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Search Results: 1 - 10 of 6009 matches for " Klawitter Marina "
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Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity
Klawitter Marina,Quero Lilian,Klasen Juergen,Gloess Alexia N
Journal of Inflammation , 2012, DOI: 10.1186/1476-9255-9-29
Abstract: Background As proinflammatory cytokines seem to play a role in discogenic back pain, substances exhibiting anti-inflammatory effects on intervertebral disc cells may be used as minimal-invasive therapeutics for intradiscal/epidural injection. The purpose of this study was to investigate the anti-inflammatory and anti-catabolic potential of curcuma, which has been used in the Indian Ayurvedic medicine to treat multiple ailments for a long time. Methods Human disc cells were treated with IL-1β to induce an inflammatory/catabolic cascade. Different extracts of curcuma as well as curcumin (= a component selected based on results with curcuma extracts and HPLC/MS analysis) were tested for their ability to reduce mRNA expression of proinflammatory cytokines and matrix degrading enzymes after 6 hours (real-time RT-PCR), followed by analysis of typical inflammatory signaling mechanisms such as NF-κB (Western Blot, Transcription Factor Assay), MAP kinases (Western Blot) and Toll-like receptors (real-time RT-PCR). Quantitative data was statistically analyzed using a Mann Whitney U test with a significance level of p < 0.05 (two-tailed). Results Results indicate that the curcuma DMSO extract significantly reduced levels of IL-6, MMP1, MMP3 and MMP13. The DMSO-soluble component curcumin, whose occurrence within the DMSO extract was verified by HPLC/MS, reduced levels of IL-1β, IL-6, IL-8, MMP1, MMP3 and MMP13 and both caused an up-regulation of TNF-α. Pathway analysis indicated that curcumin did not show involvement of NF-κB, but down-regulated TLR2 expression and inhibited the MAP kinase JNK while activating p38 and ERK. Conclusions Based on its anti-inflammatory and anti-catabolic effects, intradiscal injection of curcumin may be an attractive treatment alternative. However, whether the anti-inflammatory properties in vitro lead to analgesia in vivo will need to be confirmed in an appropriate animal model.
A Clifford algebraic Approach to Line Geometry
Daniel Klawitter
Mathematics , 2013,
Abstract: In this paper we combine methods from projective geometry, Klein's model, and Clifford algebra. We develop a Clifford algebra whose Pin group is a double cover of the group of regular projective transformations. The Clifford algebra we use is constructed as homogeneous model for the five-dimensional real projective space $P^5(\mathbb{R})$ where Klein's quadric $M_2^4$ defines the quadratic form. We discuss all entities that can be represented naturally in this homogeneous Clifford algebra model. Projective automorphisms of Klein's quadric induce projective transformations of $P^3(\mathbb{R})$ and vice versa. Cayley-Klein geometries can be represented by Clifford algebras, where the group of Cayley-Klein isometries is given by the Pin group of the corresponding Clifford algebra. Therefore, we examine the versor group and study the correspondence between versors and regular projective transformations represented as $4\times 4$ matrices. Furthermore, we give methods to compute a versor corresponding to a given projective transformation.
