Lokalisierung der Fortsatz-induzierenden Domäne von Transmembran-Agrin

Aggregation oder Überexpression der Transmembran-Isoform des extrazellulären Matrix-Proteoglycans Agrin in Neuronen führt zur Bildung zahlreicher filopodienartiger Fortsätze auf Axonen und Dendriten. Ähnliche Fortsätze können auch durch Überexpression von Transmembran-Agrin in verschiedenen nicht-neuronalen Zelllinien induziert werden. Untersuchungen zu dieser Fortsatz-induzierenden Aktivität in Neuronen und nicht-neuronalen Zellen zeigen, dass der extrazelluläre Teil von Transmembran-Agrin für die Fortsatzbildung notwendig ist. In dieser Arbeit wurde mittels verschiedener Deletions- und Mutationskonstrukte der Bereich zwischen den Cysteinen C535 und C567 der siebten Follistatin-ähnlichen Domäne von Transmembran-Agrin als essentiell für die Bildung der filopodienartigen Fortsätze identifiziert. Die siebte Follistatin-ähnliche Domäne konnte durch die erste oder sechste, jedoch nicht durch die achte Follistatin-ähnliche Domäne funktionell ersetzt werden, was für eine funktionelle Redundanz bei einigen Follistatin-ähnlichen Domänen Agrins spricht. Zudem scheint eine kritische Distanz der siebten Follistatin-ähnlichen Domäne zur Plasmamembran für die Fortsatzbildung wichtig zu sein. Diese Ergebnisse zeigen, dass unterschiedliche Regionen innerhalb Agrins für die Bildung der Synapse an der neuromuskulären Endplatte und der Fortsätze im Zentralnervensystem verantwortlich sind, und deuten auf eine Funktion der Follistatin-ähnlichen Domänen Agrins bei der Entwicklung des Zentralnervensystems hin.

Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies

Aim The aim of this study was to describe neuroimaging patterns associated with arterial ischaemic stroke (AIS) in childhood and to differentiate them according to stroke aetiology. Method Clinical and neuroimaging (acute and follow-up) findings were analysed prospectively in 79 children (48 males, 31 females) aged 2 months to 15 years 8 months (median 5y 3mo) at the time of stroke by the Swiss Neuropaediatric Stroke Registry from 2000 to 2006. Results Stroke was confirmed in the acute period in 36 out of 41 children who underwent computed tomography, in 53 of 57 who underwent T2-weighted magnetic resonance imaging (MRI) and in all 48 children who underwent diffusion-weighted MRI. AIS occurred in the anterior cerebral artery (ACA) in 63 participants and in all cases was associated with lesions of the middle cerebral artery (MCA). The lesion was cortical-subcortical in 30 out of 63 children, cortical in 25 out of 63, and subcortical in 8 of 63 children. Among participants with AIS in the posterior circulation territory, the stroke was cortical-subcortical in 8 out of 16, cortical in 5 of 16, and thalamic in 3 out of 16 children. Interpretation AIS mainly involves the anterior circulation territory, with both the ACA and the MCA being affected. The classification of Ganesan is an appropriate population-based classification for our Swiss cohort, but the neuroimaging pattern alone is insufficient to determine the aetiology of stroke in a paediatric population. The results show a poor correlation between lesion pattern and aetiology.

The influence of saliva on the dissolution of calcium fluoride after application of different fluoride gels in vitro

