losartan-potassium and Hepatitis

The development and widespread availability of recombinant products will effect blood centers through reduced product use, replacement of current products, and novel applications of new products. The greatest amount of clinical experience to date has dealt with the use of recombinant human erythropoietin (r-HuEPO) in the treatment of anemia in end-stage renal failure. Data also support its use in anemia associated with acquired immune deficiency syndrome (AIDS), cancer, and chronic inflammatory diseases. This article will focus on the effect of erythropoietin on the demand for erythrocyte use.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Blood Transfusion; Erythrocyte Transfusion; Erythropoietin; Hepatitis; Humans; Recombinant Proteins; Transfusion Reaction

Topics: Anabolic Agents; Androgens; Anemia, Aplastic; Bone Marrow Transplantation; Erythropoiesis; Erythropoietin; Hematopoietic Stem Cells; Heme; Hepatitis; Humans; Iron; Leukemia; Transplantation, Homologous; Tuberculosis, Miliary

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anabolic Agents; Anemia, Aplastic; Bone Marrow; Bone Marrow Transplantation; Capillaries; Deficiency Diseases; Erythropoietin; Hepatitis; Humans; Lectins; Splenectomy; Testosterone

AMP activated protein kinase (AMPK) is a pivotal metabolic regulatory enzyme and novel target of controlling inflammation. Our previous studies had demonstrated that 5-amino-4-imidazolecarboxamide riboside (AICAR), an AMPK activator, attenuated lipopolysaccharide (LPS)/D-galactosamine (D-gal)-induced fulminant hepatitis via suppressing inflammatory response. Since inflammation usually activates the coagulation response and aggravates inflammation-induced tissue injury, the present study was to explore the effects of AICAR on inflammation-induced activation of coagulation. Male BALB/c mice received LPS/D-gal intraperitoneal injection were used as fulminant hepatitis model. Western blot was used to detect tissue factor (TF) and hypoxia-inducible factor 1α (HIF-1α) protein expressions in hepatic tissue, as well as nuclear factor kappa B (NF-κB) p65 translocation into the nucleus. Real-time quantitative PCR was used to analyze erythropoietin (EPO) mRNA expression level. Lactic acid (LA) level in hepatic tissue was detected by kit. The results showed that LPS/D-gal induced the enhanced expression of TF, elevation of NF-κB p65 nuclear translocation, up-regulation of HIF-1α and EPO expressions, and increased LA level. These above alterations could be suppressed by AICAR. These results suggest that AICAR may down-regulate LPS/D-gal-induced TF expression (coagulation activity), and relieve hepatic hypoxia and metabolic disorder via suppressing the activity of NF-κB, which may be a novel mechanism of the beneficial effect of AICAR on LPS/D-gal-induced fulminant hepatitis.

Topics: Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Down-Regulation; Erythropoietin; Hepatitis; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Lipopolysaccharides; Male; Mice; NF-kappa B; Thromboplastin; Up-Regulation

Metformin is a widely‑used antidiabetic drug with hypoglycemic activity and previously described anti‑inflammatory properties. Previous studies have demonstrated that metformin attenuates endotoxic hepatitis, however the mechanisms remain unclear. Inflammation and coagulation are closely associated pathological processes, therefore the potential effects of metformin on key steps in activation of the coagulation system were further investigated in endotoxic hepatitis induced by lipopolysaccharide/D‑galactosamine (LPS/D‑Gal). The current study demonstrated that treatment with metformin significantly suppressed the upregulation of tissue factor and plasminogen activator inhibitor‑1 in LPS/D‑Gal‑exposed mice. In addition, a reduction in the expression of interleukin 6 and inhibition of nuclear translocation of nuclear factor‑κB were observed. These data indicate that the LPS/D‑Gal‑induced elevation of the stable protein level of hypoxia inducible factor 1α, the mRNA level of erythropoietin, vascular endothelial growth factor and matrix metalloproteinase‑3, and the hepatic level of lactic acid were also suppressed by metformin. The current study indicates that the suppressive effects of metformin on inflammation‑induced coagulation may be an additional mechanism underlying the hepatoprotective effects of metformin in mice with LPS/D‑Gal‑induced fulminant hepatitis.

