Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric mucosa causing gastritis and peptic ulcer and increasing the risk of gastric cancer. The efficacy of current antibiotic-based therapies can be limited by problems of patient compliance and increasing antibiotic resistance; the vaccine approach can overcome these limits. The present study describes the therapeutic vaccination of experimentally H. pyloriinfected beagle dogs, an animal model that reproduces several aspects of the human infection with H. pylori. The vaccine consisted of three recombinant H. pylori antigens, CagA, VacA, and NAP, formulated at different doses (10, 25, or 50 g each) with alum and administered intramuscularly either weekly or monthly. No adverse effects were observed after vaccination and a good immunoglobulin G response was generated against each of the three antigens. Bacterial colonization and gastritis were decreased after the completion of the vaccination cycle, especially in the case of the monthly immunization schedule. In conclusion, therapeutic vaccination in the beagle dog model was safe and immunogenic and was able to limit H. pylori colonization and the related gastric pathology.Helicobacter pylori is a spiral-shaped, gram-negative bacterium that infects the stomach of Ͼ50% of the population worldwide, with higher prevalence in the developing countries. H. pylori induces chronic inflammation of the stomach mucosa, causing chronic gastritis and peptic ulcer (9, 33); moreover, H. pylori infection is related to gastric mucosa-associated lymphoid tissue lymphoma (4) and to an increased risk of gastric cancer (36), as also proved in animal models (13,38).Current therapies, based on one antisecretory agent plus antibiotics, although effective in 80 to 90% of cases, face problems of patient compliance, increasing antibiotic resistance, and possible recurrence or reinfection; in spite of continuous effort to improve these treatments, no major breakthroughs have been achieved in the most recent years (30).To overcome the limits of antibiotic-based therapies, the vaccine approach has been undertaken since the last decade, leading us to identify some relevant bacterial antigens as candidates for vaccines (2). On the other hand, animal models of H. pylori infection have been developed to study the interaction between the bacterium and the host, the mechanisms of immune response to either infection or vaccination, and to determine the efficacy of both prophylactic and therapeutic vaccination (2,17,26,34). Among these animal models, that of the beagle dog reproduces several aspects of the human infection with H. pylori. In fact, in the beagle dog model, intragastric administration of H. pylori results in a long-term chronic infection, characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of macroscopic follicles in the gastric mucosa, mainly in the antral region of the stomach (28,29).Most of the examples of vaccination against H. pylori in animal models reported in the...
Helicobacter pylori has been widely recognized as an important human pathogen responsible for chronic gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Little is known about the natural history of this infection since patients are usually recognized as having the infection only after years or decades of chronic disease. Several animal models ofH. pylori infection, including those with different species of rodents, nonhuman primates, and germ-free animals, have been developed. Here we describe a new animal model in which the clinical, pathological, microbiological, and immunological aspects of human acute and chronic infection are mimicked and which allows us to monitor these aspects of infection within the same individuals. Conventional Beagle dogs were infected orally with a mouse-adapted strain of H. pylori and monitored for up to 24 weeks. Acute infection caused vomiting and diarrhea. The acute phase was followed by polymorphonuclear cell infiltration, interleukin 8 induction, mononuclear cell recruitment, and the appearance of a specific antibody response against H. pylori. The chronic phase was characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of the typical macroscopic follicles that in humans are considered possible precursors of MALT lymphoma. In conclusion, infection in this model mimics closely human infection and allows us to study those phases that cannot be studied in humans. This new model can be a unique tool for learning more about the disease and for developing strategies for treatment and prevention.
Experimental infection of beagle dogs with
Laser bonding is a promising minimally invasive approach, emerging as a valid alternative to conventional suturing techniques. It shows widely demonstrated advantages in wound treatment: immediate closuring effect, minimal inflammatory response and scar formation, reduced healing time. This laser based technique can overcome the difficulties in working through narrow surgical corridors (e.g. the modern "key-hole" surgery as well as the endoscopy setting) or in thin tissues that are impossible to treat with staples and/or stitches. We recently proposed the use of chitosan matrices, stained with conventional chromophores, to be used in laser bonding of vascular tissue. In this work we propose the same procedure to perform laser bonding of vocal folds and dura mater repair. Laser bonding of vocal folds is proposed to avoid the development of adhesions (synechiae), after conventional or CO 2 laser surgery. Laser bonding application in neurosurgery is proposed for the treatment of dural defects being the Cerebro Spinal Fluid leaks still a major issue. Vocal folds and dura mater were harvested from 9-months old porks and used in the experimental sessions within 4 hours after sacrifice. In vocal folds treatment, an IdocyanineGreen-infused chitosan patch was applied onto the anterior commissure, while the dura mater was previously incised and then bonded. A diode laser emitting at 810 nm, equipped with a 600 µm diameter optical fiber was used to weld the patch onto the tissue, by delivering single laser spots to induce local patch/tissue adhesion. The result is an immediate adhesion of the patch to the tissue. Standard histology was performed, in order to study the induced photothermal effect at the bonding sites. This preliminary experimental activity shows the advantages of the proposed technique in respect to standard surgery: simplification of the procedure; decreased foreign-body reaction; reduced inflammatory response; reduced operating times and better handling in depth. ; phone 0039 055-522 5337; fax 0039 055 522 5305
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