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

If one reviews the literature with zeal, it is increasingly apparent that few organs escape recruitment when IBD is chronic or progressive. Insights into mucosal pathophysiology have helped with understanding the more frequent extraintestinal manifestations, but the mechanisms attendant to the development of less common events (e.g. acute pancreatitis, concurrent gluten sensitive enteropathy, or active pulmonary disease) remain either poorly studied or obscure. It is particularly interesting, however, to read reports of abnormal pulmonary function, generally of the obstructive type, correlated to measurements of abnormal intestinal permeability in patients with either active pulmonary sarcoid or pulmonary involvement in Crohn's disease. It has been further speculated that similarities in the mucosal immune system of the lung and intestine are responsible for evidence of bronchial hyperreactivity in patients with active IBD. Finally, it is important to recognize that extensions of the inflammatory process are not restricted to the development of organ-based events but may be responsible for some of the most frequent systemic abnormalities detected in IBD patients. It is now also well confirmed that the cytokine environment in IBD can support activated coagulation and, in some clinical situations, overt vascular thrombosis. The cerebrovascular complications of IBD are well recognized and range from peripheral venous thrombosis to central stroke syndromes and pseudotumor cerebri. Reports of focal white matter lesions in the brains of patients with IBD or an increased incidence of polyneuropathy may be other clinical examples of regional microvascular clotting. Microvascular injury appears to be more ubiquitously present, with reports ranging from a speculated primary causative role (e.g., granulomatous vasculitis in the mesenteric circulation) to the utility of nailbed vasospasm, in Crohn's disease, as a clinical marker for disease activity. It is also reported that IL-6 suppression of erythropoietin production is a major feature of the chronic anemia seen in active IBD. Moreover, the capacity of peripheral monocytes from active IBD patients to secrete TNF and IL-8 is reported predictive for the degree of therapeutic response from recombinant erythropoietin. These collected observations constitute another excellent example of the symmetry between basic science and clinical utility. It is from the context of applied basic science that many future therapies will arise. Empiricism will lose much of its appeal as clinical observations will be increasingly translated into cellular language. Already in animal models, elemental diets diminish IL-6-related acute inflammatory injury, and reductions in dietary lipid alter the antigenicity of bacteria. Provocatively, in humans, unconfirmed reports have even associated diet therapy with the resolution of uveitis and pyoderma gangrenosum. It is likely that efforts will also be made to induce oral tolerance if specific triggering proteins are discovered or to alter bowel flora if such an arcane area of investigation becomes resurgent.
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PMID:Extraintestinal considerations in inflammatory bowel disease. 880 40

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.
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PMID:Rebamipide, an antiulcer drug, prevents DSS-induced colitis formation in rats. 1100 13

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.
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PMID:[Chronic experimental bacteremia in Yucatan micropigs]. 1164 22

Fifteen 8-week-old conventional pigs were selected from a farm where pigs were suffering from postweaning multisystemic wasting syndrome (PMWS). Ten of the animals were diseased pigs showing typical signs of PMWS (wasting and respiratory disorders) and positive for infection with porcine circovirus type 2 (PCV2), and the other five animals selected as controls were pen-mate, apparently healthy pigs. Blood samples and lymphoid tissues were taken from each animal for haematological, serological and histopathological studies. Also, cytokine mRNA expression of IL-1beta, IL-2, IL-4, IL-8, IL-10, IL-12p40 and IFN-gamma from inguinal and bronchial lymph nodes, tonsils, spleen and thymus was determined by semi-quantitative RT-PCR. Pigs suffering from PMWS showed severe alterations of haematological parameters such as anaemia, lymphopenia with decrease of CD8(+) and IgM(+) cells, monocytosis and neutrophilia. Also, extensive lymphocyte depletion and altered cytokine mRNA expression patterns were seen in most of the examined lymphoid organs. Those cytokine mRNA alterations were characterized by an overexpression of IL-10 mRNA in thymus and IFN-gamma mRNA in tonsils, and by decreases in the mRNA expression of several cytokines as IL-2 and IL-12p40 in the spleen, IL-4 in tonsils, and IFN-gamma, IL-10, IL-12p40 and IL-4 in inguinal lymph nodes. Also, the IL-10 mRNA overexpression was histologically associated with the thymic depletion and atrophy observed in PMWS pigs. In conclusion, the cytokine mRNA imbalance, specially the increased mRNA levels of IL-10 in the thymus, jointly with the histopathological and haematological disorders, are highly indicative of a T-cell immunosuppression, enhancing the notion that the immune system of PMWS-affected pigs is severely impaired.
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PMID:Cytokine mRNA expression profiles in lymphoid tissues of pigs naturally affected by postweaning multisystemic wasting syndrome. 1286 43

