Oxyhemoglobin dissociation curve and 2,3-diphosphoglycerate in chronic hypoxemia

The measurement of the oxyhemoglobin dissociation curve (ODC) and 2,3-diphosphoglycerate (2,3-DPG) in patients with chronic hypoxemia is important from the view point of tissue oxygenation. However, there have been no consistent results that explain the relation among chronic hypoxemia, 2,3-DPG and P50, which is oxygen pressure at an oxygen saturation of 50 percent. The aim of this study is to clarify what factors affect P50 and 2,3-DPG. 1) Patients with chronic hypoxemia, who showed PaO2 less than 60 Torr, had significantly higher P50 than normal subjects. 2) The concentration of Hb showed significant negative correlation with both P50 and 2,3-DPG. 3) Arterial blood pH showed significant positive correlation with both P50 and 2,3-DPG. 4) In a group with normal levels of Hb and pH, there was significant negative relationship between PaO2 and P50. 5) In a group with normal levels of Hb and pH, there was significant positive relationship between PaCO2 and P50. 6) In a group with normal levels of Hb, pH and PaCO2, there was significant negative relationship between PaO2 and 2,3-DPG. In conclusion, P50 and 2,3-DPG are affected largely by Hb concentration or blood pH, with or without hypoxemia. However there is a mechanism by which P50 and 2,3-DPG are increased by hypoxemia itself in a group with normal levels of Hb, pH and PaCO2.     

Iron Absorption: Present State of the Art

The availability of food iron is one of the major factors determining the total amount of iron absorbed. Iron is released from food in the stomach in an ionizable form or as haem. These forms are affected differently by both the composition of the diet and gastrointestinal secretions. Iron is taken up by the epithelial cells of the small intestine and is released from haem in the same cells. This uptake may be related to the iron status of the cells. Iron transport within these cells has been studied by both subcellular fractionation and electron microscopy with autoradiography. The biochemical studies have shown that much of the mucosal iron is associated with the mitochondria whereas absorbed radioiron is largely bound to ferritin in iron replete rats and to a transferrin-like protein in iron deficient animals. It has been suggested that this latter protein is the intracellular 'carrier'of iron. Serosal transport to the plasma is influenced by a number of factors and is not clearly understood. A review of the major problems in this area reveals more questions than answers.     

Reductive Electropolymerization and Electrochromism of Iron(II) Complex with Styrene-Based Ligand

The benzimidazole-based ligand containing polymerizable styrene group has been prepared via condensation of picolinaldehyde derivative containing styrene moiety and benzimidazole-based hydrazine. The ligand reacted with iron(II) tetrafluoroborate and iron(II) trifluoromethanesulfonate giving red-brown complexes of Fe(II) ions of formula [FeL₂]X₂, where X = CF₃SO₃⁻ (1) or BF₄⁻ (2). Reductive electropolymerization was used to obtain a thin layer of the polymeric complex, poly-1. Further investigation of electrochemical properties of the compound by cyclic voltammetry showed two quasi-reversible redox processes assigned to electrooxidation and electroreduction of the polymer. Spectroelectrochemical measurements confirmed that the polymer undergoes the color changes during oxidation and reduction process. The polymer in its neutral state (Fe(II)) is yellow and it exhibits absorption band at 370 nm, after oxidation to Fe(III) state absorption band shifts to 350 nm and the polymer is almost colorless. While the metal ions are reduced to Fe(I) absorption band at around 410 nm has been observed and the polymer changed its color to intense yellow. The stability of the polymer during multiple oxidation/reduction cycles has also been investigated.     

Oxyhemoglobin saturation during sleep in subjects with and without the obesity-hypoventilation syndrome

The etiology of the obesity-hypoventilation syndrome (OHS) is unknown. Recent reports that treatment of obstructive sleep apnea with nasal continuous positive-airway pressure eliminates the manifestations of OHS suggests that obstructive sleep apnea may contribute to OHS. The purpose of this study was to determine whether hypoxemia during sleep was more severe in patients with OHS than in those without OHS. In our sleep laboratory, we studied 32 subjects with a ratio of the forced expiratory volume in one second over the forced vital capacity (FEV1/FVC) greater than 0.73 and no neuromuscular disease. Seven subjects had OHS characterized by obesity and daytime hypercapnia, and 25 subjects did not. The seven patients with OHS all had sleep apnea. Of the 25 without OHS, 23 had sleep apnea. Subjects with OHS had significantly greater oxyhemoglobin desaturation during sleep than subjects without OHS, even when subjects with and without OHS were matched for sex and weight. These findings are consistent with the hypothesis that severe sleep apnea is a contributing cause of OHS.     

