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Hemoglobin CC and SC Red Cells
Published in Ronald L. Nagel, Genetically Abnormal Red Cells, 2019
Mary E. Fabry, Ronald L. Nagel
Like hemoglobin S, hemoglobin C interacts more strongly with the erythrocyte membrane than HbA. This interaction has been studied using changes in the fluorescence intensity of a membrane imbedded probe (12-(9-anthroyloxy)stearic acid) whose fluorescence is quenched when it is approached by hemoglobin.35 The affinity of HbC for the erythrocyte membrane at pH 6.8 was found to be about five times greater than that of HbA. The pH dependence of HbC binding is significantly right shifted from that observed for HbA, which has an inflection at about 6.5, as opposed to an inflection at about pH 7.2 for HbC. Deoxy hemoglobin A and C were less strongly bound than the oxy form. These experiments were done at nonphysiological (low) ionic strengths and low hemoglobin concentrations. When the NaCl concentration was increased to 50 mM, the HbC was about 90% dissociated from the membrane. However, at higher hemoglobin concentrations, the binding was stronger and higher salt concentrations were required to displace the hemoglobin. The cytoplasmic portion of band 3 was implicated as the binding site for both HbA and HbC. Hemoglobin OArab is more strongly bound than HbS and is even more tightly bound than HbC.36 This observation suggest that both the electrostatic charge and the protein conformation in the vicinity of the charged groups play a role in membrane binding. Membrane binding of abnormal hemoglobins may affect membrane proteins involved in anion or cation movement, and may play a role in the altered red cell densities observed in cells containing these mutant hemoglobins.
Targeting fetal hemoglobin expression to treat β hemoglobinopathies
Published in Expert Opinion on Therapeutic Targets, 2022
Seven women whose blood P50 of 27.3 ± 0.4 mm Hg was at the lower bound of normal had smaller babies than women with P50 of 28.5 ± 0.3 torr [107]. Among 21 normal women selected because of 3rd trimester fetal growth retardation, hemoglobin-O2 affinity was linearly related to birth weight [108,109]. Although data is inconclusive and the critical studies have not been done, limited observations on maternal P50 and the fetus suggest that gene therapy in β0 thalassemia that results in ~100% HbF and normal hemoglobin concentration might affect fetal growth. The prospects of normal pregnancies in thalassemia treated with available therapies is likely to be far worse than the management of low birth weight infants. One patient with ~23% HbF and the remainder largely HbA, perhaps akin to gene therapy in β+ thalassemia, had 34% hybrid α2γβΑ tetramers with only 5% α2γ2; P50 was low normal at 26.3 mm Hg [110]. With 100% HbF, there can be no hybrid tetramer formation.
Long-term effects of multiple concussions on prefrontal cortex oxygenation during repeated squat-stands in retired contact sport athletes
Published in Brain Injury, 2022
Luke W. Sirant, Jyotpal Singh, Steve Martin, Catherine A. Gaul, Lynneth Stuart-Hill, Darren G. Candow, Cameron Mang, J. Patrick Neary
Near-infrared spectroscopy (NIRS) is a noninvasive, optical imaging technique with excellent temporal resolution that can be used to monitor relative changes in cerebral hemodynamics (25). Previous research has used NIRS as both an accurate measure of cerebrovascular health (26,27), and as a validated tool in monitoring the recovery of concussion patients (18,28–30). Choosing the prefrontal cortex provides a practical location to measure changes in cerebral oxygenation in an area of the brain that has been shown to play an important role in many of the cognitive and motor processes disturbed by concussions. The frontal lobes contribute to medullary function, which can be affected when a brain injury occurs (14,30). Furthermore, there is evidence that prefrontal cortex oxygenation parameters are altered in aconcussion (18). Hemodynamic dysfunction in the prefrontal cortex can be readily observed using NIRS in individuals with persistent post-concussion symptoms (29), and with more serious traumatic brain injuries (31). Normally, hemodynamic changes in concussions are short lived and resolve within days to weeks (18,32), so it is unclear whether hemodynamic changes can be altered on a long-term basis. NIRS can be used to monitor tissue saturation index (TSI%; (O2Hb/O2Hb + HHb)/ x 100), and relative changes in oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), total hemoglobin (tHb; O2Hb + HHb), and hemoglobin difference (HbDiff; O2Hb – HHb). Furthermore, research has shown that measures of NIRS can be used as a surrogate of cerebral autoregulation in acute brain injury (33).
Anti-IL-8 antibody potentiates the effect of exogenous surfactant in respiratory failure caused by meconium aspiration
Published in Experimental Lung Research, 2018
Pavol Mikolka, Jana Kopincova, Petra Kosutova, Maros Kolomaznik, Andrea Calkovska, Daniela Mokra
Ventilatory parameters (VT, PIP, PEEP) were recorded and baseline values of arterial and venous blood gases (PaO2, PaCO2), hemoglobin, O2 saturation (SatO2), and parameters of acid–base balance were measured by the blood gas analyzer (RapidLab TM348, Bayer Diagnostics, Germany). Tracheal airflow and tidal volume were measured by the heated Fleisch head connected to pneumotachograph placed between endotracheal tube and outlet of the ventilator. Airway pressure was recorded using a pneumatic catheter placed in the tracheal tube and connected to electromanometer. All signals were transferred to multichannel recorder PowerLab 8/30 (AD Instruments, Germany).