Role of central and peripheral ghrelin in the mechanism of gastric mucosal defence

Ghrelin, identified in the gastric mucosa, has been involved in the control of food intake and growth hormone (GH) release, but whether this hormone influences the gastric secretion and gastric mucosal integrity has been little elucidated. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without suppression of nitric oxide (NO)-synthase or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by the H₂-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. In addition, the gastric mucosal expression of mRNA for CGRP, the most potent neuropeptide released from the sensory afferent nerves, was analyzed in rats exposed to WRS with or without ghrelin pre-treatment. Ghrelin (5–80 μg/kg i.p. or 0.6–5 μg/kg i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS. This protective effect was accompanied by a significant rise in the gastric mucosal blood flow (GBF), luminal NO concentration and plasma ghrelin and gastrin levels. Ghrelin-induced protection was abolished by vagotomy and significantly attenuated by L-NNA and deactivation of afferent nerves with neurotoxic dose of capsaicin. The signal for CGRP mRNA was significantly increased in gastric mucosa exposed to WRS as compared to that in the intact gastric mucosa and this was further enhanced in animals treated with ghrelin. We conclude that central and peripheral ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol or WRS, and these effects depend upon vagal activity and hyperemia mediated by the NOS-NO system and CGRP released from sensory afferent nerves.     

Ghrelin inhibits vascular superoxide production in spontaneously hypertensive rats

BACKGROUND: Ghrelin is a novel peptide involved in the control of appetite, but its role in vascular pathologies remains to be elucidated. Ghrelin was shown to decrease blood pressure (BP) and improve endothelial function. Its plasma levels are correlated with BP in humans. Mechanisms of these effects are unknown. Because oxidative stress and increased superoxide production by NAD(P)H oxidases (Nox) are critical in the pathogenesis of hypertension, we aimed to study the effects of ghrelin on vascular superoxide production and NAD(P)H oxidase activity in spontaneously hypertensive rats (SHR). METHODS: Aortic superoxide production and NAD(P)H oxidase activity were measured using lucigenin (5 micromol/L) chemiluminescence. Aortas from Wistar-Kyoto rats (WKY) were used as control. Direct superoxide scavenging properties of ghrelin were tested using xanthine-xanthine oxidase system. RESULTS: Both basal superoxide production and vascular NADPH oxidase activity were significantly higher in aortas from SHR, than from WKY. Preincubation of aortic segments from SHR or WKY with ghrelin caused concentration-dependent (from 50 pg/mL to 5 ng/mL) decrease of basal superoxide production. Vascular NAD(P)H oxidase activity was inhibited by ghrelin, abolishing the difference between SHR and basal WKY. Ghrelin did not affect superoxide release from the in vitro xanthine-xanthine oxidase system, indicating lack of direct superoxide scavenging properties or inhibitory effects on xanthine oxidase in vitro. Nitric oxide synthase (NOS) inhibition, using N(omega)-nitro-L-arginine methyl ester (L-NAME), partially blunted the effects of ghrelin on NADPH oxidase activity indicating potential role of nitric oxide. CONCLUSIONS: Ghrelin inhibits vascular oxidative stress in SHR. This effect is likely related to the inhibition of vascular NAD(P)H oxidases.     

Characterization of focal liver lesions with SonoVue- enhanced sonography： International multicenter-study in comparison to CT and MRI

AIM： To evaluate in a multicenter study whether the sonographic characterization of focal liver lesions can be improved using SonoVue-enhancement; and to compare this method with computed tomography （CT） and magnetic resonance imaging （MRI）.
METHODS： One hundred and thirty four patients withone focal liver lesion detected in baseline ultrasound （US） were examined with conventional US, contrastenhanced US （n = 134）, contrast-enhanced CT （n = 115） and/or dynamic contrast-enhanced MRI （n = 70）. The lesions were classified as malignant, benign or indeterminate and the type of lesion was determined. The final diagnosis based on the combined information of all imaging examinations, clinical information and histology （n = 32） was used. Comparisons were made to see whether the addition of contrast-enhanced US led to the improvement of the characterization of doubtful focal liver lesions.
RESULTS： In comparison with unenhanced US, SonoVue markedly improves sensitivity and specificity for the characterization （malignant/benign） of focal liver lesions. In comparison with CT and/or dynamic MRI, SonoVue -enhanced sonography applied for characterization of focal liver lesions was 30.2% more sensitive in the recognition of malignancy and 16.1% more specific in the exclusion of malignancy and overall 22.9% more accurate. In the subgroup with confirmative histology available （n = 30）, sensitivity was 95.5% （CEUS）, 72.2% （CT） and 81.8% （MRI）, and specificity was 75.0% （CEUS）, 37.5% （CT） and 42.9% （MRI）. The sensitivity and specificity of CEUS for the identification of focal nodular hyperplasia （FNH） and hemangiomas was 100% and 87%, resulting in an accuracy of 94.5%.
CONCLUSION： SonoVue-enhanced sonography emerges as the most sensitive, ost specific and thus most accurate imaging modality for the characterization of focal liver lesions.     

Specialisation and specialist education in prosthetic dentistry in Europe

This presentation reports on the results of a meeting of prosthodontists from selected European countries. The aim of the meeting was to analyse and promote specialisation and specialist education in Prosthetic Dentistry in Europe. Representatives for Europe were selected from the European Prosthodontic Association (EPA) board, the Education and Research Committee of International College of Prosthodontists (ICP), countries with a legally recognised speciality, countries without a recognised speciality but organised training programmes and countries with neither of these situations. Data about specialisation and specialist training in Prosthodontics in Europe was scrutinised and discussed. The programmes for countries with specialist training had relatively similar content, mostly of three years duration. There was strong agreement that a recognised speciality raises the level of care within the discipline for both specialists and non-specialists. In several of the countries where a speciality had been introduced it had been initiated by pressure from public health planning authorities. The conclusions are that from a professional viewpoint an advancement of the speciality over Europe would develop the discipline, improve oral health planning and quality of patient care. A working group for harmonisation was recommended.     