Reflections in Conics, Quadrics and Hyperquadrics via Clifford Algebra
Daniel Klawitter
Mathematics , 2014,
Abstract: In this article we present a new and not fully employed geometric algebra model. With this model a generalization of the conformal model is achieved. We discuss the geometric objects that can be represented. Furthermore, we show that the Pin group of this geometric algebra corresponds to inversions with respect to axis aligned quadrics. We discuss the construction for the two- and three-dimensional case in detail and give the construction for arbitrary dimension. Key Words: Clifford algebra, geometric algebra, generalized inversion, conic, quadric, hyperquadric
Null Polarities as Generators of the Projective Group
Daniel Klawitter
Mathematics , 2014,
Abstract: It is well-known that the group of regular projective transformations of $\mathbb{P}^3(\mathbb{R})$ is isomorphic to the group of projective automorphisms of Klein's quadric $M_2^4\subset\mathbb{P}^5(\mathbb{R})$. We introduce the Clifford algebra $\mathcal{C}\ell_{(3,3)}$ constructed over the quadratic space $\mathbb{R}^{(3,3)}$ and describe how points on Klein's quadric are embedded as null vectors, {\it i.e.}, grade-$1$ elements squaring to zero. Furthermore, we discuss how geometric entities from Klein's model can be transferred to this homogeneous Clifford algebra model. Automorphic collineations of Klein's quadric can be described by the action of the so called sandwich operator applied to vectors $\mathfrak{v}\in\bigwedge^1 V$. Vectors correspond to null polarities in $\mathbb{P}^3(\mathbb{R})$. We introduce a factorization algorithm. With the help of this algorithm we are able to factorize an arbitrary versor $\mathfrak{g}\in\mathcal{C}\ell_{(3,3)}$ into a set of non-commuting vectors $\mathfrak{v}_i\in\bigwedge^1 V,\,i=1,\dots, k,\, 1\leq k\leq 6$ corresponding to null polarities with $\mathfrak{g}=\mathfrak{v}_1\dots\mathfrak{v}_k$. Thus, we present a method to factorize every collineation in $\mathbb{P}^5(\mathbb{R})$ that is induced by a projective transformation acting on $\mathbb{P}^3(\mathbb{R})$ into a set of at most six involutoric automorphic collineations of Klein's quadric corresponding to null polarities respectively skew-symmetric $4 \times 4$ matrices. Moreover, we give an outlook for Lie's sphere geometry, i.e., the homogeneous Clifford algebra model constructed with the quadratic form corresponding to Lie's quadric $L_1^{n+1}\subset\mathbb{P}^{n+2}(\mathbb{R})$. Keywords: Clifford algebra, line geometry, Klein's quadric, null polarity, factorization
Kinematic Mappings for Cayley-Klein Geometries via Clifford Algebras
Daniel Klawitter,Markus Hagemann
Mathematics , 2013, DOI: 10.1007/s13366-013-0154-6
Abstract: This paper unifies the concept of kinematic mappings by using geometric algebras. We present a method for constructing kinematic mappings for certain Cayley-Klein geometries. These geometries are described in an algebraic setting by the homogeneous Clifford algebra model. Displacements correspond to Spin group elements. After that Spin group elements are mapped to a kinematic image space. Especially for the group of planar Euclidean displacements SE(2) the result is the kinematic mapping of Blaschke and Gr\"unwald. For the group of spatial Euclidean displacements SE(3) the result is Study's mapping. Furthermore, we classify kinematic mappings for Cayley-Klein spaces of dimension 2 and 3.
Human MMP28 expression is unresponsive to inflammatory stimuli and does not correlate to the grade of intervertebral disc degeneration
Marina Klawitter, Lilian Quero, Alessando Bertolo, Marco Mehr, Jivko Stoyanov, Andreas G Nerlich, Juergen Klasen, Nikolaus Aebli, Norbert Boos, Karin Wuertz
Journal of Negative Results in BioMedicine , 2011, DOI: 10.1186/1477-5751-10-9
Abstract: While MMP28 expression was increased in individual cases with trauma or disc degeneration, there was no significant correlation between the grade of disease and MMP28 expression. Stimulation with LPS, IL-1β, TNF-α or trichostatin A did not alter MMP28 gene expression at any investigated time point or any concentration.Our results demonstrate that gene expression of MMP28 in the IVD is not regulated by inflammatory mechanisms, is donor-dependent and cannot be positively or negatively linked to the grade of degeneration and only weakly to the occurrence of trauma. New hypotheses and future studies are needed to find the role of MMP28 in the intervertebral disc.Proteins of the matrix metalloproteinase (MMP) family play an essential role in tissue homeostasis by initiating breakdown