35 research outputs found
The effect of alexithymia and depressive feelings on pain perception in somatoform pain disorder
No full textObjective: To investigate the relationship between alexithymia and depression and their influence on the subjective versus experimental pain perception in somatoform pain disorder. Methods: Three groups consisting of 40 patients with somatoform pain disorder, 40 patients with depression, and 40 healthy controls were matched. They completed questionnaires regarding alexithymia (TAS26) and depressive feelings (BDI-II). In addition, pain patients rated their subjective pain intensity (NRS). Quantitative sensory testings were conducted in all participants examining temperature (CPT, HPT) and mechanical (MPT, PPT) thresholds. Results: Analysis of variance showed that alexithymia was significantly increased in both patient groups compared to healthy controls, but with the highest amount in somatoform pain. Regression analyses confirmed that this finding was in part due to a high comorbidity of depressive feelings in both patient groups. We found a discrepancy between increased clinical pain ratings and elevated pressure pain thresholds, indicating a less intense mechanical pain perception in somatoform pain. Correlation analyses demonstrated a significant connection of subjective pain ratings and pressure pain thresholds with depressive feelings. Conclusion: Contrary to the results of other experimental pain studies on chronic muskuloskeletal pain syndromes, we could not confirm central sensitization in somatoform pain disorder. Our findings place the somatoform pain disorder more in the direction of affective disorder such as depression. These findings may improve a better understanding of the disease and also have direct therapeutic implications. The high occurrence of alexithymia and depressive feelings in somatoform pain should be considered in diagnostic and therapeutic regimens of these patients
Microarray analysis of Akt1 activation in transgenic mouse hearts reveals transcript expression profiles associated with compensatory hypertrophy and failure
No full textTo investigate molecular mechanisms involved in the development of cardiac hypertrophy and heart failure, we developed a tetracycline-regulated transgenic system to conditionally switch a constitutively active form of the Akt1 protein kinase on or off in the adult heart. Short-term activation (2 wk) of Akt1 resulted in completely reversible hypertrophy with maintained contractility. In contrast, chronic Akt1 activation (6 wk) induced extensive cardiac hypertrophy, severe contractile dysfunction, and massive interstitial fibrosis. The focus of this study was to create a transcript expression profile of the heart as it undergoes reversible Akt1-mediated hypertrophy and during the transition from compensated hypertrophy to heart failure. Heart tissue was analyzed before transgene induction, 2 wk after transgene induction, 2 wk of transgene induction followed by 2 days of repression, 6 wk after transgene induction, and 6 wk of transgene induction followed by 2 wk of repression. Acute overexpression of Akt1 (2 wk) leads to changes in the expression of 826 transcripts relative to noninduced hearts, whereas chronic induction (6 wk) led to changes in the expression of 1,611, of which 65% represented transcripts that were regulated during the pathological phase of heart growth. Another set of genes identified was uniquely regulated during heart regression but not growth, indicating that nonoverlapping transcription programs participate in the processes of cardiac hypertrophy and atrophy. These data define the gene regulatory programs downstream of Akt that control heart size and contribute to the transition from compensatory hypertrophy to heart failure. Copyright © 2006 the American Physiological Society
Impaired revascularization in a mouse model of type 2 diabetes is associated with dysregulation of a complex angiogenic-regulatory network
No full textObjective - Diabetes is a risk factor for the development of cardiovascular diseases associated with impaired angiogenesis or increased endothelial cell apoptosis. Methods and Results - Here it is shown that angiogenic repair of ischemic hindlimbs was impaired in Lepr db/db mice, a leptin receptor-deficient model of diabetes, compared with wild-type (WT) C57BL/6 mice, as evaluated by laser Doppler flow and capillary density analyses. To identify molecular targets associated with this disease process, hindlimb cDNA expression profiles were created from adductor muscle of Lepr db/db and WT mice before and after hindlimb ischemia using Affymetrix GeneChip Mouse Expression Set microarrays. The expression patterns of numerous angiogenesis-related proteins were altered in Lepr db/db versus WT mice after ischemic injury. These transcripts included neuropilin-1, vascular endothelia growth factor-A, placental growth factor, elastin, and matrix metalloproteinases implicated in blood vessel growth and maintenance of vessel wall integrity. Conclusion - These data illustrate that impaired ischemia-induced neovascularization in type 2 diabetes is associated with the dysregulation of a complex angiogenesis-regulatory network. © 2005 American Heart Association, Inc
Angiogenic-regulatory network revealed by molecular profiling heart tissue following Akt1 induction in endothelial cells
