Association of brain functional magnetic resonance activity with response to tumor necrosis factor inhibition in rheumatoid arthritis.

Objective: To test whether brain activity predicts the response to tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA). Since clinical and laboratory parameters have proven unsuccessful in predicting response, we followed a radically different concept, hypothesizing that response to TNFi depends on central nervous system activity rather than the clinical signs of disease.

Methods: Sequential testing by functional magnetic resonance imaging (MRI) of the brain, anatomic MRI of the hand, and clinical assessment of arthritis were carried out in 10 patients with active RA before and 3, 7, and 28 days after the start of TNFi treatment.

The structural basis of MRI bone erosions: an assessment by microCT.

Objective: To determine whether erosions appearing in MRI in patients with rheumatoid arthritis (RA) represent true erosions.

Methods: 50 RA patients received 1.5 T MRI and microCT (μCT) of the dominant hand.

Bone anabolic changes progress in psoriatic arthritis patients despite treatment with methotrexate or tumour necrosis factor inhibitors.

Objectives: To investigate whether methotrexate or tumour necrosis factor inhibitors (TNFi) affect osteophyte formation in patients with psoriatic arthritis (PsA).

Methods: 41 patients with PsA were examined for the presence of osteophytes and erosions at the metacarpophalangeal joints by high-resolution micro-CT imaging. The size of each individual lesion was quantified at baseline and 1-year follow-up in PsA patients treated with TNFi (N=28) or methotrexate (N=13).

Autoantibodies against galectins are associated with antiphospholipid syndrome in patients with systemic lupus erythematosus.

The presence of autoantibodies against immunoregulatory effectors can be relevant for onset and/or the progression of autoimmune disease. Emerging insights into an immunological activity profile including a role as opsonins give reason to systematically monitor sera of patients for immunoglobulin G (IgG) autoantibodies, preferably for several galectins at the same time. Here, we report on a study of chronic inflammatory rheumatic diseases, i.

Interleukin-6 receptor blockade induces limited repair of bone erosions in rheumatoid arthritis: a micro CT study.

Introduction: Interleukin-6 receptor (IL-6R) blockade improves the signs and symptoms of rheumatoid arthritis (RA) and retards bone damage. Whether IL-6R blockade allows repair of existing bone erosions is so far unclear.

Methods: This study examined bone erosions in the metacarpophalangeal joints of 20 patients receiving treatment with the IL-6R blocker tocilizumab using micro CT (µCT).

Accumulation of impact markers in desert wetlands and implications for the Younger Dryas impact hypothesis.

The Younger Dryas impact hypothesis contends that an extraterrestrial object exploded over North America at 12.9 ka, initiating the Younger Dryas cold event, the extinction of many North American megafauna, and the demise of the Clovis archeological culture. Although the exact nature and location of the proposed impact or explosion remain unclear, alleged evidence for the fallout comes from multiple sites across North America and a site in Belgium.

Differences in the patient's and the physician's perspective of disease in psoriatic arthritis.

Objective: To define the relative impact of disease components of psoriatic arthritis (PsA) on the global burden of disease and to compare physician's and patients' ratings of disease activity.

Methods: PsA patients fulfilling the Classification Criteria for Psoriatic Arthritis (N = 55) were asked for an evaluation of the absolute and relative impact of general and specific rheumatic symptoms (ie, arthritis, enthesitis, spinal disease, dactylitis), general and specific psoriatic symptoms (skin disease, nail disease), and other common symptoms (eg, fatigue). Results were related to the respective physician's evaluations of disease-related symptoms based on visual analog scale (VAS) ratings and comparative measures of disease activity (ie, swollen and tender joint counts, MASES, PASI, NAPSI).

Renal leishmaniasis as unusual cause of nephrotic syndrome in an HIV patient.

Renal involvement is a rare complication in HIV-1-infected patients leading to various pathologies and clinical symptoms. In addition to the classic HIV-1-associated nephropathy with collapsing-type focal segmental glomerulosclerosis and characteristic tubulocystic changes, which is more common in Afro-American than in Caucasian HIV-1 patients, immune complex GNs such as membranous GN and membranoproliferative GN are particularly common renal manifestations. Besides HIV-1 itself, a number of opportunistic infections may cause renal disease in HIV-1-infected patients.

IgG4 immune response in Churg-Strauss syndrome.

Objective: T-helper type 2 responses are crucial in Churg-Strauss syndrome (CSS) and may enhance the production of IgG4 antibodies. The authors assessed the IgG4 immune response in CSS patients.

Methods: The authors included 46 consecutive patients with CSS (24 with active and 22 with quiescent disease), 26 with granulomatosis with polyangiitis (GPA, Wegener's), 25 with atopic asthma and 20 healthy controls and determined serum IgG, IgM, IgA, IgE and IgG subclass levels.

Total synthesis and biological evaluation of pederin, psymberin, and highly potent analogs.

The potent cytotoxins pederin and psymberin have been prepared through concise synthetic routes (10 and 14 steps in the longest linear sequences, respectively) that proceed via a late-stage multicomponent approach to construct the N-acyl aminal linkages. This route allowed for the facile preparation of a number of analogs that were designed to explore the importance of the alkoxy group in the N-acyl aminal and functional groups in the two major subunits on biological activity. These analogs, including a pederin/psymberin chimera, were analyzed for their growth inhibitory effects, revealing several new potent cytotoxins and leading to postulates regarding the molecular conformational and hydrogen bonding patterns that are required for biological activity.