and reorganization of the extracellular matrix. While being tightly regulated in normal physiological processes (e.g. via tissue inhibitors of metalloproteases TIMPs), dysregulation of MMPs has been implicated in many diseases. During intervertebral disc (IVD) degeneration, the expression and activity of a number of MMPs is increased, including MMPs 1, 3, 7, 9 and 13 [1]. Proinflammatory cytokines such as IL-1β and TNF-α as well as bacterial endotoxins (e.g. lipopolysaccharide LPS) can stimulate expression of various MMPs (e.g. MMPs 1, 3, 9 and 13) in the IVD, as well as in cartilage [2-10].During the recent past, five new members in the MMP family have been identified: MMP24 to MMP28. MMP28, also known as epilysin and most closely related to MMP19, is a soluble MMP that contains an activation sequence recognized by the furin endoprotease following the pro-domain [11]. It is a well-conserved MMP, with great similarity (97%) in the catalytic domain between human and mouse and overall 85% identical amino acids [12]. MMP28 is strongly expressed in testis, as well as in bone, kidneys, lung, heart, colon, intestines, brain, skin and carcinomas [12-17]. It is also expressed in cartilage, synovium
Effects of lovastatin on breast cancer cells: a proteo-metabonomic study
Jelena Klawitter, Touraj Shokati, Vanessa Moll, Uwe Christians, Jost Klawitter
Breast Cancer Research , 2010, DOI: 10.1186/bcr2485
Abstract: In this study we evaluated the effects of lovastatin acid and lactone on breast cancer MDAMB231 and MDAMB468 cells using a combination of proteomic and metabonomic profiling techniques.Lovastatin inhibited proliferation of breast cancer cell lines. MDAMB231 cells were more sensitive to its effects, and in most cases lovastatin acid showed more potency towards the manipulation of protein expression than lovastatin lactone. Increased expression of Rho inhibitor GDI-2 stabilized the non-active Ras homolog gene family member A (RhoA) leading to a decreased expression of its active, membrane-bound form. Its downstream targets cofilin, CDC42 and G3BP1 are members of the GTPase family affected by lovastatin. Our data indicated that lovastatin modulated the E2F1-pathway through the regulation of expression of prohibitin and retinoblastoma (Rb). This subsequently leads to changes of E2F-downstream targets minichromosome maintenance protein 7 (MCM7) and MutS homolog 2 (MSH2). Lovastatin also regulated the AKT-signaling pathway. Increased phosphatase and tensin homolog (PTEN) and decreased DJ-1 expression lead to a down-regulation of the active pAkt. Lovastatin's involvement in the AKT-signaling pathway was confirmed by an upregulation of its downstream target, tumor progressor NDRG1. Metabolic consequences to lovastatin exposure included suppression of glycolytic and Krebs cycle activity, and lipid biosynthesis.The combination of proteomics and metabonomics enabled us to identify several key targets essential to the antitumor activity of lovastatin. Our results imply that lovastatin has the potential to reduce the growth of breast cancer cells.Breast cancer is the second leading cause of cancer death in women. There are currently no effective therapies for advanced breast cancer, with treatment primarily aimed at palliation of symptoms and improvement of overall survival. Healthy women at high risk of breast cancer are the focus of prevention, whereas current chemotherapy tar
Combinatorial Properties of Triangle-Free Rectangle Arrangements and the Squarability Problem
Jonathan Klawitter,Martin N?llenburg,Torsten Ueckerdt
Computer Science , 2015,
Abstract: We consider arrangements of axis-aligned rectangles in the plane. A geometric arrangement specifies the coordinates of all rectangles, while a combinatorial arrangement specifies only the respective intersection type in which each pair of rectangles intersects. First, we investigate combinatorial contact arrangements, i.e., arrangements of interior-disjoint rectangles, with a triangle-free intersection graph. We show that such rectangle arrangements are in bijection with the 4-orientations of an underlying planar multigraph and prove that there is a corresponding geometric rectangle contact arrangement. Moreover, we prove that every triangle-free planar graph is the contact graph of such an arrangement. Secondly, we introduce the question whether a given rectangle arrangement has a combinatorially equivalent square arrangement. In addition to some necessary conditions and counterexamples, we show that rectangle arrangements pierced by a horizontal line are squarable under certain sufficient conditions.
