Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells

Adenocarcinoma of the third and fourth portion of the duodenum: a case report and review of the literature

A 65-year-old woman presented with abdominal pain, weight loss, fatigue, and microcytic anemia. Esophagogastroduodenoscopy, until the second part of duodenum, was normal. Ultrasound and computed tomography demonstrated a solid mass in the distal duodenum. A repeat endoscopy confirmed an ulcerative, intraluminar mass in the third and fourth part of the duodenum. Segmental resection of the third and fourth portion of the duodenum was performed. Histology revealed an adenocarcinoma. On the 4th postoperative day, the patient developed severe acute pancreatitis leading to multiple organ failure and died on the 30th postoperative day

Duodenal carcinoma at the ligament of Treitz. A molecular and clinical perspective

Background There is very small occurrence of adenocarcinoma in the small bowel. We present a case of primary duodenal adenocarcinoma and discuss the findings of the case diagnostic modalities, current knowledge on the molecular biology behind small bowel neoplasms and treatment options. Case The patient had a history of iron deficiency anemia and occult bleeding with extensive workup consisting of upper endoscopy, colonoscopy, capsule endoscopy, upper gastrointestinal series with small bowel follow through and push enteroscopy. Due to persistent abdominal pain and iron deficiency anemia the patient underwent push enteroscopy which revealed adenocarcinoma of the duodenum. The patient underwent en-bloc duodenectomy which revealed T3N1M0 adenocarcinoma of the 4th portion of the duodenum. Conclusions Primary duodenal carcinoma, although rare should be considered in the differential diagnosis of occult gastrointestinal bleeding when evaluation of the lower and upper GI tract is unremarkable. We discuss the current evaluation and management of this small bowel neoplasm

Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future

There are a number of limitations to using conventional diagnostic markers for patients with clinical suspicion of infection. As a consequence, unnecessary and prolonged exposure to antimicrobial agents adversely affect patient outcomes, while inappropriate antibiotic therapy increases antibiotic resistance. A growing body of evidence supports the use of procalcitonin (PCT) to improve diagnosis of bacterial infections and to guide antibiotic therapy. For patients with upper and lower respiratory tract infection, post-operative infections and for severe sepsis patients in the intensive care unit, randomized-controlled trials have shown a benefit of using PCT algorithms to guide decisions about initiation and/or discontinuation of antibiotic therapy. For some other types of infections, observational studies have shown promising first results, but further intervention studies are needed before use of PCT in clinical routine can be recommended. The aim of this review is to summarize the current evidence for PCT in different infections and clinical settings, and discuss the reliability of this marker when used with validated diagnostic algorithms

The experience of low back pain in people with incomplete spinal cord injury in the USA, UK and Greece

Engineering and Physical Sciences Research Council's (EPSRC

Carbapenemase-producing Klebsiella pneumoniae: (When) might we still consider treating with carbapenems?

Infections caused by carbapenemase-producing Klebsiella pneumoniae (CPKP) are increasing in frequency worldwide. CPKP isolates exhibit extensive drug resistance phenotypes, complicate therapy, and limit treatment options. Although CPKP isolates are often highly resistant to carbapenems, a proportion of these have relatively low MICs for carbapenems, raising the question of whether this class of agents has any therapeutic potential against CPKP infections. Results from animal studies and patient outcome data indicate that carbapenems retain meaningful in vitro activity against CPKP isolates with carbapenem MICs of ≤4mg/L. Accumulating clinical experience also suggests that the therapeutic efficacy of carbapenems against CPKP isolates with MICs of ≤4mg/L is enhanced when these agents are administered in combination with another active antibiotic. The results of human pharmacokinetic/pharmacodynamic studies are in line with the above observations; it is highly probable that a high-dose/prolonged-infusion regimen of a carbapenem would attain a time above the MIC value of 50% for CPKP isolates with MICs up to 4mg/L, ensuring acceptable drug exposure and favourable treatment outcome. The analyses summarized in this review support the notion that carbapenems have their place in the treatment of CPKP infections and that the currently proposed EUCAST clinical breakpoints could direct physicians in making treatment decisions. © 2011 European Society of Clinical Microbiology and Infectious Diseases

Επίδραση των στεροειδών ορμονών στην έκφραση του ογκονιδίου C-ERBB2 /NEU στα αδενοκαρκινικά κύτταρα του ανθρώπινου ενδομητρίου (Κυτταρική σειρά ISHIKAWA)

