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)

Hematopoietic prostaglandin D synthase (PGDS) is a key enzyme to produce prostaglandin (PG) D and J series. These PGs are involved in inflammation and immune system. The PGDS complementary DNA (cDNA)-expressing retrovirally transfected fibroblasts were introduced in vivo, and effect of the expression on lung injury induced by bleomycin was investigated in mice. Intravenous injection of PGDS cDNA-expressing fibroblasts significantly reduced lung edema, leukocyte infiltration in bronchoalveolar lavage (BAL) fluid, and pulmonary collagen content at 4 wk after instillation of bleomycin. Survival rate in mice instilled with the PGDS-expressing fibroblasts was higher than that in mice that received the mock transfection. Administration of 15-deoxy-Delta 12,14-PGJ2, which is a nonenzymatic metabolite of PGD2, also attenuated the lung injury, suggesting mediation of PGs produced by PGDS for the attenuation. Introduction of PGDS cDNA-expressing fibroblasts suppressed expression of basic fibroblast growth factor, connective tissue growth factor, and collagen messenger RNAs in the lungs, as well as the levels of total proteins and hemoglobin in BAL fluid. These data suggest that the suppressive effect of PGDS on the lung injury could be partly mediated by edema formation and inhibition of genes involved in the fibrotic change.
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PMID:Retrovirally introduced prostaglandin D2 synthase suppresses lung injury induced by bleomycin. 1270 14

Oxyglobin, a hemoglobin-based oxygen-carrying fluid, is indicated in the treatment of anemia in dogs and may be life saving if compatible red blood cells are not available for transfusion. The colloidal properties of Oxyglobin allow for expansion of the circulatory volume, which may be helpful in patients with hypovolemia, especially hemorrhagic shock. Oxyglobin's colloidal properties can also lead to circulatory overload, with development of pulmonary edema and pleural effusion, however, necessitating careful monitoring of the rate of administration and of the respiratory rate and effort of the patient. Measurement of total or plasma hemoglobin concentration can be used as an aid in monitoring patients receiving Oxyglobin.
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PMID:Clinical application of a hemoglobin-based oxygen-carrying solution. 1466 99

Surfactant has led to a significant reduction in neonatal mortality for premature infants with lung immaturity and respiratory distress. However, surfactant therapy has been shown to be effective in the treatment of a number of other neonatal respiratory disorders and the evidence for surfactant use in such circumstances is presented. Meconium aspiration is characterised by severe atelectasis, the influx of neutrophils, edema, and hyaline membranes, with decreased levels of SP-A and SP-B and the large aggregate fraction of lung surfactant, and altered surfactant surface morphology. Meconium contains cholesterol, free fatty acids and bilirubin all of which can interfere with surfactant function in a dose-dependent fashion. Providing larger amounts of surfactant can overcome some of this inhibition. Animal models of meconium aspiration treated with surfactant have improved histology, lung mechanics and gas exchange. Studies in human infants with meconium aspiration have found elevated concentrations of total protein, albumin, and membrane-derived phospholipid in lung lavage fluid, and haemorrhagic pulmonary edema. Clinical studies in such neonates have reported improved gas exchange and clinical outcomes following surfactant treatment. More recently surfactant lavage has been shown to be a potentially efficacious therapy for such infants. The inflammatory exudate containing plasma proteins and cytokines which accompanies neonatal pneumonia may inactivate surfactant. Surfactant treatment given to animals following the tracheal instillation of group B Streptococcal resulted in significantly less bacterial growth and improved lung function. Small clinical experiences have demonstrated the benefit of surfactant to infants with pneumonia/sepsis. Pulmonary haemorrhage, which some consider a complication of surfactant therapy, has also been effectively managed using surfactant instillation. The hemoglobin and red blood cell lipids may act to inhibit natural surfactant and treatment with surfactant has been shown to improve outcome for infants with pulmonary haemorrhage. Animal models of congenital diaphragmatic hernia (CDH) have hypoplastic lungs with evidence of decreased lamellar bodies in their type II pneumocytes and resultant surfactant deficiency, and respond to surfactant replacement with improved gas exchange and lung mechanics. The lungs of human infants with CDH contain less phospholipids and phosphatidylcholine per milligram of DNA than control infants. Case reports have reported a benefit of surfactant for infants with CDH. In the near-term infants with severe respiratory distress, surfactant is one of the therapies along with inhaled nitric oxide and high frequency ventilations, that have resulted in improved outcomes. Surfactant treatment may be of significant benefit in newborn infants with respiratory compromise secondary to a number of insults, and further prospective evidence of its efficacy in such disorders is needed.
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PMID:Surfactant use for neonatal lung injury: beyond respiratory distress syndrome. 1498 Feb 86

