Myelinosome formation represents an early stage of oligodendrocyte damage in multiple sclerosis and its animal model

Oligodendrocyte damage is a central event in the pathogenesis of the common neuro-inflammatory condition, multiple sclerosis (MS). Where and how oligodendrocyte damage is initiated in MS is not completely understood. Here, we use a combination of light and electron microscopy techniques to provide a dynamic and highly resolved view of oligodendrocyte damage in neuroinflammatory lesions. We show that both in MS and in its animal model structural damage is initiated at the myelin sheaths and only later spreads to the oligodendrocyte cell body. Early myelin damage itself is characterized by the formation of local myelin out-foldings-'myelinosomes'-, which are surrounded by phagocyte processes and promoted in their formation by anti-myelin antibodies and complement. The presence of myelinosomes in actively demyelinating MS lesions suggests that oligodendrocyte damage follows a similar pattern in the human disease, where targeting demyelination by therapeutic interventions remains a major open challenge

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Quantification of Bacterial DNA from Infected Human Root Canals Using qPCR and DAPI after Disinfection with Established and Novel Irrigation Protocols

The removal of bacterial infections within the root canal system is still a challenge. Therefore, the cleansing effect of established and new irrigation-protocols (IP) containing silver diamine fluoride (SDF) 3.8% on the whole root canal system was analyzed using quantitative PCR (qPCR) and 4′,6-diamidino-phenylindole-(DAPI)-staining. Extracted human premolars were instrumented up to F2 (ProTaper Gold) under NaCl 0.9% irrigation and incubated with Enterococcus faecalis for 42 days. Subsequently, different ultrasonically agitated IP were applied to the roots: control (no irrigation), 1. NaOCl 3%, EDTA 20%, CHX 2%, 2. NaOCl 3%, EDTA 20%, 3. NaOCl 3%, EDTA 20%, SDF 3.8%, 4. SDF 3.8%, and 5. NaCl 0.9%. One half of the root was investigated fluorescent-microscopically with DAPI. The other half was grinded in a cryogenic mill and the bacterial DNA was quantified with qPCR. The qPCR results showed a statistically significant reduction of bacteria after the application of IP 1, 2, and 3 compared to the control group. While IP 4 lead to a bacterial reduction which was not significant, IP 5 showed no reduction. These data corresponded with DAPI staining. With qPCR a new molecular-biological method for the investigation of the complete root canal system was implemented. The novel IP 3 had an equally good cleansing effect as the already established IP

Wiederentdeckte Dokumente aus dem Nachlass Adelbert von Chamissos zum Musenalmanach auf das Jahr 1804

Sproll M. Wiederentdeckte Dokumente aus dem Nachlass Adelbert von Chamissos zum Musenalmanach auf das Jahr 1804. In: Federhofer M-T, Weber J, eds. Korrespondenzen und Transformationen. Neue Perspektiven auf Adelbert von Chamisso. Palaestra. Untersuchungen zur europäischen Literatur. Vol 337. 1st ed. Göttingen: V&R unipress; 2013: 143-155

Effects of Endodontic Irrigants on Material and Surface Properties of Biocompatible Thermoplastics

Passive irrigation is an efficient method for a successful endodontic treatment. During sonic activation biocompatible polymer tips are used to activate irrigants. Compared to ultrasonic activation with metallic tips, polymer tips have the advantage of a reduced risk of fracture and minimise dentine damage. Hence, two polymers, polyether ether ketones (PEEK) and polyamide (PA6), were identified for the manufacturing of novel irrigation tips. The chemical resistance against the irrigants ethylenediaminetetraacetic acid (EDTA) 20%, chlorhexidine gluconate (CHX) 2% and sodium hypochlorite (NaOCl) 5.25% was analysed. Using microindentation, the change of hardness, elasticity, surface roughness and appearance of the polymers was determined. PA6 had a high absorption of irrigant compared to PEEK. PEEK was resistant to the investigated irrigants and showed no significant alteration of surface and mechanical properties, whereas PA6 slightly increased its hardness, elastic modulus and surface roughness during long-term exposure at 37 °C. However, PA6 tips seem to be a promising disposable product due to the material’s high deformability and low manufacturing costs. Particularly with regard to structural-dynamic properties and high chemical resistance, PEEK can be considered as a material for reusable irrigation tips

Application of Plant Extracts for the Prevention of Dental Erosion: An in situ/in vitro Study