OBJECTIVE: To determine the formation and dissolution of calcium fluoride on the enamel surface after application of two fluoride gel-saliva mixtures. METHOD AND MATERIALS: From each of 80 bovine incisors, two enamel specimens were prepared and subjected to two different treatment procedures. In group 1, 80 specimens were treated with a mixture of an amine fluoride gel (1.25% F-; pH 5.2; 5 minutes) and human saliva. In group 2, 80 enamel blocks were subjected to a mixture of sodium fluoride gel (1.25% F; pH 5.5; 5 minutes) and human saliva. Subsequent to fluoride treatment, 40 specimens from each group were stored in human saliva and sterile water, respectively. Ten specimens were removed after each of 1 hour, 24 hours, 2 days, and 5 days and analyzed according to potassium hydroxide-soluble fluoride. RESULTS: Application of amine fluoride gel resulted in a higher amount of potassium hydroxide-soluble fluoride than did sodium fluoride gel 1 hour after application. Saliva exerted an inhibitory effect according to the dissolution rate of calcium fluoride. However, after 5 days, more than 90% of the precipitated calcium fluoride was dissolved in the amine fluoride group, and almost all potassium hydroxide-soluble fluoride was lost in the sodium fluoride group. Calcium fluoride apparently dissolves rapidly, even at almost neutral pH. CONCLUSION: Considering the limitations of an in vitro study, it is concluded that highly concentrated fluoride gels should be applied at an adequate frequency to reestablish a calcium fluoride-like layer.

Remineralization of initial carious lesions in deciduous enamel after application of dentifrices of different fluoride concentrations

The aim of the present study was to evaluate the remineralization potential of five dentifrices with different fluoride concentrations. Initial caries lesions were created in 72 cylindrical enamel blocks from deciduous teeth. The specimens were randomly distributed among six experimental groups corresponding to six experimental periods. Each of the six volunteers carried two deciduous enamel specimens fixed in an intraoral appliance for a period of 4 weeks. They brushed their teeth and the enamel blocks at least two times a day with dentifrices containing 0 ppm (period 1), 250 ppm (period 2), and 500 ppm fluoride (period 3), respectively. A second group of volunteers (n = 6) used dentifrices with a fluoride content of 0 ppm (period 4), 1,000 ppm (period 5), or 1,500 ppm (period 6). At the end of the respective period, the mineral content was determined by transversal microradiography (TMR). The use of dentifrices containing 500 ppm fluoride (38% MR), 1,000 ppm fluoride (42% MR), and 1,500 ppm fluoride (42% MR) resulted in a statistically significant higher mineral recovery compared to the control group (0 ppm fluoride). Mineral recovery was similar after use of dentifrices containing 0 and 250 ppm fluoride (24%; 25%). It is concluded that it is possible to remineralize initial carious lesions in deciduous enamel in a similar way as it has been described for enamel of permanent teeth.

Clinical and antibacterial effect of an anti-inflammatory toothpaste formulation with Scutellaria baicalensis extract on experimental gingivitis

It was the aim of the study to evaluate the clinical and antibacterial effect of a dentifrice containing an anti-inflammatory plant extract (SB) versus a placebo (PLA) using an experimental gingivitis model. Forty subjects (20 per group) discontinued all oral hygiene measures for four teeth for a period of 21 days using a shield (to generate a possible gingivitis) while they could brush the other teeth normally. After brushing, the shield was removed and teeth were treated with the randomly assigned toothpaste slurry for 1 min. Löe and Silness gingival index (GI), Silness and Löe plaque index (PI), and biofilm vitality (VF%) were assessed at days 0, 14, and 21, respectively. Subjects of the PLA group developed a GI of 0.82?±?0.342 (day 14) and 1.585?±?0.218 (day 21), while the data of the SB group were significantly reduced (0.355?±?0.243 and 0.934?±?0.342, p?

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.

A role for low hepatic copper concentrations in nonalcoholic Fatty liver disease

Copper has a role in antioxidant defense, lipid peroxidation, and mitochondrial function, and copper deficiency has been linked to atherogenic dyslipidemia. We aimed to investigate the potential role of copper availability in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).

Focal cystic high-attenuation lesions: characterization in renal phantom by using photon-counting spectral CT--improved differentiation of lesion composition

To evaluate the capability of spectral computed tomography (CT) to improve the characterization of cystic high-attenuation lesions in a renal phantom and to test the hypothesis that spectral CT will improve the differentiation of cystic renal lesions with high protein content and those that have undergone hemorrhage or malignant contrast-enhancing transformation.

Cerebral sinus venous thrombosis in Swiss children

AIMo describe the characteristics of paediatric cerebral sinus venous thrombosis (CSVT) in Switzerland.

