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)

Acute respiratory distress syndrome (ARDS), is characterised by capillary permeability and pulmonary oedema formation and may complicate a variety of medical and surgical illnesses. As a self-perpetuating state of inflammatory derangement, acute lung injury (ALI)/ARDS is manifest clinically as rapid development of radiographic infiltrates, severe hypoxaemia and reduced lung compliance. Over the years, researchers have made significant progress in elucidating the pathophysiology of this complex syndrome. Therapies targeting specific pathophysiologic steps in the development or persistence of this syndrome are in various stages of laboratory and clinical testing. Results to date have shown nitric oxide (NO) to improve oxygenation in the majority of patients but fail to improve mortality. Surfactant replacement has had limited success in adults, but new formulations and delivery methods may prove beneficial. Several inflammatory mediator-targeted therapies have progressed successfully through early clinical evaluation. Among these, neutrophil elastase inhibitors have shown the most promise and are currently undergoing Phase III trials. Other mediator-targeted therapies, such as prostaglandin E1, IL-10 and platelet activating factor antagonists, have not been found efficacious in large clinical trials of ARDS. However, these therapies, along with coagulation modulators, may have a favourable impact on ARDS by improving outcomes in sepsis, the greatest risk factor for developing this condition. In the interim, supportive care through improvements in mechanical ventilation are beneficial, while specific fluid balance and nutrition strategies may prove advantageous.
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PMID:Clinical developments for treating ARDS. 1177 19

Pulmonary arterial hypertension (PAH) is commonly associated with the CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. Inhaled nitric oxide (iNO) is often used to assess acute vasoresponsiveness in patients with PAH, and reports of adverse reactions have been infrequent. We describe two of nine patients with PAH and CREST syndrome who had pulmonary edema develop during acute iNO testing. This complication was not encountered in the 46 patients with other forms of PAH tested with iNO. We suggest that iNO should be used with caution, if at all, to test acute vasoreactivity in patients with CREST syndrome.
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PMID:Pulmonary edema caused by inhaled nitric oxide therapy in two patients with pulmonary hypertension associated with the CREST syndrome. 1183 88

Acute respiratory distress syndrome is the clinical manifestation of severe, acute lung injury. It is characterized by the acute onset of diffuse, bilateral pulmonary infiltrates secondary to noncardiogenic pulmonary edema, refractory hypoxia, and decreased lung compliance. Acute respiratory distress syndrome occurs most frequently in the setting of sepsis, aspiration of gastric contents, trauma, or multiple transfusions. Its complex pathophysiology involves an inciting local or systemic event that initiates pulmonary endothelial and epithelial damage and subsequent increased permeability. Tachypnea, hypoxia, and respiratory alkalosis are typical early clinical manifestations, and they are usually followed by the appearance of diffuse pulmonary infiltrates and respiratory failure within 48 hours. Early identification and treatment of the underlying disorder, along with aggressive supportive care, are essential. Experimental therapies, including those using nitric oxide and surfactant, have not been shown to improve mortality in patients with ARDS, but new therapeutic approaches such as low-volume ventilation have been shown to decrease mortality. Many patients who survive ARDS have permanent, mild to moderate impairment of lung function. Quality of life after hospitalization with ARDS may be poorer than that in similar patients without ARDS.
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PMID:Acute respiratory distress syndrome. 1201 5

1. The effects of ozone inhalation (90 min, 2.15+/-0.05 p.p.m.) and their modification by dexamethasone (20 mg kg(-1)) or the phosphodiesterase-4 inhibitor, rolipram (1 mg kg(-1)), administered (i.p.) 24 and 0.5 h before and 24 h after ozone exposure were examined in conscious guinea-pigs. 2. Ozone caused an early-phase bronchoconstriction (EPB) as a fall in specific airways conductance (sG(aw)) measured by whole body plethysmography, followed at 5 h by a late-phase bronchoconstriction (LPB) and increased respiratory rate. Rolipram did not alter this profile but dexamethasone inhibited the EPB. 3. Airway hyperreactivity to inhaled histamine (1 mM, 20 s) occurred at 0.5, 2, 12, 24 and 48 h after ozone inhalation, the 2 h change being abolished by rolipram and dexamethasone. 4. Bronchoalveolar lavage fluid (BALF) macrophages, eosinophils and neutrophils were significantly (P<0.05) elevated at 12, 24 and 48 h after ozone exposure, the 48 h influx being significantly attenuated (P<0.05) by rolipram and dexamethasone. 5. BALF nitric oxide (NO) metabolites decreased 0.5 h after ozone exposure by 52%, recovered at 2 h and significantly increased at 12 (101%) and 24 h (127%). The elevated NO was unaffected by rolipram or dexamethasone. 6. Lung oedema, measured from wet/dry weight differences, was significant 12, 24 and 48 h after ozone exposure, the latter being significantly attenuated (P<0.05) by rolipram and dexamethasone. 7. Ozone exposure of guinea-pigs produced features common to COPD. Although rolipram and dexamethasone did not affect the airway function changes, they inhibited the inflammation, airway hyperreactivity and oedema.
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PMID:Airway function, oedema, cell infiltration and nitric oxide generation in conscious ozone-exposed guinea-pigs: effects of dexamethasone and rolipram. 1208 83