Topics: Animals; Anti-Inflammatory Agents; Blood Coagulation; Disease Models, Animal; Erythropoietin; Galactosamine; Hepatitis; Hypoglycemic Agents; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Interleukin-6; Lactic Acid; Lipopolysaccharides; Liver; Matrix Metalloproteinase 3; Metformin; Mice; NF-kappa B; Plasminogen Activator Inhibitor 1; RNA, Messenger; Thromboplastin; Up-Regulation; Vascular Endothelial Growth Factor A

To understand the molecular mechanisms underlying compound-induced hemangiosarcomas in mice, and therefore, their human relevance, a systems biology approach was undertaken using transcriptomics and Causal Network Modeling from mice treated with 2-butoxyethanol (2-BE). 2-BE is a hemolytic agent that induces hemangiosarcomas in mice. We hypothesized that the hemolysis induced by 2-BE would result in local tissue hypoxia, a well-documented trigger for endothelial cell proliferation leading to hemangiosarcoma. Gene expression data from bone marrow (BM), liver, and spleen of mice exposed to a single dose (4 h) or seven daily doses of 2-BE were used to develop a mechanistic model of hemangiosarcoma. The resulting mechanistic model confirms previous work proposing that 2-BE induces macrophage activation and inflammation in the liver. In addition, the model supports local tissue hypoxia in the liver and spleen, coupled with increased erythropoeitin signaling and erythropoiesis in the spleen and BM, and suppression of mechanisms that contribute to genomic stability, events that could be contributing factors to hemangiosarcoma formation. Finally, an immunohistochemistry method (Hypoxyprobe) demonstrated that tissue hypoxia was present in the spleen and BM. Together, the results of this study identify molecular mechanisms that initiate hemangiosarcoma, a key step in understanding safety concerns that can impact drug decision processes, and identified hypoxia as a possible contributing factor for 2-BE-induced hemangiosarcoma in mice.

Topics: Animals; Bone Marrow; Cell Cycle; Cell Differentiation; Cell Hypoxia; Cell Proliferation; Cell Transformation, Neoplastic; Disease Models, Animal; Endothelial Cells; Erythropoiesis; Erythropoietin; Ethylene Glycols; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genomic Instability; Hemangiosarcoma; Hematopoietic Stem Cells; Hemolysis; Hepatitis; Immunohistochemistry; Liver; Macrophage Activation; Male; Mice; Models, Biological; Signal Transduction; Spleen; Systems Biology; Time Factors

A 9-year-old girl who had hepatitis-associated aplastic anemia was treated intermittently with methylprednisolone pulse therapy and growth factors (granulocyte-colony stimulating factor (G-CSF), recombinant human erythropoietin (rhEpo) and cyclosporin A (CyA) for over two years. At this time, there was hematological improvement, but chromosome analysis revealed monosomy 7. After six months, there was progression to myelodysplastic syndrome (MDS) (stage in refractory anemia of excess blasts (RAEB)) with monosomy 7, monosomy 6, marker chromosome and with hematological deterioration. She received bone marrow (1.57 x 10(5) cells kg(-1) (patient body weight)) plus cord blood cell (0.3 x 10(7) cells kg(-1) (patient body weight)) transplantation from her brother, 2 years and 7 months after the diagnosis of hepatitis-associated aplastic anemia. Engraftment was achieved after two weeks, and acute graft-versus-host disease occurred in a mild form after four weeks. Hematological remission has been continuous for 20 months after bone marrow transplantation. Transformation of hepatitis-associated aplastic anemia to MDS with the monosomy 7, monosomy 6 and marker chromosome in this patient was considered to have been related to the administration of high doses of immunosuppressive drugs plus growth factors.

