Proinflammatory cytokines induce the expression of matrix metalloproteinases that play a crucial role in myocardial remodeling. Beta-adrenergic receptor stimulation influences the production of ...cytokines heralding the possibility of modulating cytokine production by beta-adrenergic blockers.
In a coxsackievirus B3 murine myocarditis model (BALB/c), effects of carvedilol and metoprolol on myocardial cytokine expression, inflammatory cell infiltration and MMP/TIMP profiles were investigated. In carvedilol-treated mice, a significant improvement in left ventricular function was documented 10 days post infection. In infected mice (n=10), IL-1beta, TNF-alpha, TGF-beta(1) and IL-10 myocardial mRNA abundance were increased significantly (240%, 200%, 161%, and 230%) compared to controls (n=10), while IL-15 mRNA was markedly reduced (70%). Infected mice showed significantly increased infiltrations with CD3-, CD4- and CD8-T-lymphocytes (730%, 1110%, 380%). In the infected mice, myocardial MMP/TIMP profiles presented a significant upregulation of membrane type-1 MMP, MMP-9, MMP-8 and MMP-3 (150%, 160%, 340%, and 270%) and a significant decrease in TIMP-4 levels (75%). Carvedilol attenuated over-expression of myocardial TGF-beta(1), IL-1beta and MMP-8 mRNA expression significantly and induced a relevant IL-10 mRNA expression in the infected mice (n=10). By an unchanged infiltration with CD3-T-lymphocytes, carvedilol showed a representative reduction in CD4-T-lymphocytes.
Carvedilol treatment in experimental myocarditis leads to reduced expression of proinflammatory cytokines and MMPs, which contributes to reduced matrix degradation and ultimately to improved structural integrity of the heart. Besides the antiadrenergic potential, carvedilol is beneficial due to a wide range of biological activities (antiinflammatory, antifibrotic, antioxidative and immunomodulatory).
The renal kallikrein-kinin system (KKS) was studied in pair-fed streptozotocin (STZ)-induced diabetic rats and compared with age-matched controls. Twelve weeks after STZ injection, rats were ...normotensive, showed hyperglycemia, proteinuria, polydipsia and reduced glomerular filtration rate (GFR) and body weight. The activities of urinary prekallikrein (PKLK) and kallikrein (KLK) were reduced accompanied by an up to 3-fold increase of bradykinin (BK) excretion compared to controls. The increased BK excretion suggests that the renal KKS in STZ-diabetes is activated and that the reduction in urinary PKLK and KLK activity may be due to an increased consumption of these enzymes or to a negative feedback mechanism. The stimulation of the renal KKS in STZ-diabetes could reflect an attempt of the organism to balance glomerular hypertension.
A framework of ferrocene-containing polymers bearing adjustable pH- and redox-active properties in aqueous electrolyte environments was developed. The electroactive metallopolymers were designed to ...possess enhanced hydrophilicity compared to the vinylferrocene (VFc) homopolymer, poly(vinylferrocene) (PVFc), by virtue of the comonomer incorporated into the macromolecule, and could also be prepared as conductive nanoporous carbon nanotube (CNT) composites that offered a variety of different redox potentials spanning a ca. 300 mV range. The presence of charged non-redox-active moieties such as methacrylate (MA) in the polymeric structure endowed it with acid dissociation properties that interacted synergistically with the redox activity of the ferrocene moieties to impart pH-dependent electrochemical behavior to the overall polymer, which was subsequently studied and compared to several Nernstian relationships in both homogeneous and heterogeneous configurations. This zwitterionic characteristic was leveraged for the enhanced electrochemical separation of several transition metal oxyanions using a P(VFc0.63-co-MA0.37)-CNT polyelectrolyte electrode, which yielded an almost twofold preference for chromium as hydrogen chromate versus its chromate form, and also exemplified the electrochemically mediated and innately reversible nature of the separation process through the capture and release of vanadium oxyanions. These investigations into pH-sensitive redox-active materials provide insight for future developments in stimuli-responsive molecular recognition, with extendibility to areas such as electrochemical sensing and selective separation for water purification.
•Comparison of different magnetic field sources and operation modes for magnetic chromatography.•Fractionation of magnetic nanoparticles in the size range of 50–400 nm at more than 30 CV/h.•High ...separation sharpness factor of 0.62.
Magnetic chromatography is a promising method for fractionation of magnetic nanoparticles with respect to their size and/or magnetic properties. In this study, we investigate the effect of different magnetic field sources and operation modes on the retention of magnetic nanoparticles which pass through a chromatographic column filled with a fine magnetizable matrix. For nanoparticles in the size range between 50 and 400 nm, both constant magnetic fields and square wave AC fields with amplitudes of around 2 mT, result in retention factors of up to 2, while still showing good particle recoveries of more than 95%. In contrast, when using the ‘on-off’ magnetic field operation reported previously, retention factors of only 1.4 could be achieved. We also demonstrate that single domain magnetic nanoparticles show retention factors of 1.2–1.4 even without the application of an external magnetic field, due to their spontaneous magnetization. By using a combination of online UV-measurement and sample collection followed by the determination of the particle size distribution (PSD) by dynamic light scattering, a quantification of the fractionation efficiency could be achieved. Despite the short column of only 12 cm and the high specific throughput of more than 30 column volumes per hour a separation sharpness of 0.62 could be attained, demonstrating the high potential of the method for scalable nanoparticle fractionation.
Micron‐sized supraparticles, consisting of a plurality of discrete nano‐ and microscale functional units, are assembled and fused by means of a droplet extrusion process. By combining nano magnetite, ...activated carbon, and conductive carbon with a polymeric binder matrix, particles are obtained which unite good magnetic properties, electrical conductivity, and adsorber activity through the high accessible surface area of the incorporated activated carbon of about 570 m2 g−1, thereby enabling a new approach toward sustainable water treatment processes. Due to the interplay of the components, it is possible to adsorb target substances, dissolved in the water which is demonstrated by the adsorption of the model dye methylene blue. A very fast adsorption kinetic and an adsorption capacity of about 400 mg g−1 is determined. By using the developed composite particles, it is also possible to electrochemically alter substances flowing through a magnetically‐stabilized fluidized‐bed reactor by electrochemically charging/discharging, significantly supported by the magnetic field enabling alternatingly optimum mobility/adsorption phases with contact/charging intervals. The electrochemical conversion can be increased up to 151% depending on the applied flow‐rate and electrical voltage. By applying an external magnetic field, a further increase of electrochemical conversion of up to 70% can be observed.
A magnetic adsorber composite supraparticle system is developed by employing an innovative extrusion process. Adsorption behavior on the model dye methylene blue and employment in a magnetically‐induced fluidized‐bed reactor for use in the electrochemical conversion of potassium ferricyanide are investigated.
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