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)

Because of an impending shortfall of allogeneic blood products within the next decades and ongoing problems such as transfusion reactions, immunomodulating side effects and the risk of bacterial, viral and prion transmission associated with relevant costs for testing and storage of banked RBC units which, additionally, suffer from aging processes, the development of alternatives has been intensified during the last 15 years. Modern chemically modified hemoglobin-based oxygen carriers (HBOC) are free of red blood cell membrane remnants eliminating renal toxicity, and they do not possess AB0 antigens which allows transfusion without knowledge of the respective blood group of a patient. Bovine polymerized cell-free hemoglobin can be stored at room temperature for three years. In contrast to the perfluorocarbon solutions, HBOC can be applied at room air oxygen concentrations. Animal experiments have shown that HBOC can compensate for intravascular volume deficits in hemorrhagic shock, including restoration of colloid osmotic pressure and organ perfusion, and deliver oxygen to organs and tissues during nearly complete blood exchange. Chemical modifications of HBOC are able to reduce the vasoconstrictive side-effect of HBOC which is caused by NO scavenging. In spite of vasoconstriction the increased oxygen extraction in presence of HBOC in combination with the plasmatic oxygen transport provides enhanced tissue oxygenation even in post-stenotic tissues. HBOC seem to improve the diffusive oxygen transport at the microcirculatory site thus decreasing tissue damage in acute pancreatitis and the heart and brain after ischemia/reperfusion injury. Clinical studies have shown that the peri-operative use of different HBOC (Hemopure, PolyHeme, Hemolink and HemAssist) can reduce the number of allogeneic RBC units and increase the avoidance rate of allogeneic transfusion in emergency bleeding, vascular, cardiac and non-cardiac surgery. Polymerized HBOC appear to have a lower potential of side effects in comparison to intra-molecularly cross-linked preparations. However, HBOC-201 (Hemopure) is the only substance which has been licensed for the treatment of patients with acute peri-operative anemia in South Africa until now.
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PMID:[Autologous transfusion - from euphoria to reason: clinical practice based on scientific knowledge. (Part IV). Artificial oxygen carriers: cell-free hemoglobin solutions -- current status 2004]. 1564 86

To understand the evolutionary forces establishing, maintaining, breaking, or precluding protein-protein interactions, a comprehensive data set of protein complexes has been analyzed to examine the overlap between protein interfaces and the most conserved or divergent protein surface areas. The most divergent areas tend to be found predominantly away from protein interfaces, although when found at interfaces, they are associated with specific lack of cross-reactivity between close homologues, like in antibody-antigen complexes. Moreover, the amino acid composition of highly variable regions is significantly different from any other protein surfaces. The variable regions present higher structural plasticity as a result of insertions and deletions, and favor charged over hydrophobic residues, a known strategy to minimize aggregation. This suggests that (1) a rapid rate of mutations at these regions might be continuously altering their properties, making difficult the coadaptation, in shape and chemical complementarity, to potential interacting partners; and (2) the existence of some form of selective pressure for variable areas away from interfaces to accumulate charged residues, perhaps as an evolutionary mechanism to increase solubility and minimize undesirable interactions within the crowded cellular environment. Finally, these results are placed into the context of the aberrant oligomerization of sickle-cell anemia hemoglobin and prion proteins.
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PMID:Does structural and chemical divergence play a role in precluding undesirable protein interactions? 1582 2

Cellular prion protein (PrPc) participates in the pathogenesis of prion diseases but its normal function remains unclear. PrPc is expressed on hematopoietic cells, including erythroid precursors. We investigated the role of PrPc in erythropoiesis in vivo with phenylhydrazine-induced acute anemia. Induction of equivalent anemia in wild-type (WT) and Prnp-/- mice resulted in a higher number of circulating reticulocytes, hematocrits and spleen weights in WT mice than in Prnp-/- mice on Days 5 and 7. Examination of bone marrow erythroid precursor cells (Ter119+) on Day 5 revealed no significant differences in the number of these cells between the two types of animals. However, a higher percentage of Ter119+ cells were going through apoptosis in Prnp-/- mice than in WT mice. Plasma erythropoietin (Epo) levels and Epo mRNA in kidneys peaked on Day 3 in response to anemia for both types of animals but rose less in Prnp-/- (5500 pg/ml ) than in WT (18,000 pg/ml) animals. Administration of recombinant human Epo to mice produced an equivalent reticulocyte response in both types of animals suggesting that the potential for erythroid generation is intact in Prnp-/- animals. These observations indicate that PrPc may modulate tissue hypoxia-sensing mechanisms or effect hypoxia target gene expression.
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PMID:Reduced erythroid cell and erythropoietin production in response to acute anemia in prion protein-deficient (Prnp-/-) mice. 1796 27

Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a fixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient's tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a "one-by-one" administration schedule. Evidence-based clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within well-constructed protocols will offer better prospects for blood conservation in selected IBD patients undergoing elective surgery.
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PMID:Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases. 1978 32

We have previously demonstrated that the concentration of normal prion proteins (PrP(C)) is increased in the serum and cerebrospinal fluid (CSF) of rats deficient in vitamin B(12) (cobalamin, Cbl). In this study, we investigated whether similar increases also occur in the serum and CSF of patients deficient in Cbl (Cbl-D), and whether the increase in serum levels can be corrected by Cbl therapy. The study involved two sample populations. The first consisted of 45 patients (13 patients with pernicious anemia [PA], 19 with other forms of anemia, and 13 healthy controls); and the second, 68 patients (five with subacute combined degeneration [SCD], 18 with amyotrophic lateral sclerosis, 22 with multiple sclerosis [MS], and 23 neurological controls). Serum PrP(C) levels were measured using an enzyme-linked-immunosorbent-assay before as well as after Cbl therapy. The mean serum PrP(C) levels in patients with PA were significantly higher than those of the controls (p=0.0017) but normalized after Cbl therapy; there was no significant change in the patients with other forms of anemia. Mean CSF PrP(C) levels in the patients with SCD were significantly higher than in the neurological controls (p<0.03). The serum and CSF PrP(C) levels of patients with PA and those with SCD were correlated significantly with serum (p=0.004) and CSF (p=0.0018) Cbl levels. In patients with MS, CSF PrP(C) concentrations were significantly lower than those of the controls regardless of their CSF Cbl levels. We found a correlation between Cbl and PrP(C) levels in the serum and CSF of Cbl-D patients, which suggests that Cbl may regulate the PrP(C) levels in the serum and CSF in humans.
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PMID:Cobalamin as a regulator of serum and cerebrospinal fluid levels of normal prions. 2314 13

Effective artificial oxygen carriers may offer a solution to tackling current transfusion medicine challenges such as blood shortages, red blood cell storage lesions, and transmission of emerging pathogens. These products, could provide additional therapeutic benefits besides oxygen delivery for an array of medical conditions. To meet these needs, we developed a hemoglobin (Hb)-based oxygen carrier, HemoTech, which utilizes the concept of pharmacologic cross-linking. It consists of purified bovine Hb cross-linked intramolecularly with open ring adenosine-5'-triphosphate (ATP) and intermolecularly with open ring adenosine, and conjugated with reduced glutathione (GSH). In this composition, ATP prevents Hb dimerization, and adenosine promotes formation of Hb polymers as well as counteracts the vasoconstrictive and pro-inflammatory properties of Hb via stimulation of adenosine receptors. ATP also serves as a regulator of vascular tone through activation of purinergic receptors. GSH blocks Hb's extravasation and glomerular filtration by lowering the isoelectric point, as well as shields heme from nitric oxide and reactive oxygen species. HemoTech and its manufacturing technology have been broadly tested, including viral and prion clearance validation studies and various nonclinical pharmacology, toxicology, genotoxicity, and efficacy tests. The clinical proof-of-concept was carried out in sickle cell anemia subjects. The preclinical and clinical studies indicate that HemoTech works as a physiologic oxygen carrier and has efficacy in treating: (i) acute blood loss anemia by providing a temporary oxygen bridge while stimulating an endogenous erythropoietic response; (ii) sickle cell disease by counteracting vaso-occlusive/inflammatory episodes and anemia; and (iii) ischemic vascular diseases particularly thrombotic and restenotic events. The pharmacologic cross-linking of Hb with ATP, adenosine, and GSH showed usefulness in designing an artificial oxygen carrier for multiple therapeutic indications.
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PMID:Artificial oxygen carrier with pharmacologic actions of adenosine-5'-triphosphate, adenosine, and reduced glutathione formulated to treat an array of medical conditions. 2498 41