C57BL/6J mice carrying the Min allele of Adenomatous polyposis coli (Apc) develop numerous adenomas along the entire length of the intestine and consequently die at an early age. This short lifespan would prevent the accumulation of somatic genetic mutations or epigenetic alterations necessary for tumor progression. To overcome this limitation, we generated F(1) Apc(Min/+) hybrids by crossing C57BR/cdcJ and SWR/J females to C57BL/6J Apc(Min/+) males. These hybrids developed few intestinal tumors and often lived longer than 1 year.
Functional dyspepsia (FD) is a heterogeneous, highly prevalent symptom complex in the community and general practice. FD is defined as the presence of symptoms considered as originated in the gastroduodenal region, in the absence of any organic, systemic, or metabolic disease that is likely to explain the symptoms. Pathogenetic features include disturbed gastric accommodation and emptying, duodenal dysmotility, heightened sensitivity, notably psychosocial disturbances and an association with a postinfective state.
Functional dyspepsia (FD) is common in children, with as many as 80% of those being evaluated for chronic abdominal pain reporting symptoms of epigastric discomfort, nausea, or fullness. It is known that patients with persistent complaints have increased comorbidities such as depression and anxiety. The interaction with psychopathologic variables has been found to mediate the association between upper abdominal pain and gastric hypersensitivity. These observations suggest that abnormal central nervous system processing of gastric stimuli may be a relevant pathophysiologic mechanism in FD.
IMPORTANCE OF THE FIELD: Dyspeptic symptoms are highly prevalent in the population and represent a major burden for healthcare systems. The ROME III criteria address and define two separate entities of functional dyspepsia: epigastric pain syndrome and postprandial distress syndrome. The etiology of dyspeptic symptoms is heterogeneous, underlying mechanisms are poorly understood and symptomatic improvement after drug therapy is often incomplete.
The antimalarial drug artemisinin from Artemisia annua demonstrated remarkably strong activity against Helicobacter pylori, the pathogen responsible for peptic ulcer diseases. In an effort to develop a novel antimicrobial chemotherapeutic agent containing such a sesquiterpene lactone endoperoxide, a series of analogues (2 natural and 15 semisynthetic molecules), including eight newly synthesized compounds, were investigated against clinical and standard strains of H. pylori. The antimicrobial spectrum against 10 H.
Helicobacter pylori infection of the stomach causes peptic ulcer disease and gastric cancer. Despite eliciting a vigorous immune response, the bacterium persists for the life of the host. An important antimicrobial mechanism is the production of NO derived from inducible NO synthase (iNOS). We have reported that macrophages can kill H. pylori in vitro by an NO-dependent mechanism, but supraphysiologic levels of the iNOS substrate l-arginine are required. Because H.
International Journal of Cancer. Journal International Du Cancer
Gene promoter CpG island hypermethylation is associated with Helicobacter pylori (H. pylori) infection and may be an important initiator of gastric carcinogenesis. To examine factors influencing methylation, we utilized bisulfite Pyrosequencing® technology for quantitative analysis of promoter DNA methylation in RPRM, APC, MGMT and TWIST1 genes using DNA from 86 gastric biopsies from Colombian residents of areas with high and low incidence of gastric cancer. H. pylori colonies were cultured from the same subjects, and gastric pathology was evaluated.
Macrophages are essential components of innate immunity, and apoptosis of these cells impairs mucosal defense to microbes. Helicobacter pylori is a gastric pathogen that infects half of the world population and causes peptic ulcer disease and gastric cancer. The host inflammatory response fails to eradicate the organism. We have reported that H. pylori induces apoptosis of macrophages by generation of polyamines from ornithine decarboxylase (ODC), which is dependent on c-Myc as a transcriptional enhancer.
BACKGROUND & AIMS: Helicobacter pylori-induced immune responses fail to eradicate the bacterium. Nitric oxide (NO) can kill H pylori. However, translation of inducible NO synthase (iNOS) and NO generation by H pylori-stimulated macrophages is inhibited by the polyamine spermine derived from ornithine decarboxylase (ODC), and is dependent on availability of the iNOS substrate L-arginine (L-Arg). We determined if spermine inhibits iNOS-mediated immunity by reducing L-Arg uptake into macrophages.