Enhanced oral bioavailability and intestinal lymphatic transport of a hydrophilic drug using liposomes

A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.     

The Governmentality of Master Planning: Housing Consumption,Aesthetics and Community on a New Estate

The emergence of advanced liberalism as a political rationality has been accompanied by a trend towards more privatized forms of governing, in which market actors assume many of the responsibilities that were formerly state-provided. As a result, the problems of rule regarding who or what to govern and by what means are increasingly preoccupying private actors. This paper examines the privatized governmentalities of rules posed by a property developer of a master planned estate, as it seeks to govern the ethical conduct of local residents by governing through community so that they voluntarily maintain the aesthetic standards of the estate, not only for their own benefit, but also out of a sense of commitment to others.     

Hochwasserschutz im Land Bremen – Anpassung an prognostizierte Klimaänderungen

Im Beitrag wird auf Besonderheiten bei der Umsetzung des Generalplans Küstenschutz Niedersachsen/Bremen im Land Bremen eingegangen. Im ersten Teil werden die Grundlagen und Ergebnisse des Generalplans sowie die administrative Aufstellung des Landes Bremen zur Anpassung des Hochwasserschutzes beschrieben. Das Instrument der Kostenvergleichsrechnung wird vorgestellt, welches in Bremen bereits im frühen Projektstadium zur Bewertung der Vorzugslösungen eingesetzt wird. Ein wichtiger Aspekt bei der Umsetzung des Generalplans sind die technischen Anforderungen, die sich aus den bestehenden Hochwasserschutzanlagen ergeben. Weiterhin müssen im Land Bremen die Maßnahmen zum Hochwasserschutz im Wesentlichen unter Berücksichtigung der bestehenden konstruktiv geprägten Ufer (Spundwände und Kaianlagen) umgesetzt werden. Dabei sind spezielle Anforderungen hinsichtlich der aktuellen und zukünftigen Nutzung insbesondere in den Hafenrevieren zu berücksichtigen. Beispielhaft werden begleitende Projekte der INROS LACKNER AG vorgestellt. Flood protection in the Federal State and the city of Bremen by adjustment of climate changes. The present article describes how the Federal State and the Free Hanseatic City of Bremen adapts its flood protection with respect to climate changes and global sea level rise. Design basics are compiled in the “Generalplan Küstenschutz Niedersachsen/Bremen” (General Plan for Coastal Protection – Lower Saxony/Bremen). Main results of the general plan will be described and administrative aspects of the adaptation of the flood protection elements in Bremen will be lined out. Special technical requirements as the consideration of existing walls and dikes will be described. Also requirements from harbour operation, recreational use and urban architecture have to be considered as the Bremen port partly undergoes a rapid change in this regard. The instrument of cost analysis will be introduced which is utilised in Bremen at an early stage of planning in order to develop cost effective measures of public founded projects. Mentioned topics will be described based on projects carried out by INROS LACKNER AG.     

The influence of diet and breed of cow on the efficiency of conversion of milk constituents to curd in cheese manufacture

The influence of diet on the efficiency of conversion of milk solids to cheese in two breeds of cow, viz. Jersey and Friesian, was examined. An increase in the efficiency of conversion of milk solids to cheese in Jersey milks produced from cows on winter diets as compared with a typical summer diet was shown to be associated with an improvement in the level of fat retention in curd. The difference in fat retention could to some extent be related to the overall fat content of the milk, the casein to fat ratio and the distribution in the size of the fat globules but these factors when considered collectively or independently could not adequately explain the differences in fat retention observed in these experiments. The level of fat retention in curd was not influenced by the thermal properties of the mik fat.     

Tailoring the Angular Mismatch in MoS2 Homobilayers through Deformation Fields

Ultrathin MoS₂ has shown remarkable characteristics at the atomic scale with an immutable disorder to weak external stimuli. Ion beam modification unlocks the potential to selectively tune the size, concentration, and morphology of defects produced at the site of impact in 2D materials. Combining experiments, first-principles calculations, atomistic simulations, and transfer learning, it is shown that irradiation-induced defects can induce a rotation-dependent moiré pattern in vertically stacked homobilayers of MoS₂ by deforming the atomically thin material and exciting surface acoustic waves (SAWs). Additionally, the direct correlation between stress and lattice disorder by probing the intrinsic defects and atomic environments are demonstrated. The method introduced in this paper sheds light on how engineering defects in the lattice can be used to tailor the angular mismatch in van der Waals (vdW) solids.     

