ABSTRACT
Most of the body iron is found within hemoglobin in red cells (the erythron), a smaller amount being distributed in other tissues such as muscles and in deposits. Iron homeostasis is a finely tuned process in which the most important regulators are probably the liver-derived hepcidin which blocks iron absorption and directs iron towards deposits and the recently discovered erythroblast-derived erythroferrone which inhibits hepcidin synthesis and therefore increases availability of iron for hemoglobin synthesis. Hepcidin secretion is increased by inflammatory cytokines and erythroferrone production increases when there is active, expanding erythropoiesis, for example after acute blood loss. We hypothesize that in pathological situations associated with erythroid precursor suppression (erythroblastopenia), anemia is the result of two major mechanisms: (1) direct erythroblast suppression leading to decreased production of red cells and (2) low iron availability due to high hepcidin levels arising as a result of low erythroferrone production. Additionally, infectious episodes and other inflammatory conditions that often complicate the course of these diseases may further promote hepcidin synthesis through increased cytokine production leading to even lower iron availability and a vicious circle of worsening anemia.
Subject(s)
Anemia/blood , Anemia/metabolism , Iron/blood , Peptide Hormones/metabolism , Cytokines/metabolism , Female , Hepcidins/chemistry , Homeostasis , Humans , Inflammation , Male , Models, BiologicalABSTRACT
We determined the hepatitis C virus (HCV) antibodies (anti-HCV) and the hepatitis B virus (HBV) surface antigen (HBsAg) in a cohort of 68 consecutive non-Hodgkin's lymphoma (NHL) patients diagnosed and treated in our institution between December 1997 and March 1999. 27 cases were diagnosed as low-grade, 33 as intermediate-grade, and eight as high-grade NHL. In 35 cases (51.4%) we found evidence of either HCV or HBV infection. Anti-HCV antibodies were found in 20 patients (29.5%) and HBsAg was found in 21 patients (30.8%). In six patients both anti-HCV and HBsAg were present. Anti-HCV were present in 12/27 low-grade NHL cases (44.4%) and in 8/41 intermediate/high-grade (aggressive) NHL cases (19.5%, P < 0.03). HBsAg was found in 10/27 low-grade NHL cases (37%) and in 11/41 aggressive NHL cases (26.8%). Evidence of liver disease, as reflected by elevated aminotransferases or typical alterations at liver biopsy, was present in eight patients. Cryoglobulins were present in six patients, all anti-HCV positive and with low-grade NHL. The prevalence of both HCV antibodies and HBsAg was significantly higher (P < 0.0001) in our NHL cases than in a sample of the general Romanian population, where the prevalence of anti-HCV was 4.9% and that of HBsAg was 6.3%. It is difficult to say whether either HCV or HBV had actually been involved in lymphomagenesis or if alpha-interferon treatment would be effective in this subset of patients.
Subject(s)
Hepatitis B/complications , Hepatitis B/epidemiology , Hepatitis C/complications , Hepatitis C/epidemiology , Lymphoma, Non-Hodgkin/virology , Adult , Aged , Cryoglobulinemia/immunology , Cryoglobulinemia/virology , Female , Hepatitis B/immunology , Hepatitis B Surface Antigens/analysis , Hepatitis C/immunology , Hepatitis C Antibodies/analysis , Humans , Male , Middle Aged , RomaniaABSTRACT
Serum cholesterol level as well as serum lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were measured in 65 samples of bone marrow blood and in matched peripheral blood taken from patients with various hematological diseases. As expected, serum LDH activities were higher and serum total cholesterol levels were lower in the bone marrow blood than in the blood taken from the cubital vein. More interestingly, an important increase of heat-labile ALP, but not of serum GGT, was found in the bone marrow blood obtained from patients characterized by a proliferating bone marrow. Actually, both LDH and ALP activities were obviously higher in the bone marrow blood of patients with megaloblastic anemia, myelodysplastic syndrome and chronic myeloid leukemia than in samples taken from patients with chronic lymphocytic leukemia, a disease characterized by a slower proliferation rate. While the expected increased LDH activity is the result of an accelerated turnover of bone marrow cells implying the release of this enzyme from the dividing and/or decaying cells, the much higher activity of the heat-labile alkaline phosphatase found in the bone marrow blood would reflect an enhanced local remodeling of bone structures, probably related to an expanded proliferating bone marrow. The lower serum cholesterol level in the bone marrow blood could be subsequent to an enhanced uptake of low density lipoproteins by specific receptors on the bone marrow cells.
Subject(s)
Alkaline Phosphatase/blood , Bone Marrow/chemistry , Cholesterol/blood , L-Lactate Dehydrogenase/blood , Adolescent , Adult , Aged , Biopsy, Needle , Bone Marrow/pathology , Female , Hematologic Diseases/blood , Humans , Male , Middle Aged , Statistics, Nonparametric , VeinsABSTRACT
When compared to values recorded in the 32 healthy control subjects, plasma protein C activity was found to be significantly decreased in the 29 patients with acute leukemia and especially in those considered to be in a critical condition. On the other hand, plasma antithrombin III activity did not significantly differ from the values noted in control subjects. The concomitantly occurring high plasma fibrinogen levels and low serum cholinesterase activity were highly suggestive for a switch of hepatic protein synthesis towards the production of acute phase proteins. It is therefore considered that in the absence of a consumption coagulopathy, changes affecting plasma protein C and antithrombin III should be related to a modified pattern of hepatic protein synthesis.
Subject(s)
Antithrombin III/analysis , Leukemia/blood , Protein C/analysis , Acute Disease , Adult , Cholesterol/blood , Cholinesterases/blood , Female , Fibrinogen/analysis , Humans , Male , Middle Aged , Reference ValuesABSTRACT
As compared to values recorded in 10 healthy normal-weight normolipidemic control subjects, serum cholesterol and apoprotein B levels as well as serum cholinesterase activity were found to be obviously decreased in the 28 patients with acute leukemia, the lowest levels being associated with the worst prognosis. The values of the above-mentioned biochemical variables in the 21 patients with chronic disorders (13 with chronic myeloproliferative disease and 8 with chronic lymphocytic leukemia) were not as low as in patients with acute leukemia. It should however be mentioned that in patients with chronic myelogenous leukemia, the lowest levels of serum cholesterol were correlated with a large tumor burden as assessed by a score taking into account for clinical and hematologic parameters. It is concluded that hypocholesterolemia could be regarded as a factor of adverse prognosis in hematologic malignancies, being probably the result of both enhanced catabolism of low density lipoproteins and impaired hepatic lipoprotein synthesis.