On the Nature of Rheumatoid Rice Bodies

The nature of rice bodies was studied, utilizing histochemistry, immunofluorescence, and scanning and transmission electron microscopy. Rice bodies were found to consist primarily of fibrous material, most of which was fibrin with small amounts of collagen. Channels containing a variety of viable cells permeated the rice bodies. Blood vessels occurred in a few rice bodies indicating a former connection with the synovial membrane. Nonvascularized rice bodies might represent a further degeneration of the vascular type. Rice bodies seem to be a nonspecific response to inflammation.     

On the Chemical Nature of Transfer Factor

Two transfer factors prepared in an experimental animal model, the guinea pig, have been tested for their susceptibility to various enzymes of known specificity. The biological activity of these immune response mediators can be destroyed by RNase III, an enzyme that degrades duplex RNA. It, therefore, appears that these transfer factors consist entirely or partly of double-stranded RNA.     

Ozone Model for Bonding of an O2 to Heme in Oxyhemoglobin

Several rather different models of the Fe—O₂ bond in oxyhemoglobin have previously been proposed, none of which provide a satisfactory explanation of several properties. We propose a new model for the bonding of an O₂ to the Fe of myoglobin and hemoglobin and report ab initio generalized valence bond and configuration interaction calculations on FeO₂ that corroborate this model. Our model is based closely upon the bonding in ozone which recent theoretical studies have shown to be basically a biradical with a singlet state stabilized by a three-center four-electron pi bond. In this model, the facile formation and dissociation of the Fe—O₂ bond is easily rationalized since the O₂ always retains its triplet ground state character. The ozone model leads naturally to a large negative electric field gradient (in agreement with Mössbauer studies) and to z-polarized (perpendicular to the heme) charge transfer transitions. It also suggests that the 1.3 eV transition, present in HbO₂ and absent in HbCO, is due to a porphyrin-to-Fe transition, analogous to that of ferric hemoglobins (e.g., HbCN).     

Studies on the Formation of Heinz Bodies. I. Methemoglobin Production and Oxyhemoglobin Destruction

A study of the changes in hemoglobin of erythrocytes incubated with varioustest substances has been reported. The concentrations of oxyhemoglobin andmethemoglobin in these erythrocytes were measured and the term "intact"hemoglobin was introduced, in order to distinguish these pigments from laterdegradation products of hemoglobin. Certain agents which are known to causeHeinz body formation and erythrocyte destruction in vivo have been shown tocause methemoglobin formation and "intact" hemoglobin destruction in vitro,and some of these agents were also shown to produce these changes in vivo.The possible significance of these findings in relation to the role of methemoglobin formation in Heinz body production has been discussed.

Submitted on May 26, 1960 Accepted on September 13, 1960     

Studies of the Oxidation of Ethanol to Acetaldehyde by Oxyhemoglobin Using Fluorigenic High-Performance Liquid Chromatography

We noted a rise in acetaldehyde levels in clinical samples of venous whole blood containing ethanol that did not occur in samples from teetotalers. Experiments were performed to define the mechanism involved in acetaldehyde production. The addition of 0.10% ethanol to whole blood produced an immediate increase in acetaldehyde due to acetaldehyde in the stock solution followed by a subsequent increase that became statistically significant by 48 hr. Separation of blood into components documented that the increase in acetaldehyde was associated with the red cell but not plasma fraction. Incubation of isolated hemoglobin with ethanol produced a rise in acetaldehyde levels. Incubation of oxygenated whole blood with ethanol produced a linear increase in acetaldehyde, whereas nitrogen-exposed blood produced no increase. The rise of acetaldehyde in the presence of ethanol was dependent on the concentration of oxygenated hemoglobin A₀. Addition of inhibitors of catalase, alcohol dehydrogenase, and glycolytic enzymes (aminotriazole, azide, pyrazole, sodium fluoride, sodium citrate, and iodoecetate) did not inhibit the rise of acetaldehyde, but addition of the hemoglobin ligand cyanide abolished the rise in acetaldehyde. Kinetic analysis with oxygenated whole blood plus inhibitors revealed a K _m of 2.5 mM and V _max of 1.42 μM/min. We conclude that oxyhemoglobin contributes to the metabolism of ethanol to acetaldehyde. These findings may explain in part the high levels of acetaldehyde found in red cells compared with plasma. The results also have implications for the optimum storage of blood samples for acetaldehyde analysis.