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Bioelectric and Biomagnetic Signal Analysis
Published in Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam, Introduction to Computational Health Informatics, 2019
Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam
Low concentration of sodium in blood is called hyponatremia. A low concentration of Na+ ion causes the lack of cell-depolarization resulting into lack of contraction of atria and ventricles reducing the blood-flow in the body. The body-cells get deoxygenated and lack necessary nutrients. Deoxygenation of body-cells leads to confusion, nausea and headaches. The PQ-interval and QRS-complex get elongated showing slow depolarization caused by lack of sodium concentration outside cells during depolarization. Severe case of hyponatremia can result into first-degree of AV-block and later turn into second-degree and third-degree AV-block.
Answers
Published in Andrew Schofield, Paul Schofield, The Complete SAQ Study Guide, 2019
Andrew Schofield, Paul Schofield
Sickle-cell disease is an autosomal recessive disease most commonly found in Africans. It is called sickle-cell disease when it is in its homozygous state (Hb SS) and is called sickle-cell trait in the heterozygous state (Hb AS). Different types of crises can present, most serious of whi ch is acute chest syndrome, which is associated with a relatively high mortality rate. After deoxygenation, the red blood cells become stiff and sickle-shaped, which can lead to vaso-occlusion of the small blood vessels causing the crises. With long-standing disease, patients can go through ‘autosplenectomy’ because of repeated infarcts in the spleen. This leaves them vulnerable to encapsulated bacteria, so they are given prophylactic penicillin. Sicklecell disease is protective against malaria.
The HbS Containing Cell
Published in Ronald L. Nagel, Genetically Abnormal Red Cells, 2019
Ronald L. Nagel, Mary E. Fabry
Rotman et al.168 and Harrington et al.169 have found that deoxy SS cells oxygenated at a rate slower than AA cells. In addition, Harrington et al.169 found that the half times of deoxygenation were normal. Low temperatures and an antisickling agent, butylurea, normalized the oxygenation rate. This data has been interpreted to mean that the physical basis for the slow kinetics is polymer formation, either because of intrinsic changes of the oxygenation rate constants secondary to polymer restrains and/or ligand diffusion problems through the gelled domains in the cytosol. Methodological problems with ligand kinetic measurements in stopped flow apparatus171 should deter the acceptance of the absolute numbers for the oxygenation and deoxygenation rates, but the relative changes are significant. The rates appear, in any case, to be fast enough not to pose additional problems to SS cells.
Emerging drugs for the treatment of sickle cell disease: a review of phase II/III trials
Published in Expert Opinion on Emerging Drugs, 2022
Jules M. Ross, Stéphanie Forté, Denis Soulières
Pyruvate kinase activation constitutes another competitive strategy in the prevention of deoxygenation. Pyruvate kinase-R (PKR) is a key enzyme in RBC metabolism, generating adenosine triphosphate (ATP) to maintain energy homeostasis, membrane integrity and deformability. It modulates 2,3-DPG levels in erythrocyte, an important intermediate in the glycolytic pathway that decreases hemoglobin oxygen affinity and thus contributes to HbS polymerization in SCD [50]. PKR was shown to be decreased in transgenic mice and sickle cell subjects [50]. Two drugs acting through PKR activation were granted Orphan Drug Status for SCD by FDA in 2020. Etavopivat (FT-4202) administration in 130 healthy individuals and SCD subjects was followed with decreased hemolysis through reduction in 2,3-DPG in healthy red blood cells and improved hemoglobin-oxygen affinity on sickle cells treated with the drug ex-vivo [51]. Of the 15 patients receiving etavopivat during this phase I study, hemoglobin increase >1 g/dL from baseline was experienced by 73% (11/15) of patients and there was a significant decline in hemolysis markers. Mitapivat (AG-348), now FDA-approved for congenital PK deficiency, displayed similar effects on 2,3- DPG in a proof-of-concept phase I study with SCA patients (HbSS only), with improvement in hemolysis and 56% (9/16) of patients reaching the same hemoglobin response [52]. The industry has already moved to phase II/III trials with HIBISCUS (etavopivat) and RISE UP (mitapivat) studying the impact of these agents on anemia and annualized VOCs in SCD (NCT04624659, NCT05031780).
The P50 value detected by the oxygenation-dissociation analyser and blood gas analyser
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Zongtang Chu, Ying Wang, Guoxing You, Quan Wang, Ning Ma, Bingting Li, Lian Zhao, Hong Zhou
Three milligrams of haemoglobin or an equal volume of RBCs were used to calculate haemoglobin content according to formula (2) after dilution in 4 ml of BLOODOX-Solution buffer mixed with 20 μL bovine serum albumin (A7034, Sigma Aldrich, St Louis, MO, USA), and 20 μL of anti-foaming agent (Sigma Aldrich, St Louis, MO, USA). The sample-buffer was drawn into a cuvette, equilibrated and brought to 37 °C, and oxygenated to 100% with air at the same time. After adjustment of the pO2 value, the sample was deoxygenated with nitrogen. A Clark oxygen electrode was used to detect changes of oxygen tension during the deoxygenation process on the x-axis of an x-y recorder, while the deoxyhemoglobin fraction was simultaneously monitored by dual-wavelength spectrophotometry at 560 and 570 nm, and displayed on the y-axis. Finally, the ODC was automatically recorded on graph paper, as shown in Figure 1(b). The P50 value was extrapolated on the x-axis as the point at which O2 saturation is 50%.
Semisynthetic supra plasma expanders: a new class of therapeutics to improve microcircualtion in sickle cell anaemia
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Fantao Meng, Dhananjaya Kaul, Sangeetha Thangaswamy, Savita Bhutoria, Gary Gerfen, Craig Branch, Marcos Intaglietta, Seetharama A. Acharya
Figure 5 shows the improvement in the haemodynamics as reflected by shear stress in NY1DD challenged with hypoxia reoxygenation protocol and with the infusion of the test material at the beginning of reoxygenation. The improvement in wall shear is considered for the improvement in haemodynamics and hence improving perfusion and of tissue oxygenation. Alb T12 exhibits very little therapeutic activity in improving the wall shear even though it exhibits significant therapeutic activity in attenuating the vaso-occlusion in induced in NY1DD by hypoxia reoxygenation. The wall shear is lower as compared to the starting level before hypoxia. This represents the presence of significant clogging of the capillaries due to the deoxygenation that occurred under hypoxia conditions. EAF hexa PEGylation of the drug Alb T12, engineering active plasma expansion activity, EAF P5K6 Alb T12 attenuates the vaso-occlusion completely and the restores the wall shear values to a level comparable to that of C57 BL. It is interesting that the supra perfusion resuscitation fluid, EAF P5K6 Alb, also restores the wall shear in NY1DD to a level far better than in the normoxic NY1DD, i.e. prior to challenging with hypoxia-reoxygenation protocol. However, it is not as good as that with the antioxidant conjugated EAF PEG albumin. Thus, in terms of re-establishing the haemodynamics, the active plasma expansion has a better therapeutic activity than the antioxidant conjugated to albumin, even though they seem to have nearly comparable therapeutic activity in terms of attenuation of vaso-occlusion or immigration of leucocytes.