Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476273 (respiratory distress)
 19,632 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-dose interleukin-2 (IL-2) immunotherapy can cause hypotension, respiratory distress, interstitial edema, and thrombocytopenia, similar to endotoxic shock. We have observed that IL-2 has no direct effect on coagulation factors in vitro, but it has been observed to alter the coagulant properties of vascular endothelium. Accordingly, we investigated the possibility that IL-2 infusions initiate plasma fibrinolysis and disseminated intravascular coagulation (DIC). We studied the clinical course, platelet count, and coagulation profile in response to IL-2 infusion in seven patients, two with metastatic melanoma and five with metastatic renal cell carcinoma. Every patient experienced hemodynamic instability and thrombocytopenia, and one patient suffered an unusual complication, mesenteric thrombosis. No patient had appreciable changes in the prothrombin time or the partial thromboplastin time, nor did factors V or VIII decline in the two patients observed. In four patients examined, we found decreased titers of Hageman factor (factor XII), high molecular weight kininogen, prekallikrein, and plasma thromboplastin antecedent, as if these had been consumed by reactions of the intrinsic pathway of thrombin formation. Circulating D-dimer fragments were found in the plasma of every patient at some point during each infusion cycle, and we observed decreased titers of plasminogen in the four patients just mentioned, suggesting that IL-2 infusions initiated fibrinolysis. Taken together, the clotting factor derangements and related toxicity phenomena cannot be ascribed firmly to DIC. Activation of the intrinsic (contact) system of coagulation, however, may provide one link between the vascular endothelial surface alterations caused by IL-2 infusions and the development of the systemic toxicity that resembles septic shock.
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PMID:Fibrinolysis, thrombocytopenia, and coagulation abnormalities complicating high-dose interleukin-2 immunotherapy. 198 12

A prospective study of 222 consecutive autopsies of cancer cases was undertaken to investigate whether carcinomatous lymphangitis and pure arterial tumor embolism of the lungs are different clinicopathological entities. The lungs were removed as a block and 15 sections (three from each lobe) were analyzed. A protocol containing clinical (ie, dyspnea, cyanosis, right ventricular failure, engorgement of jugular veins, and peripheral edema as main cause of death) and morphological (ie, right ventricle thickness and dilatation, vascular sclerosis, pulmonary infarct) data were carefully recorded in each case. Arterial tumor embolism was detected in 19 cases (8.5%) and carcinomatous lymphangitis in 44 cases (19.8%). We found no differences in relation to signs and symptoms of arterial tumor embolism and carcinomatous lymphangitis, but respiratory distress as the main cause of death was significantly more frequent in the cases with arterial involvement by tumor emboli. Morphologically, however, right ventricular hypertrophy-dilatation, histological signs of pulmonary hypertension, and hemorrhagic infarcts were more prevalent in the cases with arterial tumor embolism. This study permits us to conclude that although arterial tumor embolism and carcinomatous lymphangitis are clinically similar diseases, they are morphologically different entities. Our results suggest that the most probable pathogenesis of pulmonary endarteritis and subsequent pulmonary hypertension is the injury to the vascular endothelium caused by the arrest of tumor emboli.
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PMID:Pulmonary tumor embolism to arterial vessels and carcinomatous lymphangitis. A comparative clinicopathological study. 834 48

Hyperpermeability is the crux of pathogenesis of sudden lung edema in many pulmonary disorders, especially in acute lung injury and acute respiratory distress syndrome (ARDS). Using our modified method for assessment of pulmonary vascular permeability, we observed the effects of xanthine with xanthine oxidase (X-XO) perfused in rat pulmonary artery and the protection of vasoactive intestinal polypeptide (VIP) against the injury of pulmonary vascular permeability. After addition of xanthine oxidase in the perfusate reservoir containing xanthine, 125I-albumin leak index (125I-ALI) was remarkably increased while peak airway pressure (Paw) showed no significant increase, and perfusion pressure of pulmonary artery (Ppa) and lung wet/dry weight ratio (W/D) were only slightly increased. Xanthine plus xanthine oxidase also increased thromboxane B2 (TX B2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in the perfusate. Treatment with VIP obviously reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. The results indicated that VIP has potent protective activity against injury of pulmonary vascular permeability and may be a physiological modulator of inflammatory damage to vascular endothelium associated with toxic oxygen metabolites.
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PMID:[Vasoactive intestinal polypeptide prevents injury of pulmonary vascular permeability due to xanthine with xanthine oxidase]. 857 46

