Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to assess the changes in the clinical biochemistry of runner's anemia and its evolution during a prolonged period of high-intensity training, 11 male international class distance runners (mean time for 1 mile 4 min, 2.5 sec) were followed over a 10-month period prior to the 1984 U.S. Olympic Trials. Mean values of hemoglobin, hematocrit, and mean corpuscular hemoglobin (MCH) decreased modestly over the period of study. Means of haptoglobin, iron, and total iron binding capacity (TIBC) remained roughly constant. Percentage of saturation of TIBC by iron (% sat) averaged 30% or less in 5 of 11 runners, suggesting mild iron deficiency. Most measured haptoglobin levels were below normal range throughout the study period. The cause of runner's anemia has been demonstrated to be multifactorial, including disordered iron metabolism, iron deficiency, and hemolysis. Other studies have shown absent bone marrow iron in male athletes, secondary to hematuria, ischemia of the intestinal mucosa with bleeding, and iron losses due to heavy perspiring. Cardiorespiratory fitness, evaluated through repetitive treadmill testing, was not adversely affected in our athletes. Total creatine kinase (CK) increased significantly after a training session, while the MB fraction of CK never exceeded 3%. Total lactate dehydrogenase (LD) also rose after exercise, but the fractions represented by isozymes 1-5 were unaltered; specifically, there was no change in the LD-1/LD-2 ratio. Enzyme elevations were thus derived from skeletal muscle and not from heart.
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PMID:An analysis of serum enzyme changes and clinical biochemical abnormalities of the anemia in Olympic runners. 321 6

Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels.
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PMID:Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis. 768 Jun 72

In summary, much evidence supports the formation of toxic oxygen metabolites in ischemic reperfused tissue. Tissues are equipped with both an intracellular and extracellular antioxidant defense system. The defense system can also be divided into enzymatic and nonenzymatic defenses. Important components of a nonenzymatic antioxidant include alpha-tocopherol, ascorbic acid, and beta-carotene as well as other compounds that can react with radicals to form less reactive products such as sulfur-containing amino acids. Extracellular fluid comprises a second line of defense against oxidant injury. These extracellular antioxidants include ceruloplasmin, albumin, transferrin, haptoglobin, and uric acid. The oxidant injury can potentially occur during ischemia and reperfusion due to (1) an excess production of oxygen free radicals, (2) a decrease in antioxidant defenses, or (3) both. Because antioxidants function by removing the toxic oxygen metabolites, they are generally highly effective in reducing ischemia-reperfusion injury.
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PMID:Antioxidant effectiveness in ischemia-reperfusion tissue injury. 801 92

We investigated the long-term efficacy and the contraindications of single-session percutaneous ethanol injection (PEI) under general anesthesia in hepatocellular carcinoma (HCC). One hundred patients were treated from October, 1991, to April, 1996: 24 patients had a single capsulated HCC, 4.5 to 10 cm phi (group A); 62 had a single infiltrating tumor or multiple lesions (3 to 6), with 10 cm maximum phi (group B); 14 patients were in an advanced stage because of Child class C or of infiltrating tumors with portal thrombosis, with 14 cm lesion maximum phi (group C). Group A patients were treated because they were not operable or refused surgery. Three to 22 injections were performed (mean: 13) depending on tumor size and ethanol spread. The maximum injected volume of ethanol was 190 ml (mean: 57 ml). The procedure took 20 to 50 minutes (mean: 30 minutes). The mean hospital stay was 3.5 days. Tumor necrosis was complete in 58% of encapsulated tumors and > 70% in infiltrating lesions. The greatest lesion with complete post-PEI necrosis was 8.2 cm phi. A transient and variable increase in transaminase, bilirubin, white cell and D-dimer levels and a decrease in red cell, platelet, hemoglobin, fibrinogen and haptoglobin levels were observed. These changes were due to hepatic cell necrosis, hemolysis and focal thrombosis. One death (bleeding esophageal varices in the Child C patient)(1%) and four major complications (one peritoneal bleeding, one liver decompensation, two chemical segmentectomies with pain)(4%) were observed. 1, 2, 3 year survival rates for groups A, B and C were: 80, 63, 63%; 70, 50, 30% and 58, 14 and 0% respectively. In our experience, PEI was an efficacious procedure. The risk conditions are: superficial lesion site with severe coagulation defects, severe portal and/or pulmonary hypertension, esophageal varices at risk of bleeding, cardiac ischemia, advanced cirrhosis.
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PMID:[Single-session alcohol administration for hepatocarcinoma]. 942 44

