Modelling hematopoiesis mediated by growth factors with applications to periodic hematological diseases

Hematopoiesis is a complex biological process that leads to the production and regulation of blood cells. It is based upon differentiation of stem cells under the action of growth factors. A mathematical approach of this process is proposed to carry out explanation on some blood diseases, characterized by oscillations in circulating blood cells. A system of three differential equations with delay, corresponding to the cell cycle duration, is analyzed. The existence of a Hopf bifurcation for a positive steady-state is obtained through the study of an exponential polynomial characteristic equation with delay-dependent coefficients. Numerical simulations show that long period oscillations can be obtained in this model, corresponding to a destabilization of the feedback regulation between blood cells and growth factors. This stresses the localization of periodic hematological diseases in the feedback loop

Roles of Dietary Cobalt and Administration of Mixed Rumen Bacteria in Regulating Hematological Parameters of Pre-weaning Twin Lambs

Cobalt (Co) is required by rumen microorganism for vitamin B12 synthesis. Vitamin B12 is an important cofactor for methionine synthesis and gluconeogenesis. In young ruminants up to 6–8 wk old, the rumen has not been completely developed and rumen microorganisms are not ready to supply vitamin B12. The aim of this research was to determine the potency of mixed rumen bacteria and dietary supplementation of Co and its effect on plasma glucose, blood minerals (Co, Fe, and Zn) concentrations, and hematology of pre-weaning twin lambs. Twelve one month-old local twin lambs were assigned to 4 groups in a randomized complete block design. Lambs were fed cow milk at 10% body weight, adjusted weekly for 80 d. Mixed rumen bacteria were offered at 15 mL/d (8.295x1010 cfu). Dietary treatments were: 1) basal diet (Control), 2) basal diet + 1 mg/kg DM cyanocobalamin (VitB12) and 3) basal diet + 1 mg/kg DM of Co + administration of 15 mL mixed rumen bacteria (CoBac). There were no treatment effects on neither plasma glucose and blood mineral concentrations nor hematological profiles. This study demonstrated that pre-weaning twin lambs are not responsive to supplementation of Co and administration of mixed rumen bacteria

Subchronic Toxicity of Green Algae (Spyrogyra SP.) Ethanolic Extract on Hematologic Parameters

Green Algae, an organism with active substance such as phytomelatonin, has potential to be developed as Indonesian traditional medicine. As the long term addition of Green Algae ethanol extract (Ekstrak etanol ganggang hijau, EEGH) influences the hematology system, in this paper, the safety test was done to ensure the safety of its use through subchronic toxicity test of EEGH on the hematology parameters of Wistar rats. The test group consisted of three groups treated with EEGH 100 mg/kg, 200 mg/kg, and 400 mg/kg, while the control group was given by 0.5% CMC-Na, with 8 rats each respectively. By using blood samples taken from orbital sinus on the 29th day, common hematologic parameters (erythrocytes, leukocytes, and hemoglobin level), the parameters of hemostasis (platelets, pT, aPTT, BT) and immune parameters (Differential Leukocytes Counts include neutrophils segment, lymphocytes, monocytes, and eosinophils) were finally observed and showed that the 28 days-addition of EEGH increase the hematological parameters of Wistar rats

Efficacy of lactoferrin oral administration in the treatment of anemia and anemia of inflammation in pregnant and non-pregnant women: an interventional study

The discovery of the ferroportin-hepcidin complex has led to a critical review on the treatment of anemia and anemia of inflammation (AI). Ferroportin, the only known mammalian iron exporter from cells to blood, is negatively regulated by hepcidin, a hormone peptide able to bind to ferroportin, leading to its degradation. Therefore, new efficient therapeutic interventions acting on hepcidin and ferroportin are imperative to manage anemia and AI. Bovine milk derivative lactoferrin (bLf), a glycoprotein able to chelate two ferric ions per molecule, is emerging as a natural anti-inflammatory substance able to modulate hepcidin and ferroportin synthesis through the down-regulation of interleukin-6 (IL-6). Here, an interventional study (ClinicalTrials.gov Identifier: NCT01221844) was conducted by orally administering 100 mg of 20-30% iron-saturated bLf (corresponding to 70-84 μg of elemental iron) twice a day. This treatment was compared with the Italian standard therapy, consisting in the oral administration of 329.7 mg of ferrous sulfate once a day (corresponding to 105 mg of elemental iron). Treatments were carried out on 29 anemic women with minor ß-thalassemia (20 pregnant and 9 non-pregnant), 149 women with hereditary thrombophilia (HT) (70 pregnant and 79 non-pregnant) affected by AI and 20 anemic pregnant women suffering from various pathologies. In anemic pregnant and non-pregnant women with minor ß-thalassemia, presenting undetectable hepcidin levels, differently from ferrous sulfate management, bLf decreased IL-6 (from 25 ± 8 to 6 ± 3 pg/ml) and increased total serum iron (TSI) (from 54 ± 17 to 80 ± 9 μg/dl). BLf was also more efficient than ferrous sulfate in AI treatment in HT pregnant and non-pregnant women by decreasing both serum IL-6 (from 89 ± 8 to 58 ± 6 pg/ml) and hepcidin (from 115 ± 23 to 65 ± 10 ng/ml), thus increasing hematological parameters, such as the number of red blood cells (RBCs), the concentration of hemoglobin, TSI and serum ferritin. BLf was also efficient in treating anemia in other pathological pregnancies. Taken together all the results, bLf, showing a greater benefit and efficacy than the standard ferrous sulfate management, can be considered as a promising compound in treating anemia and AI through its ability to down-regulate IL-6, thus restoring ferroportin-mediated iron export from cells to blood in a hepcidin-dependent or independent way