Increased systemic inflammation and an impaired immune response are features of adult chronic renal failure (CRF). These patients have increased rates of infection, cardiovascular disease, anemia, and malnutrition. We measured inflammatory and immunological markers in a group of children with pre-dialytic CRF. No prior studies have explored these markers even though children with non-dialysed CRF exhibit similar complications to those seen in adults with CRF. Blood was collected from children with mild, moderate, or severe CRF and an age-matched control group. Functional leukocyte subsets were determined using flow cytometry. Circulating levels of interleukin (IL)-1beta, IL-6, IL-8, IL-12, IL-10, and tumor necrosis factor-alpha were measured using a flow cytometric bead assay. Children with severe CRF showed significantly reduced total white cell count and absolute neutrophil and lymphocyte counts. Absolute numbers of CD3+/CD45RO+ memory T cells and CD3+/CD45RO+/CD62L+ memory Th2 cells were significantly reduced in all CRF groups versus controls. Children with severe CRF showed increased CD11b expression on neutrophils and monocytes. Some patients showed increases in pro-inflammatory cytokines that were not related to their level of residual renal function. As CD11b expression mediates leukocyte adhesion to vascular endothelium, upregulation may contribute to the increased endothelial dysfunction observed in children with CRF. L-selectin mediates extravasation of leukocytes into tissue and homing of peripheral blood lymphocytes to lymph nodes. The reduction in L-selectin may inhibit these actions and predispose patients to increased infection later in life. This is the first study to comprehensively investigate leukocyte functional molecules and inflammatory cytokine profiles in children with pre-dialytic CRF and provides new immunological evidence for the clinical manifestations associated with the disease.
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PMID:Changes in leukocyte subsets: clinical implications for children with chronic renal failure. 1562 18

Immediate hemolytic transfusion reactions (IHTR) occurred in the course of delayed hemolytic transfusion reactions (DHTR). An 84-year-old man had received a blood transfusion 20 years ago. Progressive anemia developed, because of continuous bleeding from a bladder tumor. He was transfused with concentrated red blood cells (CRC) which were Rh-E antigen negative, because he had anti-E antibodies (day 0). He received CRC on day 3, and underwent resection of bladder tumor on day 6. Although crossmatch-compatible CRCs were prepared for the operation, those were not required and were kept in a refrigerator in the ward. On day 9, when a CRC kept in the ward was transfused, he suddenly had a IHTR. In order to analyze a mechanism of IHTR, the anti-Jk(b) and anti-Di(b) antibodies, anti-HLA antibodies and the concentrations of inflammatory cytokines were measured in serum samples. The anti-Jk(b) and anti-Di(b) antibodies increased prior to IHTR experienced on day 9. The concentrations of IL-6 and IL-1beta increased from day 2, while the concentration of IL-8 increased from day 7. The anti-HLA class I antibody could be detected 2 days before IHTR. Thus, the anti-Jk(b) and anti-Di(b) antibodies induced the production of inflammatory cytokines and symptoms of DHTR and IHTR. The anti-HLA class I antibody could be produced in spite of using the filer for removing leukocytes, and may take part in the induction of IHTR. Further, blood products should be transfused soon after completing a crossmatch test in patients with anti-RBC alloantibodies.
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PMID:Mechanisms responsible for delayed and immediate hemolytic transfusion reactions in a patient with anti-E + Jk(b)+ Di(b) and anti-HLA alloantibodies. 1565 12

Macrophage migration inhibitory factor (MIF) has recently been implicated in the pathogenesis of malarial anaemia. However, field studies have reported contradictory results on circulating MIF concentrations in patients with clinically overt Plasmodium falciparum malaria. We determined plasma MIF levels over time in 10 healthy volunteers during experimental P. falciparum infection. Under fully controlled conditions, MIF levels decreased significantly during early blood-stage infection and reached a nadir at day 8 post-infection. A decrease in the number of circulating lymphocytes, which are an important source of MIF production, paralleled the decrease in MIF levels. Monocyte/macrophage counts remained unchanged. At MIF nadir, the anti-inflammatory cytokine interleukin (IL)-10, which is an inhibitor of T-cell MIF production, was detectable in only 2 of 10 volunteers. Plasma concentrations of the pro-inflammatory cytokines IL-8 and IL-1beta were only marginally elevated. We conclude that circulating MIF levels decrease early in blood-stage malaria as a result of the decline in circulating lymphocytes.
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PMID:A decrease of plasma macrophage migration inhibitory factor concentration is associated with lower numbers of circulating lymphocytes in experimental Plasmodium falciparum malaria. 1817 26

