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)

Intratracheal (i.t.) administration of protein synthesis inhibitors produced pulmonary edema. Of those inhibitors studied, dactinomycin (act. D) was the most potent. Severity of lung damage due to act. D was dose- and almost age-related. Maximal intensity of pulmonary edema was reached on the 3rd day following administration and remained constant for 14 days. Histopathological studies revealed confluent edema of the entire lung. Pretreatment with act D induced tolerance to an LD100 edematogenic dose of thiourea. The effects of i.t. instillation of act. D appear to be localized in the pulmonary tissue. Lung lavage fluid collected from drug-treated rats had higher acid and alkaline phosphatase activities, higher protein content and more leukocyte infiltration than that of control.
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PMID:Effects of intratracheal instillation of dactinomycin on pulmonary edema and phosphatase activity of the lung lavage fluid in rats. 16 94

Clonogenic growth (colony-forming efficiency, CFE) of i.v. injected allogeneic W256 tumour cells in the lungs was markedly enhanced by treatment of rats with alpha-naphthyl thiourea (ANTU) injected i.p. from 2 h before to 2 h after the tumour cells. ANTU specifically increases pulmonary vascular permeability in adult rats and causes acute pulmonary oedema and pleural effusion. Inhibition of drug toxicity to the lungs by tachyphylaxis, specific antimetabolites or iodides did not abolish the effect of ANTU on CFE. CFE was not increased when cells were seeded by i.v. injection the lungs affected by advanced pulmonary oedema at 6 to 24 h after treatment with drug. ANTU did not enhance growth of intratracheally injected cells. Although ANTU has no cytotoxic or immunosuppressive action, treatment of tumour-immunized rats with ANTU caused apparent "breakdown" of tumour immunity in 50% of rats, by causing growth of tumour colonies in the lungs. Possible mechanisms for the ANTU-induced decrease in innate resistance to growth of tumour in the lungs are discussed.
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PMID:Effect of toxic thioureas on resistance of rats to growth in the lungs of intravenously and intratracheally seeded tumour cells. 61 62

The intraperitoneal administration of thiourea (TU) to mature male rats results in a significant increase in lung vascular permeability to Evans Blue dye (EBD). On the other hand, young, sexually immature rats are resistant to this effect. The increase in lung vascular permeability in response to TU in mature rats is associated with corresponding increases in lung and plasma histamine levels. The correlation of increases in lung and plasma histamine in response to TU is similar to that reported for ammonium salts which produce similar pulmonary edema.
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PMID:Effects of thiourea on pulmonary vascular permeability and on lung and plasma histamine levels in rats. 190 59

Noninvasive techniques employing external counting of radiolabeled protein have the potential for measuring pulmonary vascular protein permeability, but their specificity and sensitivity remain unclear. We tested the specificity and sensitivity of a double-radioisotope method by injecting radiolabeled albumin (131I) and erythrocytes (99mTc) into anesthetized dogs and measuring the counts of each isotope for 150 min after injection with an external gamma probe fixed over the lung. We calculated the rate of increase of albumin counts measured by the probe (which reflects the rate at which protein leaks into the extravascular space). To assess permeability we normalized the rate of increase in albumin counts for changes in labeled erythrocyte signal to minimize influence of changes in vascular surface area and thus derived an albumin leak index. We measured the albumin leak index and gravimetric lung water during hydrostatic edema (acutely elevating left atrial pressure by left atrial balloon inflation: mean pulmonary arterial wedge pressure = 22.6 Torr) and in lung injury edema induced by high- (1.0 g/kg) and low-dose (0.25 g/kg) intravenous thiourea. To test specificity we compared hydrostatic and high-dose thiourea edema. The albumin leak index increased nearly fourfold from control after thiourea injury (27.2 +/- 2.3 X 10-4 vs. 7.6 +/- 0.9 X 10-4 min-1) but did not change from control levels after elevating left atrial pressure (8.9 +/- 1.2 X 10-4 min-1) despite comparable increases in gravimetric lung water. To test sensitivity we compared low-dose thiourea with controls. Following low-dose thiourea, the albumin leak index nearly doubled despite the absence of a measurable increase in lung water. We conclude that a noninvasive double radioisotope measurement of pulmonary vascular protein leak, employing external counting techniques and a simplified method of calculation, is specific for lung injury and is also sensitive enough to detect lung injury insufficient to produce detectable pulmonary edema.
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PMID:Specificity and sensitivity of noninvasive measurement of pulmonary vascular protein leak. 392 88

Research on one group of nine anesthetized dogs pretreated with alpha-naphthyl-thiourea showed that doses of the beta-sympathicomimetic fenoterol such as those normally administered in clinical tocolysis (2 micrograms/kg per minute) lead to significant fluid displacement to the extravascular space of the lung in the sense of a preclinical interstitial edema. In a second group (N = 9) with the same pretreatment the addition of the beta-1 selective blocker, metoprolol (1.5 micrograms/kg per minute) served to antagonize the hemodynamic changes and possibly the increase of pulmonary capillary permeability induced by the beta-mimetic. Fluid displacement into the interstitium of the lung was prevented by metoprolol. These observations corroborate the hypothesis that pulmonary edema occurring during tocolytic therapy is largely a result of the use of beta-mimetics. In addition to its cardioprotective effect, the administration of the beta-1 selective blocker, metoprolol, may reduce the risk of the development of pulmonary edema in beta-sympathicomimetic therapy for premature labor.
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PMID:Influence of the beta-1 selective blocker, metoprolol, on the development of pulmonary edema in tocolytic therapy. 396 Apr 26

