Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia

High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the...

The probiotic mixture VSL#3 mediates both pro- and anti-inflammatory responses in bone marrow-derived dendritic cells from C57BL/6 and BALB/c mice

Probiotic bacteria express a wide range of molecular structures that bind to receptors on innate immune cells and mediate health-promoting effects in the host. We have recently demonstrated in a colitis model that favourable effects of the probiotic mixture VSL#3 may in part be due to the suppression of intestinal chemokine expression. To obtain...

An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: A nutrigenomics approach

Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products [resveratrol, green tea extract, α-tocopherol,...

Release of 5-aminosalicylate from an MMX mesalamine tablet during transit through a simulated gastrointestinal tract system

5-Aminosalicylate (5-ASA; mesalamine) is the current first-line treatment for mild to moderate ulcerative colitis, a chronic inflammatory condition that most commonly affects the distal part of the colon. MMX™ mesalamine (Lialda™ [US]; Mezavant™ XL [UK and Ireland]; Mezavant™ [elsewhere]; Shire Pharmaceuticals Inc., Wayne, Pa, under license from...

Integration of two-dimensional LC-MS with multivariate statistics for comparative analysis of proteomic samples

LC-MS-based proteomics requires methods with high peak capacity and a high degree of automation, integrated with data-handling tools able to cope with the massive data produced and able to quantitatively compare them. This paper describes an off-line two-dimensional (2D) LC-MS method and its integration with software tools for data preprocessing...

In search of secreted protein biomarkers for the anti-inflammatory effect of β2-adrenergic receptor agonists: Application of DIGE technology in combination with multivariate and univariate data analysis tools

Two-dimensional difference gel electrophoresis (DIGE) in combination with univariate (Student's t-test) and multivariate data analysis, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to study the anti-inflammatory effects of the β2-adrenergic receptor (β2-AR) agonist zilpaterol. U937...

Inhibition of microglial inflammation by the MLK inhibitor CEP-1347

CEP-1347 is a potent inhibitor of the mixed lineage kinases (MLKs), a distinct family of mitogen-activated protein kinase kinase kinases (MAPKKK). It blocks the activation of the c-Jun/JNK apoptotic pathway in neurons exposed to various stressors and attenuates neurodegeneration in animal models of Parkinson's disease (PD). Microglial activation...

Characterization of anti-inflammatory compounds using transcriptions, proteomics, and metabolics in combination with multivariate data analysis

The discovery of new anti-inflammatory drugs is often based on an interaction with a specific target, although other pathways often play a primary or secondary role. Anti-inflammatory drugs can be categorized into classes, based on their mechanism of action. In this article we investigate the possibility to characterize novel anti-inflammatory...

Markers for Type II Collagen Breakdown Predict the Effect of Disease-Modifying Treatment on Long-Term Radiographic Progression in Patients with Rheumatoid Arthritis

Objective. To investigate in a randomized clinical trial setting with an aggressive combination-therapy arm and a mild-monotherapy arm, whether therapy-induced changes in urinary C-terminal crosslinking telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) predict 5-year radiographic progression in patients with rheumatoid...

Thalidomide inhibits UVB-induced mouse keratinocyte apoptosis by both TNF-α-dependent and TNF-α-independent pathways

Background: Thalidomide is an anti-inflammatory pharmacologic agent that has been utilized as a therapy for a number of dermatologic diseases. Its anti-inflammatory properties have been attributed to its ability to antagonize tumor necrosis factor-alfa (TNF-α) production by monocytes. However, its mechanism of action in the skin is not known....

Rosuvastatin reduces atherosclerosis development beyond and independent of its plasma cholesterol-lowering effect in APOE*3-Leiden transgenic mice: Evidence for antiinflammatory effects of rosuvastatin

Background - Statins can exert anti-inflammatory antiatherosclerotic effects through an anti-inflammatory action, independent of lowering cholesterol. We addressed the question whether the anti-inflammatory activities of statins can reduce atherosclerosis beyond the reduction achieved by cholesterol lowering per se. Methods and Results - Two...

On the assessment of adverse drug reactions from spontaneous reporting systems: The influence of under-reporting on odds ratios

A well-known problem in spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) is under-reporting, that is, the problem that not all occurrences of ADRs are reported to the SRS. We look at the question of how to draw statistical conclusions from analyses of SRS data using reporting odds ratios. We will show that certain under...

Bone turnover, joint damage and bone mineral density in early rheumatoid arthritis treated with combination therapy including high-dose prednisolone

Objectives. Exploration of bone metabolism changes at different levels of disease activity, both with and without oral corticosteroid therapy, and prediction of changes in joint damage and bone density from the observed changes in markers of bone turnover. Methods. Data analysis from a randomized clinical trial with 155 rheumatoid arthritis (RA)...

Stereoselectivity at the B2-adrenoceptor on macrophages is a major determinant of the anti-inflammatory effects of B2-agonists

Previous research has shown that β-adrenoceptor (β-AR) agonists have potent anti-inflammatory capabilities, e.g. represented by suppression of release of the proinflammatory cytokines. Aim of this research was to determine whether the effects of β-agonists on LPS-induced TNFα and IL-10 release are influenced by their different stereochemistry....

The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor alpha expression in macrophages by inducing apoptosis

Objective. Sulfasalazine (SSZ) is a commonly used drug in the treatment of inflammatory diseases such as rheumatoid arthritis and Crohn's disease. In both diseases, the proinflammatory cytokine tumor necrosis factor α (TNFα) plays a prominent role. In these studies, we investigated the mechanism by which SSZ inhibits TNFα expression in...

Anaphylaxis caused by the unexpected presence of casein in salmon

A new process for restructured meat and fish has been introduced to the market recently. Its main compound is casein, and it may therefore endanger patients with a milk allergy. Chemicals/CAS: Anti-Inflammatory Agents; Caseins; Lactoglobulins; Methylprednisolone, 83-43-2

Inhibition of tolbutamide 4-methylhydroxylation by a series of non-steroidal anti-inflammatory drugs in V79-NH cells expressing human cytochrome P4502C10

1. To study the role of cytochrome P4502C10 in the metabolism of the non-steroidal antiinflammatory drugs (NSAIDs) diclofenac, phenylbutazone, fenoprofen, ibuprofen, flurbiprofen, ketoprofen and naproxen, a cell line was developed stably expressing CYP2C10 cDNA. A retroviral vector construct, containing a human CYP2C10 cDNA, was transfected in...