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.

Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers.

Abstract: Background Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS. Objective We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. Methods In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin–specific IgE, and albumin. We used partition-based clustering. Results Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5–negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a T H 17 profile and had mixed CRSsNP/CRSwNP. The IL-5–positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin–specific IgE. Conclusion Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.

Reduction in subthalamic 8-35 Hz oscillatory activity correlates with clinical improvement in Parkinson's disease.

Abstract: Strong synchronization of neuronal activity occurs in the 8-35 Hz band in the subthalamic nucleus (STN) of patients with Parkinson's disease (PD) and is evident as oscillatory local field potential (LFP) activity. To test whether such synchronization may contribute to bradykinesia and rigidity, we sought correlations between the suppression of synchronization at 8-35 Hz in STN and the reduction in Parkinsonism with levodopa. LFPs were recorded on and off medication from STN deep-brain stimulation electrodes in nine PD patients. LFP power was calculated over the frequencies of the most prominent spectral peak within the 8-35 Hz frequency band on each of 17 sides (off medication), and over the frequencies of any peak in the 60-90 Hz band, if present (seven sides, on medication). Levodopa-induced reduction of LFP power over these two frequency ranges was then correlated with improvement in motor impairment as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). The reduction in peak activity in the 8-35 Hz band with levodopa positively correlated with the improvement in the contralateral hemibody motor UPDRS score with levodopa (r = 0.811, P < 0.001) as well as with hemibody subscores of akinesia-rigidity (r = 0.835, P < 0.001), but not tremor. A trend for negative correlations was found between peak 60-90 Hz LFP power and UPDRS hemibody score, suggesting that positive correlations were relatively frequency-specific. Our results support a link between levodopa-induced improvements in bradykinesia and rigidity and reductions in population synchrony at frequencies < 35 Hz in the region of the STN in patients with PD.

Angiotensin Type 1 Receptor Blockers Induce Peroxisome Proliferator–Activated Receptor-γ Activity

Abstract: Background— Angiotensin type 1 receptor (AT1R) blockers (ARB) have been shown to reduce the incidence of type 2 diabetes mellitus by an unknown molecular mechanism. The peroxisome proliferator–activated receptor-γ (PPARγ) is the central regulator of insulin and glucose metabolism improving insulin sensitivity. We investigated the regulation of PPARγ function by ARBs. Methods and Results— The ARBs irbesartan and telmisartan (10 μmol/L) potently enhanced PPARγ-dependent 3T3-L1 adipocyte differentiation associated with a significant increase in mRNA expression of the adipogenic marker gene adipose protein 2 (aP2), as measured by quantitative real-time polymerase chain reaction (irbesartan: 3.3±0.1-fold induction; telmisartan: 3.1±0.3-fold induction; both P<0.01). Telmisartan showed a more pronounced induction of aP2 expression in lower, pharmacologically relevant concentrations compared with the other ARBs. The ARB losartan enhanced aP2 expression only at high concentrations (losartan 100 μmol/L: 3.6±0.3-fol...