Primary resistance to clarithromycin, metronidazole and amoxicillin of Helicobacter pylori isolated from Tunisian patients with peptic ulcers and gastritis: a prospective multicentre study

<p>Abstract</p> <p>Background</p> <p>The frequency of primary resistance to antibiotics in H. pylori isolates is increasing worldwide. In Tunisia, there are limited data regarding the pattern of H. pylori antibiotic primary resistance.</p> <p>Aim</p> <p>To evaluate the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and to detect the mutations involved in clarithromycin resistance.</p> <p>Materials and methods</p> <p>273 strains isolated from adults and children were enrolled. The primary resistance to clarithromycin, metronidazole and amoxicillin was evaluated by means of E-test minimal inhibitory concentration (MIC). The real-time PCR using Scorpion primers was performed in all cases to assess clarithromycin primary resistance and point mutations involved.</p> <p>Results</p> <p>No resistance to amoxicillin was detected. For adults, resistance to clarithromycin and metronidazole was found respectively in 14.6% and 56.8%, and respectively in 18.8% and 25% in children. Overall, the rates of global primary resistance to clarithromycin and metronidazole in Tunisia were respectively determined in 15.4% and 51.3%.</p> <p>By the use of Scorpion PCR, the A2143G was the most frequent point mutation observed (88.1%), followed by the A2142G (11.9%); the A2142C was not found and 18 of 42 patients (42.8%) were infected by both the resistant and the susceptible genotype.</p> <p>The association of clarithromycin resistance with gender was not statistically significant, but metronidazole resistant strains were isolated more frequently in females (67.8%) than in males (32.2%) and the difference was significant. As for gastroduodenal diseases, the difference between strains isolated from patients with peptic ulceration and those with non peptic ulceration was not statistically significant. When about the distribution of resistant strains to clarithromycin and metronidazole between the three Tunisian cities (Tunis, Menzel Bourguiba and Mahdia), the difference was not statistically significant.</p> <p>Conclusion</p> <p>Local data regarding the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and the main genetic mutation involved in clarithromycin resistance in vivo (A2143G) are necessary to prove a clear need for a periodic evaluation of antibiotic consumption and new therapeutic strategies in Tunisia in order to avoid the emergence of resistant strains.</p

Combined effects of <it>IL-8 </it>and <it>CXCR2 </it>gene polymorphisms on breast cancer susceptibility and aggressiveness

Abstract Background Interleukin-8 (IL-8/CXCL-8) is a prototype of the ELR+CXC chemokines that play an important role in the promotion and progression of many human cancers including breast cancer. We have recently showed the implication of polymorphism (-251) T/A of IL-8 gene in the susceptibility and prognosis of breast carcinoma. IL-8 acts through its CXCR1 and CXCR2 receptors. CXCR2, expressed on the endothelial cells, is the receptor involved in mediating the angiogenic effects of ELR+CXC chemokines and in particular IL-8. In the current study, we investigated the susceptibility and prognostic implications of the genetic variation in CXCR2 in breast carcinoma. We also confirmed the implication of IL-8 (-251) T/A polymorphism in a larger cohort. Finally, we combined the IL-8 and CXCR2 variant alleles and analyzed their effects in breast cancer risk and prognosis. Methods We used the allele-specific polymerase chain reaction to characterize the variation of IL-8 and CXCR2 for 409 unrelated Tunisian patients with breast carcinoma and 301 healthy control subjects. To estimate the relative risks, Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for the known risk factors for breast cancer. Associations of the genetic marker with the rates of breast carcinoma-specific overall survival and disease-free survival were assessed using univariate and multivariate analyses. Results A highly significant association was found between the homozygous CXCR2 (+ 1208) TT genotype (adjusted OR = 2.89; P = 0.008) and breast carcinoma. A significantly increased risk of breast carcinoma was associated with IL-8 (-251) A allele (adjusted OR = 1.86; P = 0.001). The presence of two higher risk genotypes (the TA and TT in IL-8, and the TT in CXCR2) significantly increased the risk of developing breast carcinoma (adjusted OR = 4.15; P = 0.0004). The CXCR2 (+ 1208) T allele manifested a significant association with an aggressive phenotype of breast carcinoma as defined by a large tumor size, a high histological grade, and auxiliary's lymph node metastasis. A significant association between the IL-8 (-251) A allele and the aggressive form of breast carcinoma was also found. Moreover, the presence of the IL-8 (-251) A and/or the CXCR2 (+ 1208) T allele showed a significant association with a decreased overall survival and disease-free survival in breast carcinoma patients. Conclusion Our results indicated that the polymorphisms in IL-8 and CXCR2 genes are associated with increased breast cancer risk, as well as disease progress, supporting our hypothesis for IL-8 and ELR+CXC chemokine receptor (CXCR2) involvement in breast cancer pathogenesis.</p