No full textAkt is a pivotal signaling molecule involved in the regulation of angiogenesis. In order to further elucidate the role of Akt1 in blood vessel development, a tetracycline-regulated transgenic system was utilized to conditionally activate Akt1 signaling in endothelial cells to examine transcript expression changes associated with angiogenesis in the heart. Induction of Akt1 over the course of 6 weeks led to a 33% increase in capillary density without affecting overall heart growth. Transcript expression profiles in the hearts were analyzed with an Affymetrix GeneChip Mouse Expression Set 430 2.0, which represents approximately 45,000 cDNAs and ESTs. A total of 248 transcripts were differentially expressed between transgenic and control mice (fold change >/<1.8; false discovery rate < 0.1; P < 0.01). A subset of these differentially expressed transcripts included angiogenic growth factors, cytokines, and extracellular matrix proteins. More specifically, these transcripts included VEGF-receptor2, neuropilin-1, and connective tissue growth factor, each of which is implicated in blood vessel growth and the maintenance of vessel wall integrity. Furthermore, these factors may be involved in an autocrine-regulatory feedback system, one believed to promote vessel growth. Knowledge of these and other targets could be used to treat ischemic heart disease, a disease whose broad spectrum of manifestations range from patients with only effort-induced angina without myocardial damage, through stages of myocardial ischemia that are associated with reversible and irreversible impairment in left ventricular function, to states of irreversible myocardial injury and necrosis resulting in congestive heart failure (CHF). © 2008 Springer Science+Business Media B.V
Impaired angiogenesis in glutathione peroxidase-1-deficient mice is associated with endothelial progenitor cell dysfunction
No full textSeveral vascular disease are characterized by elevated levels of reactive oxygen species (ROS). Vascular endothelium is protected from oxidant stress by expressing enzymes such as glutathione peroxidase type 1 (GPx-1). In this study, we investigated the effect of vascular oxidant stress on ischemia-induced neovascularization in a murine model of homozygous deficiency of GPx-1. GPx-1-deficient mice showed impaired revascularization following hindlimb ischemic surgery based on laser Doppler measurements of blood flow and capillary density in adductor muscle. GPx-1-deficient mice also showed an impaired ability to increase endothelial progenitor cell (EPC) levels in response to ischemic injury or subcutaneous administration of vascular endothelial growth factor protein. EPCs isolated from GPx-1-deficient mice showed a reduced ability to neutralize oxidative stress in vitro, which was associated with impaired migration toward vascular endothelial growth factor and increased sensitivity to ROS-induced apoptosis. EPCs isolated from GPx-1-deficient mice were impaired in their ability to promote angiogenesis in wild-type mice, whereas wild-type EPCs were effective in stimulating angiogenesis in GPx-1-deficient mice. These data suggest that EPC dysfunction is a mechanism by which elevated levels of ROS can contribute to vascular disease. © 2006 American Heart Association, Inc
Endemic influences of political regimes, healthcare systems, and preferences on the frequencies and incidences of nephropathies in eastern Saxony, Germany
No full textThe possible confounding influence of investigator-related preferences, available histological techniques, and healthcare systems on the frequencies and incidences of primary and secondary nephropathies was evaluated in this long-term observation
Short-term akt activation in cardiac muscle cells improves contractile function in failing hearts
Get PDFpeer reviewedAkt is a serine/threonine protein kinase that is activated by a variety of growth factors or cytokines in a phosphatidylinositol 3-kinase-dependent manner. By using a conditional transgenic system in which Akt signaling can be turned on or off in the adult heart, we previously showed that short-term Akt activation induces a physiological form of cardiac hypertrophy with enhanced coronary angiogenesis and maintained contractility. Here we tested the hypothesis that induction of physiological hypertrophy by short-term Akt activation might improve contractile function in failing hearts. When Akt signaling transiently was activated in murine hearts with impaired contractility, induced by pressure overload or doxorubicin treatment, contractile dysfunction was attenuated in both cases. Importantly, improvement of contractility was observed before the development of cardiac hypertrophy, indicating that Akt activation improves contractile function independently of its growth-promoting effects. To gain mechanistic insights into Akt-mediated positive inotropic effects, transcriptional profiles in the heart were determined in a pressure overload-induced heart failure model. Biological network analysis of differentially expressed transcripts revealed significant alterations in the expression of genes associated with cell death, and these alterations were reversed by short-term Akt activation. Thus, short-term Akt activation improves contractile function in failing hearts. This beneficial effect of Akt on contractility is hypertrophy-independent and may be mediated in part by inhibition of cell death associated with heart failure
MP130DUAL RAAS BLOCKADE WITH ALISKIREN IN PATIENTS WITH SEVERELY IMPAIRED CHRONIC KIDNEY DISEASE
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Cathepsin G is differentially expressed in primary human antigen-presenting cells
No full textCathepsins are required for the processing of antigens in order to make them suitable for loading on major histocompatibility complex (MHC) class II molecules, for subsequent presentation to CD4(+) T cells. It was shown that antigen processing in monocyte-derived dendritic cells (DC), a commonly used DC model, is different from that of primary human DC. Here, we report that the two subsets of human myeloid DC (mDC) and plasmacytoid DC (pDC) differ in their cathepsin distribution. The serine protease cathepsin G (CatG) was detected in mDC1, mDC2, pDC, cortical thymic epithelial cells (cTEC) and high levels of CatG were determined in pDC. To address the role of CatG in the processing and presentation of a Multiple Sclerosis-associated autoantigen myelin basic protein (MBP), we used a non-CatG expressing fibroblast cell line and fibroblasts, which were preloaded with purified CatG. We find that preloading fibroblasts with CatG results in a decrease of MBP84-98-specific T cell proliferation, when compared to control cells. Our data suggest a different processing signature in primary human antigen-presenting cells and CatG may be of functional importance
