Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was performed to investigate oxygen transport properties in whole blood (WB) of malaria-infected rats as well as in infected erythrocytes (IE) and noninfected erythrocytes (NIE) separated by density centrifugation. One week after inoculation with Plasmodium berghei, mean parasitemia was 26.5% and high correlations were found between parasitemia and hemoglobin concentration ([Hb]; r = -.902), mean cellular Hb concentration (MCHC; r = -.712), MetHb (r = .923), and base excess (r = -.922). Compared with control animals (C), the oxygen affinity was lower in WB under standard (pH 7.40) and simulated "in vivo" (pH 7.00) conditions (difference in P50, 5.7 and 5.1 mm Hg, respectively; 2P < .01, 2P < .05). In IE Hb and 2,3-biphosphoglycerate (2,3-BPG) concentrations were decreased (MCHC: IE 14.6 +/- 1.0, NIE 33.1 +/- 1.7 g/100 mL; [2,3-BPG]: IE 2.0 +/- 0.6, NIE 7.6 +/- 1.8 mmol/L), whereas [MetHb] and [ATP] were increased ([MetHb]: IE 19.0 +/- 3.7, NIE 0.7% +/- 0.8%; [ATP]: IE 33.5 +/- 2.4, NIE 6.2 +/- 1.0 mumol/g Hb). At pH 7.40, half-saturation oxygen tension (P50) was reduced in IE (29.6 +/- 2.6, NIE 39.2 +/- 5.4 mm Hg, 2P < .001), which correlates with lower [2,3-BPG], increased MetHb content, and higher intrinsic Hb-O2 affinity. However, at pH 7.00, the oxygen affinity was lower in IE when compared with NIE, which was most likely due to high [ATP] in IE. The resulting Bohr coefficients (BC) calculated for CO2 and lactic acid were extremely high in IE and low in NIE (at 50% O2-saturation BCCO2: IE -1.04 +/- 0.06, NIE -0.26 +/- 0.10, 2P < .001; BCLac: IE -0.82 +/- 0.16, NIE -0.47 +/- 0.07, 2P < .001), which was caused by different [2,3-BPG] and [ATP] as well as probably by structural changes of the Hb molecule. The O2 capacity was 14.1 mL per 100 mL erythrocytes in IE compared with 44.4 mL/100 mL in NIE. On the basis of the calculated arterio-venous O2 difference under "in vivo" conditions, the infected red blood cell fraction transports 30% of the O2 amount delivered to the tissues by the noninfected cells (IE 8.0, NIE 26.9 mL/100 mL red blood cells). We conclude that the O2 transport in malaria infected blood is not only affected by the degree of anemia but also by the percentage of infected erythrocytes.
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PMID:Oxygen transport properties in malaria-infected rodents--a comparison between infected and noninfected erythrocytes. 820 95

Existing experimental and theoretical evidence suggests that precapillary diffusion of O2 and CO2 occurs between arterioles and tissue under normal physiologic conditions. However, limited information is available on arteriolar gas transport during anemia. With use of a mathematical model of an arteriolar network in brain tissue, anemic hematocrits of 35, 25, and 15% were modeled to determine the effect of anemia on the exchange, the change in the equilibrium tissue O2 and CO2 tensions, and the increase in blood flow needed to restore tissue oxygenation. We found that the blood PO2 exiting the network fell from 66 mm Hg normally to 48 mm Hg during the severest anemia. Concurrently, the equilibrium tissue O2 tensions dropped from 44 to 23 mm Hg. For CO2 the exit blood PCO2 was 58 mm Hg for a 15% hematocrit, an increase of 4 mm Hg from the normal value, and equilibrium tissue PCO2 increased from 56 to 61 mm Hg. Blood flow increases from normal values necessary to offset the effects of the decreased O2 delivery to the tissue were 26, 86, and 222%, respectively, for hematocrits of 35, 25, and 15%. We compared our model results with recent experimental studies that have suggested that the amount of O2 diffusion is much higher than predicted values. We found that these experimental O2 gradients are three to four times larger than theoretical.
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PMID:A model of brain arteriolar oxygen and carbon dioxide transport during anemia. 836 Feb 93