Chronic hypoxia, viral infections/bacterial toxins, inflammation states, biochemical disorders, and genetic abnormalities are the most likely trigger of sudden infant death syndrome (SIDS). Autopsy studies have shown increased pulmonary density of macrophages and markedly more eosinophils in the lungs accompanied by increased T and B lymphocytes. The elevated levels of immunoglobulins, about 20% more muscle in the pulmonary arteries, increased airway smooth muscle cells, and increased fetal hemoglobin and erythropoietin are evidence of chronic hypoxia before death. Other abnormal findings included mucosal immune stimulation of the tracheal wall, duodenal mucosa, and palatine tonsils, and circulating interferon. Low normal or higher blood levels of cortisol often with petechiae on intrathoracic organs, depleted maternal IgG antibodies to endotoxin core (EndoCAb) and early IgM EndoCAb triggered, partial deletions of the C4 gene, and frequent IL-10-592*A polymorphism in SIDS victims as well as possible hypoxia-induced decreased production of antiinflammatory, antiimmune, and antifibrotic cytokine IL-10, may be responsible for the excessive reactions to otherwise harmless infections. In SIDS infants, during chronic hypoxia and times of infection/inflammation, several proinflammatory cytokines are released in large quantities, sometimes also representing a potential source of tissue damage if their production is not sufficiently well controlled, eg, by pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP). These proinflammatory cytokines down-regulate gene expression of major cytochrome P-450 and/or other enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity, thus affecting metabolism of several endogenous lipophilic substances, such as steroids, lipid-soluble vitamins, prostaglandins, leukotrienes, thromboxanes, and exogenous substances. In SIDS victims, chronic hypoxia, TNF-alpha and other inflammatory cytokines, and arachidonic acid (AA) as well as n-3 polyunsaturated fatty acids (FA), stimulated and/or augmented superoxide generation by polymorphonuclear leukocytes, which contributed to tissue damage. Chronic hypoxia, increased amounts of nonheme iron in the liver and adrenals of these infants, enhanced activity of CYP2C9 regarded as the functional source of reactive oxygen species (ROS) in some endothelial cells, and nicotine accumulation in tissues also intensified production of ROS. These increased quantities of proinflammatory cytokines, ROS, AA, and nitric oxide (NO) also resulted in suppression of many CYP450 and other enzymes, eg, phosphoenolpyruvate carboxykinase (PEPCK), an enzyme important in the metabolism of FA during gluconeogenesis and glyceroneogenesis. PEPCK deficit found in SIDS infants (caused also by vitamin A deficiency) and eventually enhanced by PACAP lipolysis of adipocyte triglycerides resulted in an increased FA level in blood because of their impaired reesterification to triacylglycerol in adipocytes. In turn, the overproduction and release of FA into the blood of SIDS victims could lead to the metabolic syndrome and an early phase of type 2 diabetes. This is probably the reason for the secondary overexpression of the hepatic CYP2C8/9 content and activity reported in SIDS infants, which intensified AA metabolism. Pulmonary edema and petechial hemorrhages often present in SIDS victims may be the result of the vascular leak syndrome caused by IL-2 and IFN-alpha. Chronic hypoxia with the release of proinflammatory mediators IL-1alpha, IL-1beta and IL-6, and overloading of the cardiovascular and respiratory systems due to the narrowing airways and small pulmonary arteries of these children could also contribute to the development of these abnormalities. Moreover, chronic hypoxia of SIDS infants induced also production of hypoxia-inducible factor 1alpha (HIF-1alpha), which stimulated synthesis and release of different growth factors by vascular endothelial cells and intensified subclinical inflammatory reactions in the central nervous system, perhaps potentiated also by PACAP and VIP gene mutations. These processes could lead to the development of brainstem gliosis and disorders in the release of neuromediators important for physiologic sleep regulation. All these changes as well as eventual PACAP abnormalities could result in disturbed homeostatic control of the cardiovascular and respiratory responses of SIDS victims, which, combined with the nicotine effects and metabolic trauma, finally lead to death in these often genetically predisposed children.
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PMID:Possible pathomechanisms of sudden infant death syndrome: key role of chronic hypoxia, infection/inflammation states, cytokine irregularities, and metabolic trauma in genetically predisposed infants. 1554 94