The HELLP syndrome is a dangerously severe form of preeclampsia associated with multiorgan system damage and occurs in 0.2-0.6% of all pregnancies. It usually presents with abdominal pain, often in the setting of preeclampsia. In most cases, HELLP is initiated by inadequate placental vessel development with subsequent placental ischemia, leading to the release of circulating vasoconstrictors. These powerful vasoconstrictors include thromboxane A2, angiotensin, prostaglandin F2, and endothelin-1. The ischemic placenta also produces fewer vasodilators, such as prostacyclin, prostaglandin, E2, and nitric oxide. The ensuing imbalance in vasoactive substances causes intense systemic vasospasm and multiorgan endothelial damage. Multiple genetic, coagulation, and immunologic disorders also appear to contribute to the endothelial damage. Fibrin and platelets are then deposited on the endothelial surfaces leading to the hemolytic anemia, elevated liver enzymes, and low platelets of the HELLP syndrome. The most reliable laboratory tests for the diagnosis of HELLP are a complete blood count with peripheral smear, lactate dehydrogenase, serum transaminases, and urinalysis. Supportive tests include serum haptoglobin, D-dimer fragment levels, lactate dehydrogenase isoenzymes, total bilirubin, prothrombin times, and activated partial thromboplastin times. Lactate dehydrogenase and the platelet count are the two best tests to monitor the course of the disease. Prompt delivery is the treatment of choice. The intensity of the HELLP syndrome peaks 24 hours after delivery. Extended atypical HELLP has been successfully treated with plasma exchange. The clinical laboratory professional plays an important role in the diagnosis, follow-up, and treatment of patients with the HELLP syndrome.
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PMID:HELLP! A cry for laboratory assistance: a comprehensive review of the HELLP syndrome highlighting the role of the laboratory. 984 23

Inflammatory phenomena at sites of atherosclerotic plaques are increasingly thought to be major determinants of the progression and clinical outcome of atherosclerotic disease. Therefore, attention is being paid to systemic markers/mediators which may reflect the inflammatory activity in the plaques. This study evaluates the pattern of the main proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), their soluble receptors/antagonist, and a variety of inflammatory markers, in patients with peripheral arterial disease (PAD). Eight patients with PAD suffering from claudicatio intermittens (CI), eight with critical limb ischemia (CLI) and eight controls (C) were studied. Blood samples were collected at baseline in all groups and. for C and CI, immediately after and 4 h after a 30-min treadmill test. Baseline: no differences in cytokine plasma levels were detected among the three groups. In contrast, soluble receptors of TNF (type I and II) and of IL-6, and IL-1beta receptor antagonist (IL-1ra) were increased in CI and CLI patients, as compared to C. Of note, IL-Ira correlated with the occurrence and stage of the disease in a highly significant proportion of the patients, reaching a predictive value for the disease of P < 0.0001. The opposite trend was observed for the soluble receptor of IL-1beta. Notably, in the patients no alterations could be found in white blood cell counts, expression of CD11c adherence molecule by circulating monocytes or, in vitro. O2- release from zymosan-activated neutrophils. Moreover, plasma levels of platelet activating factor (PAF), of neutrophil elastase and of the acute phase reactants C-reactive protein (CRP) and alpha1-acid glycoprotein were not found to be significantly altered. In contrast, the acute-phase proteins alpha1-antitrypsin (alpha1AT) and haptoglobin (HG) were found to be increased. Effect of treadmill: IL-1beta and TNFalpha remained at baseline levels following exercise, and IL-6 dropped to undetectable levels. Among cytokine antagonists, again the most relevant changes concerned the IL-1ra, which was significantly increased immediately after the treadmill test, both in CI and C, and returned to baseline levels after 4 h. In contrast, soluble TNFalpha, IL-1beta and IL-6 receptors, PAF, and the other markers of leukocyte activation were not found to be altered. Soluble TNFalpha and IL-6 receptors were shown to inhibit the biological effects of their ligands. Similarly, IL-1ra and the acute phase proteins alpha1AT and HG have been reported to exert anti-inflammatory functions. The increased plasma levels of these agents, together with low levels of inflammatory cytokines and other pro-inflammatory mediators such as PAF and alpha1-acid glycoprotein, appear to draw an undescribed picture, so far, of upregulation of a composite systemic anti-inflammatory mechanism in atherosclerotic patients. IL-1ra appears to be a reliable marker of the state of activation of this mechanism. These results may provide a basis for developing new insights into the pathogenesis of the atherosclerotic disease.
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PMID:Atherosclerosis and inflammation. Patterns of cytokine regulation in patients with peripheral arterial disease. 1042 95

Immunohistochemistry for haptoglobin (Hp) in the postischemic hippocampus demonstrated an immunoreactivity visible one day after reperfusion and continuing to increase until 14 days after ischemia. The immunoreactivity was most prominent in CA1 and the dentate hilar region, especially in cells with astroglial morphology. Double immunofluorescence histochemistry confirmed colocalization of the Hp and glial fibrillary acidic protein. Furthermore, a reverse transcription-polymerase chain reaction study confirmed an elevated Hp mRNA level in the postischemic hippocampus. The Hp gene expression was also upregulated in C6 and A-172 glioblastoma cell lines after H O treatment. These findings suggest that Hp is synthesized in reactive astrocytes in response to ischemia-reperfusion injury.
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PMID:Upregulation of haptoglobin in reactive astrocytes after transient forebrain ischemia in rats. 1236 55