Pulmonary hypertension (PHT) develops in sickle cell disease (SCD) and is associated with high mortality. We previously showed that erythroid cells produce placenta growth factor (PlGF), which activates monocytes to induce proinflammatory cytochemokines, contributing to the baseline inflammation and severity in SCD. In this study, we observed that PlGF increased expression of endothelin-1 (ET-1) and endothelin-B receptor (ET-BR) from human pulmonary microvascular endothelial cells (HPMVECs) and monocytes, respectively. PlGF-mediated ET-1 and ET-BR expression occurred via activation of PI-3 kinase, reactive oxygen species and hypoxia inducible factor-1 alpha (HIF-1 alpha). PlGF increased binding of HIF-1 alpha to the ET-1 and ET-BR promoters; this effect was abrogated with mutation of hypoxia response elements in the promoter regions and HIF-1 alpha siRNA and confirmed by chromatin immunoprecipitation analysis. Furthermore, PlGF-mediated ET-1 release from HPMVECs and ET-BR expression in monocytes creates a PlGF-ET-1-ET-BR loop, leading to increased expression of MCP-1 and IL-8. Our studies show that PlGF-induced expression of the potent vasoconstrictor ET-1 and its cognate ET-BR receptor occur via activation of HIF-1 alpha, independent of hypoxia. PlGF levels are intrinsically elevated from the increased red cell turnover in SCD and in other chronic anemia (eg, thalassemia) and may contribute to inflammation and PHT seen in these diseases.
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PMID:Placenta growth factor augments endothelin-1 and endothelin-B receptor expression via hypoxia-inducible factor-1 alpha. 1865 Apr 59

Inflammatory cytokines are important predictors of cardiovascular mortality especially in patients with chronic kidney disease. Here we explored the relationship of anemia and epoetin treatment to inflammatory cytokine levels in patients with chronic kidney disease. One hundred non-dialysis patients with chronic kidney disease over 18 years of age were evenly split into anemic and non-anemic cohorts. Of the 50 anemic patients, 23 were receiving erythropoiesis stimulating agents treatments. Levels of tumor necrosis factor (TNF)-alpha were found to be significantly higher and serum albumin was significantly lower with trends towards higher interleukin (IL)-6 and IL-8 in anemic compared to non-anemic patients. Further analysis by multiple logistic regression found that anemic patients treated with erythropoiesis stimulating agents had significantly higher odds for the upper two quartiles for IL-6, IL-8 and TNF-alpha compared to non-anemic patients. Our study found that the anemia of chronic kidney disease was associated with up regulation of TNF-alpha, and possibly IL-6 and IL-8 along with increased levels of these proinflammatory cytokines in patients treated with epoetin.
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PMID:Association of anemia and erythropoiesis stimulating agents with inflammatory biomarkers in chronic kidney disease. 1875 92

Hepcidin is a key regulator of iron metabolism and a mediator of anemia in inflammation. Recent in vitro studies recognized prohepcidin as a type II acute phase protein regulating via interleukin-6. The aim of the present study was to investigate the time course of plasma prohepcidin after a large cardiac surgery in relation to IL-6 and other inflammatory parameters. Patients with chronic thromboembolic hypertension (n=22, males/females 14/8, age 51.9+/-10.2 years) underwent pulmonary endarterectomy using cardiopulmonary bypass and deep hypothermic circulatory arrest were included into study. Arterial concentrations of prohepcidin, IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and C-reactive protein were measured before/after sternotomy, after circulatory arrest, after separation from bypass, and then 12, 18, 24, 36, 48 h and 72 h after the separation from bypass. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. Pulmonary endarterectomy induced a 48% fall in plasma prohepcidin; minimal concentrations were detected after separation from cardiopulmonary bypass. Prohepcidin decline correlated with an extracorporeal circulation time (p<0.01), while elevated IL-6 levels were inversely associated with duration of prohepcidin decline. Postoperative prohepcidin did not correlate with markers of iron metabolism or hemoglobin concentrations within a 72-h period after separation from CPB. Prohepcidin showed itself as a negative acute phase reactant during systemic inflammatory response syndrome associated with a cardiac surgery. Results indicate that the evolution of prohepcidin in postoperative period implies the antagonism of stimulatory effect of IL-6 and contraregulatory factors inhibiting prohepcidin synthesis or increasing prohepcidin clearance.
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PMID:Plasma prohepcidin as a negative acute phase reactant after large cardiac surgery with a deep hypothermic circulatory arrest. 1909 40


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