1,720,976 research outputs found
Effect of the antioxidant idebenone on adverse events under mycophenolate mofetil therapy in a rat model
No full textBackground. Diarrhea and anemia are side effects of mycophenolic acid (MPA), but underlying mechanisms are not fully understood. Gene expression of major-alpha-hemoglobin and catalase was suppressed in livers of mycophenolate mofetil (MMF)-treated rats, suggesting MPA attenuates cellular defense against reactive oxygen species (ROS). We investigated whether the antioxidant idebenone might alleviate MPA-related side effects. Methods. Rats were treated as follows: group 1: controls; group 2: idebenone; group 3: MMF; and group 4: MMF/idebenone. Blood was collected weekly to determine cell counts, hemoglobin, MPA, plasma albumin, total protein, creatinine, and urea concentrations. On day 28 RNA was extracted from liver, kidneys, and bone marrow (BM). Colon and jejunum were examined histologically. Results. High-dose MMF-treated rats developed diarrhea, dehydration, and weight loss. After a week, a significant decrease (P=0.001) in erythrocyte count and hemoglobin concentration was observed that was not influenced by idebenone. Degenerative changes in the jejunum were slightly attenuated by idebenone. Idebenone did not influence MPA-induced suppression of catalase. A significant suppression of major-alpha-hemoglobin and the erythropoietin (EPO)-receptor in BM of MMF-treated groups and almost complete absence of hemopoietic progenitor cells were observed. EPO-mRNA was markedly upregulated in the MMF-group and even more in the MMF/idebenone-group. Conclusion. Idebenone showed minimal benefit on MMF-related diarrhea and anemia. BM of MMF-treated rats revealed erythroid aplasia as a possible reason for anemia. Marked upregulation of EPO-mRNA presumably reflects a compensatory mechanism. Because ROS have the potential to suppress EPO expression, it can be hypothesized that enhanced EPO-mRNA expression in MMF/idebenone-treated rats is caused by antagonism of ROS
Nephrotic Syndrome in a Multiple Sclerosis Patient Receiving Long-term Interferon Beta Therapy
No full textRecombinant interferon alpha (IFN-alpha) and interferon beta (IFN-alpha) are efficient drugs for clinical use in multiple sclerosis, hepatitis C virus infection, and malignant diseases. We report a case of a 40-year-old woman with relapsing-remitting multiple sclerosis who was treated with interferon beta-1b for several years before being admitted to our department with nephrotic-range proteinuria (protein excretion, 8.3 g/d) and serum albumin level of 2.9 g/dL without any clinical and laboratory change typical for a systemic autoimmune disease. The kidney biopsy led to the diagnosis of immune complex-mediated membranoproliferative glomerulonephritis with immunoglobulin and complement deposits visible by immunohistology, as well as subendothelial deposits and tubuloreticular inclusions evident by electron microscopy. Subsequently replacing interferon beta-1b with glatiramer acetate resulted in partial remission, with proteinuria decreasing to protein excretion of 1.0 g/d 2 months thereafter. The association of a focal mesangiocapillary glomerular change and immunoglobulin-complement deposits with tubuloreticular inclusions suggests lupus nephritis. To our knowledge, this is the first report of an interferon beta-1b-induced immune complex glomerulonephritis characterized by histologic, immunohistologic, and ultrastructural features that resembled lupus nephritis, but that occurred in a patient without evidence of systemic lupus erythematosus. Our review of experimental data and earlier case reports suggests a pathogenic role of recombinant IFN in some autoimmune diseases, especially those with the potency to induce systemic lupus erythematosus-like syndromes. Am J Kidney Dis. 61(5): 786-789. (C) 2013 by the National Kidney Foundation, Inc
Distinct roles of T-cell lymphopenia and the microbial flora for gastrointestinal and CNS autoimmunity
No full textT-cell lymphopenia is a major risk factor for autoimmunity. Here we describe congenic Lewis (LEW) rats with a loss-of-function mutation in the Gimap5 gene, leading to a 92% reduction in peripheral T-cell numbers. Gimap5-deficient LEW rats developed eosinophilic autoimmune gastroenteritis accompanied by a 40-fold increase in IgE serum levels. This phenotype was ameliorated by antibiotic treatment, indicating a critical role of the microbial flora in the development of inflammatory bowel disease. Interestingly, Gimap5-deficient LEW rats showed strongly aggravated experimental autoimmune encephalomyelitis (EAE) after immunization with guinea pig myelin basic protein. This phenotype, however, persisted after antibiosis, confirming that the enhanced CNS autoimmune response in T-cell lymphopenic Gimap5-deficient LEW rats was unrelated to the composition of the microbial flora. Rather, it seems that it was caused by the 7-fold increase in the percentage of activated T cells producing IL-17 and IFN-gamma, and the skewed T-cell receptor (TCR) repertoire, both of which were the result of T-cell lymphopenia and not affected by antibiosis. This notion was supported by the observation that adoptive T-cell transfer corrected the TCR repertoire and improved EAE. Collectively, our findings confirm a critical albeit differential role of T-cell lymphopenia in the susceptibility to organ-specific autoimmune responses.-Fischer, H.J., Witte, A.-K., Walter, L., Grone, H.-J., van den Brandt, J., Reichardt, H.M. Distinct roles of T-cell lymphopenia and the microbial flora for gastrointestinal and CNS autoimmunity
