Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acid aspiration leads to increased neutrophil (PMN) oxidative metabolism, an event associated with lung leukosequestration and permeability increase. Neutropenia protected the vascular barrier function against acid injury. This study tests whether active oxygen species and elastase (which are presumably released by adherent PMNs) affect the microvascular barrier. Anesthetized rats underwent tracheostomy and insertion of a cannula into a lung segment. This was followed by localized instillation of 0.1 N HCl (n = 18) or saline (n = 18). Sequestration of PMNs in acid-aspirated and nonaspirated segments was 77 and 46 PMNs/high-power field (HPF), respectively, which was higher than control values of 11 and 8 PMNs/10 HPF in saline-aspirated and nonaspirated regions (P less than 0.05). Acid aspiration was associated with increased protein concentration in bronchoalveolar lavage (BAL) fluid to 3,550 and 2,900 micrograms/ml in the aspirated and nonaspirated lungs, respectively, which were higher than control values of 420 and 400 micrograms/ml (P less than 0.05). Acid aspiration also led to increased lung wet-to-dry weight ratios (W/D) of 6.6 and 5.4, which were higher than control values of 3.4 and 3.3 (P less than 0.05). Intravenous treatment of rats (n = 18) 90 min after aspiration with scavengers of reactive oxygen species, superoxide dismutase (1,500 U/kg), and catalase (5,000 U/kg), both conjugated to polyethylene glycol, did not reduce PMN sequestration but attenuated acid aspiration-induced increase in protein accumulation in BAL fluid in the aspirated and nonaspirated segments (990 and 610 micrograms/ml) as well as the increased lung W/D (4.6 and 4.0; all P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reactive oxygen species and elastase mediate lung permeability after acid aspiration. 139 82

The role of superoxide in scar formation following renal infection caused by mannose-sensitive (MS) piliated strains of bacteria was studied in the experimental pyelonephritis model using female Sprague-Dawley rats. The MS piliated strain stimulated renal scarring to a significantly greater extent than either the non-piliated or MR-piliated strain. Modulation of leukocytes by administering cyclophosphamide to induce neutropenia and colchicine to inhibit leukocyte migration was effective in preventing renal scarring. Treatment with superoxide dismutase during the early stage of infection was also effective in preventing scar formation. Finally, the production of superoxide by rat leukocytes was significantly larger following stimulation by MS piliated than either the non-piliated or MR piliated strains. These observations suggest that superoxide released from leukocytes plays a critical role in the development of renal scarring following a bacterial infection, especially by MS piliated strains.
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PMID:Role of superoxide in renal scarring following infection by mannose-sensitive piliated bacteria. 168 8

Ethanol-induced gastric mucosal injury closely resembles an inflammatory response. Thus, in vivo and in vitro experimental models were used to assess whether ethanol is proinflammatory in concentrations likely to be encountered by the gastric mucosa during acute intoxication. Perfusing the rat gastric lumen with progressively increasing concentrations of ethanol (10%, 20%, and 30%) resulted in a dose-dependent increase in 51Cr-ethylenediaminetetraacetic acid clearance from blood-to-gastric lumen. Rendering the animals neutropenic (with antineutrophil serum) ameliorated the ethanol-induced mucosal injury; the degree of protection was directly related to the severity of neutropenia. Neither superoxide dismutase, catalase, nor sodium benzoate offered any protection against ethanol-induced injury, indicating that neither superoxide anion, hydrogen peroxide, nor the hydroxyl radical is involved. To assess further whether ethanol could exert proinflammatory effects an in vitro model consisting of cultured bovine microvascular endothelial cells and isolated human neutrophils was used. Ethanol at concentrations of 1.0%-4.0% (but not at 0.1%-0.5%) increased neutrophil adherence to endothelial cells and enhanced neutrophil-mediated endothelial cell injury. We conclude that ethanol is proinflammatory at concentrations that may be achieved in the gastric mucosa during acute intoxication. The ethanol-induced, neutrophil-mediated cell injury does not appear to involve oxy radicals.
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PMID:Ethanol-induced injury to the rat gastric mucosa. Role of neutrophils and xanthine oxidase-derived radicals. 231 75

