Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perfluoroisobutene (PFIB) is a hydrophobic reactive gas produced by the pyrolysis of polytetrafluoroethane which induces pulmonary oedema similar to that induced by phosgene when inhaled. When a lethal dose is inhaled by Porton strain rats total non-protein thiol (NPSH) and glutathione (GSH) in the lung are reduced by between 30 and 49%, respectively. If the endogenous levels of thiols in the lung are reduced by pretreatment with buthionine sulfoximine (BSO) 16 hr before exposure to PFIB, the rats become more susceptible to the effects of the gas. The effect of BSO pretreatment on toxicity was prevented by pretreatment 30 min before exposure, with 5 mmol/kg N-acetylcysteine (NAc). NAc increased the levels of cysteine (CySH) in the lung by 150% and GSH was unaffected. Similarly pretreatment with 3 mmol/kg CySH also protected against toxicity and raised CySH levels by 100%. A series of cysteine esters and cystine dimethyl ester (CDME) have been synthesised which selectively raise lung levels of CySH in the rat lungs after intraperitoneal (i.p.) injection. The methyl ester and CDME raised lung levels of CySH by 4000 and 2000%, respectively, 10 min after i.p. injection whilst GSH levels remained unchanged. Cysteine isopropyl ester raised lung levels of CySH by 10,600% but liver levels by only 1400%. All esters except the t-butyl ester (CTBE) also raised maximal plasma levels of NPSH by up to 500%; however, when NAc was injected plasma levels increased by over 1500%. Rats treated with these esters at 3 mmol/kg and with NAc at 5 mmol/kg were protected against lethal doses of PFIB in all cases except when CTBE was used. It appears that these cysteine esters may distribute preferentially into the lung, unlike NAc. The selective enhancement of pulmonary CySH levels may provide a method for the protection of lungs against inhaled reactive toxicants by increasing intracellular CySH. Levels of CySH may also be raised in epithelial lining fluid thus reducing access of gaseous toxicants to pulmonary tissue.
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PMID:Protection by cysteine esters against chemically induced pulmonary oedema. 176 85

Clinically, lung injury is characterized by one or more of the following: altered gas exchange, dyspnea, decreased static compliance, and nonhydrostatic pulmonary edema. Although many antioxidants have been investigated in in vitro systems and in animal models, only some are at the developmental stage, or safe for clinical trials. Considerable evidence has recently accumulated supporting the hypothesis that leukocyte activation involves release of large quantities of highly reactive oxygen radicals, and hydrogen peroxide is partially responsible for diffuse microvascular and tissue injury in septic patients. Granulocyte depletion in animal models reduces the degree of fall in dynamic lung compliance and the increase in airflow resistance, lymph flow, and hypoxemia secondary to endotoxin administration. We hypothesized that the partial benefit derived from granulocyte depletion was due to the effective removal of a major source of oxygen radicals. Among the list of free radical scavengers, N-acetylcysteine stands out, because of its established usefulness in at least one human disease thought to be secondary to free radical organ damage (acetaminophen or paracetamol overdose). It is an extremely safe agent with a wide toxic-therapeutic window. An increasing number of animal studies indicate efficacy for this agent in the prevention and therapy of lung injury involving toxic oxygen species. We developed a randomized, double-blind protocol for the study of intravenous N-acetylcysteine in patients with established adult respiratory distress syndrome (ADRS). Results of this trial are preliminary. Nevertheless, they indicate that plasma and red cell glutathione levels are decreased in ADRS patients, and that N-acetylcysteine increases plasma cysteine as well as plasma and red cell glutathione. There are also indications that cardiopulmonary physiology is favorably affected by such therapy including improvements in chest radiograph edema scores, pulmonary vascular resistance, static compliance, oxygen delivery, and oxygen consumption.
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PMID:N-acetylcysteine in experimental and clinical acute lung injury. 192 12