Recent findings regarding the molecular action of steroid hormones and their role in endometrial cell transformation suggest that estrogens act as tumor promoters, propagating pre-existing DNA lesions in proto-oncogenes.Accordingly, we have investigated the effects of estrogens and other steroid ormones on erbB2 gene expression in Ishikawa human endometrial adenocarcinoma cells.We have found that the erbB2/neu transcript and its protein product are present in abundance, in the Ishikawa endometrial adenocarcinoma cell line as well as in human endometrial adenocarcinoma cells.Both cell types express the 4.6 and 2.3 Kb erbB2 mRNAs, resulting in the synthesis of the membrane 185 KDa and the truncated extracellular 100 KDa protein.Estradiol significantly increased in a time- and dose-dependent manner the content of erbB2 mRNA and the concentration of neu protein in Ishikawa cell extracts,while progesterone was devoid of any activity.The effect of estradiol was partially reversed by the antiestrogen 4-hydroxytamoxifen, which, however given alone exhibited agonistic effects.Glucocorticoid dexamethasone augmented in a time- and dose-dependent fashion the content of erbB2 mRNA and the concentration of neu Ishikawa cell extracts.The antiglucocordicoid RU 486 acted as glucocorticoid agonist increasing erbB2 gene activation.To our knowledge, this is the first expression in neoplastic human endometrial cells.Με βάση τη διεθνή βιβλιογραφία θπάρχουν ενδείξεις ότι τα στεροειδή επηρεάζουν την καρκινογένεση, ιδίως στο ενδομήτριο.Στην παρούσα εργασία μελετήσαμε την τυχούσα επίδραση των στεροειδών ορμονών στην έκφραση του ογκονιδίου c-erbB2 σε καλλιέργιας κυττάρων Ishikawa.Το ογκονίδιο c-erbB2/neu εκφράζεται στα κύτταρα Ishikawa και σε ανθρώπινα ενδομητριακά αδενοκαρκινικά κύτταρα τόσο σε επίπεδο mRNA όσο και σε επίπεδο πρωτεϊνης.Οι τύποι κυττάρων που μελετήσαμε εκφράζουν τα δύο γνωστά από τη βιβλιογραφία μεταγραφήματα (mRNAs) των 4.6 και 2.3 Κb.Τα δύο μεταγραφήματα του ογκονιδίου c-erbB2 οδηγούν αντίστοιχα στη σύνθεση της διαμεμβρανικής ογκοπρωτεϊνης μοριακού βάρους 185 Kda και της περικεκομμένης ενδοκυτταρικής πρωτεϊνης μοριακού βάρους 100 Kda.Η οιστραδιόλη αυξάνει σημαντικά κατά χρόνο- και δόσο-εξαρτώμενο τρόπο, τόσο την έκφραση του mRNA του neu ογκονιδίου, όσο και την έκφραση της ογκοπρωτεϊνης neu, ενώ η προγεστερόνη, έδειξε ότι δεν προκαλεί καμία δράση.Η δράση αυτή των οιστρογόνων φαίνεται να περνάει μέσα από τους οιστρογονικούς υποδοχείς δεδομένου ότι σύγχρονη επώαση με ταμοξιφαίνη προκαλεί μερική αναστολή της οιστρογονικής δράσης.Το αντιοιστρογόνο ταμοξιφαίνη όταν χορηγείται μόνο του δείχνει αγωνιστικές οιστρογονικές ιδιότητες, όσον αφορά την έκφραση του erbB2.Η δεξαμεθαζόνη προκαλεί την έκφραση του c-erbB2 ογκονιδίου και σε επίπεδο mRNA και σε επίπεδο πρωτεϊνης κατά δόσο- και χρόνο-εξατώμενο τρόπο

Adaptive resistance to cationic compounds in Pseudomonas aeruginosa

Adaptive resistance is an autoregulated phenomenon characterised by induction of resistance in the presence of drug and reversal to the sensitive phenotype in its absence. This type of resistance is well documented for polycationic antibiotics, including aminoglycosides and polymyxins, in Pseudomonas aeruginosa and other aerobic Gram-negative bacilli. It is not caused by selection of resistant mutants but rather by phenotypic alterations in order to survive the lethal drug effect. Adaptive resistance to aminoglycosides is mainly mediated by the MexXY-OprM efflux pump that is rapidly upregulated in bacteria surviving the first exposure to aminoglycosides and is downregulated when bacteria are no longer in contact with the drug. A two-component regulatory system designated ParR-ParS plays a major role in adaptive resistance induced by cationic peptides. In the presence of cationic peptides, ParR-ParS activates the lipopolysaccharide modification operon (arnBCADTEF) leading to increased resistance in polymyxins and aminoglycosides. The bactericidal kinetics related to adaptive resistance have important clinical implications and provide a rationale for administering cationic antibiotics in larger initial and longer interval bolus dosing. A better understanding of this phenomenon and the molecular mechanisms responsible will be essential not only for optimum use of cationic antibiotics but also for developing new agents with ability to counteract the detrimental effects of adaptive resistance and thus enhance the therapeutic efficacy of polycationic compounds. © 2010 Elsevier B.V. and the International Society of Chemotherapy