Poorly water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. In the present study, the melt ...emulsification method traditionally used to prepare solid lipid nanoparticles was adapted to produce drug nanosuspensions. The method was evaluated in comparison with the well known solvent diffusion process for ibuprofen as a model drug. Control of the preparation variables (stabilizers, drug content, homogenization procedure and cooling conditions) allowed formation of nanosuspensions with diameters less than 100
nm. The major advantage of the melt emulsification method over the solvent diffusion method is the avoidance of organic solvents during production, although the mean particle size is slightly greater. The combination of Tween 80 and PVP K25 as stabilizers yields nanosuspensions with the smallest average particle size. The formulation of ibuprofen as a nanosuspension, either in the form of lyophilized powder or granules, was very successful in enhancing dissolution rate, more than 65% of the drug being dissolved in the first 10
min compared to less than 15% of the micronized drug. The increase in in vitro dissolution rate may favourably affect bioavailability and improve safety for the patient by decreasing gastric irritancy.
Dietary plant sterols and stanols as present in our diet and in functional foods are well-known for their inhibitory effects on intestinal cholesterol absorption, which translates into lower ...low-density lipoprotein cholesterol concentrations. However, emerging evidence suggests that plant sterols and stanols have numerous additional health effects, which are largely unnoticed in the current scientific literature. Therefore, in this review we pose the intriguing question “What would have occurred if plant sterols and stanols had been discovered and embraced by disciplines such as immunology, hepatology, pulmonology or gastroenterology before being positioned as cholesterol-lowering molecules?” What would then have been the main benefits and fields of application of plant sterols and stanols today? We here discuss potential effects ranging from its presence and function intrauterine and in breast milk towards a potential role in the development of non-alcoholic steatohepatitis (NASH), cardiovascular disease (CVD), inflammatory bowel diseases (IBD) and allergic asthma. Interestingly, effects clearly depend on the route of entrance as observed in intestinal-failure associated liver disease (IFALD) during parenteral nutrition regimens. It is only until recently that effects beyond lowering of cholesterol concentrations are being explored systematically. Thus, there is a clear need to understand the full health effects of plant sterols and stanols.
•Dietary plant sterols and stanols lower low density lipoprotein cholesterol, a causal risk factor for cardiovascular diseases•Although plant sterols and stanols are poorly absorbed they are taken up by various organs, which may affect health and disease.•Plant sterols and stanols may play a crucial role in functioning of immune cells and have beneficial effects beyond lowering low density lipoprotein cholesterol•Effects of plant sterols on liver health depend on the route of administration as observed during parenteral nutrition regimens•Intracellular oxidation of plant sterols might be a protective response avoiding accumulation of plant sterols within the cell.
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► Correlation between rheology of polymer solutions and electrospinnability is proved. ► Polymer solutions effective for electrospinning should be unstructured systems. ► Solutions ...should display plasticity, rather than elasticity, in bulk and at the interface. ► Rheology in bulk and at the interface has to be considered complementary. ► Interfacial rheology is an indispensible tool when designing nanofibers.
Electrospun polymer nanofibers are gaining increasing importance in tissue engineering, wound dressing and drug delivery. Here, we present a thorough rheological study of polymer solutions in the bulk and at the interface to find correlations between those properties and the electrospinnability of the solutions and the morphology of the resultant nanofibers. Our results indicate that blended solutions of chitosan or alginate with poly(ethylene oxide) (PEO) are appropriate for electrospinning when they form conductive, unstructured fluids displaying plasticity, rather than elasticity, in the bulk and at the interface. The interfacial rheological parameters are three orders of magnitude lower than those in the bulk. We demonstrate for the first time that interfacial, rather than bulk, rheological parameters show improved correlation and can be used to predict the success of the electrospinning process. Using the interfacial parameters of samples with homologous compositions, different groups of solutions can be identified that form smooth nanofibers. However, rheological parameters of the bulk and at the interface provide complimentary information. The bulk parameters are determined by polymer concentration and directly affect jet initiation, while the interfacial behaviour determines the continuation of the jet and fibre formation. We propose that interfacial parameters are indispensible tools for the design of electrospinning experiments.
We present a dose–response meta‐analysis to quantify relative efficacy of biologic disease‐modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). There is a strong ...rationale for this analysis because, although multiple biologics are available, information on head‐to‐head comparisons is limited. Data on the percentage of patients attaining American College of Rheumatology (ACR) 20, 50, and 70 responses were extracted from 50 randomized controlled trials representing 21,500 patients, five mechanisms of action, and nine biologics. The analysis showed that all tumor necrosis factor inhibitors (anti‐TNFs) share the same dose–response relationship for ACR 20, 50, and 70, differing only in potency. Yet there are significant differences in efficacy among the anti‐TNFs due to differences in the clinical dose ranges available. At the suggested starting dose, golimumab was the least efficacious, followed by infliximab, adalimumab, etanercept, and certolizumab. Significant differences in the dose–response relationship were found between anti‐TNFs and other biologics, resulting in differences in efficacy and differential impact of dose titration.
Clinical Pharmacology & Therapeutics (2011); 90 6, 828–835. doi:10.1038/clpt.2011.256
While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. ...For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central role in injury response and tissue repair, we here suggest that multipotent stem cell therapies achieve therapeutic effect by altering the immune response to injury, thereby limiting damage due to inflammation and possibly promoting repair. These findings argue for a broader understanding of the mechanisms by which cell therapies can benefit patients.
