losartan-potassium and Osteoarthritis

We present a model of articular cartilage lesion formation to simulate the effects of cyclic loading. This model extends and modifies the reaction-diffusion-delay model by Graham et al., 2012 for the spread of a lesion formed though a single traumatic event. Our model represents 'implicitly' the effects of loading, meaning through a cyclic sink term in the equations for live cells. Our model forms the basis for in silico studies of cartilage damage relevant to questions in osteoarthritis, for example, that may not be easily answered through in vivo or in vitro studies. Computational results are presented that indicate the impact of differing levels of erythropoietin on articular cartilage lesion abatement.

Topics: Cartilage, Articular; Chondrocytes; Computer Simulation; Diffusion; Epoetin Alfa; Erythropoietin; Humans; Models, Biological; Models, Theoretical; Osteoarthritis; Recombinant Proteins; Stress, Mechanical

Injuries to articular cartilage result in the development of lesions that form on the surface of the cartilage. Such lesions are associated with articular cartilage degeneration and osteoarthritis. The typical injury response often causes collateral damage, primarily an effect of inflammation, which results in the spread of lesions beyond the region where the initial injury occurs.. We present a minimal mathematical model based on known mechanisms to investigate the spread and abatement of such lesions. The first case corresponds to the parameter values listed in Table 1, while the second case has parameter values as in Table 2. In particular we represent the "balancing act" between pro-inflammatory and anti-inflammatory cytokines that is hypothesized to be a principal mechanism in the expansion properties of cartilage damage during the typical injury response. We present preliminary results of in vitro studies that confirm the anti-inflammatory activities of the cytokine erythropoietin (EPO). We assume that the diffusion of cytokines determine the spatial behavior of injury response and lesion expansion so that a reaction diffusion system involving chemical species and chondrocyte cell state population densities is a natural way to represent cartilage injury response. We present computational results using the mathematical model showing that our representation is successful in capturing much of the interesting spatial behavior of injury associated lesion development and abatement in articular cartilage. Further, we discuss the use of this model to study the possibility of using EPO as a therapy for reducing the amount of inflammation induced collateral damage to cartilage during the typical injury response.. The mathematical model presented herein suggests that not only are anti-inflammatory cytokines, such as EPO necessary to prevent chondrocytes signaled by pro-inflammatory cytokines from entering apoptosis, they may also influence how chondrocytes respond to signaling by pro-inflammatory cytokines.

Topics: Apoptosis; Biological Transport; Cartilage, Articular; Chondrocytes; Computational Biology; Cytokines; Erythropoietin; Humans; Models, Theoretical; Osteoarthritis; Protein Interaction Mapping; Reactive Oxygen Species; Receptors, Erythropoietin; Signal Transduction; Tumor Necrosis Factor-alpha

Epidemiological studies report that a third of the cases of anaemia in older persons is unexplained. We compared erythropoietin (EPO), inflammatory markers and major comorbidities between older subjects with normal haemoglobin levels and those with different aetiologic forms of anaemia, including unexplained anaemia. Participants were a representative sample of 964 persons aged > or =65 years, with no evidence of bleeding, complete blood tests, and a complete blood count within 6 h of phlebotomy. Anaemia was defined as haemoglobin <130 g/l in men and 120 g/l in women, and classified as a result of chronic kidney disease, iron deficiency, chronic disease and B12/folate deficiency anaemia, or unexplained anaemia based on standard criteria. Of the 124 anaemic participants, 42 (36.8%) had unexplained anaemia. Participants with anaemia of chronic diseases had significantly higher interleukin-6 (IL-6) and C-reactive protein (CRP) levels, while those with unexplained anaemia had significantly lower CRP than non-anaemic controls. Iron deficiency anaemia was characterised by significantly higher EPO levels compared with other types of anaemia and normal haemoglobin, B12 and/or folate deficiency. Unexplained anaemia was characterised by unexpectedly low EPO and low lymphocyte count. Unexplained anaemia is associated with reduced kidney EPO response, low levels of pro-inflammatory markers and low lymphocyte counts.

Topics: Aged; Aging; Anemia; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus; Erythropoietin; Female; Health Surveys; Humans; Inflammation Mediators; Interleukin-6; Italy; Kidney Diseases; Lymphocyte Count; Male; Osteoarthritis; Parkinson Disease; Stroke; Tumor Necrosis Factor-alpha

Preoperative autologous donation (PAD) of blood and administration of recombinant human erythropoietin (Epoetin alfa) are two strategies for increasing red blood cell (RBC) mass preoperatively. The success of PAD depends primarily on the patient's ability to manufacture new RBCs before surgery to replace those removed during PAD. Red blood cell manufacture depends in turn on adequate supplies of iron and the increased renal production of endogenous erythropoietin following PAD. Successful PAD also requires adequate time for regeneration of predonated RBCs. Parenteral administration of Epoetin alfa causes a dose-dependent stimulation of RBC production. Its use has been studied as an adjunct to PAD and as a method to enhance endogenous erythropoiesis without PAD. Several studies suggest that administration of Epoetin alfa, begun several days before surgery, may stimulate erythropoiesis and help decrease the number of RBC transfusions required postoperatively. The precise role of Epoetin alfa in the surgical setting is not yet established, and optimal dosage regimens have not been determined.

Topics: Aged; Anemia; Blood Transfusion, Autologous; Drug Administration Schedule; Elective Surgical Procedures; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Female; Ferritins; Humans; Inflammation; Male; Osteoarthritis; Postoperative Complications; Preoperative Care; Recombinant Proteins