Mycophenolate Mofetil Enhances the Negative Effects of Sirolimus and Tacrolimus on Rat Kidney Cell Metabolism
Jelena Klawitter, Jost Klawitter, Volker Schmitz, Touraj Shokati, Ekaterina Epshtein, Joshua M. Thurman, Uwe Christians
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086202
Abstract: Background and Purpose Mycophenolate mofetil (MMF) per se is not known to have negative effects on the kidney. MMF alone or in combination with sirolimus, can be the basis of calcineurin inhibitor (CNI)-free, kidney sparing drug protocols. However, long-term outcomes in patients on MMF/SRL seem to be inferior to those treated with regimens that include the CNI tacrolimus (TAC) due to an increased risk of allo-immune reactions. Interestingly, potential enhancement of the negative effects of SRL and TAC on the kidney by MMF has never been considered. Experimental Approach It was our aim to study the effects of TAC, SRL and MMF alone and evaluate their interactions when combined on the rat kidney. For this purpose we used a comprehensive molecular marker approach including measurements of urinary 8-isoprostane concentrations (oxidative stress marker) and changes of urinary metabolite patterns (1H-NMR spectroscopy) and comparing these markers to renal function (glomerular filtration rate (GFR)) and morphologic alterations (histology). Key Results While MMF alone did not impact GFR, its interaction with SRL and TAC led to a significant decrease of rats’ renal function. The decline went in parallel with a significant increase in urinary isoprostane concentrations and an enhancement of negative effects on urinary metabolite patterns. Conclusions In broad summary, the present study showed that MMF may enhance the negative effects of TAC on kidney function and may even display nephrotoxic properties when combined with SRL.
Biomarkers of Acute Kidney Injury
Jeffrey C. Sirota,Jelena Klawitter,Charles L. Edelstein
Journal of Toxicology , 2011, DOI: 10.1155/2011/328120
Abstract: Acute kidney injury (AKI) is a common problem in both the inpatient and outpatient setting and often results from drug toxicities. Traditional methods of identifying AKI, through measurement of blood urea nitrogen and serum creatinine, are problematic in that they are slow to detect decreases in glomerular filtration rate (GFR) and are influenced by a variety of factors that are not related to GFR changes. The problems inherent in a creatinine-based diagnosis of AKI have impeded the development of proper therapeutics in AKI and posed problems in evaluating nephrotoxicity of drugs and other chemical exposures. In recent years, a number of new biomarkers of AKI with more favorable test characteristics than creatinine have been identified and studied in a variety of experimental and clinical settings. This review will consider the most well-established biomarkers and appraise the literature, with particular attention given to the use of biomarkers in identifying toxin-mediated AKI. 1. Introduction AKI, defined as a rapid decline in GFR, is a common problem, and the incidence has been increasing significantly, particularly in the hospital setting. Recent estimates have suggested that AKI accounts for 1% of all hospital admissions, complicates 7% of hospitalizations, and is present in up to 20% of critically ill patients [1]. Despite significant advances in both critical care and nephrology, the mortality rate of hospitalized patients with AKI has remained relatively unchanged at around 50% over the past few decades [2]. A wide variety of etiologies underlies community-acquired AKI, while ischemia, sepsis, and toxins (including medications) are the most common etiologies in hospitalized patients. Criteria for the diagnosis of AKI rely heavily on measurements of serum creatinine, a common practice for estimating renal function for over sixty years. Creatinine is a 113 Dalton molecule that is derived from phosphocreatinne, which in turn is a product of creatine metabolism after creatine’s release from muscle. Creatinine is freely filtered by the glomerulus and excreted thereafter without significant metabolism or reabsorption by the kidney [3]. These properties have made serum creatinine level a useful surrogate for kidney function, and the reciprocal relationship between serum creatinine and GFR has been well described [4]. A variety of equations (e.g., Cockcroft-Gault, MDRD, and CKD-EPI) have been developed to estimate GFR from a measured serum creatinine level. Despite its widespread use, however, serum creatinine has significant limitations as a tool for
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