Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured serum levels of thrombopoietin (TPO), interleukin (IL)-11, and IL-6 in 90 different samples from 67 pediatric patients with thrombocytopenia (TP). The cytokine levels were determined by enzyme-linked immunosorbent assays (ELISA), and the biological activity of TPO was measured using a cell line transfected with human c-mpl. In patients with impaired megakaryocytopoiesis, as found in diseases such as aplastic anemia, amegakaryocytic TP, or TP with absent radii, we found TPO levels which were highly elevated compared with normal values (mean=261 AU/ml, n=52, vs. 22 AU/ml in healthy controls). In contrast, patients suffering from idiopathic thrombocytopenic purpura (mean=16 AU/ml, n=31) or platelet function defects (mean=23 AU/ml, n=7) demonstrated normal TPO levels. The biological activity tested in the bioassay correlated well with the ELISA data. However, sera of some patients with amegakaryocytic TP demonstrated a remarkably higher biological activity of TPO than expected from the ELISA data. Within the different groups there was no correlation between platelet counts and TPO levels. Only 27% of all samples had elevated levels of IL-11 (mean=450 pg/ml, n=20). Elevated IL-6 serum levels were detected in only 13% of all samples analyzed (mean=42 pg/ml, n=12). We conclude that megakaryocytopoiesis is regulated mainly by TPO, that it is dependent on the platelet and the megakaryocytic mass, and that IL-11 plays an additional role in supporting the platelet production. IL-6 does not appear to be up-regulated in children with thrombocytopenia.
 ...
PMID:Serum levels of thrombopoietin, IL-11, and IL-6 in pediatric thrombocytopenias. 1052 27

In a substantial number of patients with aplastic anemia (AA), immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A (CSA) leads to long-lasting remissions and is thus regarded as standard therapy. However, no consensus exists on how to treat refractory or relapsed AA, especially when no related stem cell donor is available. For selected patients, matched unrelated donor stem cell transplant (MUDSCT) is an option. In addition, umbilical cord blood and haploidentical donors have been considered as an alternative source of stem cells. Patients without a suitable donor may benefit from a second cycle of ATG and CSA. Alternatives are alemtuzumab and high dose cyclophosphamide, both of which induce remission in more than 50% of patients with relapsed AA. Further experimental drugs are androgens, hematopoietic growth factors (interleukins IL-3, IL-6, and IL-11 and stem cell factor [SCF]), and the tumor necrosis factor (TNF)-targeting agent etanercept. Clinical trials with these agents are ongoing and will explore long-term outcomes and potential beneficial effects of drug combinations.
 ...
PMID:Treatment of refractory or relapsed acquired aplastic anemia: review of established and experimental approaches. 2163 5

Chronic benzene (BZ) exposure is associated with multiple adverse health effects and leads to progressive bone marrow failure (BMF). BZ-induced BMF is an acquired aplastic anemia characterized by severe anemia, neutropenia and thrombocytopenia, which is likely caused by immunotoxicity and oxidative stress. Previous studies showed that Epimedium polysaccharides (EPS), a natural and major herbal compound derived from Epimedium, has immunomodulatory and antioxidant potential. The purpose of this study was to evaluate the potential efficacy of EPS against BZ-induced BMF. BMF mouse model was established by subcutaneous injection of 2 ml/kg BZ in CD1 mice. Mice received daily oral treatment with 100 mg/kg high-dose EPS and 20 mg/kg low-dose EPS for four weeks. Our data showed that EPS treatment alleviated BZ-associated weight loss and increased the number of whole blood cells in peripheral blood and nucleated cells in bone marrow. Furthermore, EPS treatment decreased apoptotic rate and reactive oxygen species production, S-phase arrest in bone marrow cells. Finally, EPS treatment improved T cell-mediated immune suppression by increasing CD3+, CD4 + T-cell counts, and CD4+/CD8+ ratio. and modulated hematopoietic cytokines including EPO, IL-11, and IL-2 in peripheral blood. Our study suggests that EPS is a potential therapeutic target to attenuate hematotoxicity induced by BZ.
 ...
PMID:Epimedium polysaccharides attenuates hematotoxicity by reducing oxidative stress and enhancing immune function in mice model of benzene-induced bone marrow failure. 3201 88