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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pathophysiological and therapeutic properties of anemia in rats with adjuvant-induced arthritis (AA) were investigated. Both anemia and chronic inflammation were induced in rats by a single injection of Freund's complete adjuvant. This study confirmed other earlier data that these anemic rats with AA had reduced serum iron levels and that the anemia was characterized as mild, non-progressive, hypochromic, microcytic. In addition, our studies showed that these anemic rats had slightly but significantly enhanced erythropoietin titers, but not renal failure; there was no significant difference in blood urea nitrogen and creatinine levels in anemic and normal groups. The anemia in rats with AA was improved by recombinant human erythropoietin (r-HuEPO) at 30 and 100 U/kg/day, given i.v. for 5 days. In contrast, iron-chondroitin-sulfate colloid (10 mg/kg/day, i.v. for 5 days) failed to improve the anemia and to enhance the effects of r-HuEPO. These data suggest that anemia in rats with adjuvant-induced arthritis is distinguished, pathophysiologically and therapeutically, from iron deficiency anemia, hemolytic anemia, and renal anemia.
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PMID:Recombinant human erythropoietin, but not iron supplementation, improves anemia in rats with adjuvant-induced arthritis. 181 58

Principal concepts concerning the anemia of RA are summarized in Tables 7 and 8. These concepts have been validated by our analysis of 93 anemic RA patients and by our review of the literature. The fact that anemia in RA may have one or more etiologies, occasionally in the same patient, mandates a reasoned approach to the analysis of anemia in every RA patient in whom it may occur. In particular, iron deficiency is common and determination of bone marrow iron content via an aspirate may be required for a definitive diagnosis. In those RA patients with anemia of chronic disease, the best therapy remains control of the underlying disease, most commonly with second line drugs and/or corticosteroids. The place for recombinant erythropoietin in the therapy of this anemia has not been defined; one specific role for erythropoietin may be in the preparation of RA patients for elective surgery, particularly hip arthroplasty, where correction of the anemia may either obviate the need for transfusion or may allow for donation of blood for purposes of autologous transfusion perioperatively. The pathogenesis of the anemia of chronic disease, as seen in RA anemia, is not completely understood. Inflammatory mediators, particularly the cytokines, appear to be important factors in the impairment of erythropoiesis. The mechanism by which these cytokines impair erythroid progenitor growth and hemoglobin production in developing erythrocytes is an important area for future study.
Semin Arthritis Rheum 1990 Feb
PMID:The pathogenesis of anemia in rheumatoid arthritis: a clinical and laboratory analysis. 218 69

Erythrocytes in anemic rats with adjuvant arthritis (AA) were less deformable compared with normal rats. Swelling of the spleen was noticed in anemic rats with AA. The treatment of anemic rats with recombinant human erythropoietin (r-HuEPO; 30 and 100 U/kg, i.v., for 5 days) resulted in a normalization of both the anemia and erythrocyte deformability. It is suggested that erythrocytes with reduced deformability may be sequestered by endothelial slits of the spleen, which may play a causative role in the anemia in rats with AA.
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PMID:Reduced erythrocyte deformability in anemic rats with adjuvant arthritis. 221 74

Two anemic patients with rheumatoid arthritis were treated with recombinant human erythropoietin (EPO) for 5 months. Both patients showed significant increases in hematocrit, red cell volumes, and marrow erythroid and megakaryocyte progenitor cells. No significant toxic effects from EPO were observed. These data indicate that EPO may be effective in overcoming the pathogenetic factors that limit erythropoiesis in rheumatoid arthritis.
Arthritis Rheum 1989 May
PMID:Treatment of the anemia of rheumatoid arthritis with recombinant human erythropoietin: clinical and in vitro studies. 271 34

Human parvovirus B19 has been associated with disease only for the past few years. First isolated from sera obtained for studies on hepatitis B in 1975, it was not until 1981 that infection with this small, single-stranded DNA virus was related to aplastic crisis associated with hemolytic anemia. A nonspecific viral prodrome, the occurrence in family members, and epidemics of aplastic crisis suggested the infectious etiology. Human parvovirus infection has since been associated with arthritis, erythema infectiosum (fifth disease), fetal death, and hydrops fetalis. Through the use of recently developed serologic tests, epidemics of erythema infectiosum and parvoviral infection have been related not only to aplastic crisis but also to intrauterine infection and hydrops; DNA hybridization studies have allowed the detection of viral DNA in serum and tissue extracts. Studies have been hampered by the lack of an ability to culture the virus, but this is now possible utilizing bone marrow culture and erythropoietin. This article is a historical and clinical review of human parvovirus infection and disease and considers potential questions regarding their consequences.
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PMID:Human parvovirus B19: historical and clinical review. 284 80