Inhalation of nitric oxide has been reported to alter pulmonary blood flow in animal and human studies. This effect is related to the relaxant action of nitric oxide on arterial vascular smooth muscle cells. When nitric oxide is administered by inhalation, this effect is limited to the pulmonary vasculature as it is rapidly inactivated by hemoglobin as soon as it enters the blood stream. The effect of inhaled nitric oxide is more pronounced in well ventilated areas of the lung, where it promotes redistribution of pulmonary blood flow to regions with high ventilation-perfusion ratio decreasing pulmonary hypertension and improving oxygenation. Nitric oxide has been used to treat pulmonary hypertension and hypoxemia that occurred in thoracic surgery during one lung ventilation, postpneumonectomy pulmonary edema and lung transplantation. Inhaled nitric oxide may be a useful tool in patients with a low PaO2/FiO2 ratio during one lung ventilation. Further powered studies are still required to define the dose and timing of inhaled nitric oxide in patients who do have ischemia-reperfusion injury after lung transplantation.
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PMID:Nitric oxide in thoracic surgery. 1588 94

Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol (PCMC), Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, Chlorothymol, o-Cymen-5-ol, and Carvacrol are substituted phenols used as cosmetic biocides/preservatives and/or fragrance ingredients. Only PCMC, Thymol, and o-Cymen-5-ol are reported to be in current use, with the highest concentration of use at 0.5% for o-Cymen-5-ol in perfumes. The use of PCMC in cosmetics is restricted in Europe and Japan. Cresols can be absorbed through skin, the respiratory tract, and the digestive tract; metabolized by the liver; and excreted by the kidney as glucuronide and sulfate metabolites. Several of these cresols increase the dermal penetration of other agents, including azidothymidine. In acute oral toxicity studies, LD50 values were in the 200 to 5000 mg/kg day-1 range across several species. In short-term studies in rats and mice, an o-Cresol, m-Cresol, p-Cresol or m-Cresol/p-Cresol mixture at 30,000 ppm in the diet produced increases in liver and kidney weights, deficits in liver function, bone marrow hypocellularity, irritation to the gastrointestinal tract and nasal epithelia, and atrophy of female reproductive organs. The no observed effect levels (NOEL) of o-Cresol was 240 mg/kg in mink and 778 mg/kg in ferrets in short-term feeding studies, with no significant dose-related toxicity (excluding body weight parameters). In mice, 0.5% p-Cresol, but neither m-Cresol nor o-Cresol, caused loss of pigmentation. Short-term and subchronic oral toxicity tests performed with various cresols using mice, rats, hamsters, and rabbits resulted in no observed adverse effect levels (NOAELs) for mice of 625 ppm and rats of 50 mg/kg day-1, although the NOEL was 2000 ppm in a chronic study using rats. In rabbits, < or =160 mg/kg PCMC was found to produce irritation and erythema, but no systemic effects. Hamsters dosed with 1.5% p-Cresol in diet for 20 weeks had a greater incidence of mild and moderate forestomach hyperplasia as compared to the control. Acute inhalation toxicity studies using rats yielded LC50 values ranging from >20 mg/m(3) for o-Cresol to >583 mg/m(3) for PCMC. No deaths were recorded in mice given o-Cresol at 50 mg/m(3). Cats exposed (short-term) to 9 to 50 mg/m(3) of o-Cresol developed inflammation and irritation of the upper respiratory tract, pulmonary edema, and hemorrhage and perivascular sclerosis in the lungs. Rats exposed (subchronic) to o-Cresol at 9 mg/m(3) had changes in leukocytes, spinal cord smears, nervous activity, liver function, blood effects, clinical signs, and neurological effects. In guinea pigs, exposure to 9 mg/m(3) produced changes in hemoglobin concentrations and electrocardiograms (EKGs). Rats exposed (subchronic) to 0.05 