We studied bovine subjects that exhibited a moderate uncompensated anemia with hereditary spherocytosis inherited in an autosomal incompletely dominant mode and retarded growth. Based on the results of SDS-PAGE, immunoblotting, and electron microscopic analysis by the freeze fracture method, we show here that the proband red cells lacked the band 3 protein completely. Sequence analysis of the proband band 3 cDNA and genomic DNA showed a C --> T substitution resulting in a nonsense mutation (CGA --> TGA; Arg --> Stop) at the position corresponding to codon 646 in human red cell band 3 cDNA. The proband red cells were deficient in spectrin, ankyrin, actin, and protein 4.2, resulting in a distorted and disrupted membrane skeletal network with decreased density. Therefore, the proband red cell membranes were extremely unstable and showed the loss of surface area in several distinct ways such as invagination, vesiculation, and extrusion of microvesicles, leading to the formation of spherocytes. Total deficiency of band 3 also resulted in defective Cl-/HCO3- exchange, causing mild acidosis with decreases in the HCO3- concentration and total CO2 in the proband blood. Our results demonstrate that band 3 indeed contributes to red cell membrane stability, CO2 transport, and acid-base homeostasis, but is not always essential to the survival of this mammal.
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PMID:Defective anion transport and marked spherocytosis with membrane instability caused by hereditary total deficiency of red cell band 3 in cattle due to a nonsense mutation. 862 63

To evaluate oxygen transport function of Hb in lymphoid sarcomas, 15 patients aged 16-63 were examined for Hb oxygen capacity, concentrations of fetal Hb and creatinin, basic ligands H+, CO2, 2,3-diphosphoglycerate (2,3-DPG). Oxy-Hb dissociation curves were plotted. The patients' blood contained HbF in elevated quantities, whereas red cells had high creatinin. This emphasizes the role of hemolysis in genesis of anemia in lymphosarcomas. 70% of the examinees retained normal Hb affinity to oxygen in vivo, in 30% this affinity exceeded the standard. Compensatory mechanism responsible for low Hb affinity to oxygen in this disease fails. Therefore lymphosarcoma patients with anemia need early replacement hemotransfusions.
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PMID:[Hemoglobin oxygen-transport activity in lymphosarcomas]. 866 81

Hypertension is the main side effect developing in patients suffering from renal anemia who are treated with recombinant human erythropoietin (rHuEPO). We investigated the effect of rHuEPO on the vascular tone of isolated rabbit aorta and carotid artery under isometric conditions. The production of prostacyclin and the vasoconstrictor prostanoids PGF2 alpha and TXB2 was investigated in arterial rings incubated with rHuEPO. Endothelial cells from human umbilical veins (HUVECs) were isolated and cultured in flasks (37 degrees C, 5% CO2). After incubation with rHuEPO, the formations of prostacyclin (as its stable metabolite 6-keto-PGF1 alpha), PGF2 alpha, PGE2, thromboxane (TX) B2 and of ET-1 were measured by radioimmunoassays. rHuEPO had no direct vasoconstrictor effect, but it enhanced noradrenalin-induced contractions. This effect was more prominent in rings with intact endothelium than in rings from which the endothelium had been mechanically removed, indicating that endothelial vasoactive factors might be involved. Relaxations to acetylcholine (ACh, 1 microM) were unaltered in the presence or absence of rHuEPO, suggesting that the endothelial NO-cGMP pathway was not impaired by rHuEPO. Incubation with rHuEPO (20 to 200 U/ml) increased the release of the vasoconstrictor mediators ET-1, PGF2 alpha and TXB2, and decreased prostacyclin formation in isolated rabbit arterial rings and in HUVECs, respectively. The cyclooxygenase inhibitor indomethacin abolished the rHuEPO-induced increase in vasoconstrictor prostanoid production. ET-1 formation by HUVECs was also increased by rHuEPO in a dose-dependent manner (maximal effect +90% by rHuEPO 200 U/ml, P < 0.05). Indomethacin and the selective ETA receptor antagonist BQ123 each partly inhibited the enhancement of vascular responsiveness to noradrenalin induced by rHuEPO in rabbit carotid artery, but simultaneous administration of rHuEPO with both antagonists completely abolished the force increment. In conclusion, these studies show that a dose-dependent shift in the balance of constrictor and relaxing prostanoids as well as an increased synthesis of ET-1 induced by rHuEPO lead to the enhanced vascular responsiveness to noradrenalin in isolated rabbit arteries. The increased vascular responsiveness to noradrenalin, which is in line with clinical observations, may contribute to the hypertensive side effect associated with rHuEPO therapy in patients with chronic renal failure.
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PMID:Recombinant human erythropoietin enhances vasoconstrictor tone via endothelin-1 and constrictor prostanoids. 888 85

