[Periarthropathies]. / Periarthropathien.

Periarthropathies Abstract. The term "periarthropathy" stands for various pathologies "around" the joint and its structures, without a clear and generally accepted definition. This article tries to outline this theme and offers some examples in the section "ausgewählte Krankheitsbilder".

Porosity Modulated High-Performance Piezoelectric Nanogenerator Based on Organic/Inorganic Nanomaterials for Self-Powered Structural Health Monitoring.

In the modern era, structural health monitoring (SHM) is critically important and indispensable in the aerospace industry as an effective measure to enhance the safety and consistency of aircraft structures by deploying a reliable sensor network. The deployment of built-in sensor networks enables uninterrupted structural integrity monitoring of an aircraft, providing crucial information on operation condition, deformation, and potential damage to the structure. Sustainable and durable piezoelectric nanogenerators (PENGs) with good flexibility, high performance, and superior reliability are promising candidates for powering wireless sensor networks, particularly for aerospace SHM applications. This research demonstrates a self-powered wireless sensing system based on a porous polyvinylidene fluoride (PVDF)-based PENG, which is prominently anticipated for developing auto-operated sensor networks. Our reported porous PVDF film is made from a flexible piezoelectric polymer (PVDF) and inorganic zinc oxide (ZnO) nanoparticles. The fabricated porous PVDF-based PENG demonstrates ∼11 times and ∼8 times enhancement of output current and voltage, respectively, compared to a pure PVDF-based PENG. The porous PVDF-based PENG can produce a peak-to-peak short-circuit current of 22 µA, a peak-to-peak open-circuit voltage of 84.5 V, a peak output power of 0.46 mW (P=Voc2×Isc2), and a peak output power density of 41.02 µW/cm2 (P/A). By harnessing energy from minute vibrations, the fabricated porous PVDF-based PENG device (area of A = 11.33 cm2) can generate sufficient electrical energy to power up a customized wireless sensing and communication unit and transfer sensor data every ∼4 min. The PENG can generate sufficient electrical energy from an automobile car vibration, which reflects the scenario of potential real-life SHM systems. We anticipate that this high-performance porous PVDF-based PENG can act as a reliable power source for the sensor networks in aircraft, which minimizes potential safety risks.

Tau protein degradation is catalyzed by the ATP/ubiquitin-independent 20S proteasome under normal cell conditions.

Tau is the major protein exhibiting intracellular accumulation in Alzheimer disease. The mechanisms leading to its accumulation are not fully understood. It has been proposed that the proteasome is responsible for degrading tau but, since proteasomal inhibitors block both the ubiquitin-dependent 26S proteasome and the ubiqutin-independent 20S proteasome pathways, it is not clear which of these pathways is involved in tau degradation. Some involvement of the ubiquitin ligase, CHIP in tau degradation has also been postulated during stress. In the current studies, we utilized HT22 cells and tau-transfected E36 cells in order to test the relative importance or possible requirement of the ubiquitin-dependent 26S proteasomal system versus the ubiquitin-independent 20S proteasome, in tau degradation. By means of ATP-depletion, ubiquitinylation-deficient E36ts20 cells, a 19S proteasomal regulator subunit MSS1-siRNA approaches, and in vitro ubiquitinylation studies, we were able to demonstrate that ubiquitinylation is not required for normal tau degradation.

Inverse correlation of protein oxidation and proteasome activity in liver and lung.

Several studies have demonstrated that proteasome activity decreases whereas protein oxidation increases with aging in various tissues. However, no studies are available correlating both parameters directly comparing different tissues of one organism. Therefore, we determined whether there is an age-related change in proteasome activity and protein oxidation in heart, lung, liver, kidney and skeletal muscle samples of 6-, 10-, 18- and 26-month-old rats. There was a significant age-related increase in protein carbonyls at 18 and 26 months compared to young rats. Thereby, protein carbonyl formation was rather due to a general than a specific protein carbonylation as shown by immunblot studies. The highest increase in protein carbonyl formation was found in liver, lung and kidney samples. Proteasome activity decreased significantly with age in lung and liver samples. Proteasome activity in liver and lung decreased by factor five compared to young rats. Strong correlations between proteasome activity and protein oxidation were found in liver and lung, whereas in other tissues only a trend was found. These results demonstrate that the increase in protein oxidation and the decline in proteasome activity are correlating. Further studies are needed to determine the mechanisms which cause organ-specific aging-rates and their consequences.

