Distribution of the pilS gene in Escherichia coli pathovars,its transfer ability and influence in the typical enteropathogenic E. coli adherence phenotype

Typical enteropathogenic Escherichia coli strains (tEPEC) cause attaching/effacing lesions in eukaryotic cells and produce the bundle-forming pilus (BFP), which interweaves and aggregates bacteria, resulting in the localized adherence (LA) pattern on eukaryotic cells. Previously, we identified tEPEC strains (serotype O119:H6) that exhibited LA simultaneously with an aggregative adherence (AA)-like pattern (LA/AA-like+). Remarkably, AA is characteristically produced by strains of enteroaggregative E. coli (EAEC), another diarrheagenic E. coli pathovar. In one LA/AA-like?+?strain (Ec404/03), we identified a conjugative plasmid containing the pil operon, which encodes the Pil fimbriae. Moreover, a pil operon associated with an AA pattern and plasmid transfer had been previously described in the EAEC C1096 strain. In this study, we investigated the occurrence of the two pilS alleles (pilS_Ec404 and pilS_C1096) in tEPEC strains of different serotypes, origins and years of isolation. We also examined the potential relationship of pilS with the AA-like phenotype, its ability to be transferred by conjugation, and occurrence among strains of the other E. coli pathovars. The pilS alleles were found in 90 (55.2%) of 163 tEPEC strains, with pilS_Ec404 occurring more often (30.7%) than pilS_C1096 (25.1%). About 21 tEPEC serotypes carried pilS. The pilS alleles were found in tEPEC strains from Chile, Peru and different Brazilian cities, with the oldest strain being isolated in 1966. No absolute correlation was found between the presence of pilS and the AA-like pattern. Conjugative pilS transfer was detected in 26.2% of pilS_Ec404+ strains and in 65.1% of pilS_C1096+ strains, but only pilS_Ec404+ transconjugants were AA-like+, thus suggesting that the latter allele might need a different genetic background to express this phenotype. pilS was found in all other E. coli pathovars, where it was most prevalent in enterotoxigenic E. coli. More studies are needed to understand the mechanisms involved in the regulation of Pil expression and production.     

Recommendations for the use of fluoride in caries prevention

From a theoretical point of view, caries can be prevented by perfect oral hygiene and sugar abstinence. However, practice has shown that this approach is successful in individual cases only. For the whole population, effective caries prevention is still not realistic without the use of fluoride in various forms. The use of different fluoride preparations increases its efficacy. On the other hand, correct dosage is important to prevent the risk of dental fluorosis. Most of the European scientific dental associations no longer recommend the use of fluoride supplements, such as fluoride tablets or drops, as a standard procedure in caries prevention. This is due to the increasing evidence that the effect of fluoride is mainly the result of chemical reactions on the tooth surface. Therefore, fluoridated toothpastes, gels, varnishes, and rinses are more in focus. Besides this, fluoridated water and fluoridated salt are still important. Although they have a systemic effect, the efficacy of these fluoride applications results from local processes.     

High Vitamin D Deficiency Rate in Metabolic Inpatients: Is Bariatric Surgery Planning Found Guilty?

Background

High rates of vitamin D insufficiency are usually found in obese patients, even before any malabsorptive bariatric surgery. It is not clear whether they lack vitamin D because of different food intake, different solar exposure, or different storage pathways or bioavailability in adipose tissue. To better understand vitamin D deficiency, we studied different categories of inpatients.

Methods

We collected clinical and biological data from 457 consecutive inpatients during a year: 217 nonobese diabetic patients, 159 obese nonsurgical diabetic patients, 46 obese surgical nondiabetic patients, and 35 obese surgical diabetic patients. Statistically significant differences between two mean 25-hydroxyvitamin D (25(OH)D) levels were defined at the 5 % level using a Z-test.

Results

Vitamin D deficiency was found in 69 % of the patients, while 24 % had a normal level and 7 % an optimal level. A significant difference was found between obese (25(OH)D?=?40.3 nmol/l) and nonobese patients (25(OH)D?=?46.8 nmol/l). Patients undergoing bariatric surgery were not different from the other obese patients.

Conclusion

No significant difference in 25(OH) vitamin D level could be demonstrated between obese patients before bariatric surgery and obese patients with no obesity surgery project. No difference was found between our Parisian obese population and a Spanish obese population, which benefits from a better solar exposure. Both findings suggest that obesity itself is the link with vitamin D deficiency, independently from behavioral differences.     

Preoperative antihypertensive medication intake and acute kidney injury after major vascular surgery

Objective

Postoperative acute kidney injury (AKI) is frequent after major vascular surgery and is associated with significant morbidity and mortality. It remains unclear whether the administration of combined oral antihypertensive medications on the day of surgery can increase the risk of postoperative AKI.

Inhibition of platelet activation prevents the P‐selectin and integrin‐dependent accumulation of cancer cell microparticles and reduces tumor growth and metastasis in vivo

Venous thromboembolism constitutes one of the main causes of death during the progression of a cancer. We previously demonstrated that tissue factor (TF)‐bearing cancer cell‐derived microparticles accumulate at the site of injury in mice developing a pancreatic cancer. The presence of these microparticles at the site of thrombosis correlates with the size of the platelet‐rich thrombus. The objective of this study was to determine the involvement of TF expressed by cancer cell‐derived microparticles on thrombosis associated with cancer. We observed that pancreatic cancer cell derived microparticles expressed TF, its inhibitor tissue factor pathway inhibitor (TFPI) as well as the integrins αvβ1 and αvβ3. In mice bearing a tumor under‐expressing TF, a significant decrease in circulating TF activity associated with an increase bleeding time and a 100‐fold diminished fibrin generation and platelet accumulation at the site of injury were observed. This was mainly due to the interaction of circulating cancer cell‐derived microparticles expressing TFPI with activated platelets and fibrinogen. In an ectopic model of cancer, treatment of mice with Clopidogrel, an anti‐platelet drug, decreased the size of the tumors and restored hemostasis by preventing the accumulation of cancer cell‐derived microparticles at the site of thrombosis. In a syngeneic orthotopic model of pancreatic cancer Clopidogrel also significantly inhibited the development of metastases. Together, these results indicate that an anti‐platelet strategy may efficiently treat thrombosis associated with cancer and reduce the progression of pancreatic cancer in mice.     

PACE4 inhibitors and their peptidomimetic analogs block prostate cancer tumor progression through quiescence induction,increased apoptosis and impaired neovascularisation

Prostate cancer is the leading cancer in North American men. Current pharmacological treatments are limited to anti-androgen strategies and the development of new therapeutic approaches remains a challenge. As a fundamentally new approach, we propose the inhibition of PACE4, a member of the proprotein convertases family of enzymes, as a therapeutic target in prostate cancer. We developed an inhibitor named the Multi-Leu peptide, with potent in vitro anti-proliferative effects. However, the Multi-Leu peptide has not been tested under in vivo conditions and its potency under such conditions is most likely limited, due to the labile characteristics of peptides in general. Using a peptidomimetic approach, we modified the initial scaffold, generating the analog Ac-[DLeu]LLLRVK-Amba, which demonstrates increased inhibitory potency and stability. The systemic administration of this peptidomimetic significantly inhibits tumor progression in the LNCaP xenograft model of prostate cancer by inducing tumor cell quiescence, increased apoptosis and neovascularization impairment. Pharmacokinetic and biodistribution profiles of this inhibitor confirm adequate tumor delivery properties of the compound. We conclude that PACE4 peptidomimetic inhibitors could result in stable and potent drugs for a novel therapeutic strategy for prostate cancer.