Efficacy and safety results of micellar water, cream and serum for rosacea in comparison to a control group.

BACKGROUND: Rosacea is a common inflammatory skin disorder with centrofacial erythema, flushing, telangiectasia, papules/pustules, and possible ocular or phymatous manifestation. Patients' skin is particularly sensitive to chemical and physical stimuli leading to burning, stinging, dryness, and skin tightness. OBJECTIVE: Dermatological evaluation of the efficacy and safety of skin care products designed for centrofacial erythema in rosacea patients, in comparison with a control group using objective measurements. Rosacea symptoms (itching, tension, warmth, burning, dryness) and quality of life were examined. METHODS: Sixty Caucasians with centrofacial erythema were enrolled in an 8-week prospective study, fifty of them exclusively using the study products (micellar water, cream, and serum) with ten participants randomly assigned to a control group. Patients were evaluated at baseline (V0), at 4 weeks (V1), and at 8 weeks (V2). Three-dimensional objective measurements (VECTRA® ) as well as standardized questionnaires were used. RESULTS: Results were compared with the control group. A significant reduction of 16% in skin redness as indicated by VECTRA® analysis was seen in the intervention group comparing V0-V2. Furthermore, rosacea-associated symptoms diminished by 57.1%, while life quality of affected patients within the intervention group improved by 54.5% comparing V0-V2, respectively. CONCLUSIONS: A skin care regime suitable for sensitive and redness-prone skin led to an enhanced clinical appearance, to a decrease of associated symptoms in rosacea patients, and to an improved life quality.

Prognostic value of NT-proBNP in patients with systemic morphological right ventricles: a single-centre experience.

UNLABELLED: In systemic morphological right ventricles after atrial redirection surgery, NT-proBNP is correlated with NYHA-class, ventricular function and subaortic AV-valve regurgitation (TR). The impact of NT-proBNP on adverse clinical outcomes is, however, unknown. METHODS: This prospectively designed, longitudinal, observational study evaluated NT-proBNP in 116 patients (24.9 ± 4.2 years old, NYHA class I/II/III=97/18/1, 71 men) relative to all cardiac causes of hospitalisation, heart failure, transplantation and death. RESULTS: The mean observation time was 7.3 ± 2.4 years. In univariate Cox proportion analysis, the predictors for all causes of hospitalisation (n=41; 35.5%) were NT-proBNP (HR: 5.99; 95%CI: 3.21-11.18), NYHA class (HR: 2.98; 95%CI: 1.62-5.5), ventricular function (HR: 1.96; 95%CI: 1.27-3.02), TR (HR: 2.39; 95%CI: 1.48-3.59), ventricular septal defect repair (HR: 1.29; 95%CI: 1.08-1.53) and a history of supraventricular tachycardia (SVT) (HR: 7.13; 95%CI: 3.74-13.59). In multivariate Cox proportion analysis, NT-proBNP (HR: 3.71; 95%CI: 1.82-7.57), SVT (HR: 4.27; 95%CI: 2.03-8.94) and ventricular septal defect repair (HR: 1.41; 95%CI: 1.15-1.72) remained independently associated with all causes of hospitalisation. For heart failure, transplantation and death, the single predictors were NT-proBNP (HR: 20.67; 95%CI: 4.69-91.78), NYHA class (HR: 6.45; 95%CI: 2.75-15.14), ventricular function (HR: 2.70; 95%CI: 1.48-4.92), TR (HR: 4.11; 95%CI: 1.99-8.47), QRS duration (HR: 2.09; 95%CI: 1.06-4.12) and SVT (HR: 8.00; 95%CI: 2.82-22.69). Multivariate Cox proportion analysis identified NT-proBNP (HR: 6.82; 95%CI: 1.32-35.04) and NYHA class (HR: 6.79; 95%CI: 1.75-26.28). Using ROC curves, the ability of NT-proBNP to detect patients at risk was greater for heart failure, transplantation and death (AUC: 0.944; 95%CI: 0.900-0.988) than for all causes of hospitalisation (AUC: 0.8; 95%CI: 0.713-0.887). CONCLUSION: In systemic right ventricles, NT-proBNP is a useful risk predictor for all causes of hospitalisation and, in particular, for heart failure, transplantation and death. It therefore might be a useful tool for risk assessment in this patient population.

