A Prototype for Diagnosis of Psoriasis in Traditional Chinese Medicine

Psoriasis is a chronic, non-communicable, painful, disfiguring and disabling disease for which there is no cure, with great negative impact on patients’ quality of life (QoL). Diagnosis and treatment with traditional Chinese medical technique based on syndrome differentiation has been used in practice for a long time and proven effective, though, up to now, there are only a few available studies about the use of semantic technologies and the knowledge systems that use Traditional Chinese Medicine (TCM)-syndrome differentiation for information retrieval and automated reasoning. In this paper we use semantic techniques based on ontologies to develop a prototypical system for the diagnosis of Psoriasis. For this purpose, a domain ontology is developed for syndrome differentiation of psoriasis vulgaris (PV). This ontology is founded on an adapted version of the general formal ontology (GFO), with the evidence-based clinical practice guideline of TCM for psoriasis vulgaris (Guideline 2013) as the primary data sources. The implemented prototype, called ONTOPV, contains this domain ontology and is aimed at a decision support system for diagnosis and treatment of PV. This system uses a case-database for Case Based Reasoning (CBR), combined with fuzzy pattern recognition. Experimental results show that the ONTOPV realizes the basic functionalities of data collection, querying, browsing and navigation, and supports rule-based knowledge reasoning, and integrates fuzzy pattern recognition. It can provide users with clinical decision support for TCM syndrome differentiation in diagnosis of psoriasis.     

The in Vitro Antiplasmodial and Antiproliferative Activity of New Ferrocene-Based α-Aminocresols Targeting Hemozoin Inhibition and DNA Interaction

The conjugation of organometallic complexes to known bioactive organic frameworks is a proven strategy revered for devising new drug molecules with novel modes of action. This approach holds great promise for the generation of potent drug leads in the quest for therapeutic chemotypes with the potential to overcome the development of clinical resistance. Herein, we present the in vitro antiplasmodial and antiproliferative investigation of ferrocenyl α-aminocresol conjugates assembled by amalgamation of the organometallic ferrocene unit and an α-aminocresol scaffold possessing antimalarial activity. The compounds pursued in the study exhibited higher toxicity towards the chemosensitive (3D7) and -resistant (Dd2) strains of the Plasmodium falciparum parasite than to the human HCC70 triple-negative breast cancer cell line. Indication of cross-resistance was absent for the compounds evaluated against the multi-resistant Dd2 strain. Structure-activity analysis revealed that the phenolic hydroxy group and rotatable σ bond between the α-carbon and NH group of the α-amino-o-cresol skeleton are crucial for the biological activity of the compounds. Spectrophotometric techniques and in silico docking simulations performed on selected derivatives suggest that the compounds show a dual mode of action involving hemozoin inhibition and DNA interaction via minor-groove binding. Lastly, compound 9 a , identified as a possible lead, exhibited preferential binding for the plasmodial DNA isolated from 3D7 P. falciparum trophozoites over the mammalian calf thymus DNA, thereby substantiating the enhanced antiplasmodial activity of the compounds. The presented research demonstrates the strategy of incorporating organometallic complexes into known biologically active organic scaffolds as a viable avenue to fashion novel multimodal compounds with potential to counter the development drug resistance.     

Gehalt des Pfeffers und Kakaos an Cellulose, Lignin und Kutin

Ohne Zusammenfassung     

The penalty method for the Navier-Stokes equations

Summary The penalty finite element method as it applies to the Stokes and Navier-Stokes flow equations is reviewed. The main developments are discussed and selected but still extensive list of references is provided.     

Coagulation factor VII and the risk of coronary heart disease in healthy men

Numerous investigations have demonstrated the role of thrombus formation in the pathogenesis of coronary heart disease (CHD). A tendency to thrombosis may also be indicated by elevated levels of coagulation factor VII clotting activity (FVIIc). Significant associations of FVIIc with increased coronary risk, however, have been found only in the Northwick Park Heart Study. Here we present the results of the 8-year follow-up of FVIIc measurements in 2780 healthy men of the Prospective Cardiovascular Münster study. In the study population (age at entry, 49.3 +/- 6.1 years, mean +/- SD), 130 CHD events occurred during follow-up. FVIIc was significantly higher in subjects with coronary events than in those without (112.4 +/- 20.1% vs 108.7 +/- 21.4%, P = .023). Compared with individuals without coronary events, FVIIc was not significantly higher in men with nonfatal events (111.7 +/- 20.4%; P = .196, n = 93), but there was a tendency toward higher FVIIc activity in subjects with fatal events (114.6 +/- 19.5%; P = .076, n = 37). In the multiple logistic regression analysis, we did not find FVIIc to be an independent risk factor for CHD, and the significance of FVIIc disappeared after total cholesterol, LDL-cholesterol, and triglycerides were taken into account. The increase in the number of CHD events through higher levels of FVIIc was more pronounced in the presence of additional cardiovascular risk factors: smoking; myocardial infarction events in family; angina pectoris; high levels of fibrinogen, total cholesterol, LDL cholesterol, and triglycerides; and a low level of HDL cholesterol. We conclude that FVIIc is a risk factor for CHD, especially in the presence of additional risk factors, and must be taken into account when assessing cardiovascular risk in men.     

Three-dimensional models of estrogen receptor ligand binding domain complexes, based on related crystal structures and mutational and structure-activity relationship data

On the basis of the recently determined crystal structures of the ligand binding domains (LBDs) of the retinoic acid nuclear receptors (NRs), we present a three-dimensional (3D) molecular model of the human estrogen receptor alpha (hERalpha) LBD. A literature search for mutants affecting the binding properties has been performed; 45 out of 48 published mutants can be explained satisfactorily on the basis of the model. Estradiol has been docked into the binding pocket to probe its interactions with the protein. Energy minimizations and molecular dynamics calculations were performed for various ligand orientations. To evaluate their quality, the different models were scored using known structure-activity relationship (SAR) data for selected close estradiol homologues. The two best models explain largely the binding affinities of more distantly related ligands.