The bone marrow (BM) responds to various diseases, including infections and hemorrhagic shock, by generating immune and blood cells. These cells are derived from a finite number of lymphohematopoietic stem cells (LHSC) close to the endosteal region of the BM. This study presumes that studies on LHSC involving proteomics, computational biology, and genomics could be aided by mathematical models. A theoretical model is developed to predict the responses of proliferating (P) nonproliferating (N) BM cells during acute blood loss when the Po2 in the BM is decreased. Hematopoietic responses were simulated for otherwise healthy individuals who have been subjected to various degrees of blood loss, as represented by 3%, 5%, and 20% O2. The model is robust and could predict hematopoietic activity in the area close to the endosteum during low Po2 as for acute blood loss. Steady-state hematopoiesis at oxygen saturation (80%) in healthy individuals could not be simulated with the equations. Functional assays tested the model with an in vitro assay of the most primitive LHSC (modified long-term culture-initiating cell assay, LTC-IC). The LTC-IC assay showed that 1%, 3% - 5%, and 20% O2 mediate significant increases in the proliferation of the most primitive BM progenitors, as compared with 80% O2. Thus, the functional studies show that the theoretical model is robust and could be used to gain insights into the biology of LHSC during different degrees of blood loss. The utility of such a model in surgical trauma is discussed.
The process by which hematopoietic stem cells (HSCs) residing in the bone marrow differentiate into blood cells is known as hematopoiesis. In the event of hemorrhagic shock, it is crucial for the HSC to rapidly differentiate into new committed erythroid progenitor cells that will give rise to erythrocytes. Growth factors and cytokines enhance the self-renewing process of HSC and are therefore crucial to restoring normal levels of blood cells in the body. Hematopoietic inducing agents (HIAs) such as the cytokine erythropoietin and granulocyte-colony-stimulating factor play a vital role in hematopoiesis because they are capable of inducing the proliferation of stem cells. The aim of the current study is to mathematically model the effect of HIA on the proliferation rate of hematopoietic stem cells at varying levels of oxygenation. The role of HIA was analyzed by constructing a set of coupled ordinary differential equations upon which mathematical analysis was performed. The model makes predictions of hematopoietic activity during low oxygen levels (ranging from 3% to 15%) similar to conditions ranging from acute blood loss to normal conditions.
BackgroundHematopoiesis is a complex process that encompasses both pro-mitotic and anti-mitotic stimuli. Pharmacological agents used in chemotherapy have a prominent anti-mitotic effect. The approach of inhibiting cell proliferation is rational with respect to the rapidly dividing malignant cells. However, it poses a serious problem with respect to cell proliferation of cell types required for the ‘house-keeping’ operations of the human body. One such affected system is hematopoiesis. Chemotherapy induced anemia is an undesired side effect of chemotherapy that can lead to serious complications. Patients exhibiting anemia or leukopenia during chemotherapy are frequently administered a hematopoietic inducing agent that enhances hematopoiesis.MethodsIn previous work, we derived a mathematical model consisting of a set of delay differential equations that was dependent on the effect of a hematopoietic inducing agent. The aim of the current work was to formulate a mathematical model that captures both the effect of a chemotherapeutic agent in combination with a hematopoietic inducing agent. Steady state solutions and stability analysis of the system of equations is performed and numerical simulations of the stem cell population are provided.ResultsNumerical simulations confirm that our mathematical model captures the desired result which is that the use of hematopoietic agents in conjunction with chemotherapeutic agents can decrease the negative secondary effects often experienced by patients.ConclusionsThe proposed model indicates that the introduction of hematopoietic inducing agents have clinical potential to offset the deleterious effects of chemotherapy treatment. Furthermore, the proposed model is relevant in that it enhances the understanding of stem cell dynamics and provides insight on the stem cell kinetics.
Over the last thirty years international migration, defined as voluntary plus involuntary movement of people across borders, has increased enormously. Approximately half of all international migration has taken place within the developing countries and the annual growth rate has been steeper compared to the one of developed countries. Surprisingly, the vast parts of the literature on international migration concentrate on the North-South migration, without considering the South-South one. The scope of this paper is threefold: to analyze the phenomenon of international migration within developing countries, to provide a theoretical framework to study its effect on the receiving countrys economic development and to assess some of its security implications.
Over the last twenty years, many contributions appeared on the relationship between working during school and academic performance using both quantitative and qualitative research methods. The obvious assumption is that a full time working student will show a lower academic performance relatively to a part time working student or a full time student. However, the empirical evidence doesnt seem to support this assumption because other variables affect the academic performance such as talent, motivation, ambition, and efficiency of studying time. We believe that the efficiency of studying time can be influenced by physical activity which paradoxically has been totally ignored in the literature. Thus, the scope of this paper is to examine the relationship between academic performance and working hours by explicitly considering the role of physical activity.
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