Deletion of Smad7 Ameliorates Intestinal Inflammation and Contributes to Fibrosis.

Background: Patients suffering from inflammatory bowel diseases (IBDs) express increased mucosal levels of transforming growth factor (TGF)-β compared with non-IBD controls. SMAD7 negatively regulates TGF-β signaling. An earlier study aiming to target Smad7 showed a lack of clinical benefit.

[Understand, assess and manage the pain of children with profound intellectual and multiple disabilities].

Children with profound intellectual and multiple disabilities are highly vulnerable. It is related to their numerous medical issues, their reliance on complex care as well as support for daily living activities. They also have frequent reason to visit emergent care.

pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis.

Local extracellular acidification occurs at sites of inflammation. Proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1, also known as GPR68) responds to decreases in extracellular pH. Our previous studies show a role for OGR1 in the pathogenesis of mucosal inflammation, suggesting a link between tissue pH and immune responses.

MMP9 expression in intestinal fistula from patients with fistulizing CD and from human xenograft mouse model.

Fistula treatment represents a major unmet medical need in the therapy of Crohn's disease (CD). Current medical therapies, such as anti-TNF antibody treatments, are often insufficient and do not achieve permanent fistula closure. Previously published data point toward a critical role for metalloproteinase-9 (MMP-9)/gelatinase B in fistula pathogenesis.

New Therapeutic Approach for Intestinal Fibrosis Through Inhibition of pH-Sensing Receptor GPR4.

Background: Patients suffering from inflammatory bowel diseases (IBDs) express increased mucosal levels of pH-sensing receptors compared with non-IBD controls. Acidification leads to angiogenesis and extracellular matrix remodeling. We aimed to determine the expression of pH-sensing G protein-coupled receptor 4 (GPR4) in fibrotic lesions in Crohn's disease (CD) patients.

Succinate Activates EMT in Intestinal Epithelial Cells through SUCNR1: A Novel Protagonist in Fistula Development.

The pathogenesis of Crohn's disease-associated fibrostenosis and fistulas imply the epithelial-to-mesenchymal transition (EMT) process. As succinate and its receptor (SUCNR1) are involved in intestinal inflammation and fibrosis, we investigated their relevance in EMT and Crohn's disease (CD) fistulas. Succinate levels and SUCNR1-expression were analyzed in intestinal resections from non-Inflammatory Bowel Disease (non-IBD) subjects and CD patients with stenosing-B2 or penetrating-B3 complications and in a murine heterotopic-transplant model of intestinal fibrosis.

WNT2b Activates Epithelial-mesenchymal Transition Through FZD4: Relevance in Penetrating Crohn´s Disease.

Background And Aims: Epithelial-mesenchymal transition [EMT] has been related to fibrosis and fistula formation, common complications associated with Crohn´s disease [CD]. The WNT signalling pathway mediates EMT, and specific WNT/FZD interactions have been related to the activation of this process in several diseases. We aim to analyse the relevance of EMT and WNT ligands and receptors in the penetrating behaviour of CD.

The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis.

Intestinal fibrosis and stenosis are common complications of Crohn's disease [CD], frequently requiring surgery. Anti-inflammatory strategies can only partially prevent fibrosis; hence, anti-fibrotic therapies remain an unmet clinical need. Oxysterols are oxidised cholesterol derivatives with important roles in various biological processes.

β -integrin serves as a novel serum tumor marker for colorectal carcinoma.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β -integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts.

Tofacitinib for the Treatment of Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a difficult-to-treat inflammatory skin condition that affects inflammatory bowel disease (IBD) patients. There is no standardized approach for PG treatment. We report the results of 3 patients with Crohn's disease (CD) and refractory PG who had failed several therapies with biologics and were started on tofacitinib for severe inflammatory arthritis with resolution of their PG.

Severity of local inflammation does not impact development of fibrosis in mouse models of intestinal fibrosis.

Intestinal fibrosis is thought to be a consequence of excessive tissue repair, and constitutes a common problem in patients with Crohn's disease (CD). While fibrosis seems to require inflammation as a prerequisite it is unclear whether the severity or persistence of inflammation influences the degree of fibrosis. Our aim was to investigate the role of sustained inflammation in fibrogenesis.

Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis.

Background And Aims: pH-sensing ovarian cancer G-protein coupled receptor-1 [OGR1/GPR68] is regulated by key inflammatory cytokines. Patients suffering from inflammatory bowel diseases [IBDs] express increased mucosal levels of OGR1 compared with non-IBD controls. pH-sensing may be relevant for progression of fibrosis, as extracellular acidification leads to fibroblast activation and extracellular matrix remodelling.

BCL2 Regulates Differentiation of Intestinal Fibroblasts.

Background: Fibrosis in patients with Crohn's disease (CD) results from an imbalance toward excessive fibrous tissue formation driven by fibroblasts. Activation of fibroblasts is linked to the B-cell lymphoma 2 (BCL2) family, which is involved in the induction of apoptosis. We investigated the impact of BCL2 repression on fibrogenesis.

