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High-Dose Immune Suppression without Hematopoietic Stem Cells for Autoimmune Diseases
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Aplastic anemia is a potentially fatal bone marrow failure disorder that manifests as pancytopenia in conjuction with a hypocellular bone marrow. The disease is classified as moderate, severe and very severe. Severe aplastic anemia (SAA) is defined as bone marrow cellularity of less than 25% and markedly decreased values of at least two of three hematopoietic lineages (neutrophil count <0.5 × 109/L, platelet count <20 × 109/L and absolute reticulocyte count of <60,000). Very severe aplastic anemia satisfies the above criteria except the neutrophil count is <0.2 × 109, while moderate aplastic anemia is characterized by a hypocellular bone marrow but with cytopenias that do not meet the criteria for severe disease. The 2 year mortality rate with supportive care alone of patients with severe or very severe aplastic is roughly 80%,1 necessitating prompt therapeutic intervention. In contrast, moderate aplastic anemia is seldom life-threatening and in many instances requires no therapy.
Dithiocarbamate Compounds
Published in Fina P. Kaloyanova, Mostafa A. El Batawi, Human Toxicology of Pesticides, 2019
Fina P. Kaloyanova, Mostafa A. El Batawi
Functional disturbances of the CNS were found. Lung changes were diagnosed in 6.3% of the subjects; liver pathology, manifested by hepatocholecystitis and hepatitis of toxicochemical etiology, was established in 33%. Gastritis with a secretory deficit was frequently found. Hyperplasia or dysfunction of the thyroid gland was found in 7.1% of the persons investigated. The increased reticulocyte number in peripheral blood indicated tension and a good regeneration ability of the bone marrow. Leukopenia, due mainly to a decrease of neutrophils and eosinophils was also present. Mihail et al. observed similar effects along with qualitative changes in leukocytes, e.g., fatty degeneration in the cytoplasm and barely noticeable neutrophilic granularity.13 Anisocytosis and polysegmented neutrophiles with degenerative changes in nuclear structure were established in 78% of the subjects. In all cases significant fragmentation of the different neutrophiles segments was noted. Analogous changes were observed in lymphocytes.
In Vivo
Published in Nguyễn T. K. Thanh, Clinical Applications of Magnetic Nanoparticles, 2018
Antonella Antonelli, Mauro Magnani
The number of circulating RBCs must be adequate to supply oxygen to tissues. In the case of hypoxia, the haemopoietic stem cells in the bone marrow, stimulated by erythropoietin, go through various phases of development until the mature RBCs can be released into the bloodstream. The mature RBCs are released from the bone marrow into the blood at the reticulocyte stage and reticulocytes become fully functional RBCs after 1–2 days. This process of developing from erythropoietic bone marrow cells to mature RBCs takes only a few days.2 The final stage of maturation, when the cell lacks a nucleus, mitochondria and endoplasmic reticulum requires iron, vitamin B12 and folic acid. The enzymes within the RBC allow it to produce small amounts of energy. Glucose, which is the main energy source for these cells, is metabolized in the glycolytic pathway anaerobically to pyruvate or lactate, producing two molecules of adenosine triphosphate (ATP) per molecule of glucose that is used. Thus, glycolysis is the main energy pathway, and it is regulated in the hexokinase (Hk) and phosphofructokinase steps.3 The most important and functional component of RBCs is haemoglobin, which accounts for the oxygen carrying capacity of these cells. In addition to carrying oxygen, which is the main function of RBCs, they carry out the following functions: (1) conversion of carbon dioxide in bicarbonate, thanks to the enzyme carbonic anhydrase, and its transport to the lungs where it is expelled; and (2) control of pH in the bloodstream by acting as an acid-base buffer.