Viral macrophage inflammatory protein-II improves acute rejection in allogeneic rat kidney transplants
No full textDuring rejection, leukocytes are recruited from the peripheral circulation into the graft leading to the damage of endothelial cells, capillary perfusion failure and graft loss. Chemokines play a pivotal role in the recruitment of leukocytes to the endothelium. Viral macrophage inflammatory protein-II (vMIP-II), a human herpes virus-8 DNA-encoded protein, is a broad-spectrum chemokine antagonist. The aim of the study was to prove the beneficial activity of vMIP-II treatment on acute rat kidney allograft damage. Heterotopic rat kidney transplantation was performed in the Fischer 344 to Lewis transplantation model and animals were treated with vMIP-II (2 x 15 A mu g or 100 A mu g/day) for 7 days. Rejection-induced damage was analyzed by histology, and microcirculatory changes within the graft were analyzed by in vivo microscopy. Viral macrophage inflammatory protein-II significantly improved acute glomerular damage and tubulointerstitial inflammation and lowered the extent of vascular and tubulointerstitial damage of the treated allografts. Functional microcirculation of peritubular capillaries was significantly improved in vivo, and the firm adherence of leukocytes was significantly reduced by vMIP-II treatment. The administration of the broad-spectrum antagonist vMIP-II improved acute renal allograft damage, mainly by a reduction in leukocyte recruitment with a subsequently improved renal cortical microcirculation in vivo.[SFB 405]; [B10
Drug-Induced Granulomatous Interstitial Nephritis in a Patient With Ankylosing Spondylitis During Therapy With Adalimumab
No full textTumor necrosis factor alpha (TNF-alpha) inhibitors are used in the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn disease, ankylosing spondylitis, and juvenile idiopathic arthritis. Use of TNF inhibitors is associated with the induction of autoimmunity (systemic lupus erythematosus, vasculitis, psoriasis, and sarcoidosis/sarcoid-like granulomas). We report a case of interstitial granulomatous nephritis in a patient with ankylosing spondylitis after 18 months of treatment with adalimumab. Previously reported cases of sarcoid-like reactions secondary to the use of TNF-alpha inhibitors involved the liver, lung, lymph nodes, central nervous system, and skin. Granulomatous nephritis after adalimumab treatment has not been described. Close observation of patients undergoing treatment with TNF inhibitors for evolving signs and symptoms of autoimmunity is required. Organ involvement is unpredictable, which makes correct diagnosis and management extremely challenging. Am J Kidney Dis 56:e17-e21. (C) 2010 by the National Kidney Foundation, Inc
STAT-1 decoy oligodeoxynucleotide inhibition of acute rejection in mouse heart transplants
No full textDuring acute rejection of cardiac transplants endothelial cell-leukocyte interaction fuelled by co-stimulatory molecules like CD40/CD154 may ultimately lead to graft loss. One key player in up-regulating the expression of such pro-inflammatory gene products is the interferon-gamma-dependent transcription factor STAT-1. Hence down-regulating interferon-gamma-stimulated pro-inflammatory gene expression in the graft endothelial cells by employing a decoy oligodeoxynucleotide (dODN) neutralising STAT-1 may protect the graft. To verify this hypothesis, heterotopic mouse heart transplantation was performed in the allogeneic B10.A(2R) to C57BL/6 and syngeneic C57BL/6 to C57BL/6 strain combination without immunosuppression. Graft vessels were pre-treated with STAT-1 dODN, mutant control ODN (10 mu M each) or vehicle (Ringer solution). Cellular rejection (vascular and interstitial component) was graded histologically and CD40, ICAM-1, VCAM-1, MCP-1, E-selectin and RANTES expression in the graft monitored by real time PCR 24 h and 9 days post-transplantation. Nine days after transplantation both rejection scores were significantly diminished by 85 and 70%, respectively, in STAT-1 dODN-treated allografts as compared to mutant control ODN-treated allografts. According to immunohistochemistry analysis, this was accompanied by a reduced infiltration of monocyte/macrophages and T cells into the graft myocardium. In addition, pro-inflammatory gene expression was strongly impaired by more than 80% in STAT-1 dODN-treated allografts 24 h post-transplantation but not in mutant control ODN or vehicle-treated allografts. This inhibitory effect on pro-inflammatory gene expression was no longer detectable 9 days post-transplantation. Single periprocedural treatment with a STAT-1 dODN thus effectively reduces cellular rejection in mouse heart allografts. This effect is associated both with an early decline in pro-inflammatory gene expression and a later drop in mononuclear cell infiltration
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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