Thiourea (TU), a very effective hydroxyl radical (.OH) scavenger, has little value as a probe of .OH in vivo because it causes fatal pulmonary edema. To test the hypothesis that TU-induced lung injury results from .OH-mediated oxidation of TU to toxic cyanamide, we pretreated rats with .OH scavengers, dimethylsulfoxide (DMSO), ethanol, and mannitol, prior to treatment with TU (3 mg/kg), preventing 91, 63, and 53%, respectively, of increases in lung weight to body weight ratios and 93, 67, and 46% of increases in lung lavage albumin concentrations. Furthermore, treatment of rats with cyanamide (CYN) (100 mg/kg) also caused increases in lung weight to body weight ratios (CYN: 7.39 +/- 0.57 X 10(-3) vs. controls: 5.46 +/- 0.26). N,N'-dimethylation of TU (DMTU) prevented TU toxicity, because treatment with DMTU did not significantly increase lung weight to body weight ratios (DMTU: 5.12 +/- 0.16 X 10(-3) vs. controls: 5.46 +/- 0.26) or lung lavage albumin (DMTU: 14 +/- 1 mg/100 ml vs. controls: 11 +/- 1). DMTU remained a very effective in vivo .OH scavenger, increasing survival of lethally irradiated mice treated with 600 mg/kg DMTU to 79% compared with 8% in untreated controls.
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PMID:Prevention of thiourea-induced pulmonary edema by hydroxyl-radical scavengers. 641 79

We describe neutrophil chemoattractant activity that is produced by cultured bovine aortic and pulmonary arterial endothelial cells when incubated with thiourea, a substance that causes increased permeability pulmonary edema in animals. The chemoattractant activity was present in culture supernates and cell lysates of endothelial cells incubated with thiourea but was not present in untreated cells. Production of chemoattractant activity was not associated with cell death; viable cell counts and cell homogenate angiotensin converting enzyme levels were not affected, and Cr release was only slightly elevated after incubation with thiourea. At least 1.5 h of incubation with 0.5 mM thiourea was necessary for generation of neutrophil chemoattractant activity. Culture supernates from pulmonary vascular smooth muscle cells and lung fibroblasts did not show increased neutrophil chemoattractant activity after incubation with thiourea. The chemoattractant had both chemokinetic and chemotactic properties, was heat stable, and was extractable into organic solvents. Meclofenamate, a cyclooxygenase inhibitor, minimally inhibited chemoattractant production, whereas 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of both cyclooxygenase and lipoxygenase, completely abolished generation of chemoattractant activity, suggesting that the activity could be a product of arachidonic acid metabolism. These results demonstrate that endothelial cells can produce a substance(s) with neutrophil chemotactic activity. Production of neutrophil chemoattractant activity by endothelial cells could be important in polymorphonuclear leukocyte accumulation at injured vascular sites.
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PMID:Thiourea causes endothelial cells in tissue culture to produce neutrophil chemoattractant activity. 643 Jan 36

Administration of E. coli LPS prior to 3.5 mg/Kg dose of thiourea has been reported to protect rats against pulmonary edema and pleural effusion. However, LPS of Shigella sonnei (either in phase I or II) did not show any protective effect. These data might suggest a different mechanism of endotoxins on membranes.
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PMID:[Action of various bacterial endotoxins on pleurisy and pulmonary edema induced by thiourea]. 643 66

Administration of endotoxin prior to an LD50 dose of thiourea protected rats against pulmonary edema and pleural effusion. These results are similar to those seen with endotoxin pretreatment and pulmonary O2 toxicity.
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PMID:Effect of endotoxin on thiourea induced pulmonary edema and pleural effusion. 678 99

The effect of pulmonary oedema on the pharmacokinetic function of rat lungs was studied using prostaglandin E2 (PGE2) as substrate; oedema was induced by alpha-naphthyl thiourea (ANTU). Male rats were given a single i.p. injection of ANTU (10 mg/kg). Lung wet weight, dry:wet weight ratio and pleural transudate were measured at fixed times up to 50 hr after treatment. Wet weight was increased after 4 hr and remained higher than controls until 50 hr; dry:wet weight ratios were different only at 6 and 16 hr. Survival of PGE2 (measured by bioassay) was increased at 4 hr, reached a peak value of about six times the control survival at 6 hr and returned to normal by 50 hr. Using 14C-PGE2 as substrate, survival was maximal at 16 hr and back to normal by 50 hr. The efflux profiles of radioactivity showed an increase in T1/2 by 4 hr rising to a maximum at 28 hr and a normal value at 50 hr. Changes in PGE2 survival precede the period of oedema (assessed by dry:wet ratio) and could be used as an early warning of oedematous states. This altered pharmacokinetic function of lung could also have systemic effects.
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PMID:Decreased inactivation of prostaglandin E2 in isolated lungs from rats with alpha-naphthyl thiourea-induced pulmonary oedema. 681 45


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