Topics: Anemia, Aplastic; Bone Marrow Transplantation; Child; Chromosomes, Human, Pair 6; Chromosomes, Human, Pair 7; Cord Blood Stem Cell Transplantation; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Growth Substances; Hepatitis; Humans; Immunosuppressive Agents; Monosomy; Myelodysplastic Syndromes; Recombinant Proteins; Transplantation, Homologous; Treatment Outcome

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Erythropoietin; Hematocrit; Hepatitis; Humans; Liver; Male; Polycythemia; Renal Dialysis

A 45-year-old woman who had undergone bilateral nephrectomy and splenectomy and who had been under haemodialysis since 1966 developed non-A non-B cytolytic hepatitis in October, 1978. Her haematocrit and haemoglobin levels had been stable at 39% and 6 g/dl respectively for more than one year when, two months after the onset of hepatitis, spontaneous improvement of anaemia was observed. This persisted side-by-side with hepatic cytolysis until march, 1980. At that time, the total red cell volume was 24% above normal, the haematocrit was 41% and the haemoglobin level 13 g/dl. It was than that serum erythropoietin was measured and found to be 82 mU/ml (normal values : 5-10 mU/ml). During the following months hepatic cytolysis and polycythaemia gradually subsided, and the serum erythropoietin level decreased. This case suggests that extrarenal erythropoietin can be secreted by the liver in anephric adults with uraemia, that hepatocytes undergoing regeneration after cytolysis in adults may have the same capability or erythropoietin secretion as in foetuses, and that in some haemodialyzed patients bone marrow responses to erythropoietin remains unaltered.

Topics: Erythropoietin; Female; Hepatitis; Humans; Liver; Middle Aged; Nephrectomy; Polycythemia; Renal Dialysis; Splenectomy

Topics: Anemia, Hemolytic; Cell Membrane; Erythropoiesis; Erythropoietin; Ethanol; Folic Acid; Hematopoiesis; Hematopoietic Stem Cells; Hepatitis; Humans; Intestinal Absorption; Iron; Megakaryocytes; Mitochondria; Mononuclear Phagocyte System; Nutrition Disorders; Pancreatitis; Pyridoxal Phosphate

Three cases of adult pure red cell aplasia (PRCA) ARE REPORTED. All patients proved refractory to various combinations of androgens and corticosteroids. The first case, harboring a thymoma, showed a complete clinical remission following cyclophosphamide therapy. The second and third responded similarly to either a combined cyclophosphamide + antilymphocyte globulin (ALG) treatment or to ALG administration preceded by a small dosage of cyclophosphamide, which had proved ineffective when administered alone. Serum IgG inhibitors to erythropoiesis were demonstrated in all cases by means of in vivo and/or in vitro techniques. The inhibitor(s), although directed against the erythroid marrow in both the first and third patients (PRCA type A), apparently functioned as an antibody to circulating erythropoientin (Ep) in the second case (PRCA type B). The inhibitor(s) was always absent in postremission samples. Additionally, experimental models for both types of human PRCA were established in normal rodents. The present studies support the contention that adult PRCA is an autoimmune disease. The therapeutic role of cytotoxic-immunodepressive agents in PRCA patients is confirmed. It is emphasized that ALG may represent an additional therapeutic tool in cases resistant to cyclophosphamide and/or steroids. In addition, cyclophosphamide proved effective in a patient harboring a thymoma not amenable to surgery. Finally, it is postulated that IgG serum autoantibodies, directed against either an early erythroid precursor (PRCA type A) or, more rarely, circulating Ep (PRCA type B), play a major role in the pathogenesis of the disease.

Topics: Aged; Anemia, Aplastic; Antibodies, Antinuclear; Antilymphocyte Serum; Autoantibodies; Blood Transfusion; Bone Marrow Examination; Cyclophosphamide; Dexamethasone; Diabetic Coma; Erythrocytes; Erythropoietin; Female; Heart Failure; Hematocrit; Hepatitis; Humans; Immunoglobulin G; Iron; Male; Middle Aged; Radiography, Thoracic; Sarcoma, Kaposi; Serum Globulins; Skin Manifestations; Thymoma

Topics: Agranulocytosis; Anemia, Aplastic; Anemia, Macrocytic; Bone Marrow Examination; Bone Neoplasms; Breast Neoplasms; Dihydrotestosterone; Erythropoiesis; Erythropoietin; Female; Hepatitis; Humans; Iron; Iron Radioisotopes; Male; Oxymetholone; Prednisolone; Sepsis; Transfusion Reaction