Protective effect of antioxidants against sarcoplasmic reticulum (SR) oxidation by Fenton reaction, however without prevention of Ca-pump activity.

The Ca(2+)-ATPase of the sarcoplasmic reticulum (SERCA) of rabbit skeletal muscle was oxidized by Fe2+/H2O2/ascorbic acid (AA), a system which generates HO(.) radicals according to the Fenton reaction: (Fe2(+)+H2O2-->HO(.)+OH(-)+Fe(3+)) under conditions similar to the pathological state of inflammation. Under these conditions, when hydroxyl-radicals and/or ferryl-radicals are generated, a 50% decrease of the SERCA activity was observed, a significant decrease of SH groups and an increase of protein carbonyl groups and lipid peroxidation were identified. Two new bands, time dependent in density, appeared in the SERCA protein electrophoresis after incubation with the Fenton system (at approximately 50 and 75kDa), probably due to structural changes as supported also by trypsin digestion. Immunoblotting of DNPH derivatized protein bound carbonyls detected a time dependent increase after incubation of SERCA with the Fenton system. Trolox and the pyridoindole stobadine (50microM) protected SR against oxidation induced via the Fenton system by preventing SH group oxidation and lipid peroxidation. Pycnogenol((R)) and EGb761 (40microg/ml) protected SERCA in addition against protein bound carbonyl formation. In spite of the antioxidant effects, trolox and stobadine were not able to prevent a decrease in the SERCA Ca(2+)-ATPase activity. Pycnogenol and EGb761 even enhanced the decrease of the Ca(2+)-ATPase activity induced by the Fenton system, probably by secondary oxidative reactions.

Limited degradation of oxidized calmodulin by proteasome: formation of peptides.

Oxidized proteins are recognized and degraded preferentially by the proteasome. This is true for numerous proteins including calmodulin (CaM). The degradation of CaM was investigated in a human fibroblast cell line under conditions of oxidative stress. Low molecular CaM fragments or peptides were found under such conditions. In in vitro experiments it was investigated whether this CaM breakdown product formation is induced by protein oxidation or is due to a limited proteolysis-derived degradation by the 20S proteasome. Native unoxidized CaM was not degraded by 20S proteasome, oxidized CaM was degraded in a time- and H2O2 concentration-dependent manner. Peptides of similar molecular weight were detected in isolated calmodulin as in oxidatively stressed fibroblasts. The peptides were identified using isolated calmodulin. Therefore, in oxidatively stressed fibroblasts and in vitro CaM is forming oxidation-driven fragments and proteasomal cleavage peptides of approximately 30 amino acids which undergo a slow or no degradation.

Irradiation of GAPDH: a model for environmentally induced protein damage.

Environmental factors, including sunlight, are able to induce severe oxidative protein damage. The modified proteins are either repaired, degraded or escape from degradation and aggregate. In the present study we tested the effect of different sunlight components such as UV-A, UV-B, and infrared radiation on protein oxidation in vitro. We chose glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a model enzyme and analyzed the irradiation-induced enzyme activity loss, fragmentation and aggregation, and quantified various oxidative amino acid modifications. Since gamma-irradiation was used in numerous studies before, we used it for comparative purposes. Infrared radiation was unable to damage GAPDH in the dose range tested (0-1000 J/cm(2)). UV-A led to a decrease in free thiol content, which was connected with a loss in enzyme activity, while only at very high doses could moderate protein aggregation and fragmentation be observed. UV-B (0-2 J/cm(2)) and gamma-irradiation (0-500 Gy) led to a dose-dependent increase in protein modification. Interestingly, UV-B acted on specific amino acids, such as arginine, proline, and tyrosine, whereas gamma-irradiation acted more randomly. The possibility of using the amino acid oxidation pattern as a biomarker of the source of damage is discussed.

Postanoxic damage of microglial cells is mediated by xanthine oxidase and cyclooxygenase.

Brain ischemia and the following reperfusion are important causes for brain damage and leading causes of brain morbidity and human mortality. Numerous observations exist describing the neuronal damage during ischemia/reperfusion, but the outcome of such conditions towards glial cells still remains to be elucidated. Microglia are resident macrophages in the brain. In this study, we investigated the anoxia/reoxygenation caused damage to a microglial cell line via determination of energy metabolism, free radical production by dichlorofluorescein fluorescence and nitric oxide production by Griess reagent. Consequences of oxidant production were determined by measurements of protein oxidation and lipid peroxidation, as well. By using site-specific antioxidants and inhibitors of various oxidant-producing pathways, we identified major sources of free radical production in the postanoxic microglial cells. The protective influences of these compounds were tested by measurements of cell viability and apoptosis. Although, numerous free radical generating systems may contribute to the postanoxic microglial cell damage, the xanthine oxidase- and the cyclooxygenase-mediated oxidant production seems to be of major importance.