Injury to the central nervous system and ear lead to immediate neuron and hair cell loss (green), respectively. Neuron/hair cell loss continues over subsequent months, exacerbating neurological impairments. Recent studies indicate this could result from chronic inflammation and unresolved proinflammatory signals (red). Treatment with mesenchymal progenitor cells (blue) improves neuron/hair cell survival, potentially via anti‐inflammatory mechanisms.
Structural steels provide a broad spectrum of heat, creep and wear resistance at different microstructures and hardness levels. Two different steel grades were chosen for investigation and simulated ...repair welds with different parameters were performed, aiming on the influence of heat input during welding and the resulting microstructure on the high temperature abrasion resistance. The impact on the wear resistance and its temperature dependence was evaluated within a high temperature three-body abrasion test and a hot hardness test rig. Results indicate a strong dependence of present microstructural phases and hardness on the wear resistance entailed by different welding parameters. Optimised parameters and low energy input during welding leads to stable hot hardness progress and wear conditions for the investigated materials.
•Repair/overlay welding can increase the wear resistance of the steel grades.•Optimised welding leads to stable hot hardness and wear behaviour.•Higher energy input and higher interpass temperature cause unstable wear behaviour.•Suboptimal welding conditions lead to lowered hardness and higher wear rates.•The importance of welding parameters on abrasive wear resistance was pointed out.
Scheme of electrospinning process and the effects of aligned and randomly oriented nanofibers on cell growth (morphology, mobility, and cell penetration).
Despite a lot of intensive research in the ...field of polymer nanofibers as wound-healing and tissue-regeneration materials, the behavior of cells in contact with nanofibers in vitro as well as in vivo is still not well understood. However, this knowledge is crucial for the design of nanofibrillar materials that are suitable for biomedical applications. Therefore, in this study, we present the preparation of poly(vinyl alcohol) (PVA) nanofibers from a physico-chemically characterized polymer solution by electrospinning together with a stabilization method to preserve the morphology of the nanofibers in aqueous conditions. An investigation of the effects of a nanofibrillar scaffold on the growth of human keratinocytes showed that randomly oriented PVA nanofibers delay the keratinocytes’ adhesion but improve their strength, greatly alter their morphology, increase their metabolic activity, and limit their mobility. We have shown that due to the small interfiber pores, the whole cells are unable to penetrate into nanofibrillar network efficiently. However, flexible cell parts can penetrate into the nanofibrillar network, whereas the cell nuclei stay on the surface of electrospun scaffold. Additional reason for poor cell mobility is random orientation of nanofibers, which does not provide continuous routes for successful cell infiltration. Therefore, nanofibrillar support with nanosized interfiber pores could potentially be used to enable an efficient cell proliferation and accelerate surface-wound healing, but not for three-dimensional tissue regeneration. Finally, we showed that aligned nanofibers can successfully direct the migration and proliferation of cells, which is a crucial property of nanomaterials for the successful regeneration of tissues with a highly organized structure.
The aim of this review is to describe the state-of-the-art in the analysis of A- and B-trichothecene mycotoxins in cereals and to support knowledge and experience exchange between laboratories in the ...field of Fusarium mycotoxin analysis. Current screening tests and quantitative methods for the most prevalent type-A and -B trichothecenes, HT-2 and T-2-toxin, and deoxynivalenol (DON) are reviewed. This includes the extraction and clean-up procedures and chromatographic methods (TLC, HPLC, GC) applied and the immunochemical methods, especially enzyme-linked immunosorbent assay (ELISA), employed for the determination of these mycotoxins. Results from recent intercomparison studies of the determination of DON are also discussed. Experience gained during these intercomparisons clearly shows the need for further improvement in the determination of trichothecenes, to obtain more accurate and comparable results. This also indicates there is a strong need for the development of further certified reference materials (CRM) which would enable comparison of measurement results between different European laboratories for several A- and B-trichothecenes. For both A- and B-trichothecenes there is still a lack of simple and reliable screening methods enabling the rapid detection of these mycotoxins at low cost.
Seasonal patterns in hospitalizations have been observed in various psychiatric disorders, however, it is unclear whether they also exist in schizophrenia. Previous studies found mixed results and ...those reporting the presence of seasonality differ regarding the characteristics of these patterns. Further, they are inconclusive whether sex is an influencing factor. The aim of this study was therefore to examine if seasonal patterns in hospitalizations can be found in schizophrenia, with special regard to a possible influence of sex, by using a large national dataset.
Data on all hospital admissions within Austria due to schizophrenia (F20.0-F20.6) for the time period of 2003-2016 were included. Age standardized monthly variation of hospitalization for women and men was analyzed and the level of significance adjusted for multiple testing.
The database comprised of 110,735 admissions (59.6% men). Significant seasonal variations were found in the total sample with hospitalization peaks in January and June and a trough in December (p < 0.0001). No significant difference in these patterns was found between women and men with schizophrenia (p < 0.0001).
Our study shows that schizophrenia-related hospitalizations follow a seasonal pattern in both men and women. The distribution of peaks might be influenced by photoperiod changes which trigger worsening of symptoms and lead to exacerbations in schizophrenia. Further research is necessary to identify underlying factors influencing seasonal patterns and to assess whether a subgroup of patients with schizophrenia is especially vulnerable to the impact of seasonal variations.
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