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Fernandez-Penas P.,Hospital Universitario Of La Princesa | Fernandez-Penas P.,University of Sydney | Jones-Caballero M.,Hospital Universitario Of La Princesa | Espallardo O.,Merck Serono | Garcia-Diez A.,Hospital Universitario Of La Princesa
British Journal of Dermatology | Year: 2012

Background Severity assessment of patients with psoriasis is a critical issue. Classical clinical assessment has recently been combined with quality of life (QoL) scores, but several instruments are used. Moreover, studies have focused on patients with moderate to severe psoriasis. Objectives To compare the characteristics of QoL instruments in patients with the full range of psoriasis severity attending dermatology clinics. Methods Observational, prospective, multicentre study. Patients completed Skindex-29 (anchor) and a second instrument randomly selected from Dermatology Life Quality Index (DLQI), Psoriasis Disability Index (PDI) and Medical Outcome Study Short Form 36 (SF-36). Results Demographic data, Psoriasis Area and Severity Index and affected body surface area were not different between the three groups. Skindex-29 showed a weak but significant correlation with clinical severity; only PDI showed similar correlation. PDI, DLQI and SF-36 showed a substantial floor effect in patients with mild to severe psoriasis. Skindex-29 showed strong correlations with the other three QoL instruments. SF-36 was more sensitive than the other instruments in detecting worse QoL in male patients. Conclusions Skindex-29 has better sensitivity to clinical severity with minimal floor effect, and covers the main domains explored by the other three QoL instruments in patients with mild to severe psoriasis. © 2012 The Authors. BJD © 2012 British Association of Dermatologists. Source

Gorreta F.,Genetics and Biomarkers Exploratory Medicine | Carbone W.,Merck Serono | Barzaghi D.,Medestea Research and Production S.p.A
Methods in Molecular Biology | Year: 2012

The introduction of microarray technology, which is a multiplexed hybridization-based process, allows simultaneous analysis of a large number of nucleic acid transcripts. This massively parallel analysis of a cellular genome will become essential for guiding disease diagnosis and molecular profiling of an individual patient's tumor. Nucleic acid based microarrays can be used for: gene expression profiling, single-nucleotide polymorphisms (SNPs) detection, array-comparative genomic hybridizations, comparisons of DNA-methylation status, and microRNA evaluation. A multitude of commercial platforms are available to construct and analyze the microarrays. Typical workflow for a microarray experiment is: preparation of cDNA or gDNA, array construction, hybridization, fluorescent detection, and analysis. Since many sources of variability can affect the outcome of one experiment and there is a multitide of microarray platforms available, microarray standards have been developed to provide industry-wide quality control and information related to each microarray. In this chapter, we review array construction, methodologies, and applications relevant to molecular profiling. © 2012 Springer Science+Business Media, LLC. Source

Tian Y.,Johns Hopkins University | Yao Z.,Merck Serono | Roden R.B.S.,Johns Hopkins University | Zhang H.,Johns Hopkins University
Proteomics | Year: 2011

Ovarian cancer is the most lethal gynecologic malignancy in adult women. The origin of epithelial ovarian tumors is both morphologically and biologically heterogeneous, and different subtypes of ovarian tumors have different clinical outcomes. In spite of the heterogeneous nature of ovarian carcinoma, the current biomarkers and treatments for this disease are not subtype-specific. To discover the molecular basis of the ovarian tumor subtypes, we analyzed extracellular glycoproteins of seven common subtypes and normal ovary tissues using quantitative glycoproteomic analysis. Glycoproteins for different ovarian tumor subtypes were identified by liquid chromatography-tandem mass spectrometry and quantitated by spectral counting and then verified by iTRAQ labeling and Western blotting. Glycoproteins uniquely expressed in different subtypes of ovarian tumors or commonly expressed in most subtypes were identified. Using Western blots, we verified that mesothelin was overexpressed in serous carcinoma and transitional-cell carcinoma, CEA5 and CEA6 were overexpressed only in mucinous carcinoma, while versican and periostin were overexpressed in most subtypes of ovarian tumors. This study presents the first proteomic characterization of different ovarian tumor subtypes. The identified glycoproteins for histological subtypes of ovarian tumors will facilitate the understanding of the molecular basis, diagnosis of ovarian tumor subtypes, and predictions for treatment responses to therapeutic agents. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Bunz S.-C.,Aalen University of Applied Sciences | Cutillo F.,Merck Serono | Neususs C.,Aalen University of Applied Sciences
Analytical and Bioanalytical Chemistry | Year: 2013