We investigated the lung injury that occurs following reexpansion of a unilateral pneumothorax and determined the effect of superoxide dismutase (SOD) infused immediately prior to reexpansion on this injury. After 7 days of at least 80% right pneumothorax, rabbits received intravenous infusions of either SOD (n = 7), heat-inactivated SOD (n = 1), or vehicle (n = 7) immediately before lung reexpansion. Lung injury was assessed by measuring the systemic white cell counts, pulmonary blood volumes, extravascular albumin, extravascular lung water, wet/dry weight ratios, and histology 2 h after reexpansion. The reexpanded lung showed increased extravascular albumin, extravascular lung water and wet/dry weight ratios with decreased blood volumes compared to the uninjured lung. SOD delayed the onset of leukopenia and neutropenia at 3 and 7 min after reexpansion, but the white cell counts had decreased to the same level in both groups by 30 min. SOD had no effect on the degree of injury after 2 h. While a single bolus of SOD given immediately before reexpansion delayed the onset of this injury, it did not affect the injury that subsequently developed in the lung.
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PMID:Evaluation of reexpansion pulmonary edema following unilateral pneumothorax in rabbits and the effect of superoxide dismutase. 239 1

In the present investigation, the involvement of PMNLs and oxygen free radicals was explored in rats with postischemic perfusion disturbances of the brain. Reversible forebrain ischemia was induced by bilateral clamping of both carotid arteries in combination with hemorrhagic hypotension. This procedure resulted in a reproducible DPH 1 hr after start of recirculation. Neutropenia was induced by sheep ANS. One group received ANS before and a second group immediately after termination of ischemia. Two additional groups received SOD before or immediately after ischemia. Regional postischemic CBF was determined by [14C]iodoantipyrine autoradiography. It was found that CBF significantly improved in cortical structures of animals treated with ANS before ischemia. Treatment with ANS at the end of ischemia had no effect on the postischemic CBF depression. Neither was injection of SOD effective to influence DPH, irrespective whether given before or after ischemia. It is concluded that PMNLs play a role in the development of DPH of the brain, whereas free radical mechanisms seem to be less relevant.
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PMID:Effects of neutrophil depletion and superoxide dismutase on postischemic hypoperfusion of rat brain. 239 65

Reactive oxygen species have been proposed as pathophysiological factors responsible for the hypodynamic circulatory response to gram-negative endotoxin. To test this hypothesis, we examined the cardiorespiratory effects of mechanistically different oxygen free radical scavenging agents during Escherichia coli endotoxemia in beagle dogs. Pentobarbital-anesthetized dogs were instrumented for repeated sampling of cardiorespiratory, hematologic, and tissue blood flow (radiolabeled 15-micron microspheres) indexes. Four groups were studied: 1) time-matched control dogs (n = 6); 2) dogs receiving only endotoxin (1.5 mg/kg; n = 6); 3) dogs receiving endotoxin and combination therapy with allopurinol (150 mg/kg) plus superoxide dismutase (5 mg/kg) and catalase (5 mg/kg; n = 6); and 4) dogs receiving endotoxin and deferoxamine (30 mg/kg; n = 5). Measured variables in control dogs were constant during the 4-h study, whereas endotoxin-injected dogs consistently demonstrated the following: 1) maintained reductions in blood pressure (greater than 45%), left ventricular systolic pressure (greater than 43%), left ventricular maximum rate of pressure development (+/- dP/dtmax) (greater than 41%), cardiac index (greater than 33%), and blood flow in all sampled tissues except liver and skeletal muscle; 2) transient tachypnea, bradycardia, and arterial acidosis; and 3) persistent neutropenia and hemoconcentration. Neither of the free radical scavenging protocols significantly improved measured variables during endotoxemia (P greater than 0.05). This lack of efficacy suggests that superoxide anion, hydrogen peroxide, and hydroxyl radical may lack primary pathophysiological importance during the development of E. coli endotoxicosis in intact dogs.
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PMID:Evidence for lack of importance of oxygen free radicals in Escherichia coli endotoxemia in dogs. 328 94

Intravascular complement activation in rats following thermal injury or vascular infusion of cobra venom factor results in acute lung injury as determined morphologically and measured by increases in lung vascular permeability. The acute lung injury is associated with the early appearance of C5-derived chemotactic activity in the circulation coincident with the development of neutropenia. The lung injury is closely linked to availability of complement and neutrophils and can be prevented by systemic treatment of animals with a combination of superoxide dismutase and catalase, specific inhibitors of toxic oxygen metabolites. These data suggest that intravascular complement activation leads to activation of neutrophils and their intrapulmonary capillary sequestration, and subsequent acute lung injury, which is associated with production and release of oxygen-derived free radicals by C5a-activated blood neutrophils.
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PMID:Lung injury secondary to chemotactic factor-induced leukocyte activation. 634 Apr 40

