RESUMO
Infection with Helicobacter pylori strains containing high number of EPIYA-C phosphorylation sites in the CagA is associated with significant gastritis and increased risk of developing pre-malignant gastric lesions and gastric carcinoma. However, these findings have not been reproduced in animal models yet. Therefore, we investigated the effect on the gastric mucosa of Mongolian gerbil (Meriones unguiculatus) infected with CagA-positive H. pylori strains exhibiting one or three EPIYA-C phosphorilation sites. Mongolian gerbils were inoculated with H. pylori clonal isolates containing one or three EPIYA-C phosphorylation sites. Control group was composed by uninfected animals challenged with Brucella broth alone. Gastric fragments were evaluated by the modified Sydney System and digital morphometry. Clonal relatedness between the isolates was considered by the identical RAPD-PCR profiles and sequencing of five housekeeping genes, vacA i/d region and of oipA. The other virulence markers were present in both isolates (vacA s1i1d1m1, iceA2, and intact dupA). CagA of both isolates was translocated and phosphorylated in AGS cells. After 45 days of infection, there was a significant increase in the number of inflammatory cells and in the area of the lamina propria in the infected animals, notably in those infected by the CagA-positive strain with three EPIYA-C phosphorylation sites. After six months of infection, a high number of EPIYA-C phosphorylation sites was associated with progressive increase in the intensity of gastritis and in the area of the lamina propria. Atrophy, intestinal metaplasia, and dysplasia were also observed more frequently in animals infected with the CagA-positive isolate with three EPIYA-C sites. We conclude that infection with H. pylori strain carrying a high number of CagA EPIYA-C phosphorylation sites is associated with more severe gastric lesions in an animal model of H. pylori infection.
Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Infecções por Helicobacter/patologia , Estômago/patologia , Idoso , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA Bacteriano/genética , Progressão da Doença , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gerbillinae , Infecções por Helicobacter/microbiologia , Humanos , Dados de Sequência Molecular , Fosforilação , Transporte Proteico , Neoplasias Gástricas/patologia , Urease/análise , Urease/metabolismoRESUMO
The use of ilioischial cage reconstruction for pelvic discontinuity has been replaced by the Trabecular Metal (Zimmer, Warsaw, Indiana) cup-cage technique in our institution, due to the unsatisfactory outcome of using a cage alone in this situation. We report the outcome of 26 pelvic discontinuities in 24 patients (20 women and four men, mean age 65 years (44 to 84)) treated by the cup-cage technique at a mean follow-up of 82 months (12 to 113) and compared them with a series of 19 pelvic discontinuities in 19 patients (18 women and one man, mean age 70 years (42 to 86)) treated with a cage at a mean follow-up of 69 months (1 to 170). The clinical and radiological outcomes as well as the survivorship of the groups were compared. In all, four of the cup-cage group (15%) and 13 (68%) of the cage group failed due to septic or aseptic loosening. The seven-year survivorship was 87.2% (95% confidence interval (CI) 71 to 103) for the cup-cage group and 49.9% (95% CI 15 to 84) for the cage-alone group (p = 0.009). There were four major complications in the cup-cage group and nine in the cage group. Radiological union of the discontinuity was found in all successful cases in the cup-cage group and three of the successful cage cases. Three hips in the cup-cage group developed early radiological migration of the components, which stabilised with a successful outcome. Cup-cage reconstruction is a reliable technique for treating pelvic discontinuity in mid-term follow-up and is preferred to ilioischial cage reconstruction. If the continuity of the bone graft at the discontinuity site is not disrupted, early migration of the components does not necessarily result in failure.