The first limiting factor of dietary zinc deficiency has been described as a loss of the protective role of zinc against auto-oxidation of membrane sulfhydryl (SH) compounds. It has now been established that the prohormones (nutriuretic peptides) of the intestinal guanylin family are activated extracellularly by conversion of cysteines in the peptide to disulfide bridges. The induction of uroguanylin mRNA is elevated in intestinal zinc deficiency and nutriuretic peptides regulate epithelial transport of salt and water. Nitric oxide (NO) is also a modulator of salt and water transport. The constitutive forms of nitric oxide synthase (cNOS) in neurons and endothelial cells are calcium-dependent. The inducible form of nitric oxide synthase (iNOS) is activated by bacterial entero-toxins and damaged mucosa with NO penetrating the cell and acting directly on guanylate cyclase. The activated receptor-guanylate cyclases initiating the intracellular cycle 3'-5' guanasine monophosphate (cyclic GMP) cascade in target cells results in a flux of chloride and water into the intestinal lumen. Most of the actions of NO are mediated by activation of cyclic GMP. High-altitude pulmonary edema (HAPE) is associated with a defect in transepithelial water transport. It is suggested that dietary zinc, by modulating thiol oxidation to disulfides in guanylin prohormones to active hormones, is associated with salt and water secretion such that the overworked heart in hypoxemia increases the production and release of natriuretic peptides to activate guanylate cyclase receptors in target tissue in sudden infant death syndrome.
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PMID:Sudden infant death syndrome: is it a transepithelial transport disorder? 1232 27

In the course of investigations on mechanisms underlying development of neurogenic pulmonary edema (NPE), we have evaluated effects of nitric oxide (NO) in the central nervous system on incidence and severity in the fibrin-induced pulmonary edema model. Rats left-unilaterally vagotomized 1, 2 and 4 weeks before injections of fibrinogen and thrombin into the cisterna magna, after cutting the right vagus nerve, grouped as LVIW, LV2W or LV4W, respectively. The brain NO synthase (NOS) mRNA level in the left medulla oblongata was elevated in the LV2W group, compared to the control, but decreased in the LV4W rats. Incidences of pulmonary edema were 100% in the control group, decreasing to 78% in LV1W group, 17% in LV2W group, and back to 72% in LV4W group. The lung water ratio, a parameter of severity, demonstrated a similar pattern of change as the incidence. The lowered incidence and severity obtained in the LV2W group were reversed by intracisternal injection of N-nitro-L-arginine methyl ester (L-NAME). From these results, we propose that an increase in nitric oxide, possibly in the nucleus tractus solitarius 2 weeks after left vagotomy, may have an inhibitory action on the development of neurogenic pulmonary edema in rats.
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PMID:Inhibition of fibrin-induced neurogenic pulmonary edema by previous unilateral left-vagotomy correlates with increased levels of brain nitric oxide synthase in the nucleus tractus solitarii of rats. 1249 29

One hundred and five patients with Plasmodium falciparum were included, forty-three with cerebral malaria and sixty-two without cerebral manifestations. The main clinical presentations in cerebral malaria patients were fever (76.4%), pallor (72%), splenomegaly (60.5%), deep coma (39.5%), jaundice (18.6%), pulmonary oedema (13.9%), subconjunctival haemorrhage (13.9%), severe anemia (Hb<5mg/l) (53.5%), hypoglycemia (glucose<40mg/dl) (67.4%) and haemoglobinuria (6.9%) while in non cerebral malaria patients the clinical presentations were fever (83.8%), pallor (67.7%), splenomegaly (66%), jaundice (9.7%), severe anemia (Hb<5gm/dl) (51.6%) and hypoglycemia (glucose<40mg/dl) (3.2%). Nine patients from cerebral malaria group died after admission. Serum level of nitric oxide (nitrite plus nitrate) were assayed for all patients, serum level of nitric oxide were highly significant in patients with cerebral malaria than those without (34.6 +/- 2.3n. mol/ml VS 12.9 +/- 1.3n. mol/ml; P<0.01). In cerebral malaria, nitric oxide levels were highly elevated in patients with deeper coma than those with lighter coma (48.2 +/- 3.1n. mol/ml VS 24.4 +/- 1.3n. mol/ml; P<0.001) and also higher among patients with longer duration of coma (>72 hours) than among patients with shorter duration of coma (<72 hours) (54.5 +/- 2.8 n. mol/ml V.S. 23.6 +/- 3.1n. mol/ml; P<0.001). Also, nitric oxide levels were correlated with clinical outcome, fatal cases (9 patients) having significantly higher nitric oxide levels than survivors (56.2 +/- 3.1 n. mol/ml VS 32.5 +/- 1.3 n. mol/ml; P<0.001). Thus, higher levels of nitric oxide are associated with indices of disease severity and may predict outcome in-patients with cerebral malaria. These data are consistent with the hypothesis that nitric oxide is involved in the pathogenesis of cerebral malaria.
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PMID:Plasma levels of nitric oxide in association with severe Plasmodium falciparum in Yemen. 1256 1