Factor H deficiency is responsible for thrombotic microangiopathy (TMA) via uncontrolled activation of the alternative pathway of the complement system. Ocular TMA has never been reported in patients with factor H abnormalities. A male patient with congenital homozygote factor H deficiency reached end-stage renal disease at the age of 10 years. Hemodialysis was uneventful for 3 years, when, suddenly, unilateral ocular pain and blurred vision occurred while he had febrile pharyngitis. Ophthalmologic examination found vitreous bleeding, elevated ocular pressure, choroidal hemorrhage (ultrasound biomicroscopy) and retinal ischemia (fluorescein angiography). C-reactive protein concentration was increased, while haptoglobin levels remained normal. We suspected that TMA due to factor H deficiency was responsible for the ocular manifestations and immediately initiated daily plasma exchanges (PEs) with fresh frozen plasma (FFP) for 10 days followed by three sessions per week. Factor H serum level increased from 6% to 82%, and C3 level normalized. Progressively, ocular pain decreased, and visual acuity and ophthalmologic findings showed improvement. When there is permanent activation of the alternative pathway in patients with end-stage renal disease (ESRD), the search for secondary targets might be of interest. In nephrectomized patients, no biological parameter can predict isolated ocular TMA. Early ophthalmologic investigation and substitution of factor H via FFP may avoid irreversible damage.
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PMID:Ocular involvement in hemolytic uremic syndrome due to factor H deficiency--are there therapeutic consequences? 1761 7

Cell-free hemoglobin (Hb) enhances the oxidation-related toxicity associated with inflammation, ischemia, and hemolytic disorders. Hb is highly vulnerable to oxidative damage, and irreversible structural changes involving iron/heme oxidation, heme-adduct products, and amino acid oxidation have been reported. Specific structural features of Hb, such as unconstrained alpha-chains and molecular size, determine the efficiency of interactions between the endogenous Hb scavengers haptoglobin (Hp) and CD163. Using HPLC, mass spectrometry, and Western blotting, we show that H(2)O(2)-mediated Hb oxidation results in the formation of covalently stabilized globin multimers, with prominent intramolecular crosslinking between alpha-globin chains. These structural alterations are associated with reduced Hp binding, reduced CD163 interaction, and severely impaired endocytosis of oxidized Hb by the Hp-CD163 pathway. As a result, when exposed to oxidized Hb, CD163-positive HEK293 cells and human macrophages do not increase hemeoxygenase-1 (HO-1) expression, the physiological anti-oxidative macrophage response to Hb exposure. Failed Hb clearance, inadequate HO-1 expression, and the subsequent accumulation of oxidatively damaged Hb species might thus contribute to pathologies related to oxidative stress.
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PMID:The reaction of hydrogen peroxide with hemoglobin induces extensive alpha-globin crosslinking and impairs the interaction of hemoglobin with endogenous scavenger pathways. 1870 38

Hemolysis is a fact in all extracorporeal circuits, as shown in various studies by the increasing levels of plasma-free hemoglobin (PfHb) and decreasing levels of haptoglobin during and after cardiopulmonary bypass (CPB). Beside complete red blood cell (RBC) destruction or hemolysis, RBCs can also be damaged on a sublethal level, resulting in altered rheological properties. Increased levels of free RBC constituents together with an exhaust of their scavengers result in a variety of serious clinical sequela, such as increased systemic and pulmonary vascular resistance, altered coagulation profile, platelet dysfunction, renal tubular damage, and increased mortality. Sublethal RBC damage is characterized by decreased microperfusion and hypoxic RBCs, leading to end organ dysfunction caused by cellular ischemia. Isolated extracorporeal circuit components can be considered non-hemolytic if used according to recommendations, but extracorporeal circuit composition and management during CPB can still be optimized, avoiding cell damaging mechanical forces. Although most RBC destruction in standard CPB remains within the capacity of the endogenous clearing mechanisms, in some cases, levels of PfHb do substantially rise, and precautionary measures need to be taken. Higher degree of hemolysis can be expected in young children, after extensive surgery, and in prolonged support as in patients supported by ventricular assist devices (VADs) or extracorporeal membrane oxygenation (ECMO). These patients are especially susceptible to the toxic influences of unscavenged RBC constituents and the loss of rheologic properties of the RBCs. Considering the high percentage of neurologic and renal sequela in post-cardiotomy patients, all imbalances possibly contributing to these morbidities should be focused on and prevented, if not treated. Considering the severity of the consequences of RBC damage, the high incidence of this complication, and especially the lack of interventional strategies in cases of suspected or confirmed RBC damage, there may be a need for a treatment algorithm for this phenomenon.
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PMID:Hemolysis in cardiac surgery patients undergoing cardiopulmonary bypass: a review in search of a treatment algorithm. 1919 55


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