The need for an alternative method to determine intravascular volumes
Published in European Journal of Sport Science, 2018
L. M. Lobigs, P. Peeling, B. Dawson, Y. O. Schumacher
Within the Athlete’s Biological Passport (ABP), [Hb] is a primary marker used to detect illegal blood manipulation [e.g. blood transfusion or recombinant erythropoietin (rHuEPO) abuse to increase Hbmass and thus endurance performance] (Sottas, Robinson, & Saugy, 2010). The ABP relies on the longitudinal analysis of key biomarkers of erythropoiesis (e.g. [Hb], reticulocyte percentage, haematocrit (HCT)), and develops individualised reference limits, using Bayesian modelling, to detect blood manipulation. Initially, both intra-individual and inter-individual variance components are used to calculate preliminary (population-based) reference limits, however, as more individual information is provided, the reference calculations begin to solely rely upon intra-individual variance. Essentially, as more individual haematologic data are introduced to the ABP, more specific reference limits are developed. Currently, PV fluctuations represent the majority of variance associated with the concentration-based ABP markers (once the inter-individual components are removed) (Figure 1) (Sottas, Kapke, Vesterqvist, & Leroux, 2011).
Iron balance and iron supplementation for the female athlete: A practical approach
Published in European Journal of Sport Science, 2018
Charles R Pedlar, Carlo Brugnara, Georgie Bruinvels, Richard Burden
A closer consideration of the red blood cell morphology provides variables such as mean corpuscular haemoglobin (MCH), mean cell volume (MCV) and reticulocyte haemoglobin concentration (CHr or Ret-He) and this may have diagnostic utility for certain types of anaemia or latent anaemia. Additional biochemistry markers including serum transferrin receptor, serum iron, serum transferrin and transferrin saturation may also assist with the identification of iron deficiency (Archer & Brugnara, 2015). Assessment of total haemoglobin mass via the carbon monoxide rebreathing technique is also gaining favour as a tool for identifying iron deficiency and assessing responses to treatment in athletes (Garvican, Lobigs, Telford, Fallon, & Gore, 2011; Wachsmuth et al., 2015).
Environmental pollutant ENU induced leukemic NF-kB signaling amelioration by Eclipta alba in murine model
Published in International Journal of Environmental Health Research, 2022
Subhashree Bhattacharyya, Sujata Law
In leukemic group, an excessive decrease in body weight (11.33 ± 0.763 g) and physical appearance was noticed compared to control (31.66 ± 1.04 g; P = 0.001), hence indicating a strong side effect of the ENU induced leukemic mice. Conversely, slight positive changes in the body weight and physical condition was observed post treatment (16.15 ± 1.20 g; P = 0.06; Figure 1B). Increased survivability (Leukemia s Treated: 15.5 ± 1.29 vs 23 ± 2.16; P < 0.001) of treated group, as compared to the leukemic group hinted towards the preliminary signs of the anti-cancer effect of the extract (Figure 1C). Blood hemogram depicted significant leucocytosis in leukemic mice (32.14 ± 0.79 × 103 cells/mm3, P < 0.001) compared to control (7.66 ± 0.60 × 103 cells/mm3). Marked decrease by 1.3-fold in WBC count of treated group (24.06 ± 2.53 × 103 cells/mm3; P = 0.002) compared to leukemic mice was observed while confirming the preliminary effects of Eclipta alba (Figure 2C i–iv). Red blood cell (RBC) count and reticulocyte count was significantly elevated in leukemic group (11.08 ± 0.62 × 106 cells/mm3; P < 0.001 and 1.94 ± 0.03%; P < 0.001) compared to control (7.71 ± 0.33 × 106 cells/mm3 and 0.573 ± 0 .219%). Moreover, Eclipta alba significantly decreased both RBC and reticulocyte count (9.58 ± 0.52 × 106 cells/mm3; P = 0.026 and 1.58 ± 0.07%; P = 0.043) compared to leukemic group by 1.1 and 1.2-fold, respectively. Hemoglobin content was increased in Leukemic group (19.42 ± 0.38 g/dl; P < 0.001) compared to control (16.16 ± 0.52 g/dl). Significant decrease was observed in treated group (18.21 ± 0.20 g/dl; P = 0.022) compared to leukemic mice. Furthermore, a sharp rise in blast percentage was depicted in the blood film study of leukemic group (36.83 ± 1.607%), which significantly declined by 1.2-fold in treated group (30.66 ± 1.527%; P = 0.009), hence reinforcing the therapeutic potential of Eclipta alba extract. Hematological analysis revealed the occurrence of abnormal blasts, hypo-lobulated ring neutrophils and infiltration of dysplastic neutrophils in leukemic blood smear (Figure 2A i–v) indicative of leukemic onset. Peripheral blood count was regarded as the initial predictive tool to ascertain leukemic progression post treatment with Eclipta alba.