Hyperglycemia and Hyperlipidemia Act Synergistically to Induce Renal Disease in LDL Receptor-Deficient BALB Mice

Diabetic nephropathy is the leading cause of end-stage renal disease in Western countries, but only a portion of diabetic patients develop diabetic nephropathy. Dyslipidemia represents an important aspect of the metabolic imbalance in diabetic patients. In this study, we addressed the impact of combined hyperlipidemia and hyperglycemia on renal pathology. Kidneys from wildtype (WT) or LDL receptor-deficient BALB/cBy mice (BALB. LDLR -/-) were examined at 22 weeks of age. Diabetes was induced by administration of streptozotocin and mice were randomly assigned to either standard chow or Western diet. Chow fed BALB. LDLR -/- mice did not demonstrate renal abnormalities, whereas BALB. LDLR -/- mice fed a Western diet showed occasional glomerular and tubulointerstitial foam cells. Diabetic WT mice had modestly increased glomerular cellularity and extracellular matrix. Hyperlipidemic and diabetic BALB. LDLR -/- mice exhibited an increase in glomerular cellularity and extracellular matrix, accumulation of glomerular and tubulointerstitial foam cells and mesangial lipid deposits. The tubular epithelium demonstrated pronounced lipid induced tubular degeneration with increased tubular epithelial cell turnover. Hyperlipidemia and hyperglycemia seem to act synergistically in inducing renal injury in the BALB. LDLR-/- mouse. This model of diabetic nephropathy is unique in its development of tubular lesions and may represent a good model for hyperlipidemia-exacerbated diabetic nephropathy. Copyright (C) 2004 S. Karger AG, Basel

Charakterisierung und Optimierung parasitärer Elemente in Umrichtern mit niedrigen Zwischenkreisspannungen und hohen Betriebsströmen

