Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human erythropoietin (rHuEPO) can dramatically improve anemia in dialysis patients, but about 20% of patients show a poor response to this agent. It has been reported that cytokines, including interleukin (IL)-1 beta, may inhibit the maturation of erythrocytes. To investigate the mechanisms of unresponsiveness to rHuEPO, we isolated peripheral blood mononuclear cells from 12 patients on continuous ambulatory peritoneal dialysis who were receiving maintenance rHuEPO therapy for renal anemia. Cells were cultured with rHuEPO and IL-1 beta production was assessed. In the six patients who did not respond to rHuEPO therapy, there was a marked increase in IL-1 beta during culture with rHuEPO. In contrast, the addition of rHuEPO to cultures of cells from the six responding patients caused little increase in IL-1 beta, and there was a significant difference between the two groups. Induction of IL-1 beta by rHuEPO may be one cause of persistent anemia in dialysis patients.
 ...
PMID:Stimulation of interleukin-1 beta production may be involved in unresponsiveness to erythropoietin therapy. 897 Aug 30

We reported a 59-year-old woman who received a diagnosis of psoriasis vulgaris at the age of 35 and had been under medical treatment. She was admitted to our department on August 16, 1993 because of lymphadenopathy, arthralgia and neuralgia. We observed cervical and axillar lymphadenopathy 1-3 cm in diameter, anemia and leukothrombocytosis. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and immunoglobulin G (IgG), but not M-protein were observed by immunological analysis of the serum. Bone marrow aspiration biopsy revealed hypercellularity with myeloid hyperplasia and slight increase in plasma cells. Elevated levels of serum interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) were detected; IL-6 was 62.1 pg/ml and G-CSF was 66 pg/ml, but IL-1 alpha, IL-1 beta and TNF-alpha were within the normal range. Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia was diagnosed by lymph-node biopsy and the patient received following treatment with prednisolone and hydroxyurea. Leukocytes, platelets and skin eruptions increased again when the steroid dose was tapered, so we changed treatments to MP (melphalan, prednisolone) therapy. In addition, various neurological abnormalities such as convulsions, loss of consciousness and peripheral polyneuritis were observed. Despite treatment her condition deteriorated and she finally died. Very few reports show these neurological abnormalities in IPL or Castleman's disease therefore we think this is a very rare case.
 ...
PMID:[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia in a patient who died of progressive peripheral polyneuritis and cerebral dysfunction]. 905 65

Proinflammatory cytokines play an important role in the pathogenesis of anemia in inflammatory diseases. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been reported to inhibit the synthesis of erythropoietin (EPO) in vitro. To evaluate the in vivo significance of this observation, we have investigated effects of the administration of bacterial lipopolysaccharide (LPS) and IL-1 beta on renal EPO production in rats. Measurements by competitive reverse-transcription polymerase chain reaction showed that EPO mRNA levels were significantly reduced in the kidneys of normoxic rats 6 h after the injection of LPS (0.1 or 1 mg/kg). In addition, LPS and IL-1 beta (1 microgram/kg) inhibited the increase in EPO mRNA and plasma EPO levels when administered to rats before hypoxia exposure (8% O2 in the inspiratory gas). Evidence for an inflammatory reaction in the kidneys of LPS-treated rats was provided by measurements of greatly elevated renal TNF-alpha mRNA levels. Furthermore, kidneys isolated from LPS-created rats produced less immunoreactive EPO when perfused hypoxically in vitro for 2 h. Thus mediators of the immune response inhibit renal EPO gene expression in vivo, which is relevant with respect to the impaired synthesis of EPO in inflammatory diseases in humans.
 ...
PMID:Erythropoietin gene expression is suppressed after lipopolysaccharide or interleukin-1 beta injections in rats. 932 87

A percentage of hemodialysis (HD) patients are resistant to recombinant human erythropoietin (rHuEPO), a phenomenon that occurs less frequently in patients dialyzed with biocompatible membranes (M) and in peritoneal dialysis. The authors evaluated the effects of paired filtration dialysis (PFD)--a dialysis technique based on the use of an emophan M in conjunction with a polysulphone M--on erythropoiesis in HD patients resistant to rHuEPO. Twelve HD patients with anemia resistant to long-term therapy with rHuEPO (200.24 U/kg body weight three times per week intravenously for 10.2 months) were studied. Patients had been treated for an average of 46.9 months with bicarbonate HD, using cuprophan M (Phase A) and, successively, for 12 months by PFD (Phase B). The following parameters were evaluated monthly: 1) hemoglobin and hematocrit values; 2) serum levels of erythropoietin (EPO); and 3) serum levels of interleukin (IL)-3, IL-6, IL-10, IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). At the end of Phase A and Phase B, patients underwent bone marrow biopsies to evaluate 1) bone marrow burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) proliferative capacity, and 2) bone marrow mononuclear cell EPO-receptor (EPO-R) number. During Phase B, there was a progressive rise in hematocrit and hemoglobin values, so that within the sixth month, the rHuEPO dose was reduced to 80 +/- 15 U/kg body weight three times per week. At the same time, an increase in serum IL-3, IL-6, and IL-10 levels was seen, whereas serum IL-1 beta, TNF-alpha, and IFN-gamma levels decreased. This was accompanied by a rise in BFU-E and CFU-E growth and in bone marrow mononuclear cell EPO-R number. During Phase B, after the dialysis session, serum EPO levels increased by about 30% in comparison with pre dialysis values, whereas during Phase A they decreased by about 14%. In HD patients, EPO resistance may caused either by absorption of rHuEPO to the cuprophan M, or an increased release of cytokines that inhibit erythropoiesis, such as IL-1 beta, TNF-alpha, and IFN-gamma, and to a decrease in stimulatory cytokines such as IL-3, IL-6, and IL-10. These negative phenomena are reversed by the use of biocompatible dialysis techniques such as PFD.
 ...
PMID:Recombinant human erythropoietin resistance in hemodialysis. Effects of paired filtration dialysis. 936 Jan