Objectives: Antiadherent and antibacterial effects of certain plant extracts have been proven to be beneficial in preventive dentistry. In the present in situ/in vitro crossover study, the impact of plant extracts rich in polyphenols on the erosion-protective properties of the in situ pellicle was evaluated. Methods: Individual splints were prepared for 12 subjects for intraoral exposure of bovine enamel specimens. Following formation of a 1-min pellicle, watery plant extracts(leaves of the wild form of Ribes nigrum , the wild form of Origanum as well as a combination of both) were administered for 10 min in situ. Alternatively, a mouth rinse with fluorides (Elmex Kariesschutz) was performed for 1 min. After further oral exposure for 19/28 min, respectively, slabs were removed and incubated with HCl in vitro over 120 s (pH 2, 2.3, 3). The resulting calcium and phosphate release was quantified photometrically. Slabs with and without a 30-min in situ pellicle served as controls. The modification of pellicle ultrastructure was evaluated by transmission electron microscopy (TEM). Results: Plant extracts modulated the erosion-protective properties of the native in situ pellicle in all test groups in a pH-dependent manner. The combination of R. nigrum leaves and Origanum enhanced the protective properties of the pellicle at all pH values; the administration of this preparation was comparable, yet superior, to the effect of the fluoridated mouth rinse. TEM images indicated that rinsing with R. nigrum leaves /Origanum yielded a distinctly thicker and more electron-dense pellicle. Conclusion: The combination of certain plant extracts offers a novel approach to the complementary prevention of dental erosion

Odontoblast-like differentiation and mineral formation of pulpsphere derived cells on human root canal dentin in vitro

Background The revitalization or regeneration of the dental pulp is a preferable goal in current endodontic research. In this study, human dental pulp cell (DPC) spheres were applied to human root canal samples to evaluate their potential adoption for physiological tissue-like regeneration of the dental root canal by odontoblastic differentiation as well as cell-induced mineral formation. Methods DPC were cultivated into three-dimensional cell spheres and seeded on human root canal specimens. The evaluation of sphere formation, tissue-like behavior and differentiation as well as mineral formation of the cells was carried out with the aid of optical light microscopy, immunohistochemical staining and scanning electron microscopy (SEM). Results Spheres and cells migrated out of the spheres showed an intense cell-cell- and cell-dentin-contact with the formation of extra cellular matrix. In addition, the ingrowth of cell processes into dentinal tubules and the interaction of cell processes with the tubule walls were detected by SEM-imaging. Immunohistochemical staining of the odontoblast specific matrix proteins, dentin matrix protein-1, and dentin sialoprotein revealed an odontoblast-like cell differentiation in contact with the dentin surface. This differentiation was confirmed by SEM-imaging of cells with an odontoblast specific phenotype and cell induced mineral formation. Conclusions The results of the present study reveal the high potential of pulp cells organized in spheres for dental tissue engineering. The odontoblast-like differentiation and the cell induced mineral formation display the possibility of a complete or partial “dentinal filling” of the root canal and the opportunity to combine this method with other current strategies

Mapping of the Micro-Mechanical Properties of Human Root Dentin by Means of Microindentation

The extensive knowledge of root dentin’s mechanical properties is necessary for the prediction of microstructural alterations and the teeth’s deformations as well as their fracture behavior. Standardized microindentation tests were applied to apical, medial, and cervical root sections of a mandibular human first molar to determine the spatial distribution of the hard tissue’s properties (indentation modulus, indentation hardness, Martens hardness, indentation creep). Using an indentation mapping approach, the inhomogeneity of mechanical properties in longitudinal as well as in transversal directions were measured. As a result, the tooth showed strongly inhomogeneous material properties, which depended on the longitudinal and transversal positions. In the transversal cutting planes of the cervical, medial, apical sections, the properties showed a comparable distribution. A statistical evaluation revealed an indentation modulus between 12.2 GPa and 17.8 GPa, indentation hardness between 0.4 GPa and 0.64 GPa and an indentation creep between 8.6% and 10.7%. The established standardized method is a starting point for further investigations concerning the intensive description of the inhomogeneous mechanical properties of human dentin and other types of dentin

Quantification of Bacterial DNA from Infected Human Root Canals Using qPCR and DAPI after Disinfection with Established and Novel Irrigation Protocols

The removal of bacterial infections within the root canal system is still a challenge. Therefore, the cleansing effect of established and new irrigation-protocols (IP) containing silver diamine fluoride (SDF) 3.8% on the whole root canal system was analyzed using quantitative PCR (qPCR) and 4′,6-diamidino-phenylindole-(DAPI)-staining. Extracted human premolars were instrumented up to F2 (ProTaper Gold) under NaCl 0.9% irrigation and incubated with Enterococcus faecalis for 42 days. Subsequently, different ultrasonically agitated IP were applied to the roots: control (no irrigation), 1. NaOCl 3%, EDTA 20%, CHX 2%, 2. NaOCl 3%, EDTA 20%, 3. NaOCl 3%, EDTA 20%, SDF 3.8%, 4. SDF 3.8%, and 5. NaCl 0.9%. One half of the root was investigated fluorescent-microscopically with DAPI. The other half was grinded in a cryogenic mill and the bacterial DNA was quantified with qPCR. The qPCR results showed a statistically significant reduction of bacteria after the application of IP 1, 2, and 3 compared to the control group. While IP 4 lead to a bacterial reduction which was not significant, IP 5 showed no reduction. These data corresponded with DAPI staining. With qPCR a new molecular-biological method for the investigation of the complete root canal system was implemented. The novel IP 3 had an equally good cleansing effect as the already established IP