Intracellular Helicobacter pylori and Gastric Carcinogenesis: An “Old” Frontier Worth Revisiting

Gastroenterology (Impact Factor: 16.72). 04/2007; 132(3):1177-80. DOI: 10.1053/j.gastro.2007.01.068
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    ABSTRACT: BACKGROUND-GOALS: We used transmission electron microscopy and immunohistochemistry (IHC) to investigate how Helicobacter pylori affects the gastric mucosa of humans. Gastric biopsy specimens were obtained from 15 patients with gastric discomfort. The samples were processed using both microscopic examinations and a real-time polymerase chain reaction to detect H. pylori DNA. IHC staining was performed with an avidin-biotin complex immunoperoxidase kit for paraffin-embedded tissue sections. Polyclonal rabbit anti-H. pylori was used as a primary antibody. IHC-applied slides with brown-stained spiral bacteria on the luminal surface and in the intercellular spaces of the gastric epithelium; electron-dense spiral H. pylori of approximately 200 to 300 nm in diameter both in the gastric lumen and between the gastric epithelial cells; coccoid or ellipsoid H. pylori attached to the epithelial cells through egg-cup-like pedestals; coccoid H. pylori within the endocytotic vesicles in the apical cytoplasmic part of the epithelial cells, thus suggesting their internalization by phagocytosis; electron-dense spiral H. pylori within the membrane-bounded vacuoles of both the gastric epithelial cells, and the lamina propria; a prominent vacuolization of gastric epithelial cells invaded by H. pylori; and swollen and lytic gastric epithelial cells that suggest a mucosal erosion and may lead to peptic ulcer. All of these microscopic findings were not present in the H. pylori DNA-negative specimens that were used as the control group. This is the first histomicrobiologic study to show gastric cells invaded by H. pylori in patients with H. pylori infection confirmed by real-time polymerase chain reaction.
    Journal of clinical gastroenterology 11/2009; 44(6):416-22. DOI:10.1097/MCG.0b013e3181c21c69 · 3.50 Impact Factor
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    ABSTRACT: The most evident challenge to treatment of Helicobacter pylori, a bacterium responsible for gastritis, peptic ulcers and gastric cancer, is the increasing rate of resistance to all currently used therapeutic antibiotics. Thus, the development of novel therapies is urgently required. N-geranyl-N'-(2-adamantyl) ethane-1, 2-diamine (SQ109) is an ethylene diamine-based antitubercular drug that is currently in clinical trials for the treatment of tuberculosis (TB). Previous pharmacokinetic studies of SQ109 revealed that persistently high concentrations of SQ109 remain in the stomach 4 hours post oral administration in rats. This finding, combined with the need for new anti-Helicobacter therapies, prompted us to define the in vitro efficacy of SQ109 against H. pylori. Liquid broth micro-dilution was used for susceptibility studies to determine the antimicrobial activity of SQ109 against a total of 6 laboratory strains and 20 clinical isolates of H. pylori; the clinical isolates included a multi-drug resistant strain. All strains tested were susceptible to SQ109 with MIC and MBC ranges of 6-10 µM and 50-60 µM, respectively. SQ109 killing kinetics were concentration- and time-dependent. SQ109 killed H. pylori in 8-10 h at 140 µM (2MBCs) or 4-6 h at 200 µM (~3MBCs). Importantly, though the kinetics of killing were altered, SQ109 retained potent bactericidal activity against H. pylori at low pH. Additionally, SQ109 demonstrated robust thermal stability and was effective at killing slow growing or static bacteria. In fact, pretreatment of cultures with a bacteriostatic concentration of chloramphenicol (Cm) synergized the effects of typically bacteriostatic concentrations of SQ109 to the level of five-logs of bacterial killing. A molar-to-molar comparison of the efficacy of SQ109 as compared to metronidazole (MTZ), amoxicillin (AMX), rifampicin (RIF) and clarithromycin (CLR), revealed that SQ109 was superior to MTZ, AMX and RIF but not to CLR. Finally, the frequency of resistance to SQ109 was low and electron microscopy studies revealed that SQ109 interacted with bacterial inner membrane and cytoplasmic content(s). Collectively, our in vitro data demonstrate that SQ109 is an effective monotherapy against susceptible and multi-drug resistant strains of H. pylori and may be useful alone or in combination with other antibiotics for development as a new class of anti-Helicobacter drugs.
    PLoS ONE 07/2013; 8(7):e68917. DOI:10.1371/journal.pone.0068917 · 3.23 Impact Factor
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    ABSTRACT: We present the results of electron microscopic, microbiological, immunohistochemical, and molecular genetic studies of gastric biopsy specimens taken for diagnostic purposes according by clinical indications during examination of patients with gastrointestinal pathology. Immune homeostasis of the gastric mucosa against the background of infection with various pathogen strains of Helicobacter pylori was studied in patients of different age groups with peptic ulcer, gastritis, metaplasia, and cancer. Some peculiarities of Helicobacter pylori contamination in the gastric mucosa were demonstrated. Immune homeostasis of the gastric mucosa in different pathologies was analyzed depending on the Helicobacter pylori genotype.
    Bulletin of Experimental Biology and Medicine 06/2015; 159(1). DOI:10.1007/s10517-015-2913-x · 0.36 Impact Factor