The glycosylation of proteins is of particular interest in biopharmaceutical applications. The detailed characterization of glycosylation based on the released carbohydrates is mandatory since the protein stability, folding, and efficacy are strongly dependent on the structural diversity inherent in the glycan moieties of a glycoprotein. For glycan pattern analysis, capillary electrophoresis with laser-induced fluorescence using 8-aminopyrene-1,3,6-trisulfonic acid (APTS)-labeled glycans is used frequently. In this paper, a robust capillary electrophoresis-mass spectroscopy method both for the analysis of APTS-labeled glycans and unlabeled charged glycans is presented. The background electrolyte consists of 0.7 M ammonia and 0.1 M ε-aminocaproic acid in water/methanol 30:70 (v/v). High separation efficiency including separation of structural isomers was obtained. The method was validated in terms of reproducibility and linearity. Submicromolar sensitivity is achieved with linearity up to 24 μM. The ability to analyze APTS-labeled, as well as unlabeled, charged glycans enables the determination of labeling and ionization efficiency: APTS-labeled glycans show a factor of three better ionization efficiency compared to non-labeled native glycans. The presented method is applied to the analysis of pharmaceutical products. Furthermore, the system can be applied to the analysis of 2-ANSA-labeled glycans, though separation efficiency is limited. [Figure not available: see fulltext.] © 2013 Springer-Verlag Berlin Heidelberg. Source

Hermann R.,Clinical Research Appliance | Von Richter O.,Merck Serono
Planta Medica | Year: 2012

The use of herbal/botanical products, also referred to as complementary and alternative medicines (CAM), worldwide enjoys increasing popularity. It appears in particular highly prevalent in patient populations already exposed to complex treatment algorithms and polypharmacotherapy, frequently involving narrow therapeutic index drugs. Accordingly, the potential clinical dimension and relevance of herb-drug interactions has received considerable attention over the last years. However, review of pertinent literature indicates that the available clinical evidence in this regard is still limited and sometimes inconclusive. Also, communication of herb-drug interaction data in the biopharmaceutical/medical literature is often complex and confusing, not always unbiased, and in many cases appears not to strive for clear-cut and useful guidance in terms of the clinical relevance of such findings. This systematic review summarizes and interprets the published evidence on clinical herb-drug interaction studies which examined the potential of six popular herbal drugs (Echinacea, garlic, gingko, ginseng, goldenseal, and milk thistle) as perpetrators of pharmacokinetic (PK) drug interactions. Reported effect sizes were systematically categorized according to FDA drug interaction guideline criteria. A total of 66 clinical PK interaction studies, meeting the scope of the present review, were identified. The clinical evidence was found to be most robust and informative for Gingko biloba (GB; 21 studies) and milk thistle/silymarin (MT; 13), and appears still limited for ginseng (9), goldenseal/berberine (GS; 8), garlic (8), and Echinacea (7). Collectively, the available evidence indicates that, at commonly recommended doses, none of these herbs act as potent or moderate inhibitors or inducers of cytochrome P450 (CYP) enzymes or P-glycoprotein (ABCB1). Weak effects in terms of either induction or inhibition were found for GB (presystemic/hepatic CYP3A4 induction/inhibition, CYP2C19 induction at high doses), milk thistle/silymarin (CYP2C9 inhibition), GS/berberine (CYP3A4 and CYP2D6 inhibition), Echinacea (presystemic/hepatic CYP3A4 inhibition/induction, CYP1A2 and CYP2C9 inhibition at high doses). Information was found not always complete for the major drug metabolizing CYP enzymes in the less well-studied herbs and is largely limited to P-glycoprotein (ABCB1) when effects on drug transporters have been investigated. © Georg Thieme Verlag KG Stuttgart · New York. Source

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