Gastric perception thresholds are low and sensory neuropeptide levels high in helicobacter pylori-positive functional dyspepsia

BACKGROUND AND AIMS: In functional dyspepsia (FD) decreased perception levels can be shown on gastric distension. Substance P (SP) and calcitonin gene-related peptide (CGRP) are involved in the sensitization of afferent neuronal pathways due to chronic inflammation. The role of Helicobacter pylori-induced gastric mucosal inflammation in the pathogenesis of FD is controversial. The aim of this study was to assess whether FD patients have altered mucosal concentrations of CGRP and SP, and to investigate whether this is associated with visceral hypersensitivity or H. pylori infection. METHODS: Gastrointestinal symptoms, H. pylori status, perception thresholds at gastric balloon distension, and gastric mucosal concentrations of CGRP and SP were determined in 13 FD patients and 18 healthy controls (HC). RESULTS: In H. pylori-positive FD patients discomfort and pain thresholds on gastric distension were lower compared to other groups. Antral mucosal levels of CGRP and SP were higher in H. pylori-positive subjects. In FD significantly negative correlations between discomfort and pain thresholds and antral mucosal concentrations of CGRP and SP were observed. CONCLUSIONS: In FD low perception thresholds on gastric distension are associated with high levels of CGRP and SP in the antrum, suggesting that sensory neuropeptides are involved in FD pathophysiology.     

Chemokines and Antimicrobial Peptides Have a cag-Dependent Early Response to Helicobacter pylori Infection in Primary Human Gastric Epithelial Cells

Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128ΔcagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection.     

Diagnosis and mortality prediction in pulmonary hypertension: the value of the electrocardiogram-derived ventricular gradient

PurposeThe aim of this study was to investigate the use of the electrocardiogram-derived ventricular gradient, projected on the x-axis (VGx), for detection of pulmonary hypertension (PH) and for prediction of all-cause mortality in PH patients.MethodsIn patients referred for PH screening (n = 216), the VGx was calculated semiautomatically from the electrocardiogram and was defined as abnormal when less than 24 mV·ms. The VGx of PH patients was compared with the VGx of patients without PH. The association between a reduced VGx and mortality was investigated in PH patients.ResultsPatients with PH (n = 117) had a significantly reduced VGx: 14 ± 27 vs 45 ± 23 mV·ms, P < .001. Furthermore, a severely reduced VGx (<0 mV·ms) was associated with increased mortality in PH patients: hazard ratio, 1.025 (95% confidence interval, 1.006-1.045; P = .012) per mV·ms VGx decrease.ConclusionReduced VGx is associated with the presence of PH and, more importantly, within PH patients, a severely reduced VGx predicts mortality.     

The competition between enamel and dentin adhesion within a cavity: An in vitro evaluation of class V restorations

To gain more insight into the consequences of curing contraction within the tooth cavity, we assessed the margin behavior of 12 contemporary restorative systems in class V restorations with margins located on enamel and dentin after mechanical loading and water storage. Mixed class V cavities were prepared on extracted human molars and restored using five etch and rinse and seven self-etch adhesive systems with their corresponding composites. Marginal adaptation was evaluated by using a computer-assisted quantitative marginal analysis in a scanning electron microscope (SEM) on epoxy replicas before, after thermal and mechanical stressing and after 1 year of water storage. The interactions of "testing conditions", "adhesive-composite combination" and "tooth substrate" with "marginal adaptation" were evaluated by two-way ANOVA. Fatigue, stress and storage conditions had significant effects on the marginal adaptation. Only two groups (Optibond FL and G Bond) presented equal percentages of marginal adaptation on enamel and dentin; in the other groups, the rate of degradation was product dependent. All materials tested showed a distinct behavior on enamel and dentin. In addition to mechanical resistance and long-term stability, differences within materials also exist in their ability to simultaneously bond to enamel and dentin.     

An insight into the sialotranscriptome of Triatoma matogrossensis, a kissing bug associated with fogo selvagem in South America

Triatoma matogrossensis is a Hemiptera that belongs to the oliveirai complex, a vector of Chagas' disease that feeds on vertebrate blood in all life stages. Hematophagous insects' salivary glands (SGs) produce potent pharmacologic compounds that counteract host hemostasis, including anticlotting, antiplatelet, and vasodilatory molecules. Exposure to T. matogrossensis was also found to be a risk factor associated with the endemic form of the autoimmune skin disease pemphigus foliaceus, which is described in the same regions where Chagas' disease is observed in Brazil. To obtain a further insight into the salivary biochemical and pharmacologic diversity of this kissing bug and to identify possible allergens that might be associated with this autoimmune disease, a cDNA library from its SGs was randomly sequenced. We present the analysis of a set of 2,230 (SG) cDNA sequences, 1,182 of which coded for proteins of a putative secretory nature.