Charité

About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.

Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses

Abstract: Intrinsic antioxidant defenses are important for neuronal longevity. We found that in rat neurons, synaptic activity, acting via NMDA receptor (NMDAR) signaling, boosted antioxidant defenses by making changes to the thioredoxin-peroxiredoxin (Prx) system. Synaptic activity enhanced thioredoxin activity, facilitated the reduction of overoxidized Prxs and promoted resistance to oxidative stress. Resistance was mediated by coordinated transcriptional changes; synaptic NMDAR activity inactivated a previously unknown Forkhead box O target gene, the thioredoxin inhibitor Txnip. Conversely, NMDAR blockade upregulated Txnip in vivo and in vitro, where it bound thioredoxin and promoted vulnerability to oxidative damage. Synaptic activity also upregulated the Prx reactivating genes Sesn2 (sestrin 2) and Srxn1 (sulfiredoxin), via C/EBPβ and AP-1, respectively. Mimicking these expression changes was sufficient to strengthen antioxidant defenses. Trans-synaptic stimulation of synaptic NMDARs was crucial for boosting antioxidant defenses; chronic bath activation of all (synaptic and extrasynaptic) NMDARs induced no antioxidative effects. Thus, synaptic NMDAR activity may influence the progression of pathological processes associated with oxidative damage.

The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria?

Abstract: Ankylosing spondylitis (AS) is a common chronic inflammatory disease with an estimated prevalence of 0.2–1.2% (1–4). The disease typically starts during the third decade of life and has a substantial socioeconomic impact on the patient and society (5–7). Until recently, the treatment options for AS were limited. The mainstays of treatment were regular physical therapy and nonsteroidal antiinflammatory drugs (NSAIDs) (8). In contrast, disease-modifying antirheumatic drugs (DMARDs) as well as corticosteroids, which are quite effective in some of the other chronic inflammatory diseases such as rheumatoid arthritis (RA), show only very limited or no efficacy in AS (9–11). Thus, in the past, a delayed diagnosis did not have much of an adverse consequence because of the lack of highly effective therapeutic choices. Most recently, it has been convincingly demonstrated that the tumor necrosis factor (TNF )– blocking agents infliximab and etanercept have a strong and prompt effect on almost all features of AS, such as clinical disease activity, physical function, spinal mobility, peripheral arthritis, enthesitis, and levels of acutephase reactants (12–19). In several studies of AS patients whose disease was refractory to NSAIDs and physical therapy, 50% of the patients have demonstrated at least a 50% improvement when treated with either of the two TNF -blocking compounds. It has also been shown that active juxtaarticular bony inflammation (“bone edema”), as detected by magnetic resonance imaging (MRI), can be suppressed (20,21), and it is hoped that this kind of treatment will also favorably influence long-term outcome, including reduction or prevention of radiologic progression. Recent data also show that AS patients with a short disease duration and good functional status are more likely to respond to TNF -blocking agents than patients with longstanding disease and impaired function (22). Thus, an early and reliable diagnosis of AS has now become an important and very relevant issue.

Two Novel Equations to Estimate Kidney Function in Persons Aged 70 Years or Older

Abstract: Accurate assessment of kidney function can assist appropriate clinical care, but most estimates of creatinine clearance were developed in populations that included no or few older adults and do not...

EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria.

Abstract: This guideline, together with its sister guideline on the classification of urticaria (Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Gimenez-Arnau AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: definition, classification and diagnosis of urticaria. Allergy 2009;64: 1417-1426), is the result of a consensus reached during a panel discussion at the Third International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). As members of the panel, the authors had prepared their suggestions regarding management of urticaria before the meeting. The draft of the guideline took into account all available evidence in the literature (including Medline and Embase searches and hand searches of abstracts at international allergy congresses in 2004-2008) and was based on the existing consensus reports of the first and the second symposia in 2000 and 2004. These suggestions were then discussed in detail among the panel members and with the over 200 international specialists of the meeting to achieve a consensus using a simple voting system where appropriate. Urticaria has a profound impact on the quality of life and effective treatment is, therefore, required. The recommended first line treatment is new generation, nonsedating H(1)-antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase in dosage of nonsedating H(1)-antihistamines, it is recommended that second-line therapies should be added to the antihistamine treatment. In the choice of second-line treatment, both their costs and risk/benefit profiles are most important to consider. Corticosteroids are not recommended for long-term treatment due to their unavoidable severe adverse effects. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).