Reversible inhibition of mammalian glutamine synthetase by tyrosine nitration.

The effect of tyrosine nitration on mammalian GS activity and stability was studied in vitro. Peroxynitrite at a concentration of 5 micro mol/l produced tyrosine nitration and inactivation of GS, whereas 50 micro mol/l peroxynitrite additionally increased S-nitrosylation and carbonylation and degradation of GS by the 20S proteasome. (-)Epicatechin completely prevented both, tyrosine nitration and inactivation of GS by peroxynitrite (5 micro mol/l). Further, a putative "denitrase" activity restored the activity of peroxynitrite (5 micro mol/l)-treated GS. The data point to a potential regulation of GS activity by a reversible tyrosine nitration. High levels of oxidative stress may irreversibly damage and predispose the enzyme to proteasomal degradation.

Clinical oxidation parameters of aging.

Aging is a complex progressive physiological alteration of the organism which ultimately leads to death. During the whole life a human being is confronted with oxidative stress. To measure how this oxidative stress is developing during the aging process and how it changes the cellular metabolism several substances have been pronounced as biomarkers including lipid peroxidation (LPO) products, protein oxidation products, antioxidative acting enzymes, minerals, vitamins, glutathione, flavonoids, bilirubin and uric acid (UA). But none of them could develop to the leading one which is accepted by the whole scientific community to determine the life expectancy of the individual person or biological age or age-related health status. Further there are many conflicting data about the changes of each single biomarker during the aging process. There are so many different influences acting on the concentration or activity of single substances or single enzymes that it is not possible to measure only one clinical marker and determine how healthy an individual is or to predict the life expectancy of the corresponding person. Therefore, always a set or pattern of clinical biomarkers should be used to determine the oxidation status of the person. This set should include at least one marker for the LPO, the protein oxidation and the total antioxidative status and ideally also one for DNA damages.

Ferritin oxidation and proteasomal degradation: protection by antioxidants.

The accumulation of oxidatively damaged proteins is a well-known hallmark of aging and several neurodegenerative diseases including Alzheimer's, Parkinson's and Huntigton's diseases. These highly oxidized protein aggregates are in general not degradable by the main intracellular proteolytic machinery, the proteasomal system. One possible strategy to reduce the accumulation of such oxidized protein aggregates is the prevention of the formation of oxidized protein derivatives or to reduce the protein oxidation to a degree that can be handled by the proteasome. To do so an antioxidative strategy might be successful. Therefore, we undertook the present study to test whether antioxidants are able to prevent the protein oxidation and to influence the proteasomal degradation of moderate oxidized proteins. As a model protein we choose ferritin. H2O2 induced a concentration dependent increase of protein oxidation accompanied by an increased proteolytic susceptibility. This increase of proteolytic susceptibility is limited to moderate hydrogen peroxide concentrations, whereas higher concentrations are accompanied by protein aggregate formation. Protective effects of the vitamin E derivative Trolox, the pyridoindole derivative Stobadine and of the standardized extracts of flavonoids from bark of Pinus Pinaster Pycnogenol and from leaves of Ginkgo biloba (EGb 761) were studied on moderate damaged ferritin.

Tocopherol-mediated modulation of age-related changes in microglial cells: turnover of extracellular oxidized protein material.

Proteins accumulate during aging and form insoluble protein aggregates. Microglia are responsible for their removal from the brain. During aging, changes within the microglia might play a crucial role in the malfunctioning of these cells. Therefore, we isolated primary microglial cells from adult rats and compared their activation status and their ability to degrade proteins to that of microglial cells isolated from newborn animals. The ability of adult microglial cells to degrade proteins is substantially decreased. However, the preincubation of microglial cells with vitamin E improves significantly the degradation of such modified proteins. The degradation of proteins from apoptotic vesicles is decreased in microglia isolated from adult rats. This might be the result of a suppression of the CD36 receptor due to vitamin E treatment. We concluded that microglial cells isolated from adult organisms have different metabolic properties and seem to be a more valuable model to study age-related diseases.

Degradation of glycated bovine serum albumin in microglial cells.