The human pulmonary edema fluid concentrations of LTC4 and of LTD4 and LTE4, derived peptidolytically from LTC4, were assessed by radioimmunoassays of the mediators resolved by reverse-phase high-performance liquid chromatography. The mean pulmonary edema fluid concentration (+/- SD) of LTD4 of 19.2 +/- 25.6 nM for 12 patients with the adult respiratory distress syndrome and of LTE4 of 192 +/- 309 nM for 10 of the patients were significantly higher (P less than 0.005 and P less than 0.05) than those of 2.2 +/- 2.4 and 11.0 +/- 18.2 nM, respectively, for 10 patients with cardiogenic pulmonary edema, whereas the lower mean concentrations of LTC4 were not significantly different for the two groups. Pulmonary edema fluid from five patients with adult respiratory distress syndrome, one with cardiogenic pulmonary edema, and one with an indeterminate syndrome contained similar concentrations of peptidoleukotriene peptidases. The LTC4 and LTD4 peptidolytic activities in ARDS fluids were 81 and 142 kD, respectively, by gel filtration. The extents of peptidolysis of [3]LTC4 and [3]LTD4 by 100 microliter of pulmonary edema fluid attained respective mean maximum levels of 74.5 +/- 2.9% (N = 5) and 37.7 +/- 10.2% (N = 4) after 30 min at 37 degrees C and were inhibited by serine-borate and by cysteine, respectively. The predominance of LTD4 and LTE4 over LTC4 in states of altered pulmonary vascular pressure and permeability thus is attributable to two distinct peptidases.
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PMID:Sulfidopeptide-leukotriene peptidases in pulmonary edema fluid from patients with the adult respiratory distress syndrome. 284 67

Arachidonic acid metabolites produced by cyclooxygenase and lipoxygenase pathways affect pulmonary transvascular fluid and protein fluxes after pulmonary microvascular injury. Some of these products may contribute to the increase microvascular endothelial permeability whereas others may increase pulmonary microvascular filtration pressure. Prostaglandin (PG) E2, PGF2 alpha and cyclic endoperoxides increase microvascular pressure and thus increase the transvascular fluid filtration rate. Thromboxanes increase microvascular pressure and in addition may promote neutrophil adherence to endothelium and platelet aggregation, whereas prostacyclin has opposing actions. The cysteine-containing leukotrienes (LTs) (LTC4, LTD4, and LTE4) increase pulmonary microvascular pressure via a thromboxane-mediated mechanism, and LTB4 may increase pulmonary vascular permeability. Arachidonic acid metabolites do not appear to alter directly pulmonary endothelial membrane permeability but may contribute to the increased permeability by their actions on blood-formed elements. The pulmonary vasoconstrictor arachidonic aid metabolites increase microvascular hydrostatic pressure and may thereby enhance the degree of pulmonary edema.
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PMID:Pulmonary microvascular effects of arachidonic acid metabolites and their role in lung vascular injury. 298 32

Recently there has been a great deal of interest in exploring possible ways to protect the lung from oxidant damage. Since sulfhydryl compounds are among the most important endogenous antioxidants, their therapeutic use has been proposed. Glutathione (GSH), the main intracellular nonprotein sulfhydryl, plays an important role in the maintenance of cellular proteins and lipids in their functional state. With oxidant stress, GSH acts to protect cell constituents as evidenced by increased turnover to GSSG, formation of mixed disulfides with proteins, utilization of NADPH, and utilization of glucose in the pentose pathway. When GSH is experimentally lowered (e.g., by protein deficiency or with diethylmaleate) the toxic effects of oxidant stress are exacerbated as evidenced by increased membrane and cell damage, pulmonary edema, and mortality. Several recent investigations have shown that sulfhydryl reagents (particularly N-acetyl cysteine, a cell-permeable GSH precursor) can provide significant protection against certain pulmonary toxins. N-acetyl cysteine reduced the lethal effects of 100% O2 in rats by 65%. Therefore, the therapeutic potential of sulfhydryl reagents in the treatment and prevention of oxidant injury and the mechanisms involved are an important direction for lung research.
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PMID:Protective role of sulfhydryl reagents in oxidant lung injury. 306 90