After 14 days' bone marrow maturation, neutrophil granulocytes reach the tissues where for 1-2 days they form the army whose phagocytic function was described by llya Metchnikoff in 1882. At that time, Paul Ehrlich was developing his neutrophil secretory theory which had less success until it returned with a vengeance in the last decade. Neutrophils are not only phagocytes. Above all they are cells that secrete bactericidal effectors and regulators (amplifiers and modulators) of the inflammatory focus. More and more sophisticated methods are being used to study phagocytosis, from the point of view both of the mechanism of chemotaxis and its role in inflammation and of the mediators of oxygen-dependent bactericidal action (superoxide anion, oxygenated water, hydroxyl radicals, myeloperoxidase, halogen ions and superoxide dismutase). In addition, the importance of oxygen-independent bactericidal mechanisms has been confirmed by the discovery of proteins such as BPI (Bactericidal Permeability Increasing Protein). Study of neutrophil dysfunction throws light on a number of neutrophil regulatory and effector mechanisms; it also proves useful in explaining the recurrent infections observed in some congenital disorders (chronic granulomatous disease, the "lazy leucocyte syndrome", the Chediak-Higashi syndrome, ichthyrosis , Job's syndrome...) or those associated with transitory neutrophil disorders (measles, severe bacterial infection...). Neutropenia induced by some antibiotics is easily demonstrated, but the interactions between these antibiotics and neutrophils are complex: phagocyte concentration of antibiotic, neutrophil inactivation of antibiotic, effect of antibiotic on microbe-leucocyte interaction such as an alteration in phagocytic and chemotactic response. The neutrophil is the first blood cell to arrive at the inflammatory focus; it is also at the centre of the response, next to the humoral mediators which both act upon it and which it itself secretes.
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PMID:[Neutrophil functions and interactions in the inflammatory reaction]. 673 54

Acute thermal injury (70 degrees C, 30 sec) to rat skin results in progressive consumptive depletion of the complement system. Individual complement components (C3, C4, C6) each show reductions in hemolytic activity. Crossed immunoelectrophoresis analysis of serum from thermally injured rats reveals conversion of C3 compatible with activation of the complement system. During the first hour following thermal injury, C5a-related chemotactic activity appears in the serum and is temporally related to the development of neutropenia. Lung injury, as revealed by increases in lung permeability, develops progressively during a 6-hour period and parallels changes in complement levels. Morphologically, lung changes include leukoaggregates within pulmonary capillaries and the presence of intra-alveolar hemorrhage. Protection from lung injury following remote thermal injury to skin is afforded by depleting animals of complement or neutrophils, or by systemic treatment of animals with a combination of catalase and superoxide dismutase. Antihistamine drugs have no protective effect. These data suggest that acute thermal injury leads to systemic complement activation, neutrophil activation, and acute lung injury that is related to production of toxic oxygen products by activated blood neutrophils.
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PMID:Oxygen radical dependent lung damage following thermal injury of rat skin. 684 28

Intravascular activation of the complement system with cobra venom factor results in acute lung injury, which has been quantitated by increases in lung vascular permeability. Cobra venom factor preparations devoid of phospholipase A2 activity retain full lung-damaging capacity. The lung injury is associated with the preceding appearance of chemotactic activity in the serum coincident with the development of a profound neutropenia. The chemotactic activity is immunochemically related to human C5a. Morphologic studies have revealed discontinuities in the endothelial cell lining of lung alveolar capillaries, damage and/or destruction of endothelial cells in these areas, plugging of pulmonary capillaries with neutrophils that are in direct contact with vascular basement membrane, the presence of fibrin in alveolar spaces and in areas adjacent to damaged endothelial cells, and intraalveolar hemorrhage. Lung injury is dramatically attenuated in animals that have been previously neutrophil depleted. Teh intravenous injection of superoxide dismutase or catalase also provides significant protection from the pulmonary damage. Very little protection from the pulmonary damage. Very little protection is afforded by pretreatment of rats with antihistamine. These studies suggest that intravascular activation of the complement system leads to neutrophil aggregation and activation, intrapulmonary capillary sequestration of neutrophils, and vascular injury, which may be related to production of toxic oxygen metabolites by complement-activated neutrophils.
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PMID:Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites. 706 50


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