Predictive value of hematological and phenotypical parameters on postchemotherapy leukocyte recovery

Background: Grade IV chemotherapy toxicity is defined as absolute neutrophil count <500/μL. The nadir is considered as the lowest neutrophil number following chemotherapy, and generally is not expected before the 7th day from the start of chemotherapy. The usual prophylactic dose of rHu-G-CSF (Filgrastim) is 300 μg/day, starting 24-48 h after chemotherapy until hematological recovery. However, individual patient response is largely variable, so that rHu-G-CSF doses can be different. The aim of this study was to verify if peripheral blood automated flow cytochemistry and flow cytometry analysis may be helpful in predicting the individual response and saving rHu-G-CSF. Methods: During Grade IV neutropenia, blood counts from 30 cancer patients were analyzed daily by ADVIA 120 automated flow cytochemistry analyzer and by Facscalibur flow cytometer till the nadir. "Large unstained cells" (LUCs), myeloperoxidase index (MPXI), blasts, and various cell subpopulations in the peripheral blood were studied. At nadir rHu-G-CSF was started and 81 chemotherapy cycles were analyzed. Cycles were stratified according to their number and to two dose-levels of rHuG-CSF needed to recovery (300-600 vs. 900-1200 μg) and analyzed in relation to mean values of MPXI and mean absolute number of LUCs in the nadir phase. The linear regressions of LUCs % over time in relation to two dose-levels of rHu-G-CSF and uni-multivariate analysis of lymphocyte subpopulations, CD34+ cells, MPXI, and blasts were also performed. Results: In the nadir phase, the increase of MPXI above the upper limit of normality (>10; median 27.7), characterized a slow hematological recovery. MPXI levels were directly related to the cycle number and inversely related to the absolute number of LUCs and CD34 +/CD45+ cells. A faster hematological recovery was associated with a higher LUC increase per day (0.56% vs. 0.25%), higher blast (median 36.7/μL vs. 19.5/μL) and CD34+/CD45+ cell (median 2.2/μL vs. 0.82/μL) counts. Conclusions: Our study showed that some biological indicators such as MPXI, LUCs, blasts, and CD34 +/CD45+ cells may be of clinical relevance in predicting individual hematological response to rHu-G-CSF. Special attention should be paid when nadir MPXI exceeds the upper limit of normality because the hematological recovery may be delayed. © 2009 Clinical Cytometry Society

Sensitivity and specificity of detection methods for erythropoietin doping in cyclists

Recombinant human erythropoietin (rHuEPO) is used as doping a substance. Anti-doping efforts include urine and blood testing and monitoring the athlete biological passport (ABP). As data on the performance of these methods are incomplete, this study aimed to evaluate the performance of two common urine assays and the ABP. In a randomized, double-blinded, placebo-controlled trial, 48 trained cyclists received a mean dose of 6000 IU rHuEPO (epoetin beta) or placebo by weekly injection for eight weeks. Seven timed urine and blood samples were collected per subject. Urine samples were analyzed by sarcosyl-PAGE and isoelectric focusing methods in the accredited DoCoLab in Ghent. A selection of samples, including any with false presumptive findings, underwent a second sarcosyl-PAGE confirmation analysis. Hematological parameters were used to construct a module similar to the ABP and analyzed by two evaluators from an Athlete Passport Management Unit. Sensitivity of the sarcosyl-PAGE and isoelectric focusing assays for the detection of erythropoietin abuse were 63.8% and 58.6%, respectively, with a false presumptive finding rate of 4.3% and 6%. None of the false presumptive findings tested positive in the confirmation analysis. Sensitivity was highest between 2 and 6 days after dosing, and dropped rapidly outside this window. Sensitivity of the ABP was 91.3%. Specificity of the urine assays was high; however, the detection window of rHuEPO was narrow, leading to questionable sensitivity. The ABP, integrating longitudinal data, is more sensitive, but there are still subjects that evade detection. Combining these methods might improve performance, but will not resolve all observed shortcomings

Toxicological Study Employing Repeated Doses of Garcinielliptone FC, a Polyisoprenylated-Benzophenone Isolated from Seed of Platonia Insignis Mart

The major constituent from the hexane extract of the seeds of P. insignis is GFC (garcinielliptone FC). Doses of 25, 50and 75 mg/kg of GFC were aseptically suspended in 0.05% Tween 80 dissolved in 0.9% saline (vehicle) and orally administered for30, 90 and 120 consecutive days to adult Swiss mice. In this work, the repeated oral administration, in animals of both sexes,demonstrates that this compound is not able to induce mortality and/or behavioral changes in adult mice. In addition, body weightgain, feed intake and disposal of excreta were not altered by the administration of this compound with repeated doses. Furthermore,no differences in weight and macroscopic structure of the brain, liver, kidney, lung, heart and spleen between groups of male andfemale adult mice were observed after treatment. During the periods of treatment, GFC produced no significant changes onhaematological and biochemical parameters in male and female mice treated with all doses used. The aim of this study was toinvestigate the toxicological potential of GFC through behavioral, hematological, biochemical and morphological parameters inanimals in order to ensure the safe use of Platonia insignis in folk medicine.Fil: Silva, Ana P.. Federal University of Piauí; BrasilFil: Filho, José Carlos C. L. S.. North Union of Parana; BrasilFil: da Costa Júnior, Joaquim S.. Federal Institute of Piauí; BrasilFil: Peláez, Walter José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Faillace, Martín Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Falcão Ferraz, Alexandre de B.. Lutheran University of Brazil; BrasilFil: David, Jorge M.. Institute Of Chemistry, Federal University Of Bahia; Brasil. Universidade Federal da Bahia; BrasilFil: Freitas, Rivelilson M.. Federal University of Bahia; Brasi