia at the squamous portion of the gastric mucosa (R= 54.5%; RTV= 45.4%). TV, alone, did not induce gross or histological alterations in the gastric mucosa. TV did note change the morphologic pattern of the proliferative lesions induced by DGR. Conclusions: DGR induces the development of PL in the pyloric mucosa and at the gastrojejunal stoma. TV does not change the morphologic pattern of the proliferative lesions induced by DGR. TV alone is not able to induce morphologic lesions in the gastric mucosa.

Effect of erythromycin on motility and gastric emptying in dogs, by AC Biosusceptometry

We employed ACB to characterize Gastric Emptying Time (GET - T1/2) and Gastric Activity Contraction (GAC) in dogs after erythromycin administration. An erythromycin dose of 50 mg was infused, after 24 h of fasting. Without erythromycin administration, ACB recorded GET of 157.5 ± 13.6 min (mean ± SD) and GAC of 4.4 ± 0.5 cpm (cycles per minute). After erythromycin administration was measured a GET of 84.2 ± 19.7 min. GAC was measured before, during and after erythromycin administration and results were, respectively, 4.4 ± 0.5, 4.9 ± 0.6 and 4.2 ± 0.3 cpm. Erythromycin produced efficient prokinetic action in gastric emptying and increased gastric motility in dogs. © 2007 Elsevier B.V. All rights reserved.

Apoptosis in different gastric lesions and gastric cancer: Relationship with Helicobacter pylori, overexpression of p53 and aneuploidy

Apoptosis has an essential function in maintaining the integrity of the gastrointestinal mucosa. Its deregulation is associated with the occurrence of lesions such as in atrophic gastritis, peptic ulcers, intestinal metaplasia, and stomach tumorigenesis. Thus, the aim of the present study was to investigate the frequency of apoptotic cells (apoptotic index, AI) by using two different immunohistochemical techniques, TUNEL and anti-activated caspase-3 antibody (CPP32), in gastric dyspepsia [chronic gastritis (CG, N = 34), chronic atrophic gastritis (CAG, N = 11), gastric ulcer (GU, N = 17), and intestinal metaplasia (IM, N = 15)], normal gastric mucosae (NM, N = 8), and gastric adenocarcinoma (GC, N = 12). The relationship was investigated between the AI and Helicobacter pylori infection, diagnosed by PCR, overexpression of p53 protein determined by immunohistochemistry, and aneuploidy by fluorescence in situ hybridization, as performed by our laboratory in previous studies. No significant differences were observed in AI between the different groups, whether by the TUNEL technique (F = 1.60; P = 0.1670) or by CPP32 antibody (F = 1.70; P = 0.1420). Nonetheless, CAG and CG groups had AI statistically higher than those of normal mucosae. These two groups (CAG and CG) also showed a higher frequency of apoptosis-positive cases (TUNEL+ or CPP32+). Generally, there was no correlation between the AI detected by the TUNEL and CPP32 techniques in the groups studied, except in the GC group (r = 0.70). Moreover, there was no significant association between apoptosis and H. pylori infection, overexpression of p53 protein and aneuploidy, but the H. pylori-positive cases only of GU (P = 0.0233) and IM (P = 0.0253) groups displayed a statistically higher AI compared to H. pylori-negative NM, when the CPP32 antibody technique was used. Thus, CG and CAG have increased apoptosis, which may occur independent of an association with H. pylori infection, aneuploidy and overexpression of p53 protein. ©FUNPEC-RP.

A novel biomagnetic instrumentation with four magnetoresistive sensors to evaluate gastric motility.

A novel instrumentation using anisotropic magnetoresistive (AMR) sensors associated with magnetic coils excitation was developed to evaluate gastrointestinal tract motility parameters. The susceptometer has four sensors that were used to measure the gastric activity contractions (GAC) in anaesthetized dogs, its performance was evaluated by manometry with good results.

AC biosusceptometry as a method for measuring gastric contraction

the aim of this study was to validate the Alternate Current Biosusceptometry (ACB) for monitoring gastric contractions in rats. In vitro data were obtained to establish the relationship between ACB and the strain-gauge (SG) signal amplitude. In vivo experiments were performed on rats with magnetic markers and SGs previously implanted under the gastric serosa. The effects of the prandial state in gastric motility profiles were obtained. The correlation between in vitro signal amplitudes was strong (R = 0.989). The temporal cross-correlation between the ACB and SG signal amplitude was higher in the postprandial than in the fasting state. Irregular signal profiles, low contraction amplitudes, and smaller signal-to-noise ratios explained the poor correlation for fasting-state recordings. The contraction frequencies using ACB were 0.068 ± 0.007 Hz (postprandial) and 0.058 ± 0.007 Hz (fasting) and those using SG were 0.066 ± 0.006 Hz (postprandial) and 0.059 ± 0.008 Hz (fasting) (P < 0.003). When a magnetic tracer was ingested, there was a strong correlation and a small phasedifference between techniques. We conclude that ACB provides an accurate and sensitive technique for studies of GI motility in the rat. © 2010 IEEE.

Anti-nociceptive effects of Carpolobia lutea G. Don (Polygalaceae) leaf fractions in animal models

Leaves from Carpolobia lutea (Polygalaceae) were screened to establish the antiulcer ethnomedicinal claim and to quantitatively isolate, elucidate the active compounds by semi-preparative HPLC. The anti-nociceptive effects of Carpolobia lutea (CL) G. Don (Polygalaceae) organic leaf extracts were tested in experimental models in mice. The anti-nociceptive mechanism was determined using tail-flick test, acetic acid-induced abdominal constrictions, formalin-induced hind paw licking and the hot plate test. The fractions (ethanol, ethyl acetate, chloroform, n-hexane) and crude ethyl acetate extract of CL (770 mg/kg, i.p.) produced significant inhibitions of both phases of the formalin-induced pain in mice, a reduction in acetic acid-induced writhing as well as and an elevation of the pain threshold in the hot plate test in mice. The inhibitions were greater to those produced by indomethacin (5 mg/kg, i.p.). Ethyl acetate fraction revealed cinnamic and coumaric acids derivatives, which are described for the first time in literature. These cinnamalglucosides polyphenols characterised from CL may in part account for the pharmacological activities. These findings confirm its ethnomedical use in anti-inflammatory pain and in pains from gastric ulcer-associated symptoms. © 2011 Springer Basel AG.