Platelet vascular hemostasis was assessed in 32 patients with slight craniocerebral injuries (SCCI) (Glasgow coma score 14-15) (group 1) on days 1, 3, 5, and 7 and in 84 patients (score 3-8) (group 2) in the same terms and on days 9, 14, and 21 after the injury. Under study were platelet count, spontaneous platelet aggregation and that induced by ADP, adrenalin, and ristomicin. Moderate disorders of platelet vascular hemostasis were revealed in all the patients; they were most of all expressed on day 5 and were mainly due to moderate disorders of the athrombogenicity of the vascular endothelium. The injury caused a manifest dysfunction of platelets connected with the developing disseminated intravascular blood coagulation and, specifically, with injury to the vascular endothelium. Spontaneous aggregation of platelets was the maximum on day 5 and coincided in time with an increase in Willebrand factor-dependent ristomicin-induced platelet aggregation (Willebrand factor is a marker of injury to the vascular endothelium). An increase of ristomicin-induced platelet aggregation was more often observed in the patients who died than in the survivors, and in those developing the respiratory distress syndrome (stages II-IV) and that combined with pneumonia.
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PMID:[Thrombocytic hemostasis in patients with severe craniocerebral trauma]. 902 46

Reactive oxygen species (ROS) are constantly produced in human beings under normal circumstances. Antioxidant systems help defend the body against ROS but may be overwhelmed during periods of oxidative stress, which can cause lipid peroxidation, damage to DNA, and cell death. Critical illness, such as sepsis or adult respiratory distress syndrome, can drastically increase the production of ROS and lead to oxidative stress. Sources of oxidative stress during critical illness include activation of the phagocytic cells of the immune system (the respiratory burst), the production of nitric oxide by the vascular endothelium, the release of iron and copper ions and metalloproteins, and the vascular damage caused by ischemia reperfusion. Only indirect measurements of ROS are available, but the presence of oxidative stress in critical illness is supported by clinical studies. In general, serum antioxidant vitamin concentrations seem to decrease and measures of oxidative stress seem to increase in critically ill populations. Oxidative stress has been associated with sepsis, shock, a need for mechanical ventilation, organ dysfunction, acute respiratory distress syndrome, disseminated intravascular coagulation, surgery, and the presence of an acute-phase response. In addition, higher levels of oxidative stress seem to occur in patients with more notable injuries. Dietary supplementation with antioxidant vitamins seems to be the logical answer to decreasing serum antioxidant concentrations, but antioxidants may have adverse effects. The benefit of supplementing antioxidants in critically ill populations has not been shown and requires further study.
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PMID:Oxidative stress in critical care: is antioxidant supplementation beneficial? 973

Mechanism in the pathogenesis of acute respiratory distress syndrome which is the clinical feature of pulmonary involvement in retinoic acid (RA) syndrome has been investigated. Pulmonary infiltration of matured neutrophils and leukemic cells is thought to be associated with the pathogenesis of pulmonary involvement in RA syndrome; however. Little is known about the mechanism in pulmonary infiltration of these cells. In the present study, we examined the effect of RA on IL-1beta and IL-1ra production by human alveolar macrophages in order to clarify the mechanism in pulmonary infiltration of neutrophils, since IL-1 has been shown to initiate neutrophil recruitment into the lung through up-regulated expression of adhesion molecules on vascular endothelium. RA enhanced IL-1beta and inhibited IL-1ra production by 4beta phorbol 12beta-myristate-13alpha acetate (PMA)- and lipopolysaccharide (LPS)-stimulated human alveolar macrophages. These results show that RA differentially regulates IL-1beta and IL-1ra production by alveolar macrophages and indicate that an imbalanced production between IL-1beta and IL-1ra may contribute to initiating neutrophil recruitment into the lung through up-regulated expression of adhesion molecules.
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PMID:Retinoic acid differentially regulates interleukin-1beta and interleukin-1 receptor antagonist production by human alveolar macrophages. 978 9

Targeted delivery of drugs to vascular endothelium promises more effective and specific therapies in many disease conditions, including acute lung injury (ALI). This study evaluates the therapeutic effect of drug targeting to PECAM (platelet/endothelial cell adhesion molecule-1) in vivo in the context of pulmonary oxidative stress. Endothelial injury by reactive oxygen species (e.g., H2O2) is involved in many disease conditions, including ALI/acute respiratory distress syndrome and ischemia-reperfusion. To optimize delivery of antioxidant therapeutics, we conjugated catalase with PECAM antibodies and tested properties of anti-PECAM/catalase conjugates in cell culture and mice. Anti-PECAM/catalase, but not an IgG/catalase counterpart, bound specifically to PECAM-expressing cells, augmented their H2O2-degrading capacity, and protected them against H2O2 toxicity. Anti-PECAM/catalase, but not IgG/catalase, rapidly accumulated in the lungs after intravenous injection in mice, where it was confined to the pulmonary endothelium. To test its protective effect, we employed a murine model of oxidative lung injury induced by glucose oxidase coupled with thrombomodulin antibody (anti-TM/GOX). After intravenous injection in mice, anti-TM/GOX binds to pulmonary endothelium and produces H2O2, which causes lung injury and 100% lethality within 7 h. Coinjection of anti-PECAM/catalase protected against anti-TM/GOX-induced pulmonary oxidative stress, injury, and lethality, whereas polyethylene glycol catalase or IgG/catalase conjugates afforded only marginal protective effects. This result validates vascular immunotargeting as a prospective strategy for therapeutic interventions aimed at immediate protective effects, e.g., for augmentation of antioxidant defense in the pulmonary endothelium and treatment of ALI.
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PMID:PECAM-directed delivery of catalase to endothelium protects against pulmonary vascular oxidative stress. 1285 Dec 8