CCAAT/enhancer-binding protein beta inhibits proliferation in monocytic cells by affecting the retinoblastoma protein/E2F/cyclin E pathway but is not directly required for macrophage morphology.

Monocytic differentiation is orchestrated by complex networks that are not fully understood. This study further elucidates the involvement of transcription factor CCAAT/enhancer-binding protein ß (C/EBPß). Initially, we demonstrated a marked increase in nuclear C/EBPß-liver-enriched activating protein* (LAP*)/liver-enriched activating protein (LAP) levels and LAP/liver-enriched inhibiting protein (LIP) ratios in phorbol 12-myristate 13-acetate (PMA)-treated differentiating THP-1 premonocytic cells accompanied by reduced proliferation. To directly study C/EBPß effects on monocytic cells, we generated novel THP-1-derived (low endogenous C/EBPß) cell lines stably overexpressing C/EBPß isoforms. Most importantly, cells predominantly overexpressing LAP* (C/EBPß-long), but not those overexpressing LIP (C/EBPß-short), exhibited a reduced proliferation, with no effect on morphology. PMA-induced inhibition of proliferation was attenuated in C/EBPß-short cells. In C/EBPß(WT) macrophage-like cells (high endogenous C/EBPß), we measured a reduced proliferation/cycling index compared with C/EBPß(KO). The typical macrophage morphology was only observed in C/EBPß(WT), whereas C/EBPß(KO) stayed round. C/EBPα did not compensate for C/EBPß effects on proliferation/morphology. Serum reduction, an independent approach known to inhibit proliferation, induced macrophage morphology in C/EBPß(KO) macrophage-like cells but not THP-1. In PMA-treated THP-1 and C/EBPß-long cells, a reduced phosphorylation of cell cycle repressor retinoblastoma was found. In addition, C/EBPß-long cells showed reduced c-Myc expression accompanied by increased CDK inhibitor p27 and reduced cyclin D1 levels. Finally, C/EBPß-long and C/EBPß(WT) cells exhibited low E2F1 and cyclin E levels, and C/EBPß overexpression was found to inhibit cyclin E1 promoter-dependent transcription. Our results suggest that C/EBPß reduces monocytic proliferation by affecting the retinoblastoma/E2F/cyclin E pathway and that it may contribute to, but is not directly required for, macrophage morphology. Inhibition of proliferation by C/EBPß may be important for coordinated monocytic differentiation.

ITD- and FL-induced FLT3 signal transduction leads to increased C/EBPbeta-LIP expression and LIP/LAP ratio by different signalling modules.

FLT3 receptor-associated signalling plays a role in proliferation and leukaemia. The transcription factor C/EBPbeta may be involved in malignancy with its alternative translation product C/EBPbeta-LIP. We investigated a potential connection between FLT3 signalling and the C/EBPbeta system in FLT3-internal tandem duplication (ITD)-positive leukaemia cells and FLT3-ITD- or FLT3-wild type (WT)-transfected 32D cells. In FLT3-ITD-positive cells or when ITD sequences were inserted into the FLT3-WT receptor, significant LIP levels, increased LIP/LAP ratios, and enhanced proliferation rates were detected, which were reduced by FLT3 inhibition. In FLT3-WT cells, incubation with FLT3 receptor ligand (FL) also elevated LIP, LIP/LAP, and proliferation, albeit to a lesser extent. CEBPB-directed siRNA decreased both LIP and proliferation rates in FLT3-ITD-positive and FL-stimulated FLT3-WT-positive cells. PI3K inhibition affected ITD-associated and FL-induced LIP levels. Rapamycin, an inhibitor of mTOR involved in CEBPB translation, completely blocked the increase in LIP in FL-stimulated FLT3-WT- but not FLT3-ITD-positive cells. In contrast, the ITD-associated LIP elevation was mediated by p(90)-ribosomal-S6-kinase. This is the first report showing a LIP increase in the presence of ITD or following FL exposure. Our data suggest fundamental differences in the signalling cascades activated via ITD mutations or following FL stimulation, indicating the need for adapted molecular therapy.

C/EBPbeta enhances NF-kappaB-associated signalling by reducing the level of IkappaB-alpha.