Serum immunoreactive erythropoietin (EP) levels were measured in 116 patients with rheumatoid arthritis (RA) and 20 control patients with iron deficiency anemia. Serum EP levels were significantly higher in the 46 anemic RA patients than in the 70 nonanemic RA patients (mean +/- SD 31.0 +/- 19.8 mU/ml versus 16.8 +/- 12.4 mU/ml; P less than 0.0001). Furthermore, although a significant inverse correlation between the serum EP level and the hemoglobin value was present in the anemic RA patients (r = -0.57, P less than 0.0001), the regression coefficient describing the relationship between serum EP and hemoglobin was significantly lower for the anemic RA patients than for patients with iron deficiency anemia (F = 6.01, P less than 0.025).
Arthritis Rheum 1988 Oct
PMID:Serum immunoreactive erythropoietin in rheumatoid arthritis: impaired response to anemia. 317 10

New information on the treatment of juvenile rheumatoid arthritis emphasizes more aggressive control of arthritis, particularly the use of methotrexate, both in low- and higher-dose regimens. Information concerning drug toxicity, including that of the nonsteroidal anti-inflammatory drugs, second-line agents, and methotrexate, suggests that these drugs are well tolerated in children. A new corticosteroid, deflazacort, minimizes bone demineralization and growth retardation. Adjunctive measures, including erythropoietin, pain management techniques, conditioning programs, and nutrition, have demonstrated advantages in some children with juvenile rheumatoid arthritis.
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PMID:Treatment of juvenile rheumatoid arthritis. 769 Nov 40

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released.
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PMID:Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis. 863 55

Intramyocardial injection of genes encoding angiogenic factors could provide a useful approach for the treatment of ischemic heart disease. However, uncontrolled expression of angiogenic factors in vivo may cause some unwanted side effects, such as hemangioma formation, retinopathy, and arthritis. It may also induce occult tumor growth and artherosclerotic plaque progression. Because hypoxia-inducible factor 1 is up-regulated in a variety of hypoxic conditions and it regulates gene expression by binding to a cis-acting hypoxia-responsive element (HRE), we propose to use HRE, found in the 3' end of the erythropoietin gene to control gene expression in ischemic myocardium. A concatemer of nine copies of the consensus sequence of HRE isolated from the erythropoietin enhancer was used to mediate hypoxia induction. We constructed two adeno-associated viral vectors in which LacZ and vascular endothelial growth factor (VEGF) expressions were controlled by this HRE concatemer and a minimal simian virus 40 promoter. Both LacZ and VEGF expression were induced by hypoxia and/or anoxia in several cell lines transduced with these vectors. The functions of these vectors in ischemic myocardium were tested by injecting them into normal and ischemic mouse myocardium created by occlusion of the left anterior descending coronary artery. The expression of LacZ gene was induced eight times and of VEGF 20 times in ischemic myocardium compared with normal myocardium after the viral vector transduction. Hence, HRE is a good candidate for the control of angiogenic factor gene expression in ischemic myocardium.
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PMID:Adeno-associated viral vector-mediated hypoxia response element-regulated gene expression in mouse ischemic heart model. 1208 14

In recent work we reported that systemically administered erythropoietin (EPO) crosses the blood-brain barrier and has protective effects in animal models of cerebral ischemia, brain trauma and in a rat model of experimental autoimmune encephalomyelitis (EAE). Here we characterize the effect of systemic EPO on the inflammatory component of actively induced, acute EAE in Lewis rats. Administration of EPO at doses of 500-5000 U/kg bw i.p., daily from day 3 after immunization with myelin basic protein (MBP), delayed the onset of EAE and decreased its clinical score at peak time (days 12-13). Immunohistochemical analysis of the spinal cord using anti-glial fibrillary acidic protein (GFAP) and anti-CD11b antibodies showed that EPO markedly diminished inflammation and glial activation/proliferation. EAE induced significant levels of TNF and IL-6 in the spinal cord, where IL-6 was maximum at the onset of the disease (day 10) and TNF at its peak (day 12). EPO delayed the increase of TNF levels, without altering their peak levels, and markedly reduced those of IL-6 suggesting that the decreased inflammation and clinical score may be in part upon attenuation of IL-6. On the other hand, EPO was without effect in a model of adjuvant-induced arthritis in Lewis rats, suggesting a specificity towards autoimmune demyelinating diseases. These data suggest that EPO might act as a protective cytokine in inflammatory pathologies of the CNS.
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PMID:Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis. 1236 12


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