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

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

Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat

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.

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)

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.

Effects of the ethyl acetate fraction of Alchornea triplinervia on healing gastric ulcer in rats

Alchornea triplinervia (Spreng.) Muell. Arg (Euphorbiaceae) is a medicinal plant commonly used by people living in the Cerrado region of Brazil to treat gastrointestinal ulcers. We previously described the gastroprotective action of methanolic extract (ME) of Alchornea triplinervia and the ethyl acetate fraction (EAF) in increasing of prostaglandin E 2 (PGE 2) gastric levels in the mucosa. In this work we evaluated the effect of EAF in promoting the healing process in rats with acetic acid-induced gastric ulcers. In addition, toxicity was investigated during treatment with EAF. After 14 days of treatment with EAF, the potent stimulator of gastric cell proliferation contributed to the acceleration of gastric ulcer healing. Upon immunohistochemical analysis, we observed a pronounced expression of COX-2, mainly in the submucosal layer. The 14-day EAF treatment also significantly increased the number of neutrophils in the gastric mucosa regeneration area. The EAF induced angiogenesis on gastric mucosa, observed as an increase of the number of blood vessels supplying the stomach in rats treated with EAF. Oral administration for 14 days of the ethyl acetate fraction from Alchornea triplinervia accelerated the healing of gastric ulcers in rats by promoting epithelial cell proliferation, increasing the number of neutrophils and stimulation of mucus production. This fraction, which contained mainly phenolic compounds, contributed to gastric mucosa healing. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Jaw musculature of the Meiglyptini (Aves: Piciformes: Picidae)

The Meiglyptini comprise eight species of woodpeckers grouped into three genera, two of which contain three species ( Meiglyptes and Mulleripicus), while one genus includes two species ( Hemicircus). The purpose of this study is to describe the mandibular apparatus found in six species of Meiglyptini and to compare them with each other and with other woodpecker species. The results reveal a number of structures that are worth mentioning: (i) the components of the external mandibular adductor system of Hemicircus concretus, particularly the M. adductor mandibulae externus caudalis medialis, are underdeveloped compared with the other investigated species; (ii) the muscles of the internal mandibular system are structurally different among Meiglyptes species and are less developed, both in size and in structure, in H. concretus; (iii) the M protractor quadrati is vestigial in Meiglyptes species; (iv) the muscles of the protractor system of the quadrate are relatively undeveloped in H. concretus; (v) most of the muscles of the pterygoideus system are structurally differentiated in Meiglyptes species. It appears that the complexity of the mandibular apparatus is associated with the type of food consumed, as the apparatus of the frugivorous species H. concretus is markedly different from that of the insectivorous species. © 2012 The Royal Swedish Academy of Sciences.

Jaw musculature of the Picini (Aves: Piciformes: Picidae)

The Picini tribe comprises 25 Old World woodpecker species grouped into seven genera that are widely distributed in Asia and include several representatives from the Eurasian region. Given the absence of detailed anatomical studies of Picini in the literature, the purposes of this study were to describe the jaw musculature of 14 species of Picini in detail and to compare the musculature patterns of these species. The results of this analysis indicate the following: (1) there is a clear association between the ventralis lateralis and dorsalis lateralis muscles through fleshy fibers that are connected in all species, (2) the jaw musculature of the genus Picus differs from that of other Picini genera in terms of the poor development of the protractor muscle system of the quadrate (M. protractor quadrati and M. protractor pterygoidei), (3) generally, the M. pseudotemporalis superficialis originates in the ventrocaudal region of the laterosphenoid (the lower part of the orbit), with the only noteworthy exception being an origin in the upper part of the orbit in Dinopium javanense, and (4) the protractor pterygoidei muscle is more developed in Blythipicus rubiginosus, Dinopium rafflesii, and D. javanense than in the other species. © 2012 Reginaldo José Donatelli.

Myenteric denervation in gastric carcinogenesis: Differential modulation of nitric oxide and annexin-A1

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

Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

Gastric cancer is a leading cause of cancer-related mortality, and the presence of lymph node metastasis an important prognostic factor. Downregulation of RKIP has been associated with tumor progression and metastasis in several types of neoplasms, being currently categorized as a metastasis suppressor gene. Our aim was to determine the expression levels of RKIP in gastric tissues and to evaluate its impact in the clinical outcome of gastric carcinoma patients. RKIP expression levels were studied by immunohistochemistry in a series of gastric tissues. Overall, we analysed 222 non-neoplastic gastric tissues, 152 primary tumors and 42 lymph node metastasis samples. We observed that RKIP was highly expressed in ∼83% of non-neoplastic tissues (including normal tissue and metaplasia), was lost in ∼56% of primary tumors and in ∼90% of lymph node metastasis samples. Loss of RKIP expression was significantly associated with several markers of poor clinical outcome, including the presence of lymph node metastasis. Furthermore, the absence of RKIP protein constitutes an independent prognostic marker for these patients. In conclusion, RKIP expression is significantly lost during gastric carcinoma progression being almost absent in lymph node metastasis samples. Of note, we showed that the absence of RKIP expression is associated with poor outcome features of gastric cancer patients, this being also an independent prognostic marker.