Isovolemic hemodilution does not appear to impair CO2 elimination nor cause CO2 retention despite the important role of red blood cells in blood CO2 transport. We studied this phenomenon and its physiological basis in eight New Zealand White rabbits that were anesthetized, paralyzed, and mechanically ventilated at a fixed minute ventilation. Isovolemic anemia was induced by simultaneous blood withdrawal and infusion of 6% hetastarch in sequential stages; exchange transfusions ranged from 15-30 ml in volume. Variables measured after each hemodilution included hematocrit (Hct), arterial and venous blood gases, mixed expired PCO2 and PO2, and blood pressure; also, O2 consumption, CO2 production, cardiac output (Q), and physiological dead space were calculated. Data were analyzed by comparison of changes in variables with changes in Hct and by using the model of capillary gas exchange described by Bidani (J. Appl. Physiol. 70: 1686-1699, 1991). There was complete compensation for anemia with stability of venous and arterial PCO2 between Hct values of 36 +/- 3 and 12 +/- 1%, which was predicted by the mathematical model. Over this range of hemodilution, Q rose 50%, and the O2 extraction ratio increased 61% without a decline in CO2 production or a rise in alveolar ventilation. The dominant compensations maintaining CO2 transport in normovolemic anemia include an increased Q and an augmented Haldane effect arising from the accompanying greater O2 extraction.
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PMID:CO2 transport in normovolemic anemia: complete compensation and stability of blood CO2 tensions. 921 69

Intracellular pyrimidine nucleotides (PyN) can be synthesized de novo from glutamine, CO2, and ATP, or they can be salvaged from preformed pyrimidine nucleosides. The antiproliferative and immunosuppressive activities of brequinar sodium (BQR) are thought to be due to the inhibition of the activity of dihydroorotate dehydrogenase, which results in a suppression of de novo pyrimidine synthesis. Here we describe the effects of the pyrimidine nucleoSide, uridine, on the antiproliferative and immunosuppressive activities of BQR. In vitro reduction of PyN levels in Con A-stimulated T cells and inhibition of cell proliferation by low concentrations of BQR (< or =65 microM) are reversed by uridine. However, uridine is unable to reverse the effects of high concentrations of BQR (> or =65 microM). The ability of BQR to induce anemia in BALB/c mice is prevented by the coadministration of uridine. In contrast, the immunosuppressive activity of BQR is unaffected by similar doses of uridine. PyN levels in the bone marrow, but not in the spleen, are depressed in mice treated with BQR. These observations suggest that the induction of anemia by BQR is due to depletion of intracellular PyN in hemopoietic stem cells located in the bone marrow. They also suggest that the mechanism of immunosuppression by BQR may be only marginally dependent on depletion of intracellular PyN in lymphocytes located in the periphery. We report a novel activity of BQR: inhibition of tyrosine phosphorylation, and hypothesize that the immunosuppressive activity may be due, in part, to this unsuspected ability of BQR to inhibit tyrosine phosphorylation in lymphocytes.
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PMID:In vitro and in vivo mechanisms of action of the antiproliferative and immunosuppressive agent, brequinar sodium. 955 20

