The fibronectin EDA isoform (EDA FN) is instrumental in fibrogenesis but, to date, its expression and function in bone marrow (BM) fibrosis have not been explored. We found that mice constitutively ...expressing the EDA domain (EIIIA
), but not EDA knockout mice, are more prone to develop BM fibrosis upon treatment with the thrombopoietin (TPO) mimetic romiplostim (TPO
). Mechanistically, EDA FN binds to TLR4 and sustains progenitor cell proliferation and megakaryopoiesis in a TPO-independent fashion, inducing LPS-like responses, such as NF-κB activation and release of profibrotic IL-6. Pharmacological inhibition of TLR4 or TLR4 deletion in TPO
mice abrogated Mk hyperplasia, BM fibrosis, IL-6 release, extramedullary hematopoiesis, and splenomegaly. Finally, developing a novel ELISA assay, we analyzed samples from patients affected by primary myelofibrosis (PMF), a well-known pathological situation caused by altered TPO signaling, and found that the EDA FN is increased in plasma and BM biopsies of PMF patients as compared with healthy controls, correlating with fibrotic phase.
The small proteoglycan decorin plays an important role in the organisation of the extracellular matrix by binding to several components, including collagen and fibronectin. In this work, we report ...the dose-dependent and saturable interaction of decorin with the adhesive glycoprotein, von Willebrand factor (VWF). This interaction was mediated by the glycosaminoglycan side chain of decorin and was critically regulated by the degree of sulfation, but not by the amount of iduronic acid. Both chondroitin sulfate and dermatan sulfate, in addition to heparin, were found to bind VWF equally well. Although soluble decorin prevented VWF binding to heparin, purified VWF-A1 domain failed to interact with the proteoglycan. These results identify VWF as a new partner for the small proteoglycan, decorin, in the structural organisation of the extracellular matrix.
Bibliotecas a Sul Agenjo, Xavier; Alvim, Luísa; Barrulas, Joaquina ...
12/2023
Book
Open access
Bibliotecas a Sul é uma obra de investigação e divulgação académica que analisa o fenómeno das bibliotecas nas suas múltiplas vertentes de serviço e uso e pretende elucidar aspetos relacionados com ...as bibliotecas do sul de Portugal continental, no âmbito da missão do CIDEHUS – Centro Interdisciplinar de História, Culturas e Sociedades. Os estudos e contributos são inéditos e realizados especificamente para esta obra, maioritariamente por membros integrados no CIDEHUS, cruzando várias disciplinas na área da biblioteconomia e dos estudos de cultura. Inclui, ainda, uma homenagem a Maria José Moura, bibliotecária eborense e impulsionadora das bibliotecas públicas em Portugal.
The oxidative damage of RBC membranes in hemodialysis (HD) patients increases red blood cell (RBC) susceptibility to hemolysis and impairs cell survival. Reduction of the oxidative stress might lead ...to better control of anemia and reduction of the erythropoietin (rhEPO) dose.
We studied 38 stable HD patients, given a mean dose of rhEPO of 104+/-65 U/kg BW/week, at baseline and during antioxidant treatment with either a full or a 50% dose of EPO. Antioxidant treatment involved the combined use of glutathione, GSH (1200 mg i.v. at the end of each dialysis session) and a vitamin E-bonded HD membrane, CL-E. RBC and reticulocyte counts were done monthly. RBC survival (51Cr T/2) was assayed in 18 patients before and after the end of the study. Oxidative status was determined in 10 patients by measuring plasma concentrations of malondyhaldeide-4-hydroxynonenal (MDA-4HNE), reactive oxygen molecular species (ROMs), and oxydized-LDL (oxLDL) as indices of oxidative stress, alpha-tocopherol and total thiols as single antioxidants, and TAS as a marker of total antioxidant plasma activity.
Antioxidant treatment significantly reduced the high basal plasma concentrations of MDA4HNE and oxLDL, and significantly increased those of alpha-tocopherol, whereas TAS and thiols were unmodified. These changes lasted after the reduction of EPO. Anemia significantly improved with treatment, due to a significant increase in RBC survival. A close direct linear relationship was detected between plasma levels of vitamin E and hemoglobin.
Adequate control of oxidative stress achieves better control of anemia in HD patients. Since several antioxidant systems are impaired in uremia, the combined use of the CL-E membrane and GSH seems to be the best antioxidant therapy so far, with significant saving of the rhEPO dose.
Introdução As Bibliotecas Públicas são um serviço público essencial à concretização dos Direitos Humanos, nomeadamente os relativos à liberdade de pensamento, à educação, à participação na vida ...cultural da comunidade, ao usufruto das artes e dos progressos científicos (Declaração Universal dos Direitos Humanos, 1948). Em 1994, foi publicado o Manifesto sobre as Bibliotecas Públicas, preparado pela Federação Internacional das Associações de Bibliotecários e de Bibliotecas (IFLA) e a UNESCO. Ne...
Designated a Reference Reviews Top Ten Print Reference Source 2005 The Encyclopedia of Women's Health meets this challenge by bringing together an impressive array of experts on topics from ...reproductive issues to gastrointestinal illnesses. This skilfully edited volume, informed by current health issues and health-care realities, offers readers practical information, historical aspects, and future directions, all meticulously researched and conveniently presented. Key features include: -Accessible A-to-Z coverage, including AIDS, birth control, hormone replacement therapy, teen pregnancy, sexual harassment, violence, body image, access to health care and more. -Entries spanning the medical, psychological, sociocultural, spiritual, and legal arenas. -Medical topics explored from both conventional and complementary perspectives. -Cross-cultural data illustrate issues as they apply to minority women, rural women, the elderly, and other underserved populations. -Special chapters on disparities in women's health and health care. -Historical overview of women in health - as patients and as professionals. -Suggested readings and resource lists.
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