mg/m(3) Mixed Cresols by inhalation exhibited central nervous system (CNS) excitation, denaturation of lung protein, and decreased weight gain. All cresols appear to be ocular irritants. Numerous sensitization studies have been reported and most positive reactions were seen with higher concentrations of Cresol ingredients. Developmental toxicity is seen in studies of m-Cresol, o-Cresol, and p-Cresol, but only at maternally toxic levels. In a reproductive toxicity study of a mixture of m-Cresol and p-Cresol using mice under a continuous breeding protocol, 1.0% caused minimal adult reproductive and significant postnatal toxicity in the presence of systemic maternal toxicity. The o-Cresol NOAEL was 0.2% for both reproductive and general toxicity in both generations. Cresol ingredients were generally nongenotoxic in bacterial, fruit fly, and mammalian cell assays. Thymol did not induce primary lung tumors in mice. No skin tumors were found in mice exposed dermally to m-Cresol, o-Cresol, or p-Cresol for 12 weeks. In the trypthan blue exclusion assay, antitumor effects were observed for Thymol and Carvacrol. Clinical patch testing with 2% PCMC may produce irritant reactions, particularly in people with multiple patch test reactions, that are misinterpreted as allergic responses. o-Cresol, p-Cresol, Thymol, Carvacrol, and o-Cymen-5-ol caused no dermal irritation at or above use concentrations. In two predictive patch tests, PCMC did not produce a sensitization reaction. Overall, these ingredients are not significant sensitizing or photosensitizing agents. The Cosmetic Ingredient Review (CIR) Expert Panel noted some of these ingredients may increase the penetration of other cosmetic ingredients and advised cosmetic formulators to take this into consideration. The CIR Expert Panel concluded that the toxic effects of these ingredients are observed at doses higher than would be available from cosmetics. A concentration limitation of 0.5% was chosen to ensure the absence of a chemical leukoderma effect. For p-Cresol and Mixed Cresols (which contain p-Cresol), the Panel considered that the available data are insufficient to support the safety of these two ingredients in cosmetics. Studies that would demonstrate no chemical leukoderma at concentrations of use of p-Cresol and Mixed Cresols, or would demonstrate a dose response from which a safe concentration could be derived, are needed.
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PMID:Final report on the safety assessment of sodium p-chloro-m-cresol, p-chloro-m-cresol, chlorothymol, mixed cresols, m-cresol, o-cresol, p-cresol, isopropyl cresols, thymol, o-cymen-5-ol, and carvacrol. 1683 30

An 8-year-old mixed-breed dog was anesthetized for colonoscopy. Moderate sedation was produced by premedication with glycopyrrolate, acepromazine, and hydromorphone, and anesthesia was induced by IV injection of diazepam and ketamine. Frothy, reddish-colored fluid flowed from the endotracheal tube immediately after endotracheal intubation but ceased after several minutes. Furosemide was injected IV. Anesthesia was maintained by sevoflurane in oxygen. Ventilation and arterial blood pressure were satisfactory, however, after oxygen was administered to maintain normal hemoglobin saturation. Radiography revealed changes consistent with a diagnosis of pulmonary edema. The following day, ventricular premature contractions developed and atrial dissociation, valvular regurgitation, and pulmonary hypertension were diagnosed on echocardiography. The proposed etiology is either profound transient hypotension and/or pulmonary hypertension induced by ketamine. The cardiac abnormalities that were present the following day suggest that myocardial dysfunction after induction of anesthesia was more severe than was apparent as assessed by routine physical examination and monitoring methods.
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PMID:Acute pulmonary edema after diazepam-ketamine in a dog. 1756 75

