Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice.

Chronic cholestasis is associated with increased bacterial infections and sepsis resulting in higher mortality in humans. In the current study, we investigated the relevance of gp130-dependent pathways after bile duct ligation (BDL). BDL was performed in conditional gp130 knockout (loxP/Cre system) mice and respective controls.

The adiponectin paralog CORS-26 has anti-inflammatory properties and is produced by human monocytic cells.

The adiponectin paralog CORS-26 (collagenous repeat-containing sequence of 26kDa protein) is a member of the C1q/TNF-alpha molecular superfamily. CORS-26 is a secreted protein and baculovirus-produced CORS-26 released in the supernatant of insect cells forms stable trimers. Adiponectin exerts anti-inflammatory effects in LPS-treated monocytic cells and CORS-26 also reduces IL-6 and TNF-alpha secretion but does not increase IL-10.

Androgen conversion in osteoarthritis and rheumatoid arthritis synoviocytes--androstenedione and testosterone inhibit estrogen formation and favor production of more potent 5alpha-reduced androgens.

In synovial cells of patients with osteoarthritis (OA) and rheumatoid arthritis (RA), conversion products of major anti-inflammatory androgens are as yet unknown but may be proinflammatory. Therefore, therapy with androgens in RA could be a problem. This study was carried out in order to compare conversion products of androgens in RA and OA synoviocytes.

The effect of chromoendoscopy on the diagnostic improvement of gastric ulcers by endoscopists with different levels of experience.

Background: In recent years chromoendoscopy has become popular as a diagnostic enhancement tool in endoscopy. Using the macroscopic description of gastric ulcers, experienced endoscopists may be able to differentiate malignant and benign lesions. The aim of our study was to determine whether indigo carmine staining improves the ulcer differentiation by experienced and inexperienced endoscopists.

CpG motifs of bacterial DNA essentially contribute to the perpetuation of chronic intestinal inflammation.

Background & Aims: Recently, we demonstrated a proinflammatory effect of cytosin-guanosin dinucleotide (CpG)-oligodeoxynucleotide (ODN) treatment in established dextran sulphate sodium (DSS)-induced colitis. Here, we investigated whether DNA derived from luminal bacteria plays a role in the perpetuation of chronic intestinal inflammation.

Methods: Toll-like receptor (TLR9)-deficient and wild-type (wt) control mice were used for the induction of chronic DSS colitis.

Promoter-hypermethylation is causing functional relevant downregulation of methylthioadenosine phosphorylase (MTAP) expression in hepatocellular carcinoma.

The methylthioadenosine phosphorylase (MTAP) gene is localized in the chromosomal region 9p21. Here, frequently homozygous deletions occur in several kinds of cancer associated with the loss of tumour suppressor genes as p16 and p15. The aim of this study was to analyse MTAP expression in hepatocellular carcinoma (HCC) and to get an insight into the regulation and functional role of MTAP in hepatocancerogenesis.

Anti-TNF antibody treatment improves glucocorticoid induced insulin-like growth factor 1 (IGF1) resistance without influencing myoglobin and IGF1 binding proteins 1 and 3.

Background: Insulin-like growth factor 1 (IGF1) is an important determinant of muscle mass because it promotes growth and suppresses protein degradation. IGF1 is decreased in rheumatoid arthritis and juvenile idiopathic arthritis because its synthesis is inhibited by inflammation. In parallel, glucocorticoids induce IGF1 resistance and add to muscle degradation.

Immune status and risk for infection in patients receiving chronic immunosuppressive therapy.

Objective: Chronic immunosuppressive therapy may be complicated by infections indicating a more or less profound immune defect. However, immune monitoring to estimate the risk for infection has so far not been performed routinely. The aim of this study was (1) to investigate the effects of commonly used immunosuppressive treatment regimens on lymphocyte subsets and cytokine release from stimulated whole blood cultures in patients with rheumatic or autoimmune diseases; and (2) to determine whether such measurements could be used as predictors of infection, and if so, to determine their predictive value for subsequent infectious complications.