1. The intraperitoneal administration of cysteine, N-acetylcysteine, the methyl, isopropyl, cyclo pentyl, neo pentyl, cyclo hexyl and tertiary butyl esters of cysteine and of cystine dimethyl ester increased the levels of total non-protein sulphydryls and cysteine in the bronchioalveolar lavage fluid and plasma of rats. In all cases the non-protein sulphydryl levels reflected the increased cysteine levels. 2. Cysteine, N-acetylcysteine, the cysteine esters and cystine dimethyl ester raised the levels of non-protein sulphydryls and hence cysteine in the bronchioalveolar lining fluid as follows: CIPE > CCPE > CME > CDME > CneoPE > CCHE > Nac > CySH > CTBE. 3. Plasma levels of NPSH were increased as follows: Nac > CySH > CCPE > CCHE > CneoPE > CIPE > CME > CDME > CTBE. 4. All except CTBE have been shown to protect against the lethal effects of inhaled perfluoroisobutene, a pyrolysis product of polytetrafluoroethene which induces a fulminating pulmonary oedema. 5. This study showed that by raising the levels of thiols in the bronchioalveolar lavage fluid (BALF), the epithelial cells lining the bronchiolar, alveolar regions of the lung could be protected against inhaled toxicants. 6. It is proposed that increased thiol levels in the BALF may contribute to the overall protection induced by these compounds by reacting with inhaled electrophiles to prevent or reduce damage to tissue in close proximity to the airways.
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PMID:Thiol levels in rat bronchio-alveolar lavage fluid after administration of cysteine esters. 785 97

Reactive oxygen metabolites (ROMs) are thought to play a key role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Accordingly, the use of ROM scavengers, such as N-acetyl-cysteine or dimethylthiourea, as therapeutic adjuncts to prevent oxidant-mediated damage to the lung have been evaluated extensively in animal models of ARDS. Results with this approach have been quite variable among studies. Another strategy that has been examined in animal models of ARDS is the administration of various enzymes, particularly superoxide dismutase (SOD) or catalase (CAT), in an effort to promote the conversion of ROMs to inactive metabolites. In theory, this strategy should be more effective than the use of ROM scavengers since a single molecule of a catalytically active molecule can neutralize a large number of molecules of a reactive species, whereas most scavengers act in a stoichiometric fashion to neutralize radicals on a mole-for-mole basis. This notion is supported by studies showing that prophylactic treatment with CAT provides impressive protection against acute lung injury induced in experimental animals by the administration of lipopolysaccharide (LPS). Results with SOD have been more variable. Recently, we have utilized a porcine model of LPS-induced ARDS to investigate the therapeutic potential of EUK-8, a novel, synthetic, low molecular salen-manganese complex that exhibits both SOD-like and CAT-like activities in vitro. Using both pre- and post-treatment designs, we have documented that treatment with EUK-8 significantly attenuates many of the features of LPS-induced acute lung injury, including arterial hypoxemia, pulmonary hypertension, decreased dynamic pulmonary compliance, and pulmonary edema. These findings support the view that salen-manganese complexes warrant further evaluation as therapeutic agents for treatment or prevention of sepsis-related ARDS in humans.
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PMID:Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury. 882 94

1. Perfluoroisobutene, a pyrolysis product of polyetrafluoroethene may cause pulmonary oedema and death when inhaled. Oral N-acetylcysteine has shown protection against inhalation of perfluoroisobutene and in this study we have tried to elucidate the mechanism by which protection is mediated. 2. Protection against the lethal effects of inhaled perfluoroisobutene has been shown when N-acetylcysteine has been orally administered 4, 6 or 8 h before gas exposure. 3. Plasma levels of cysteine, glutathione and N-acetylcysteine were increased for up to 7 h following oral administration of Nac. 4. N-acetylcysteine was not detected in the bronchioalveolar lavage fluid following oral administration. 5. Duration of protection in vivo has been related to the duration of increased thiol levels in the plasma.
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PMID:Oral N-acetylcysteine protects against perfluoroisobutene toxicity in rats. 915 46