BCL-2 levels do not predict azathioprine treatment response in inflammatory bowel disease, but inhibition induces lymphocyte apoptosis and ameliorates colitis in mice.

In inflammatory bowel disease (IBD), inflammation is sustained by an exaggerated response of lymphocytes. This results from enhanced expression of anti-apoptotic B cell lymphoma (BCL-2) and BCL-XL associated with a diminished turnover. Azathioprine (AZA) directly targets BCL-2 family-mediated apoptosis.

Complex regional pain syndrome type I in children: What is new?

Complex regional pain syndrome type I (CRPS-I), although first described by the French surgeon Ambroise Paré as far back as the 16th century, nevertheless remains shrouded in mystery. The most common symptoms are pain in an entire hand or foot, allodynia, functional impairment induced by the pain, local oedema and skin color changes and transient sweating abnormalities. Most cases occur after a minor injury (i.

Anti-MMP-9 Antibody: A Promising Therapeutic Strategy for Treatment of Inflammatory Bowel Disease Complications with Fibrosis.

Background: Despite medical treatments or surgical options, more than one-third of patients with Crohn's disease suffer from recurring fistulae. Matrix metalloprotease 9 (MMP-9), a type IV collagenase that cleaves components of the extracellular matrix leading to tissue remodeling, is upregulated in crypt abscesses and around fistulae suggesting an important role for this enzyme in fistula formation. Our aims were (1) to correlate serum levels of MMP-9 degradation products in patients with CD with the presence of fistulae and (2) to investigate the impact of selective MMP-9 inhibition in a mouse model of intestinal fibrosis.

Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis.

Background: Fibrosis as a common problem in patients with Crohn's disease is a result of an imbalance toward excessive tissue repair. At present, there is no specific treatment option. Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis with both antifibrotic and anti-inflammatory effects.

Impact of policies regulating foreign physician migration to Switzerland: a modelling case study in anaesthesia.

Background: Several countries have developed policies that restrict or limit duration of stay, clinical privileges or the number of residency permits allocated to migrating physicians. Switzerland is currently preparing a new law limiting overall foreign immigration. The impact of such restrictive policies is currently unknown.

First evidence of a polygenic susceptibility to pain in a pediatric cohort.

Background: There is currently no evidence about the genetic bases of postoperative pain variability in children.

Methods: We prospectively followed a cohort of 168 children after orthopedic or abdominal surgery, who were under morphine patient-controlled analgesia. The children and their parents were genotyped for 6 candidate-gene polymorphisms (single-nucleotide polymorphisms [SNPs]) implicated in nociception and opiate metabolism: ABCB1C3435T, COMTVal158Met, NTRK1His40Tyr, OPRMA118G, POMCArg236Gln, and a haplotype of CYP2D6.

[Prevention of postoperative hyperalgesia].

Three types of hyperalgesia can occur during the postoperative period: primary hyperalgesia, which disappears with wound healing, secondary or central hyperalgesia, which can lead to chronic pain, and opiate-induced hyperalgesia. Different drugs, most of which are NMDA receptors antagonists, are used to decrease or prevent the risk of central or opiate-induced hyperalgesia. However, it is difficult to determine whether they are really effective and at which dosage: the results of most published studies are difficult to interpret because of methodological problems.

Swiss healthcare cost containment policies and their impact on anaesthetists' density and satisfaction.

Introduction: To control healthcare costs, Federal and Cantonal states have introduced policies to limit expenses and the number of practising physicians. It is unclear to date whether these policies have had a real impact on anaesthetists in Switzerland. The aim of the current study was to assess the density, characteristics and satisfaction of anaesthetists in Latin Switzerland and to compare the results with data collected before the introduction of cost containment policies in 2002.

Control of the establishment of aversive memory by calcineurin and Zif268.

Emotional memory is a rapidly acquired and persistent form of memory, and its robustness is in part determined by the initial strength of the memory. Here, we provide new evidence that the protein phosphatase calcineurin (CaN), a potent negative regulator of neuronal signaling that is known to constrain learning and memory, critically regulates the establishment of emotional memory through mechanisms involving the immediate early gene Zif268 (also known as Egr1). We found that CaN is inhibited in the amygdala during the establishment of aversive memory, but Zif268 is activated.

Cardiac rhythm and left ventricular function of infants at 1 MAC sevoflurane and halothane.

Background: The implementation of sevoflurane in pediatric anesthesia practice led to a decrease in the incidence of cardiac arrest previously reported with halothane. Nevertheless, the effects of sevoflurane on cardiac rhythm and function have not been systematically investigated in infants. Thus, we compared cardiac rhythm and left ventricular function at 1 MAC sevoflurane and halothane anesthesia and investigated the potential benefit effect of atropine.