Zinc finger protein 267 is up-regulated during the activation process of human hepatic stellate cells and functions as a negative transcriptional regulator of MMP-10.

Activation of hepatic stellate cells (HSCs) is the central event in the development of liver fibrosis and cirrhosis. The transdifferentiation process of quiescent into activated HSCs requires a complete reprogramming in gene expression, which is governed by modulation of transcriptional activators or repressors. Using microarray analysis to identify genes differentially expressed during the activation process of human HSCs, zinc finger protein 267 (ZNF267) mRNA was up-regulated in activated HSCs and in cirrhotic human liver.

Caucasian patients with type 2 diabetes mellitus have elevated levels of monocyte chemoattractant protein-1 that are not influenced by the -2518 A-->G promoter polymorphism.

Aim: To investigate the association of serum levels and the -2518 A-->G promoter polymorphism of the gene for chemokine monocyte chemoattractant protein-1 (MCP-1), a major chemoattractant of monocytes and activated lymphocytes, with metabolic parameters as well as insulin, leptin and the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in 534 Caucasian patients with type 2 diabetes mellitus.

Methods: MCP-1 concentrations were measured by enzyme-linked immunosorbent assay. MCP-1 genotyping was performed by RFLP analysis in a subset of 426 patients.

Hypothesis paper Brain talks with fat--evidence for a hypothalamic-pituitary-adipose axis?

The adipose tissue signals to the brain via its secretory products. However, it is unknown whether the brain itself can directly contact the fat tissue. In order to test this hypothesis, the adipocytic expression of receptors for pituitary hormones and hypothalamic peptides was investigated.

Adrenal and gonadal hormone variations during a febrile attack in a woman with tumor necrosis factor receptor-associated periodic syndrome.

Context: TNF-receptor-associated periodic syndrome (TRAPS) is a hereditary fever syndrome that results from mutations in the TNF-receptor superfamily 1A gene (TNFRSF1A). It is characterized by periodic fever, arthralgia, abdominal pain, myalgia, headache, and skin lesions.

Objective: Because adrenal and gonadal hormone cascades are modulated by TNF, this study aimed to investigate specific hormones and enzyme steps during an attack phase in a woman with TRAPS.

Ablation of the sympathetic nervous system decreases gram-negative and increases gram-positive bacterial dissemination: key roles for tumor necrosis factor/phagocytes and interleukin-4/lymphocytes.

The sympathetic nervous system is intensely activated during bacteremia, but its immediate influence on the bacterial tissue burden remains unclear. We demonstrate that prior ablation of the sympathetic nervous system decreases this dissemination of Pseudomonas aeruginosa or Escherichia coli through a mechanism of increased secretion of peritoneal tumor necrosis factor, improved phagocytic response of peritoneal cells, and increased influx of monocytes into the peritoneal cavity. When gram-positive Staphylococcus aureus strains were used, sympathectomy increased the bacterial tissue burden, which was caused by a reduction in corticosterone tonus, and decreased both interleukin-4 secretion from peritoneal cells and the influx of lymphocytes into the peritoneal cavity.

Regulation of adiponectin receptor 1 in human hepatocytes by agonists of nuclear receptors.

The adiponectin receptors AdipoR1 and AdipoR2 have been identified to mediate the insulin-sensitizing effects of adiponectin. Although AdipoR2 was suggested to be the main receptor for this adipokine in hepatocytes, AdipoR1 protein is highly abundant in primary human hepatocytes and hepatocytic cell lines. Nuclear receptors are main regulators of lipid metabolism and activation of peroxisome proliferator-activated receptor alpha and gamma, retinoid X receptor (RXR), and liver X receptor (LXR) by specific ligands may influence AdipoR1 abundance.

In vitro cultivation of an insect Microsporidian Tubulinosema ratisbonensis in mammalian cells.