Excessive local production of nitric oxide (NO) has been suggested to play a role in rodent models of airway inflammation and in pulmonary diseases such as asthma. However, even given the plethora of data available including gene expression data, pharmacological data, and gene deletion studies in animal models, it is still not clear which nitric-oxide synthase (NOS) isoform is involved in eosinophilic airway inflammation. In this rat study, the nonselective NOS inhibitor L-NAME (N(G)-nitro-L-arginine methyl ester), but not a selective inducible NOS (iNOS) inhibitor 1400W (N-3-(aminomethyl)benzyl)acetamidine), impacted on Sephadex-induced inflammation by significantly inhibiting lung edema, eosinophil infiltration, tumor necrosis factor alpha, interleukin-13, and eotaxin levels in the lung tissue. Furthermore, iNOS gene expression was not induced following Sephadex administration, which confirms that iNOS does not play a role in this model. To demonstrate that this phenomenon was not restricted to this model of asthma, L-NAME, but not 1400W, was shown to reduce eosinophilia in an antigen-induced model. However, in contrast to the Sephadex model, there was an induction of iNOS gene expression after antigen challenge. In a model of aerosolized lipopolysaccharide-induced inflammation, where iNOS gene expression is increased, 1400W inhibited the increased neutrophilia. These data suggest that the compound has been administered using an appropriate dosing regimen for iNOS inhibition in the rat lung. In conclusion, it appears that constitutive, not inducible, NOS isoforms are important in NO production in models of allergic inflammation, which questions whether there is a role for iNOS inhibitors as therapy for the treatment of asthma.
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PMID:Pharmacological assessment of the nitric-oxide synthase isoform involved in eosinophilic inflammation in a rat model of sephadex-induced airway inflammation. 1260 8

Acute pulmonary oedema usually has a fatal outcome. In this clinical report, we present rare cases of pulmonary oedema that were associated with Japanese B encephalitis, lymphangitis in breast carcinoma, fat embolism due to long-bone fracture, and the rupture of cerebral mycotic aneurysms. A total of 18 patients in the four disease categories were collected in two teaching hospitals in Taipei and Hualien. Upon admission, routine and specific examinations were taken and all patients showed clear lungs by chest X-ray; however, signs of acute pulmonary oedema occurred within 7 days. After resuscitation, all patients died of acute pulmonary oedema. In patients with fat embolism, the levels of non-esterified plasma fatty acids, cGMP, 5-hydroxytryptamine (serotonin) and nitrates/nitrites were increased during pulmonary oedema. Immunohistochemical staining revealed virus infection and neuronal death, predominantly in the medial, ventral and caudal medulla in cases of Japanese B encephalitis. The pulmonary oedema due to central sympathetic activation in Japanese B encephalitis may be related to destruction of depressor mechanisms in the medulla. The rupture of mycotic aneurysms is known to cause cerebral compression that results in acute pulmonary oedema. Blockade of lymphatics, capillaries and venules in breast carcinoma with lymphangitis causes the development of rapid lung oedema. The pathogenesis of pulmonary oedema is much more complicated in fat embolism. Mediators such as cGMP, 5-hydroxytryptamine, nitric oxide and presumably other chemical substances may also be involved.
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PMID:Acute pulmonary oedema: rare causes and possible mechanisms. 1260 84

We investigated the role of the nuclear enzyme poly (ADP ribose) synthetase (PARS) in the pathogenesis of combined burn and smoke inhalation (burn/smoke) injury in an ovine model. Eighteen sheep were operatively prepared for chronic study. PARS inhibition was achieved by treatment with a novel and selective PARS inhibitor INO-1001. The PARS inhibitor attenuated 1) lung edema formation, 2) deterioration of gas exchange, 3) changes in airway blood flow, 4) changes in airway pressure, 5) lung histological injury, and 6) systemic vascular leakage. Lipid oxidation and plasma nitrite/nitrate (stable breakdown products of nitric oxide) levels were suppressed with the use of INO-1001. We conclude that PARS inhibition attenuates various aspects of the pathophysiological response in a clinically relevant experimental model of burn/smoke inhalation injury.
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PMID:Effect of poly(ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep. 1262 33


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