Parasitäre Elemente sind physikalischer Bestandteil jedes elektrischen Leiters oder Halbleiters. Sie werden heute als Hauptursache für die meist unerwünschten Abweichungen vom idealen Verhalten einer leistungselektronischen Schaltung betrachtet und können unter bestimmten Bedingungen sogar eine Fehlfunktion oder einen Ausfall der Schaltung verursachen. Es ist daher von besonderem Interesse, ihre grundlegenden Ursachen zu verstehen, ihre Größe zu bestimmen und geeignete Optimierungsmaßnahmen zu ergreifen, die ihre negativen Auswirkungen auf ein vertretbares Maß reduzieren oder gar eine nutzbringende Verwendung ihrer Eigenschaften ermöglichen. Im Rahmen dieser Arbeit werden die Ursachen, die Auswirkungen und die Möglichkeiten zur Bestimmung von parasitären Elementen in der Leistungselektronik untersucht. Dabei liegt der Schwerpunkt auf der Analyse von Umrichtern mit hohen Betriebsströmen und Leistungs-MOSFETs niedriger Spannungsfestigkeit als Halbleitern, da sich in den damit verbundenen Applikationen insbesondere die Auswirkungen von parasitären Induktivitäten gut darstellen lassen. Die Bestimmung von parasitären Elementen erfolgt auf analytische, simulative und messtechnische Weise. Die für Fragestellungen der Leistungselektronik geeigneten Verfahren werden zu Beginn der Arbeit vorgestellt. Die Analyse der Auswirkungen parasitärer Elemente zeigt vielschichtige Abhängigkeiten verschiedener elektrischer, aber auch thermischer und lebensdauerbezogener Parameter von der Größe der parasitären Induktivitäten. Des Weiteren werden die Wechselwirkungen von parasitären Elementen und der Emission leitungsgebundener Störungen untersucht und qualitiative Zusammenhänge herausgearbeitet. Dabei steht die Betrachtung des leistungselektronischen Gesamtsystems im Vordergrund, um systematisch die beeinflussten Parameter aufzuzeigen. Es wird gezeigt, dass im Zuge einer erfolgreichen Systemoptimierung ganzheitliche Ansätze verfolgt werden müssen, bei denen eine kombinierte Optimierung von elektrischen, thermischen und mechanischen Eigenschaften des Umrichters anzustreben sind. Diese wirken sich auf das Design der verwendeten Leistungsmodule, der Zwischenkreisverschienung und der Kondensatoranbindung aus. Basierend auf den erzielten Ergebnissen werden Optimierungsansätze und -methoden erarbeitet und auf ihre Anwendbarkeit untersucht. Als praxisrelevantes Beispiel wird darauf aufbauend die Entwicklung und Optimierung eines Antriebsumrichters für niedrige Zwischenkreisspannungen und hohe Betriebsströme gezeigt.Parasitic elements are an inevitable part of any type of electrical conductors or semiconductors. They are considered to be the main reason for the undesired differences between the idealized (theoretical) and real behaviour of power electronic circuits. Their influence on the circuit can lead to malfunction or even to complete failure in the worst case scenario. Therefore the understanding of the basic principles of parasitic elements, the analysis and estimation of their size, the optimization and prevention of their negative effects or even their conscious usage to achieve desired effects is of particular interest. In the framework of this thesis the basic principles, the resulting effects and the methods for an analysis of the parasitic elements are investigated. The focus is on the analysis of high current applications with low-voltage power MOSFETs as semiconductors, as these applications are very sensitive with regard to the consequences of parasitic inductances. The characterization of parasitic elements is based on analytical, simulative and measurement methods. Different approaches suitable for power electronic applications are given and compared in the first part of the thesis. The analysis of their effects reveals eclectic dependencies not only to electrical, but also to thermal and reliability-related properties. Additionally, the interaction of parasitic elements and conducted electromagnetic interferences is investigated and qualitative coherence is ascertained. The system approach is used to determine and characterize influenced parameters. It is shown that the full system optimization has to include comprehensive approaches with respect to electrical, thermal and mechanical properties, as all these parts have strong interactions and influence the overall performance of the inverter. The optimization methods take into account the design of the power modules used, the shape of the dc link busbar as well as the connection of the dc link capacitors. Based on the results obtained, optimization approaches and methods are developed and tested with regard to their applicability to power electronics. To give a practice-oriented example for the mentioned methods, the development and optimization of the power section of a battery powered inverter for high currents and low dc link voltages is presented

Familienskript

Zusätzlich zur herkömmlichen Einstellungsforschung und Untersuchung alltagstheoretischer Vorstellungen zur Familie will der Autor durch das vorliegende Konstrukt "Familienscript" Planungs- und Handlungsaspekte in Bezug auf Familie stärker in die Forschung einbeziehen. Als Themenbereiche werden u.a. die Struktur der Familie, Verhältnis Individuum Paar, Familie, Außenstehende, Rollen von Frau und Mann, Kinder in der Familie, materielle Grundlagen, aber auch emotionale Bedeutung der Familie und Intimität in der Familie oder Konflikte und Regulationsformen in der Familie abgedeckt. Die theoretische und empirische Brauchbarkeit des Konstruktes bzw. des Instruments "Familienscript" ist Gegenstand des Beitrages. (ST

Fahrstiladaptive Auslegung integraler Sicherheitssysteme am Beispiel des reversiblen Gurtstraffers

Magdeburg, Univ., Fak. für Elektrotechnik und Informationstechnik, Diss., 2013von Florian Mühlfel

Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model

ABSTRACT: BACKGROUND: Experimental studies provide evidence that inhaled nanoparticles may translocate over the airspace epithelium and cause increased cellular inflammation. Little is known, however, about the dependence of particle size or material on translocation characteristics, inflammatory response and intracellular localization. RESULTS: Using a triple cell co-culture model of the human airway wall composed of epithelial cells, macrophages and dendritic cells we quantified the entering of fine (1 mum) and nano-sized (0.078 mum) polystyrene particles by laser scanning microscopy. The number distribution of particles within the cell types was significantly different between fine and nano-sized particles suggesting different translocation characteristics. Analysis of the intracellular localization of gold (0.025 mum) and titanium dioxide (0.02-0.03 mum) nanoparticles by energy filtering transmission electron microscopy showed differences in intracellular localization depending on particle composition. Titanium dioxide nanoparticles were detected as single particles without membranes as well as in membrane-bound agglomerations. Gold nanoparticles were found inside the cells as free particles only. The potential of the different particle types (different sizes and different materials) to induce a cellular response was determined by measurements of the tumour necrosis factor-alpha in the supernatants. We measured a 2-3 fold increase of tumour necrosis factor-alpha in the supernatants after applying 1 mum polystyrene particles, gold nanoparticles, but not with polystyrene and titanium dioxide nanoparticles. CONCLUSION: Quantitative laser scanning microscopy provided evidence that the translocation and entering characteristics of particles are size-dependent. Energy filtering transmission electron microscopy showed that the intracellular localization of nanoparticles depends on the particle material. Both particle size and material affect the cellular responses to particle exposure as measured by the generation of tumour necrosis factor-alpha

Particles induce apical plasma membrane enlargement in epithelial lung cell line depending on particle surface area dose

<p>Abstract</p> <p>Background</p> <p>Airborne particles entering the respiratory tract may interact with the apical plasma membrane (APM) of epithelial cells and enter them. Differences in the entering mechanisms of fine (between 0.1 μm and 2.5 μm) and ultrafine ( ≤ 0.1 μm) particles may be associated with different effects on the APM. Therefore, we studied particle-induced changes in APM surface area in relation to applied and intracellular particle size, surface and number.</p> <p>Methods</p> <p>Human pulmonary epithelial cells (A549 cell line) were incubated with various concentrations of different sized fluorescent polystyrene spheres without surface charge (∅ fine – 1.062 μm, ultrafine – 0.041 μm) by submersed exposure for 24 h. APM surface area of A549 cells was estimated by design-based stereology and transmission electron microscopy. Intracellular particles were visualized and quantified by confocal laser scanning microscopy.</p> <p>Results</p> <p>Particle exposure induced an increase in APM surface area compared to negative control (p < 0.01) at the same surface area concentration of fine and ultrafine particles a finding not observed at low particle concentrations. Ultrafine particle entering was less pronounced than fine particle entering into epithelial cells, however, at the same particle surface area dose, the number of intracellular ultrafine particles was higher than that of fine particles. The number of intracellular particles showed a stronger increase for fine than for ultrafine particles at rising particle concentrations.</p> <p>Conclusion</p> <p>This study demonstrates a particle-induced enlargement of the APM surface area of a pulmonary epithelial cell line, depending on particle surface area dose. Particle uptake by epithelial cells does not seem to be responsible for this effect. We propose that direct interactions between particle surface area and cell membrane cause the enlargement of the APM.</p

Visualization and quantitative analysis of nanoparticles in the respiratory tract by transmission electron microscopy

Nanotechnology in its widest sense seeks to exploit the special biophysical and chemical properties of materials at the nanoscale. While the potential technological, diagnostic or therapeutic applications are promising there is a growing body of evidence that the special technological features of nanoparticulate material are associated with biological effects formerly not attributed to the same materials at a larger particle scale. Therefore, studies that address the potential hazards of nanoparticles on biological systems including human health are required. Due to its large surface area the lung is one of the major sites of interaction with inhaled nanoparticles. One of the great challenges of studying particle-lung interactions is the microscopic visualization of nanoparticles within tissues or single cells both in vivo and in vitro. Once a certain type of nanoparticle can be identified unambiguously using microscopic methods it is desirable to quantify the particle distribution within a cell, an organ or the whole organism. Transmission electron microscopy provides an ideal tool to perform qualitative and quantitative analyses of particle-related structural changes of the respiratory tract, to reveal the localization of nanoparticles within tissues and cells and to investigate the 3D nature of nanoparticle-lung interactions