Erythropoietin secretion was evaluated in the anaemia of chronic disorders in elderly patients, since it has been shown that this secretion is impaired in adults. We looked for a possible role of inflammatory cytokines: tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on erythropoietin production. The influence of nutritional status on the anaemia was also investigated. Erythropoietin secretion was significantly increased in elderly patients with anaemia of chronic disorders (ACD) and inversely correlated with haemoglobin concentrations in infectious and inflammatory diseases. Plasma TNF alpha levels were significantly enhanced only in cancerous patients, but no correlation could be established between TNF alpha and erythropoietin or haemoglobin. No noticeable increase of IL-1 beta levels was observed in ACD. These findings suggest that systemic TNF alpha or IL-1 beta are not involved in the erythropoietin response to ACD. Albumin levels were decreased in anaemic patients. Further investigations of the effects of a nutritional supplementation in elderly patients with ACD may be of interest.
 ...
PMID:Factors involved in the anaemia of chronic disorders in elderly patients. 938 84

Cadmium (Cd) is an environmental pollutant. Chronic exposure of humans to Cd results in various maladies, including anemia and altered immune function. Metallothionein (MT) has been proposed to play an important role in Cd detoxication. Thus, we hypothesized that intracellular MT protects against Cd-induced hematotoxicity and immunotoxicity. Control and MT-I/II knock-out (MT-null) mice were given s.c. injections of CdCl2 over a wide range of doses, 6 times/week for up to 10 weeks. Cd-induced anemia was evident after 5 weeks of exposure and progressed with time. MT-null mice were about 10 times more susceptible to Cd-induced anemia, as evidenced by decreased erythrocytes (25%), hemoglobin concentration (30%), and hematocrit (35%) after 10 weeks of Cd injections. Cd produced dose- and time-dependent increases in neutrophils (7x), along with a marked elevation of serum IL-1 beta (6x) and TNF-alpha (20x) levels. MT-null mice were more susceptible than controls to Cd-induced alterations in peripheral leukocytes and cytokine levels. Chronic exposure to Cd also produced dose- and time-dependent splenomegaly (5x), with loss of lymphoid structure, inflammation, hyperplasia, appearance of giant cells, and fibrosis. Thymus weights were decreased by Cd in a dose-dependent manner (60%). MT-null mice were also approximately 10 times more susceptible than controls to these lesions. In conclusion, the present study demonstrates that repeated injections of Cd produces hematotoxic and immunotoxic effects, and intracellular MT protects against these chronic Cd-induced effects.
 ...
PMID:Metallothionein-null mice are highly susceptible to the hematotoxic and immunotoxic effects of chronic CdCl2 exposure. 1049 73

Blood-dialyzer interaction in hemodialysis has the potential to activate mononuclear cells leading to the production of inflammatory cytokines. The extent of activation is dependent on the dialyzer material used and is considered an index of biocompatibility. Cytokines, such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6, may induce an inflammatory state and are believed to play a significant role in dialysis-related morbidity. The interleukin hypothesis suggests that the release of proinflammatory cytokines acts as an underlying pathophysiologic event in hemodialysis-related acute manifestations, such as fever and hypotension. Nevertheless, a cytokine overproduction may alter sleep pattern in chronic hemodialyzed patients, thus explaining the presence of sleep disorders in these patients. A potential role of cytokines in chronic-related morbidity has also been suggested. High levels of some inflammatory cytokines are often associated with anemia caused by hyporesponsiveness to erythropoietin. Cytokine production may also play a relevant role in bone remodeling by regulating osteoblast/osteoclast cell functions and parathyroid hormone (PTH). Finally, cytokine release may have a long-term deleterious effect on mortality of uremic patients by altering immune response and increasing susceptibility to infections. Bioincompatibility of dialytic membranes may also contribute to malnutrition in dialysis patients by increasing the monocyte release of catabolic cytokines such as TNF-alpha and IL-6. Bioincompatible dialytic treatment may induce an inappropriate monocyte activation and cytokine production, which, in turn, may mediate some of the immune and metabolic dysfunction associated with hemodialysis. The use of biocompatible dialytic membranes appears to reduce the monocyte activation and to improve the survival of hemodialysis patients.
 ...
PMID:Clinical relevance of cytokine production in hemodialysis. 1093 6