The aim of the present study was to assess blood lactate concentrations ([LA], mmol x L(-1)) and oxygen uptake (VO2, L x min(-1), mL x kg(-1) x min(-1)) during incremental exercise in subjects with sickle cell trait (SCT) only, i.e., sedentary subjects with SCT without anemia and/or associated alpha thalassemia. Anemia was ruled out using hemoglobin (Hb) level, and alphathalassemia was ruled out using hemoglobin S (HbS) percentage and concomitant Hb level and mean corpuscular volume (MCV). Comparison was made with control subjects with normal Hb, matched for physical fitness, anthropometric data, and hematological parameters. All subjects underwent an incremental exercise test (IET) using an electromagnetic cycle ergometer. Ventilatory data, i.e., minute ventilation (VE, L x min(-1)), oxygen uptake (VO2, mL x min(-1), mL x Kg(-1) x min(-1)) carbon dioxide production (VO2, mL x min(-1)), ventilatory equivalent for O2(VE x VO2(-1))and for CO2 (VE x VO2(-1)), and respiratory exchange ratio (RER, VO2 x VO2(-1)), were collected every minute during IET and the recovery period using a breath-by-breath automated system. Heart rate (HR, beats x min(-1)) was measured every minute using an EKG. Blood sampling was done every minute during IET and the first 5 min of the recovery period, and then every 5 min until the 20th minute of recovery. [LA] were determined by an enzymatic method with a spectrophotometer. Comparisons of all mean cardioventilatory variables showed no significant differences in subjects with SCT versus controls during IET and recovery. In contrast, analysis of variance revealed significantly lower time courses of [LA] during IET (P < 0.05) and recovery (P < 0.05), whereas time courses of VO2 were similar (P > 0.05). We conclude that the lower [LA] exhibited by subjects with SCT during incremental exercise and the subsequent recovery was not associated with concomitant oxygen uptake impairment.
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PMID:Blood lactate concentrations during incremental exercise in subjects with sickle cell trait. 958 4

1. Low birthweight is now recognized as an important risk factor for early postnatal respiratory illness and it is becoming evident that low birthweight can increase the risk for airway dysfunction in children and adults. Our studies have been aimed at determining how low birthweight, resulting from intra-uterine growth restriction (IUGR), affects the control of breathing and the structural and functional development of the lung. 2. We have measured ventilatory responsiveness to progressive hypoxia and progressive hypercapnia during the first weeks after birth in postnatal lambs in which IUGR was induced by chronic placental insufficiency. It was found that the postnatal increase in ventilatory sensitivity to hypoxia observed in control lambs was diminished in low birthweight lambs; in contrast, the sensitivity to hypercapnia was not affected. In other studies, we found that IUGR caused by maternal anaemia led to elevated CO2 levels during sleep and wakefulness. 3. Our findings suggest that the prenatal development of the brain-stem or respiratory chemoreceptors may be affected by intra-uterine factors associated with IUGR, such as foetal hypoxaemia or hypoglycaemia. It is also possible that the structure of respiratory muscles and, hence, their ability to maintain a high level of ventilation may be affected by IUGR. 4. Recently, we studied the influence of IUGR on foetal lung development, in particular its effects on foetal lung liquid, a major determinant of lung growth, as well as alveolar structure and pulmonary surfactant. Lung liquid secretion and volume, in relation to bodyweight, were unaffected; however, there was evidence of structural and functional immaturity in the lungs. In foetuses exposed to IUGR, the air-blood barrier was thicker and, after birth, the diffusing capacity of the lungs for carbon monoxide was lower. In contrast, surfactant protein gene expression was enhanced, particularly in foetuses with high levels of circulating cortisol. 5. Further studies are needed to characterize the effects of specific types of prenatal compromise on postnatal control of ventilation and lung function, to determine mechanisms underlying these effects and to determine the capacity for postnatal recovery.
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PMID:Effects of intra-uterine growth restriction on the control of breathing and lung development after birth. 1069 39

The present study evaluated the acid-base status of anemic rats by using two approaches of acid-base analysis: one based on the base excess (BE) calculation and the other based on Stewart's physicochemical analysis. Two sets of experimental data, derived from two different methods of inducing anemia, were used: repetitive doses of phenylhydrazine (PHZ) and bleeding (BL). A significant uncompensated respiratory alkalosis was found in both groups of anemic rats. BE increased slightly, whereas strong ion difference ([SID]) and weak acid buffers ([A(TOT)]) remained unchanged in anemic rats. The reasons for the absence of compensation for hypocapnia and the differences in the behaviour of acid-base variables are discussed. BE increase was considered paradoxical; its calculation was affected by the experimental conditions and BE had little physiological relevance during anemia. The absence of metabolic renal compensation in anemic rats could be due to a lower pH in the kidney due to anemic hypoxia. Finally, the changes in buffer strength related to low Hb and low P(CO2) might influence plasma [SID] through counteracted shifts of strong ions between erythrocytes and plasma, finally resulting in unchanged [SID] during anemia.
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PMID:Acid-base analysis during experimental anemia in rats. 1107 77


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