Lamellar body ultrastructure revisited: high-pressure freezing and cryo-electron microscopy of vitreous sections

Lamellar bodies are the storage sites for lung surfactant within type II alveolar epithelial cells. The structure-function models of lamellar bodies are based on microscopic analyses of chemically fixed tissue. Despite available alternative fixation methods that are less prone to artifacts, such as cryofixation by high-pressure freezing, the nature of the lung, being mostly air filled, makes it difficult to take advantage of these improved methods. In this paper, we propose a new approach and show for the first time the ultrastructure of intracellular lamellar bodies based on cryo-electron microscopy of vitreous sections in the range of nanometer resolution. Thus, unspoiled by chemical fixation, dehydration and contrasting agents, a close to native structure is revealed. Our approach uses perfluorocarbon to substitute the air in the alveoli. Lung tissue was subsequently high-pressure frozen, cryosectioned and observed in a cryo-electron microscope. The lamellar bodies clearly show a tight lamellar morphology. The periodicity of these lamellae was 7.3nm. Lamellar bifurcations were observed in our cryosections. The technical approach described in this paper allows the examination of the native cellular ultrastructure of the surfactant system under near in vivo conditions, and therefore opens up prospectives for scrutinizing various theories of lamellar body biogenesis, exocytosis and recyclin

Effect of voluntary exercise on number and volume of cardiomyocytes and their mitochondria in the mouse left ventricle

Voluntary exercise (VE) has a beneficial influence on the heart and mean lifespan. The present study evaluates structural adaptations of cardiomyocytes and their mitochondria due to VE by new, unbiased stereological methods. Female, 7-9-week-old mice were randomly assigned to a control (CG, n=7) or VE group (EG, n=7). EG animals were housed in cages with free access to a running wheel and had a mean running distance of 6.7 (1.8)km per day. After 4weeks, the hearts of all mice were processed for light and electron microscopy. We estimated the number and volume of cardiomyocytes by the disector method and the number and volume of mitochondria by estimation of the Euler number. In comparison to CG, VE did not have an effect on the myocardial volume of the left ventricle (CG: 93 (10), EG: 103 (17) (mm3)), the number of cardiomyocytes (CG: 2.81 (0.27), EG: 2.82 (0.43) (×106)) and their number-weighted mean volume. However, the composition of the cardiomyocytes changed due to VE. The total volume of mitochondria (CG: 21.8 (4.9), EG: 32.2 (4.3) (mm3), P<0.01) and the total number (CG: 3.76 (0.44), EG: 7.02 (1.13) (×1010), P<0.001) were significantly higher in EG than in CG. The mean number-weighted mitochondrial volume was smaller in EG than in CG (P<0.05). In summary, VE does not alter ventricular volume nor cardiomyocyte volume or number but the oxidative capacity of cardiomyocytes by an increased mitochondrial number and total volume in the left ventricle. These structural changes may participate in the beneficial effects of V

Intracellular imaging of nanoparticles: Is it an elemental mistake to believe what you see?

In order to understand how nanoparticles (NPs <100 nm) interact with cellular systems, potentially causing adverse effects, it is important to be able to detect and localize them within cells. Due to the small size of NPs, transmission electron microscopy (TEM) is an appropriate technique to use for visualizing NPs inside cells, since light microscopy fails to resolve them at a single particle level. However, the presence of other cellular and non-cellular nano-sized structures in TEM cell samples, which may resemble NPs in size, morphology and electron density, can obstruct the precise intracellular identification of NPs. Therefore, elemental analysis is recommended to confirm the presence of NPs inside the cell. The present study highlights the necessity to perform elemental analysis, specifically energy filtering TEM, to confirm intracellular NP localization using the example of quantum dots (QDs). Recently, QDs have gained increased attention due to their fluorescent characteristics, and possible applications for biomedical imaging have been suggested. Nevertheless, potential adverse effects cannot be excluded and some studies point to a correlation between intracellular particle localization and toxic effects