This study was conducted to investigate the efficacy of rebamipide against experimental colitis induced by dextran sulfate sodium (DSS) in a rat model of inflammatory bowel disease. Experimental colitis was induced in male Wistar rats by oral administration of 3% DSS solution for one week. The rats were provided with standard diet containing 0.105% rebamipide (160 mg/kg/day) for 1 week. In rats treated with rebamipide, clinical (body weight loss, bloody diarrhea, reduced physical activity, severe anemia, shortened colonic length, and perianal injury) and histopathological (pathological lesion score) findings of DSS colitis were significantly less than in rats with DSS colitis not treated with rebamipide. Rebamipide thus inhibited the induction of colitis. Rebamipide significantly reduced concentrations of both interleukin-1alpha and GRO/CINC-1 (IL-8-like substance) and cell infiltrates in colonic wall, in parallel with decreased activity of myeloperoxidase. It also reduced expression of IL-1 mRNA but did not influence expression of GRO/CINC-1 mRNA. The attenuation of colonic indices of colitis by rebamipide in this rat model suggests that this drug might have beneficial effects in the treatment of human ulcerative colitis. These effects of rebamipide are attributable to its inhibition of inflammatory cytokine-mediated granulocyte (neutrophil) infiltration into the colon.
 ...
PMID:Rebamipide, an antiulcer drug, prevents DSS-induced colitis formation in rats. 1100 13

Despite considerable progress in recent years in the understanding of the biology of multiple myeloma (MM), this disease remains incurable, although many new therapeutic approaches are under evaluation. The rapid development of recombinant technologies has permitted the production of large amounts of cytokines and growth factors, favoring the use of biotherapies also in this disease. Among these products, the interferons have been the most extensively used in clinical trials, giving the most promising results especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies, or to high dose chemotherapies followed by bone marrow (BM) or peripheral blood stem cell (PBSC) transplantation. However, more recently, a large number of cytokines and growth factors have been introduced in the clinical practice. Data of the use of erythropoietin have consistently demonstrated the role of this growth factor in ameliorating the grade of anemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Using hematopoietic growth factor in the mobilization of PBSC, the quantity of progenitor cells in the peripheral blood increased and the hematological toxicity of chemotherapy could be reduced. Despite the large amount of experimental data indicating a role for interleukins, as IL-2 and IL-6, in controlling tumor growth, there are only few clinical studies dealing with their use in MM. Results show that they arrest tumor progression rather than aid tumor regression, for this reason it appears that IL-2 and anti IL-6 antibodies should be investigated as maintenance therapy, in MM patients responding to chemotherapy. In the future it will be necessary to clarify for MM patients the role of other cytokines such as IL-1 beta and TNF alpha. A possible strategy to improve the clinical outcome of MM patients is to prevent the regrowth of residual tumor cells by establishing adoptive immunity at the stages of minimal residual disease previous obtained using chemotherapy. To this end a possible strategy is to induce an immune response against residual tumor cells by passive (using monoclonal antibodies) or active (using the idiotype expressed by malignant cells) immunotherapy.
 ...
PMID:[The role of biotherapy in multiple myeloma]. 1107 35

We previously reported that cyclic plasma perfusion suppressed lipolytic activity in malignant tumor-bearing animals and reversed their body weight loss. In this study we investigated the relation between this phenomenon and interleukin (IL)-1 alpha, IL-1 beta, IL-6, interferon-gamma, leukemia inhibitory factor, tumor necrosis factor-alpha, and anemia-inducing substance (AIS) in vitro by examining changes in their levels in the plasma of advanced ovarian cancer patients. When the patients' plasma was incubated with noncoated charcoal for one hour, its lipolytic activity decreased by 39.0 +/- 2.4%, which was similar to the results obtained with the plasma of healthy subjects. IL-1 alpha, IL-1 beta, interferon-gamma, leukemia inhibitory factor, and tumor necrosis factor-alpha did not adsorb the charcoal. IL-6 was 3.7% adsorbed, but this did not cause a significant difference (p = 0.131). Nor was the recombinant form of these cytokines adsorbed to the charcoal. AIS, however, was 98.1% adsorbed. These results indicate that AIS is strongly associated with the reduction in lipolytic activity by cyclic plasma perfusion through noncoated charcoal resin.
 ...
PMID:Anemia-inducing substance is related to elimination of lipolytic hyperactivity by cyclic plasma perfusion in human cancer cachexia. 1114 89


<< Previous 1 2 3 Next >>