Risk of infections in rheumatoid arthritis patients treated with tocilizumab.

Objectives: To investigate the occurrence and risk factors for infections in RA patients treated with tocilizumab.

Methods: A cohort of all RA patients (n = 112) starting tocilizumab therapy between October 2008 and March 2010 in Northern Bavaria was screened for infections. Mild/moderate and severe infections were recorded.

Adult-onset Still's disease and chronic recurrent multifocal osteomyelitis: a hitherto undescribed manifestation of autoinflammation.

Still's disease and chronic recurrent multifocal osteomyelitis (CRMO) are febrile rheumatic diseases of unknown etiology, which predominantly affect children but can also have their initial manifestation in adults. Both can present as intermittent, relapsing episodes and are considered potential candidates within the expanding spectrum of autoinflammatory disorders, although no genetic abnormalities have been described for either of them. Here, we describe a man with an initial manifestation of abacterial multifocal osteitis at the age of 41.

Repair of bone erosions in rheumatoid arthritis treated with tumour necrosis factor inhibitors is based on bone apposition at the base of the erosion.

Objectives: To investigate whether bone erosions in patients with rheumatoid arthritis (RA) show evidence of repair.

Methods: 127 erosions were identified in metacarpophalangeal joints 2-4 of the right hands of 30 RA patients treated with tumour necrosis factor inhibitors (TNFi) and 21 sex, age and disease activity-matched patients treated with methotrexate. All erosions were assessed for their exact maximal width and depth by high-resolution µCT imaging at baseline and after 1 year.

Characterization of 2-(2,6-dichloro-benzyl)-thiazolo[5,4-d]pyrimidin-7-yl]-(4-trifluoromethyl-phenyl)-amine (JNJ-39729209) as a novel TRPV1 antagonist.

As an integrator of multiple nociceptive and/or inflammatory stimuli, TRPV1 is an attractive therapeutic target for the treatment of various painful disorders. Several TRPV1 antagonists have been advanced into clinical trials and the initial observations suggest that TRPV1 antagonism may be associated with mild hyperthermia and thermal insensitivity in man. However, no clinical efficacy studies have been described to date, making an assessment of risk:benefit impossible.

Effect of measurement backaction on adiabatic coherent electron transport.

We study the backaction of a nearby measurement device on electrons undergoing coherent transfer via adiabatic passage (CTAP) in a triple-well system. The measurement is provided by a quantum point contact capacitively coupled to the middle well. We account for this continuous measurement by treating the whole {triple-well+detector} as a closed quantum system.

Recent advances in the biology and medicinal chemistry of TRPA1.

The transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is a nonselective cation channel that is highly expressed in small-diameter sensory neurons, where it functions as a polymodal receptor, responsible for detecting potentially harmful chemicals, mechanical forces and temperatures. TRPA1 is also activated and/or sensitized by multiple endogenous inflammatory mediators. As such, TRPA1 likely mediates the pain and neurogenic inflammation caused by exposure to reactive chemicals.

[Large-joint synovectomy in the era of biological therapies].

Since the mid 1980s, a global decrease in surgical procedures related to rheumatoid arthritis (RA) has been documented for joint-preserving procedures such as synovectomy as well as joint replacement surgery. This reflects improvements in the early management of rheumatoid arthritis and availability of more effective medical treatment. The present review summarizes the recent literature on the frequency of orthopaedic surgery in RA patients as well as the role of synovectomy in the rheumatoid hip, knee and shoulder in times of biological RA therapy.

Blockade of TNF-α rapidly inhibits pain responses in the central nervous system.

There has been a consistent gap in understanding how TNF-α neutralization affects the disease state of arthritis patients so rapidly, considering that joint inflammation in rheumatoid arthritis is a chronic condition with structural changes. We thus hypothesized that neutralization of TNF-α acts through the CNS before directly affecting joint inflammation. Through use of functional MRI (fMRI), we demonstrate that within 24 h after neutralization of TNF-α, nociceptive CNS activity in the thalamus and somatosensoric cortex, but also the activation of the limbic system, is blocked.

Use of methotrexate in adult-onset Still's disease.

Adult-onset Still's disease, a febrile, multisystem rheumatic disease, has variable outcomes. Some patients experience remission after a single or multiple inflammatory episodes, while others progress to a chronic course with substantial joint destruction. Although no controlled clinical trials with immunosuppressive agents in this disease have been reported, a number of small uncontrolled studies and case reports describe the use of methotrexate therapy.

1,2-diamino-ethane-substituted-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepines as TRPV1 antagonists with improved properties.

Based upon a previously reported lead compound 1, a series of 1,2-diamino-ethane-substituted-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepines were synthesized and evaluated for improved physiochemical and pharmacokinetic properties while maintaining TRPV1 antagonist activity. Structure-activity relationship studies directed toward improving the aqueous solubility (pH 2 and fasted-state simulated intestinal fluid (SIF)) and rat pharmacokinetics led to the discovery of compound 13. Aqueous solubility of compound 13 (pH 2 ≥237 μg/mL and SIF=11 μg/mL) was significantly improved over compound 1 (pH 2=5 μg/mL and SIF=0.