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Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C.
Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome.
Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome.
On 26th November 2010 around 3000 psychiatrists rose up for a minute's silence in the great hall of the International Congress Centrum in Berlin. What they had heard before, was deeply impressive and memorable to the audience. Professor Frank Schneider, president of the German Society for Psychiatry, Psychotherapy and Neurology (DGPPN) asked the psychiatric victims and their relatives of the Nazi era for forgiveness to an extent as only a few German Doctors done before. ...
Termite mounds represent abundant microhabitats of high biodiversity in tropical savanna ecosystems and are an important source of landscape heterogeneity in Sub–Saharan West Africa. Floristic composition as well as density, structure and zonation of plant cover on the mounds were investigated in northern Benin and compared to the adjacent savanna vegetation. A total of 57 abandoned and densely vegetated termite mounds of comparable size and similarly affected by erosion located in different types of savannas inside and outside of the W National Park and in cotton fields were studied. This study revealed that termitaria are special habitats differing in density, composition and structure from surrounding savannas. The plant cover of termite mounds showed a distinctive zonation. Succulents, geophytes, and lianas were much more abundant on mounds, the family Capparaceae was found exclusively on mounds. The floristic composition and vegetation on termitaria proved to be rather homogeneous; although those mounds located in cotton fields differed by higher abundance of Poaceae and lower species richness.
Grass savannas on lateritic crusts are characteristic landscape elements of the Sudanian savannas. In the W National Park and its surroundings in SE-Burkina Faso, plant diversity of savannas on and adjacent to bowé was assessed by a survey of 19 bowal areas with relevés along transects in each of these. The vegetation structure and species composition of the herb and shrub strata, soil depth, particle size and the concentration of Na+, K+, Mg2+, Ca2+, H+, C and N were recorded on each bowal and its surroundings. Our results show that soils on lateritic crusts are rather shallow and acidic compared to the surrounding savanna woodlands. Nutrient availability is hence comparatively low. The observed flora comprises 130 species mainly belonging to the families Combretaceae, Cyperaceae, Leguminosae and Poaceae with a predominance of therophytes and a comparatively high share of C4 species. In the pastures surrounding the National Park a higher species richness was found than inside the Park due to the occurrence of pioneers, ruderal and unpalatable plants. Savannas on lateritic crusts exhibit due to their extreme edaphic and hydrological conditions a specific flora distinct from their surroundings.
The present study addresses the problem whether negative priming (NP) is due to information processing in perception, recognition or selection. We argue that most NP studies confound priming and perceptual similarity of prime-probe episodes and implement a color-switch paradigm in order to resolve the issue. In a series of three identity negative priming experiments with verbal naming response, we determined when NP and positive priming (PP) occur during a trial. The first experiment assessed the impact of target color on priming effects. It consisted of two blocks, each with a different fixed target color. With respect to target color no differential priming effects were found. In Experiment 2 the target color was indicated by a cue for each trial. Here we resolved the confounding of perceptual similarity and priming condition. In trials with coinciding colors for prime and probe, we found priming effects similar to Experiment 1. However, trials with a target color switch showed such effects only in trials with role-reversal (distractor-to-target or target-to-distractor), whereas the positive priming (PP) effect in the target-repetition trials disappeared. Finally, Experiment 3 split trial processing into two phases by presenting the trial-wise color cue only after the stimulus objects had been recognized. We found recognition in every priming condition to be faster than in control trials. We were hence led to the conclusion that PP is strongly affected by perception, in contrast to NP which emerges during selection, i.e., the two effects cannot be explained by a single mechanism.
Denervation-induced changes in excitatory synaptic strength were studied following entorhinal deafferentation of hippocampal granule cells in mature (≥3 weeks old) mouse organotypic entorhino-hippocampal slice cultures. Whole-cell patch-clamp recordings revealed an increase in excitatory synaptic strength in response to denervation during the first week after denervation. By the end of the second week synaptic strength had returned to baseline. Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength. To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin. In these cultures, the effects of denervation and activity blockade were not additive, suggesting that similar mechanisms are involved. Finally, we investigated whether entorhinal denervation, which removes afferents from the distal dendrites of granule cells while leaving the associational afferents to the proximal dendrites of granule cells intact, results in a global or a local up-scaling of granule cell synapses. By using computational modeling and local electrical stimulations in Strontium (Sr2+)-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3–4 days post lesion. Taken together, our data show that entorhinal denervation results in homeostatic functional changes of excitatory postsynapses of denervated dentate granule cells in vitro.
Background: The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood.
Methodology/Principal Findings: In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor.
Conclusions/Significance: This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.
Introduction: In order to assess the significance of drug levels measured in intensive care medicine, clinical and forensic toxicology, as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. Therefore, it makes sense to offer a carefully referenced compilation of therapeutic and toxic plasma concentration ranges, as well as half-lives, of a large number of drugs and other xenobiotics for quick and comprehensive information.
Methods: Data have been abstracted from original papers and text books, as well as from previous compilations, and have been completed with data collected in our own forensic and clinical toxicology laboratory. The data presented in the table and corresponding annotations have been developed over the past 20 years and longer. A previous compilation has been completely revised and updated. In addition, more than 170 substances, especially drugs that have been introduced to the market since 2003 as well as illegal drugs, which became known to cause intoxications, were added. All data were carefully referenced and more than 200 new references were included. Moreover, the annotations providing details were completely revised and more than 100 annotations were added.
Results: For nearly 1,000 drugs and other xenobiotics, therapeutic ("normal") and, if data were available, toxic and comatose-fatal blood-plasma concentrations and elimination half-lives were compiled in a table.
Conclusions: In case of intoxications, the concentration of the ingested substances and/or metabolites in blood plasma better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment and monitoring of acute and chronic intoxications, and to support forensic and clinical expert opinions.
Most of the grass savannas on lateritic crusts found in the North-Western of Benin are free of trees and a shrub layer is only sparsely developed. The only constant member of the shrub layer is Terminalia laxiflora. Intermediate constancy show Entada africana and Annona senegalensis. With regard to the herbaceous layer two types can be identified: On very shallow soils (<2 cm) Loudetia togoensis is highly constant and often dominating. The same is true for Andropogon pseudapricus on soils of a little bit more than 2 cm. In those types, Lepidagathis anobrya and Spermacoce filifolia show very high constancy (constancy class V) and Cyanotis lanata and Melliniella micrantha occur with high constancy (IV).