Estimation of the dietary acrylamide exposure of the Polish population

The objective of our study was to determine acrylamide content in the Polish foods and to assess the average dietary acrylamide exposure of the Polish population. We analysed the acrylamide content in Polish food using GCQ-MS/MS method. The daily dietary acrylamide exposure was computed using a probabilistic approach for the total Polish population (1–96 years) and for the following age groups: 1–6, 7–18 and 19–96, using Monte Carlo simulation technique. To assess the Polish population exposure to acrylamide present in food, food consumption data was taken from the ‘Household Food Consumption and Anthropometric Survey in Poland’. The mean content of acrylamide in tested 225 samples of foodstuffs taken randomly all over Poland, ranged widely from 11 to 3647 μg/kg of product. For the total Polish population (1–96 years) the estimated acrylamide mean exposure is 0.43 μg/kg of body weight per day. The main sources of dietary acrylamide in Polish population were as follow: bread – supplied 45% of total dietary acrylamide intake, French fries and potato crisps – 23%, roasted coffee – 19%.     

Masseter segmentation using an improved watershed algorithm with unsupervised classification

The watershed algorithm always produces a complete division of the image. However, it is susceptible to over-segmentation and sensitivity to false edges. In medical images this leads to unfavorable representations of the anatomy. We address these drawbacks by introducing automated thresholding and post-segmentation merging. The automated thresholding step is based on the histogram of the gradient magnitude map while post-segmentation merging is based on a criterion which measures the similarity in intensity values between two neighboring partitions. Our improved watershed algorithm is able to merge more than 90% of the initial partitions, which indicates that a large amount of over-segmentation has been reduced. To further improve the segmentation results, we make use of K-means clustering to provide an initial coarse segmentation of the highly textured image before the improved watershed algorithm is applied to it. When applied to the segmentation of the masseter from 60 magnetic resonance images of 10 subjects, the proposed algorithm achieved an overlap index (κ) of 90.6%, and was able to merge 98% of the initial partitions on average. The segmentation results are comparable to those obtained using the gradient vector flow snake.     

Helicobacter pylori promotes apoptosis, activates cyclooxygenase (COX)-2 and inhibits heat shock protein HSP70 in gastric cancer epithelial cells

Objective

Apoptosis plays an important role in the regulation of gastric epithelial cell number and gastrointestinal disorders induced by Helicobacter pylori (Hp). Heat shock proteins (HSPs) are involved in cell integrity, cell growth and in gastric mucosa colonized by Hp. COX-2 was implicated in Hp-induced carcinogenesis but the effects of this germ and CagA cytotoxin on HSP70, COX-2, Bax and Bcl-2 in gastric cancer epithelial cells have been little studied.

Material and methods

We determined the expression for HSP70, Bax and Bcl-2 in human gastric epithelial MKN7 cells incubated with live strain Hp (cagA?+?vacA+) with or without co-incubation with exogenous CagA and NS-398, the selective COX-2 inhibitor. After 3–48?h of incubation, the expression of HSP70, COX-2, Bax and Bcl-2 mRNA and proteins were determined by RT-PCR and immunoprecipitation.

Results

Hp inhibited expression for HSP70 and this was significantly potentiated by exogenous CagA. Co-incubation of epithelial cells with Hp, without or with CagA increased Bax expression and simultaneously decreased expression for Bcl-2. The increase in COX-2 mRNA and Bax expression were significantly inhibited by NS-398. We conclude that Hp promotes apoptosis in adenocarcinoma gastric epithelial cells in vitro and this is associated with activation of COX-2 and inhibition of HSP70.     

Intrauterine exposure to lead may enhance sensitization to common inhalant allergens in early childhood: a prospective prebirth cohort study

Background

Several in vivo and in vitro studies have shown that metal-rich particles may enhance allergic responses to house dust mites and induce an increased release of allergy-related cytokines.

Objectives

The main goal of this analysis is to define the possible association of intrauterine exposure to lead and mercury with the occurrence of skin sensitization to common aeroallergens in early childhood.

Material and methods

The present study refers to a sample of 224 women in the second trimester of pregnancy recruited from Krakow inner city area who had full term pregnancies and whose children underwent skin prick testing (SPT) at the age of 5. Lead and mercury levels were assessed in cord blood and retested in children at age of 5 years. Aeroallergen concentrations in house dust were measured at the age of 3 years. The main health outcome (atopic status) was defined as the positive SPT to at least one common aeroallergen (Der f1, Der p1, Can f1 and Fel d1) at the age of 5 years. In the statistical analysis of the association between atopic status of children and exposure to metals, the study considered a set of covariates such as maternal characteristics (age, education, atopy), child’s gender, number of older siblings, prenatal (measured via cord blood cotinine) and postnatal environmental tobacco smoke together with exposure to polycyclic aromatic hydrocarbons (PAH) as measured by PAH-DNA adducts.

Results and conclusion

In the binary regression analysis, which controlled for the confounders, the risk ratio (RR) estimate for atopic sensitization was significantly associated with the lead exposure (RR=2.25, 95%CI: 1.21−4.19). In conclusion, the data suggest that even very low-level of prenatal lead exposure may be implicated in enhancing sensitization to common aeroallergens in early childhood.