NF-kappaB and C/EBPbeta proteins are involved in the regulation of genes which play a role in inflammation, immunity and malignant processes. The present study focuses on the question of how these systems cross talk "upstream" of the promoter level and investigates the regulation of NF-kappaB-associated signalling by C/EBPbeta. In C/EBPbeta(ko) macrophage-like cells stimulated with TNF or LPS a reduced 3kappaB-dependent transcription was detected compared to the wild type. This was accompanied by elevated nuclear p65 and NF-kappaB activity in the presence of C/EBPbeta. In addition, overexpression of C/EBPbeta in HeLa cells increased the nuclear level of coexpressed p65. Remarkably, the constitutive level of IkappaB-alpha was significantly higher in C/EBPbeta(ko) cells; and this higher level was readjusted following stimulus-induced proteolysis. The IkappaB-alpha protein stability was comparable in both macrophage-like cell types with a somewhat higher stability in unstimulated C/EBPbeta(ko) cells. Following stimulation with TNF, higher IkappaB-alpha mRNA levels were induced in C/EBPbeta(ko) cells. The autoregulatory recovery of IkappaB-alpha protein following activation was completely blocked by transcriptional inhibition, regardless if C/EBPbeta was present. Finally, we showed that C/EBPbeta overexpression in HeLa cells blocked TNF-mediated inducibility of the IkappaB-alpha promoter. Taken together, our results indicate that regulation of the IkappaB-alpha level is one of the underlying mechanisms by which C/EBPbeta controls NF-kappaB-associated signalling. C/EBPbeta may belong to the group of proteins in the regulatory machinery which adjusts the IkappaB-alpha level in different cell types under various conditions with physiological and pathophysiological implications.

Ozonized low density lipoprotein (ozLDL) inhibits NF-kappaB and IRAK-1-associated signaling.

OBJECTIVE: Recent studies have provided strong evidence for the presence of ozone in atherosclerotic lesions. In addition, modification of LDL has been suggested to be involved in atherosclerosis. In the present study we wanted to investigate whether LDL exposed to ozone (ozLDL) is able to modulate the NF-kappaB system, as a paradigm for inflammatory signaling. METHODS AND RESULTS: We showed that activation of NF-kappaB by lipopolysaccharide (LPS), a prototypic inducer of innate immunity, was reversibly inhibited by ozLDL in monocytic THP-1 cells in a dose-dependent manner, whereas tumor necrosis factor (TNF) signaling was not affected. This was not attributable to a direct ozone effect or solely the presence of lipoprotein, and neither required direct contact to LPS nor was accompanied by a change in LPS binding. Comparable inhibitory effects of ozLDL were observed in human monocyte/macrophages and endothelial cells. The presence of ozLDL led to a decrease in LPS-induced IkappaB alpha proteolysis and a reduction of kappaB-dependent transcription/target-gene expression. Furthermore, ozLDL markedly lowered stimulus-induced IkappaB kinase (IKK) activity and phosphorylation/proteolysis of interleukin (IL)-1 receptor-associated kinase-1 (IRAK-1). Finally, cholesterol ozonization products were identified as effective ozLDL inhibitory compounds. CONCLUSIONS: Our study demonstrated that ozLDL inhibited NF-kappaB and IRAK-1-associated signaling which may impair immune function and promote apoptosis.

Effect of ozone on oral cells compared with established antimicrobials.

Ozone has been proposed as an alternative antiseptic agent in dentistry based on reports of its antimicrobial effects in both gaseous and aqueous forms. This study investigated whether gaseous ozone (4 x 10(6) microg m(-3)) and aqueous ozone (1.25-20 microg ml(-1)) exert any cytotoxic effects on human oral epithelial (BHY) cells and gingival fibroblast (HGF-1) cells compared with established antiseptics [chlorhexidine digluconate (CHX) 2%, 0.2%; sodium hypochlorite (NaOCl) 5.25%, 2.25%; hydrogen peroxide (H(2)O(2)) 3%], over a time of 1 min, and compared with the antibiotic, metronidazole, over 24 h. Cell counts, metabolic activity, Sp-1 binding, actin levels, and apoptosis were evaluated. Ozone gas was found to have toxic effects on both cell types. Essentially no cytotoxic signs were observed for aqueous ozone. CHX (2%, 0.2%) was highly toxic to BHY cells, and slightly (2%) and non-toxic (0.2%) to HGF-1 cells. NaOCl and H(2)O(2) resulted in markedly reduced cell viability (BHY, HGF-1), whereas metronidazole displayed mild toxicity only to BHY cells. Taken together, aqueous ozone revealed the highest level of biocompatibility of the tested antiseptics.