Glycated protein products are formed upon binding of sugars to lysine and arginine residues and have been shown to accumulate during aging and in pathologies such as Alzheimer disease and diabetes. Often these glycated proteins are transformed into advanced glycation end products (AGEs) by a series of intramolecular rearrangements. In the study presented here we tested the ability of microglial cells to degrade BSA-AGE formed by glycation reactions of bovine serum albumin (BSA) with glucose and fructose. Microglial cells are able to degrade BSA-AGEs to a certain degree by proteasomal and lysosomal pathways. However, the proteasome and lysosomal proteases are severely inhibited by cross-linked BSA-AGEs. BSA-AGEs are furthermore able to activate microglial cells. This activation is accompanied by an enhanced degradation of BSA-AGE. Therefore, we conclude that microglial cells are able to degrade glycated proteins, although cross-linked protein-AGEs have an inhibitory effect on proteolytic systems in microglial cells.

Age-associated analysis of oxidative stress parameters in human plasma and erythrocytes.

Oxidative damage accumulation in macromolecules has been considered as a cause of cellular damage and pathology. Rarely, the oxidative stress parameters in healthy humans related to the individual age have been reported. The purpose of this study was to examine the redox status in plasma and erythrocytes of healthy individuals and determine correlations between these parameters and the aging process. The following parameters were used: malondialdehyde (MDA), protein carbonyls (PCO), 4-hydroxy-2,3-trans-nonenal (HNE), reduced glutathione (GSH), glutathione disulfide (GSSG) and uric acid (UA) in blood and plasma samples of 194 healthy women and men of ages ranging from 18 to 84 years. The results indicate that the balance of oxidant and antioxidant systems in plasma shifts in favor of accelerated oxidation during ageing. That is demonstrated by increases of MDA, HNE, GSSG and by the slight decrease of erythrocytic GSH with age. As the content of UA is more determined by metabolic and nutritional influences than by the balance between prooxidants and antioxidants there was no significant age-related change observed. For plasma concentrations of HNE the first time age-dependent reference values for healthy humans are presented.

Anti-fibrosclerotic effects of shock wave therapy in lipedema and cellulite.

In vivo measurements in 26 female patients with lipedema and cellulite parameters were carried out before and after therapy by means of complex physical decongestive therapy (CPDT) including manual lymph drainage and compression as main components and/or shock wave therapy (SWT). Oxidative stress parameters of blood serum and biomechanic skin properties/smoothening of dermis and hypodermis surface were evaluated. Oxidative stress in lipedema and cellulite was demonstrated by increased serum concentrations of malondialdehyde (MDA) and plasma protein carbonyls compared with healthy control persons. Both MDA and protein carbonyls in blood plasma decreased after serial shock wave application and CPDT. The SWT itself and CPDT itself lead to MDA release from edematous tissue into the plasma. Obviously both therapy types, SWT and CPDT, mitigate oxidative stress in lipedema and cellulite. In parallel SWT improved significantly the biomechanic skin properties leading to smoothening of dermis and hypodermis surface. Significant correlation between MDA depletion of edematous and lipid enriched dermis and improvement of mechanic skin properties was demonstrated. From these findings it is concluded, that a release of lipid peroxidation (LPO) products from edematous dermis is an important sclerosis-preventing effect of SWT and/or CPDT in lipedema and cellulite. Expression of factors stimulating angiogenesis and lymphangiogenesis such as VEGF was not induced by SWT and/or CPDT and, therefore, not involved in beneficial effects by SWT and/or CPDT.

Characterization of the synthetic compatible solute homoectoine as a potent PCR enhancer.

Different substances such as dimethyl sulfoxide, tetramethylene sulfoxide, 2-pyrollidone, and the naturally occurring compatible solute betaine enhance PCR amplification of GC-rich DNA templates with high melting temperatures. In particular, cyclic compatible solutes outperform traditional PCR enhancers. We therefore investigated the effects that cyclic naturally occurring ectoine-type compatible solutes and their synthetic derivatives have on melting temperature of double-stranded DNA (dsDNA) and on PCR amplification of different templates. L-ectoine, betaine, and derivatives of L-ectoine decreased, whereas beta-hydroxyectoine increased, the melting temperature of dsDNA. The ability to decrease the melting temperature was greatest for homoectoine, a new synthetic derivative of l-ectoine. Furthermore, compatible solutes, especially homoectoine, enhanced PCR amplification of GC-rich DNA (72.6% GC content; effective range: 0.1-0.5M).