Preventing erosion with novel agents

Objectives: This in vitro study aimed to investigate the protective effect of four commercial novel agents against erosion. Methods: Ninety human molars were distributed into 9 groups, and after incubation in human saliva for 2 h, a pellicle was formed. Subsequently, the specimens were submitted to demineralization (orange juice, pH 3.6, 3 min) and remineralization (paste slurry containing one of the tested novel agents, 3 min) cycles, two times per day, for 4 days. The tested agents were: (1) DenShield Tooth; active ingredient: 7.5% W/W NovaMin® (calcium sodium phosphosilicate); (2) Nanosensitive hca; active ingredient: 7.5% W/W NovaMin®; (3) GC Tooth Mousse; active ingredient: 10% Recaldent™ (CPP-ACP); (4) GC MI Paste Plus; active ingredients: 10% Recaldent™, 900 ppm fluoride. Two experimental procedures were performed: in procedure 1, the tested agents were applied prior to the erosive attack, and in procedure 2 after the erosive attack. A control group receiving no prophylactic treatment was included. Surface nanohardness (SNH) of enamel specimens was measured after pellicle formation and after completion of daily cyclic treatment. Results: SNH significantly decreased at the end of the experiment for all groups (p < 0.05). In both procedures, there was no statistically significant difference between the control group and those treated with paste slurries (p > 0.05). In addition, the changes in SNH (ΔSNH = SNHbaseline − SNHfinal) did not show statistically significant difference between both procedures (p > 0.05). Conclusion: Tooth erosion cannot be prevented or repaired by these novel agents, regardless of fluoride content.

Clinical Study Monitoring the pH on Tooth Surfaces in Patients with and without Erosion

The aim of this study was to compare tooth surface pH after drinking orange juice or water in 39 patients with dental erosion and in 17 controls. The following investigations were carried out: measurement of pH values on selected tooth surfaces after ingestion of orange juice followed by ingestion of water (acid clearance), measurement of salivary flow rate and buffering capacity. Compared with the controls, patients with erosion showed significantly greater decreases in pH after drinking orange juice, and the pH stayed lower for a longer period of time (p < 0.05). Saliva parameters showed no significant differences between the two patient groups except for a lower buffering capacity at pH 5.5 in the erosion group.

Fluorides - mode of action and recommendations for use

Summary Various authors have shown that the caries decline in the industrialized countries during recent decades is based on the use of fluorides, of which local fluoride application in the form of fluoridated toothpastes is of primary importance. The caries-protective potential of fluorapatite is quite low; in contrast, dissolved fluorides in the vicinity of enamel are effective both in promoting remineralization and inhibiting demineralization. Considering the fact that the caries decline occurred at the same time that local fluoridation measures became widely used, the conclusion seems justified that regular application of F⁻ can inhibit caries.

Expression patterns of neurexin-1 and neuroligins in brain and retina of the chick embryo: Neuroligin-3 is absent in retina

Neuroligins (NLs) constitute a family of cell-surface proteins that interact with neurexins (beta-Nxs), another class of neuronal cell-surface proteins, one of each class functioning together in synapse formation. The localization of the various neurexins and neuroligins, however, has not yet been clarified in chicken. Therefore, we studied the expression patterns of neurexin-1 (Nx-1) and neuroligin-1 and -3 during embryonic development of the chick retina and brain by reverse-transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). While neurexin-1 increased continuously in both brain and retina, the expression of both neuroligins was more variable. As shown by ISH, Nx-1 is expressed in the inner half retina along with differentiation of ganglion and amacrine cells. Transcripts of NL-1 were detected as early as day 4 and increased with the maturation of the different brain regions. In different brain regions, NL-1 showed a different time regulation. Remarkably, neuroligin-3 was entirely absent in retina. This study indicates that synaptogenetic processes in brain and retina use different molecular machineries, whereby the neuroligins might represent the more distinctly regulated part of the neurexin-neuroligin complexes. Noticeably, NL-3 does not seem to be involved in the making of retinal synapses.