Targeting Mucin Protein Enables Rapid and Efficient Ovarian Cancer Cell Capture: Role of Nanoparticle Properties in Efficient Capture and Culture

The development of specific and sensitive immunomagnetic cell separation nanotechnologies is central to enhancing the diagnostic relevance of circulating tumor cells (CTCs) and improving cancer patient outcomes. The limited number of specific biomarkers used to enrich a phenotypically diverse set of CTCs from liquid biopsies has limited CTC yields and purity. The ultra-high molecular weight mucin, mucin16 (MUC16) is shown to physically shield key membrane proteins responsible for activating immune responses against ovarian cancer cells and may interfere with the binding of magnetic nanoparticles to popular immunomagnetic cell capture antigens. MUC16 is expressed in ≈90% of ovarian cancers and is almost universal in High Grade Serous Epithelial Ovarian Cancer. This work demonstrates that cell bound MUC16 is an effective target for rapid immunomagnetic extraction of expressor cells with near quantitative yield, high purity and viability from serum. The results provide a mechanistic insight into the effects of nanoparticle physical properties and immunomagnetic labeling on the efficiency of immunomagnetic cell isolation. The growth of these cells has also been studied after separation, demonstrating that nanoparticle size impacts cell-particle behavior and growth rate. These results present the successful isolation of “masked” CTCs enabling new strategies for the detection of cancer recurrence and select and monitor chemotherapy.     

Prevention of Bone Destruction by Mechanical Loading Is Not Enhanced by the Bruton’s Tyrosine Kinase Inhibitor CC-292 in Myeloma Bone Disease

Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown whether treatment with the Bruton’s tyrosine kinase inhibitor CC-292 (spebrutinib), which regulates osteoclast differentiation and function, augments the anabolic effect of mechanical loading. CC-292 was administered alone and in combination with axial compressive tibial loading in the MOPC315.BM.Luc model for three weeks. However, neither CC-292 alone nor its use in combination with mechanical loading was more effective in reducing osteolytic bone disease or rescuing bone mass than mechanical stimuli alone, as evidenced by microcomputed tomography (microCT) and histomorphometric analysis. Further studies are needed to investigate novel anti-myeloma and anti-resorptive strategies in combination with physical stimuli to improve treatment of MMBD.     

Associations between the Complement System and Choroidal Neovascularization in Wet Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness affecting the elderly in the Western world. The most severe form of AMD, wet AMD (wAMD), is characterized by choroidal neovascularization (CNV) and acute vision loss. The current treatment for these patients comprises monthly intravitreal injections of anti-vascular endothelial growth factor (VEGF) antibodies, but this treatment is expensive, uncomfortable for the patient, and only effective in some individuals. AMD is a complex disease that has strong associations with the complement system. All three initiating complement pathways may be relevant in CNV formation, but most evidence indicates a major role for the alternative pathway (AP) and for the terminal complement complex, as well as certain complement peptides generated upon complement activation. Since the complement system is associated with AMD and CNV, a complement inhibitor may be a therapeutic option for patients with wAMD. The aim of this review is to (i) reflect on the possible complement targets in the context of wAMD pathology, (ii) investigate the results of prior clinical trials with complement inhibitors for wAMD patients, and (iii) outline important considerations when developing a future strategy for the treatment of wAMD.     

Evaluation of residual stresses during brazing of Al2O3-ZrO2 to cemented tungsten carbide

In the context of the assembly of a cutting tool for wood machining, this article proposes to evaluate the residual stress in a ceramic plate (Al₂O₃-ZrO₂) induced by a brazing step with a cemented tungsten carbide (WC-Co) through a brazing filler (Ag-Cu-Ti). The residual stresses were evaluated using neutron and X-ray diffraction method. Moreover, a mathematical model was used in the case of a three layer assembly, which is based on mechanical properties such as: the thermal coefficient, the Young's modulus, the Poisson's ratio and the thickness of each layer. The observation of the chemical mapping of the brazing filler before and after the assembly, using energy dispersive X-ray spectroscopy (EDX), showed the chemical migration of the titanium to the ceramic oxide and the tungsten carbide. It was estimated that the brazed assembly is under a flexural stress, with a maximum in a compressive stress area near the brazing joint which reaches 85.6 MPa. This stress value reaches 12% of the bending strength allowed by the ceramic (716 MPa). The discussion proposes to highlight the limits of each method. The mathematical model has however shown good accuracy to give a first estimated residual stress in the ceramic plate.