Adult Respiratory Distress Syndrome is a disease with functional lung heterogeneity and thus a ventilator-delivered breath may over-distend non-involved areas. In rats we examined ventilator-delivered tidal volume (TV) breaths of 7 and 20 ml/kg on lung water as evidence of lung injury. We examined the role of aquaporins on ventilator-induced lung injury (VILI) by infusing HgCl(2) which inhibits aquaporins by binding cysteine. Wet to dry lung weight ratio (W/D) as evidence of lung water was 4.47+/-0.1 SEM in controls, 4.6+/-0.1 and 5.5+/-0.2 (P<0.05) in rats ventilated at 7 and 20 ml/kg, respectively. Pulmonary artery pressure (PAP) rose from 23+/-1 to 26+/-1 mmHg (P<0.05, n=7) and cardiac output fell from 104+/-2 to 67+/-3 ml/min (P<0.05) in rats ventilated at 20 ml/kg. Left ventricular end diastolic pressure (n=3) was unchanged. Evans Blue dye, an albumin marker, increased from a control 37+/-11 to 97+/-41 mg/g wet lung in TV 20 rats (P<0.05). HgCl(2) infused slowly by tail vein did not significantly raise PAP, but did increase W/D to 6+/-0.2 (P<0.05) in rats ventilated at 20 ml/kg but not at 7 ml/kg. Equimolar cysteine infusions prevented the HgCl(2) from increasing the W/D above that seen with TV 20 ml/kg. Thus ventilation with TV of 20 ml/kg produced a protein-rich lung edema. Aquaporin channels may have a protective effect in VILI.
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PMID:Aquaporin channels may modulate ventilator-induced lung injury. 1116 7

MODALITIES FOR THE DIAGNOSIS OF VENOUS THROMBOEMBOLISM: Currently rely on the confrontation of the initial clinical data and the results of D-dimer measurements, a venous Doppler, although reliable, is not a first-line exploration. REGARDING TREATMENT: Indications for thrombolysis are currently limited to massive pulmonary oedema with shock. Alteplase added to heparin improves the progression of severe embolism; it spares the patients from heavy interventions of resuscitation but the mortality remains the same. Concerning anticoagulant treatments, prolonged antivitamin K at classical doses is more effective than low doses and for limited duration if phlebitis is an idiopathic one. FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION: Treatment of these heart failures, formerly know as 'diastolic' is similar to that of the acute phase of systolic heart failure. However, care should be taken with vasodilatators. CONCERNING HEART FAILURE IN GENERAL: The brain natriuretic peptide (BNP) represents a remarkable progress for the aetiological diagnosis of dyspnoea (inferior to 80 pg/ml in the case of pulmonary origin, superior to 300 pg/ml in the case of cardiac origin or severe pulmonary embolism). Regarding treatment, for acute heart failure, it is still the association of nitrates and diuretics, with oxygen therapy and eventually inotropics. Beta-blockers, which have revolutionized the treatment of chronic heart failure, must be maintained whenever possible in the case of the onset of acute pulmonary oedema. Multisite pacing is increasingly used in refractory chronic heart failure. Implantable defibrillation has become common practice. Non-invasive ventilation (Bi or C-PAP) is interesting in acute cardiogenic pulmonary oedema. THE PREVENTIVE ROLE OF N ACETYL-CYSTEINE: N acetyl cysteine reduces the incidence of nephropathies induced by the radio contrast products in patients with chronic kidney failure. Combined with hydratation, it must be proposed the day before and on the day of the procedure in any patient with diabetes or kidney failure.
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PMID:[Diagnostic and therapeutic progress. Venous thromboembolism, cardiac insufficiency and radio contrast agents]. 1522 98


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