Acute respiratory distress syndrome (ARDS) can be derived from two pathogenetic pathways: a direct insult on lung cells (pulmonary ARDS (ARDSp)) or indirectly (extrapulmonary ARDS (ARDSexp)). This review reports and discusses differences in biochemical activation, histology, morphological aspects, respiratory mechanics and response to different ventilatory strategies between ARDSp and ARDSexp. In ARDSp the direct insult primarily affects the alveolar epithelium with a local alveolar inflammatory response while in ARDSexp the indirect insult affects the vascular endothelium by inflammatory mediators through the bloodstream. Radiological pattern in ARDSp is characterised by a prevalent alveolar consolidation while the ARDSexp by a prevalent ground-glass opacification. In ARDSp the lung elastance, while in ARDSexp the chest wall and intra-abdominal chest elastance are increased. The effects of positive end-expiratory pressure, recruitment manoeuvres and prone position are clearly greater in ARDSexp. Although these two types of acute respiratory distress syndrome have different pathogenic pathways, morphological aspects, respiratory mechanics, and different response to ventilatory strategies, at the present, is still not clear, if this distinction can really ameliorate the outcome.
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PMID:Pulmonary and extrapulmonary acute respiratory distress syndrome are different. 1294 1

We studied cell-specific protein expression of all the major antioxidant enzymes (AOEs) and related proteins, such as copper-zinc superoxide dismutase (CuZnSOD), manganese SOD (MnSOD), extracellular SOD (ECSOD), catalase, the heavy and light chains of gamma-glutamylcysteine synthetase (gamma-GCS-l and gamma-GCS-h, also called glutamate cysteine ligase), the rate-limiting enzyme in glutathione synthesis, hemeoxygenase-1 (HO-1), and thioredoxin (Trx), in developing human lung, respiratory distress syndrome, and bronchopulmonary dysplasia by immunohistochemistry. Generally, after 17 weeks of gestational age, MnSOD was predominantly expressed in bronchial epithelium, alveolar epithelium, and macrophages, CuZnSOD was expressed in bronchial epithelium, ECSOD was expressed in bronchial epithelium, vascular endothelium, and the extracellular matrix, catalase was expressed in bronchial epithelium and alveolar macrophages, gamma-GCS-h was expressed in bronchial epithelium and endothelium, and gamma-GCS-l was expressed in bronchial epithelium. Trx was restricted to bronchial epithelium and to a lesser extent to alveolar macrophages, and HO-1 found in alveolar macrophages. Basically, the expression of these enzymes was similar in normal and diseased lung. It can be concluded that various AOEs and related proteins differ in their distribution and expression in lung before term, but generally it seems that infants are better adapted to high oxygen tension than might be expected.
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PMID:Distribution of antioxidant enzymes in developing human lung, respiratory distress syndrome, and bronchopulmonary dysplasia. 1531 90

The Kunitz-type proteinase inhibitor, tissue factor pathway inhibitor (TFPI), is the only endogenous inhibitor of the tissue factor (TF)-mediated coagulation pathway that plays a dominant role in normal haemostasis. TFPI exerts its action by binding to factor Xa (FXa) forming a TFPI-FXa complex that then, in a second step, binds and effectively inhibits the TF-factor VIIa (FVIIa) complex. Both full-length TFPI and chemically modified forms (e.g., truncated, glycosylated or phosphorylated TFPI variants) exert various pharmacological effects. The anticoagulant and antiplatelet actions of TFPI, its potency in inhibiting thrombin and FXa generation, as well as its favourable antithrombotic effectiveness seen in different animal models of venous and arterial thrombosis make this inhibitor a promising agent that could be potentially useful in several clinical indications. The inhibitory action of TFPI is accelerated by heparin. Heparin, as well as low molecular weight heparin (LMWH) derivatives, release TFPI from the vascular endothelium, an effect which seems to contribute mainly to the antithrombotic effectiveness of these drugs. The clinical relevance of TFPI is still undefined. Based on the beneficial actions in animal studies, as well as on the results obtained in first clinical investigations, TFPI is expected to be effective in the treatment of various diseases, such as disseminated intravascular coagulation, sepsis, coronary syndromes, stroke and acute respiratory distress syndrome (ARD). Further clinical trials should clarify the role of TFPI and more importantly define its potential usefulness as a prophylactic and/or therapeutic agent.
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PMID:Recombinant TFPI and variants: potential implications in the treatment of cardiovascular disorders. 1599 20


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