Tubulinosema ratisbonensis is a microsporidian pathogen of Drosophila melanogaster belonging to the family Tubulinosematidae. The microsporidia in this family mainly cause infections in invertebrate hosts, but two members of this family, Brachiola vesicularum and Brachiola algerae, have been found to cause infections in humans as well. Moreover, B.

Influence of intestinal bacteria on induction of regulatory T cells: lessons from a transfer model of colitis.

Background: The resident flora plays a critical role in initiation and perpetuation of intestinal inflammation, as demonstrated in experimental models of colitis where animals fail to develop disease under germ free conditions. However, the importance of exposure to commensal bacteria before the onset of colitis is unclear. Our aim was to investigate the influence of previous exposure of donor animals to bacterial antigens on colitis development using a transfer model.

Up-regulation of nNOS and associated increase in nitrergic vasodilation in superior mesenteric arteries in pre-hepatic portal hypertension.

Background/aims: Splanchnic arterial vasodilation in portal hypertension has been attributed largely to vascular NO overproduction. Three NO-synthase (NOS) isoforms have been identified of which e(ndothelial)-NOS has been found up-regulated and i(nducible)-NOS not expressed in the splanchnic circulation in portal hypertension. So far, n(euronal)-NOS has not been investigated and hence, the current study evaluates nNOS-expression and nNOS-mediated vasorelaxation in a model of portal vein-ligated rats (PVL).

Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamic-pituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems.

Objective: To study in parallel the outflow of the sympathetic nervous system (SNS) and the hypothalamic-pituitary adrenal (HPA) axis tone in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods: 32 patients with SLE, 62 with RA, and 65 healthy subjects (HS) were included. To measure the tone of the HPA axis, plasma ACTH and serum cortisol were determined.

Reduced capacity for the reactivation of glucocorticoids in rheumatoid arthritis synovial cells: possible role of the sympathetic nervous system?

Objective: Cortisol, the biologically active glucocorticoid, is a major endogenous antiinflammatory factor in rheumatoid arthritis (RA). The aim of this study was to examine the local conversion of cortisol to biologically inactive cortisone and vice versa (the cortisol-cortisone shuttle) in RA and osteoarthritis (OA) patients.

Methods: Thin-layer chromatography and phosphorimaging were used to examine the cortisol-cortisone shuttle in mixed synovial cells.

Tumor necrosis factor inhibits conversion of dehydroepiandrosterone sulfate (DHEAS) to DHEA in rheumatoid arthritis synovial cells: a prerequisite for local androgen deficiency.

Objective: Use of anti-tumor necrosis factor (anti-TNF) antibody therapy in rheumatoid arthritis (RA) has expanded our understanding of possible mechanisms by which this treatment reduces inflammation. Beyond its effects on local immune responses, anti-TNF treatment may also modulate the local hormone supply. Because androgens are thought to inhibit immune responses, their presence in inflamed tissue is an additional important antiinflammatory factor.

Analysis of intestinal haem-oxygenase-1 (HO-1) in clinical and experimental colitis.

Haem-oxygenase-1 (HO-1) has been shown to exert anti-inflammatory, anti-apoptotic and anti-proliferative effects. We investigated HO-1 expression in patients with inflammatory bowel disease (IBD) and could demonstrate a scattered expression of HO-1 in the intestinal epithelium of severely inflamed colonic mucosa of patients with IBD compared to control specimens such as diverticulitis, suggesting dysregulated expression in IBD. To further analyse potential mechanisms of HO-1 induction in the intestine we employed an in vitro epithelial cell apoptosis model and an experimental colitis model.

[Acute coronary syndrome in a 17-year-old female with systemic lupus erythematosus].

A 17-year-old female was admitted to the hospital with epigastric pain radiating into the chest and neck. The patient had a known, long-standing history of systemic lupus erythematosus (SLE) with predominantly renal involvement. Diagnostic examinations including left heart catheterization showed acute myocardial infarction based on a coronary three-vessel disease.