Bacillus anthracis infections are frequently associated with severe and often irreversible hypotensive shock despite appropriate antibiotics and aggressive hemodynamic and pulmonary support. Based on the observations that the anthrax secreted proteins-protective antigen (PA), lethal factor (LF), and edema factor (EF) also produce shock and mortality in animal models, we chose to characterize further the clinical chemistries and microscopic pathology of toxin treated rats. Groups of three male Sprague Dawley rats received bolus intravenous infusions of PA/LF, PA/EF, LF, or EF alone and blood samples and tissues were collected and assayed for chemistries and tissue pathology. In PA/LF and PA/EF treated animals but not other groups, chemistries showed transaminasemia and elevated lactate dehydrogenase. PA/LF treated animals alone showed elevated hemoglobin and hematocrits; PA/EF treated animals alone showed lymphopenia. Pathology was remarkable for pulmonary edema in PA/LF treated rat lungs and pulmonary hemorrhage in PA/EF treated rat lungs. These results are consistent with our and others' previous findings that the morbidity and mortality associated with anthrax are not cytokine-mediated but due to a direct effect of the toxins on the cardiovascular system along with toxin-specific alterations in blood counts. PA/LF pathology matches that seen with acute cardiac failure, and PA/EF pathology coincides with direct vascular endothelial injury. These observations provide a rational basis for drug interventions to reduce the effect of these toxins on the heart and blood vessels.
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PMID:Anthrax toxin-induced shock in rats is associated with pulmonary edema and hemorrhage. 1822 26

During exercise in humans, the alveolar-arterial O(2) tension difference ((A-a)DO(2)) increases with exercise intensity and is an important factor determining the absolute level of oxygen binding to hemoglobin and therefore the level of systemic oxygen transport. During exercise in hypoxia, the (A-a)DO(2) is accentuated. Using the multiple inert gas elimination technique it has been shown that during exercise in acute hypoxia the contribution of ventilation-perfusion inequality to (A-a)DO(2) is rather small and in the absence of pulmonary edema intrapulmonary shunts can be ruled out. This implies that the main mechanism limiting pulmonary gas exchange is diffusion limitation. It is presumed that an elevation of cardiac output during exercise in acute hypoxia should increase the (A-a)DO(2). However, no studies have examined how variations in cardiac output independently affect pulmonary diffusion with increases in exercise intensity. We have consistently observed that during steady-state, submaximal (100-120 W) exercise on the cycle ergometer in hypoxia the lung can accommodate an increase in cardiac output of approximately 2 L x min(-1) without any significant effect on pulmonary gas exchange. This result contrasts with the predicted effect of cardiac output on (A-a)DO(2) using the model of Piiper and Scheid, and thus indicates that an elevation of cardiac output is not necessarily accompanied by a reduction of mean transit time and (or) diffusion limitation during submaximal exercise in acute hypoxia. It remains to be determined what is the influence of changes in cardiac output per se on pulmonary gas exchange during high-intensity exercise.
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PMID:Is pulmonary gas exchange during exercise in hypoxia impaired with the increase of cardiac output? 1846 Nov 16

Transfusion-related acute lung injury (TRALI) is characterized by pulmonary edema and hypoxemia within 6 hours of transfusion in the absence of other causes of acute lung injury or circulatory overload and is now considered the leading cause of transfusion-related death. We report a female patient who showed hypoxemia after transfusion without any other causes of acute lung injury. The patient is a 43-year-old woman, who received emergency transurethral hemostasis for bladder hemorrhage with hematuria and low hemoglobin concentration (3.2 g x dl(-1)). General anesthesia was maintained with sevoflurane, remifentanil, and vecuronium. Two units of RBC were transfused during operation. Since she showed high blood pressure, tachycardia, and a painful expression after operation, we extubated her. Although we gave her O2 6 l x min(-1) after extubation, she showed low oxygen saturation (90%), thus we started bag-mask ventilation. However, she complained of dyspnea and the chest X-ray revealed bilateral diffuse pulmonary edema following hypoxemia (80%). Thus we inserted endotracheal tube and started positive pressure assist ventilation. The next day, hypoxemia was improved under PEEP therapy. The anti-HLA antibody in the transfused plasma was positive. We conclude that the early recognition and management of TRALI is essential during and after operation.
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PMID:[Anesthetic management of a patient with transfusion-related acute lung injury (TRALI)]. 1871 14


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