The relationship between coagulation disorders and the risk of bleeding in cirrhotic patients

Introduction and Objectives: For long, bleeding in cirrhotic patients has been associated with acquired coagulation disorders. The aim of our study was to investigate the impact of acquired coagulation disorders on bleeding risk in cirrhotic patients. Materials and methods: Blood samples were collected from 51 cirrhotic patients with (H+) or without (H−) bleeding events and 50 controls matched by age and sex. Thrombin generation was assessed as endogenous thrombin potential (ETP). Hemostatic balance was assessed by means of ratios of pro- to anticoagulant factors and by ETP ratio with/without protein C (PC) activator (ETP ratio). Results: Bleeding events occurred in 9 patients (17.6%). Compared with controls, VIII/anticoagulant factors, VII/PC and XII/PC were significantly higher in (H+) patients. No significant difference as regards all ratios across patient groups was detected. ETP ratio was significantly higher in (H+) patients than in controls (p = 0.017). However, there was no significant difference between patient groups as regards ETP ratio. Conclusion: Hemostatic balance is shifted toward a hypercoagulability state even in cirrhotic patients who experienced bleeding. These findings provide evidence against traditional concept of hemostasis-related bleeding tendency in cirrhotic patients

Association between an angiotensin-converting enzyme gene polymorphism and Alzheimer’s disease in a Tunisian population

Abstract Background The angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D or indel) polymorphism has long been linked to Alzheimer’s disease (AD), but the interpretation of established data remains controversial. The aim of this study was to determine whether the angiotensin-converting enzyme is associated with the risk of Alzheimer’s disease in Tunisian patients. Methods We analyzed the genotype and allele frequency distribution of the ACE I/D gene polymorphism in 60 Tunisian AD patients and 120 healthy controls. Results There is a significantly increased risk of AD in carriers of the D/D genotype (51.67% in patients vs. 31.67% in controls; p = .008, OR = 2.32). The D allele was also more frequently found in patients compared with controls (71.67% vs. 56.25%; p = .003, OR = 2.0). Moreover, as assessed by the Mini-Mental State Examination, patient D/D carriers were more frequently found to score in the severe category of dementia (65%) as compared to the moderate category (32%) or mild category (3%). Conclusions The D/D genotype and D allele of the ACE I/D polymorphism were associated with an increased risk in the development of AD in a Tunisian population. Furthermore, at the time of patient evaluation (average age 75 years), patients suffering with severe dementia were found predominantly in D/D carriers and, conversely, the D/D genotype and D allele were more frequently found in AD patients with severe dementia. These preliminary exploratory results should be confirmed in larger studies and further work is required to explore and interpret possible alternative findings in diverse populations

Rôle de la cellule épithéliale dans l’homéostasie intestinale et les maladies inflammatoires chroniques de l’intestin

La maladie de Crohn (MC) et la rectocolite hémorragique (RCH) sont les principales maladies inflammatoires chroniques de l’intestin (MICI), dont l’étiopathogénie est actuellement mal définie. Au cours de ces maladies, la participation de la cellule épithéliale dans l’installation et la pérennisation de l’inflammation intestinale est de plus en plus impliquée. En effet, l’épithélium intestinal, situé à l’interface entre le milieu intérieur tissulaire et la lumière intestinale, est le pivot des mécanismes de l’homéostasie de la barrière intestinale. Cet épithélium peut être schématiquement considérée comme constitué de trois « barrières » distinctes : une barrière physique, une barrière chimique et une barrière immunitaire. Cette fonction de barrière peut être altérée par différents mécanismes physiopathologiques, comme dans les MICI. Le rôle de la cellule épithéliale dans l’homéostasie intestinale et son implication dans les MICI sont analysés dans cette revue