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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3-Methylindole has been shown in previous work to cause pulmonary edema and emphysema in cattle and goats. In this paper, evidence is presented to show that 3-methylindole induces structural perturbations in bovine erythrocyte membranes. The structural perturbations which were induced as a function of 3-methylindole concentration in the membranes were measured by EPR using the attachment of maleimide spin label to the sulfhydryl groups of membrane proteins and by intercalation of methyl-5- doxylstearate, methyl-12-doxylstearate, and methyl-16-doxylstearate into the lipid region. The EPR spectra of the malemide spin-labeled membrane proteins became more immobilized as the concentration of 3-methyl-indole increased. The order parameter describing the EPR spectra of methyl-5-doxylstearate decreased from 0.69 to 0.55 as the concentration of 3-methylindole increased. The acyl chains in the region of the carbon 5 position were converted to a less ordered structure. The EPR-spectra of methyl-12-doxylstearate was a superposition representing at least three tumbling rates. As the concentration of 3-methylindole increased, the major fraction of the methyl-12-doxylstearate probes experienced an increase in tumbling rate and a smaller fraction is observed a strongly immobilized state. The EPR spectra of methyl-16-doxylstearate were not perceptibly changed in the presence of 3-methylindole. The concentration dependence suggests that 3-methylindole preferentially intercalates into the ordered region of the alkyl chains sampled by the methyl-5-doxylstearate. These results confirm that 3-methylindole induced structural changes at the molecular level.
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PMID:An EPR study of structural perturbations induced by methylindole in the protein and lipid regions of erythrocyte membranes. 16 12

Intraruminal administration of 0.25 g of 3-methylindole (3MI; skatole/kg of body weight) to seven young calves generally caused mild respiratory signs and lesions, accompanied by only slight changes in cardiopulmonary function. Moderate depression, trembling, and irregular respiratory rate were observed between postadministration hours (PAH) 6 and 12. By PAH 24 at this dosage, abnormal clinical signs were not present. Statistically significant (P less than or equal to 0.05) changes observed in blood gas data from the seven calves were a decrease in aortic oxygen tension at PAH 12, increases in free-flowing venous oxygen tension in the intervals between PAH 6 and 12 and between PAH 6 and 24, and an increase in occluded venous oxygen tension at PAH 24. All calves had increases (although generally not statistically significant) in heart rate, cardiac output, cardiac index, stroke volume, and stroke index after 3MI administration. Mean aortic and pulmonary arterial pressure changes were generally small and variable. At necropsy, the lungs of the calves did not collapse when the thorax was opened. Patchy areas of consolidation (0.5 cm in diameter) were scattered throughout the parenchyma. Pulmonary edema or emphysema was not observed grossly. Microscopically, the alveolar septae were irregularly thickened because of edema, infiltration by polymorphonuclear and mononuclear cells, and vascular congestion. Interstitial lesions were patchy in distribution and severity and corresponded to the areas of consolidation observed grossly. Alveolar epithelial hypertrophy and hyperplasia were present, and an occasional focus of alevoli contained fluid of edema. Degeneration of individual hepatocytes was observed in scattered areas of the liver, especially in the periportal areas. It was concluded that differences in 3MI dosage response may exist between young calves and adult cattle in which calves are more resistant to the pulmonary cytotoxicity of 3MI.
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PMID:Pathophysiologic studies of calves given 3-methylindole intraruminally. 51 32

3-Methylindole, a ruminal fermentation product of tryptophan, induces acute pulmonary edema and emphysema in cattle, and 3-methylindole is present in the ruminal fluid and blood of cows with a natually occurring form of this disease. Monensin, a polyether antibiotic and widely used feed additive for beef cattle, prevented tryptophan-induced acute bovine pulmonary edema and emphysema. Monensin acted by reducing the ruminal conversion of L-tryptophan to 3-methylindole both in vitro and in vivo. Lasalocid, also a polyether antibiotic, showed similar effects in vitro. These results provide a promising approach to prevention of this major respiratory disease of cattle.
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PMID:Monensin and the prevention of tryptophan-induced acute bovine pulmonary edema and emphysema. 66 43

Ruminal administration of 3-methylindole in goats severe pulmonary edema and respiratory distress. Electron microscopic studies of lungs reveal extensive degeneration and necrosis of alveolar membranous pneumocytes and bronchiolar epithelium. The necrosis of the pneumocytes is followed by proliferation of granular pneumocytes, which repopulate the alveolar basal lamina scaffold. 3-Methylindole may also induce proliferation of smooth endoplasmic reticulum in the remaining membranous pneumocytes and nonciliated columnar cells, indicating that these two cell types are involved in the xenobiotic function of the lung. The results suggest that 3-methylindole in cigarette smoke may play an important role in the pathogenesis of small airway disease and emphysema, and that patients with severe liver diseases or portocaval shunt may be predisposed to diffuse alveolar damage by 3-methylindole produced in the intestinal tract.
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PMID:3-methylindole-induced pulmonary injury in goats. 86 17

The effects of intraruminal administration of 3-methylindole (3MI; skatole) were determined in goats. The 3MI was given to 4 goats at the dose level of 0.3 g/kg of body weight, to 2 goats at 0.2 g/kg, and to 2 goats at 0.1 g/kg; 3 nontreated goats were used as controls. Clinical signs of acute progressive respiratory tract disease were seen in all treated goats. Goats given the largest dose of 3MI (0.3 g/kg) died between 5 and 11 hours after treatment; those given smaller doses (0.2 and 0.1 g/kg) died between 79 and 92 hours. Increased plasma concentrations of 3MI were detected in goats give 0.1 or 0.2 g/kg within 3 hours after administration. By 24 and 36 hours, the concentrations of 3MI in the plasma decreased to low or nondetectable amounts and remained low for the duration of the experiment. Clinical signs of respiratory distress in the goats progressed after 3MI had been cleared from the plasma. Diffuse pulmonary edema and hydrothorax were extensive in goats which died early in the course of the experimentally induced disease. In goats which died at later stages, the lungs were firm and had less watery transudate. Temporal variations in the nature of pulmonic changes were even more obvious by microscopic examination. Diffuse pulmonary edema was the predominant early change. Small foci of emphysema were apparently caused by overdistention of some clusters of alveoli. Marked septal thickening and proliferation of alveolar cells were the prominent changes in goats which died between 79 and 92 hours after treatment. Incubation of L-tryptophan with caprine ruminal fluid resulted in formation of indoleacetic acid, indole, and 3MI. Similar incubations did not convert indoleacetic acid to 3MI. Control incubations showed 3MI as a fermentation metabolite, indicating it exists in caprine ruminal fluid in vivo. Results demonstrated that goats are susceptible to intraruminal administration of 3MI. The transitory appearance of 3MI in the plasma associated with progressive respiratory tract disease was similar to observations in cattle give 3MI. Clinical signs and lesions seen at necropsy were qualitatively similar to those reported in cattle given tryptophan and indoleacetic acid.
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PMID:Induction of pulmonary edema and emphysema in goats by intraruminal administration of 3-methylindole. 93 87

Intraruminal and intravenous administration of 3-methylindole (3MI; skatole) caused interstitial pulmonary edema and emphysema in cattle. In 3 adult heifers given the intraruminal dose of 0.2 g of 3 MI per kilogram of body weight, clinical signs of respiratory disease appeared between 6 and 12 hours after dosing, and death due to pulmonary edema and emphysema occurred at 33, 69, and 72 hours. The mean plasma concentration of 3MI became maximal (18.5 mug/ml) at 3 hours and then decreased to low concentrations by 48 hours. In 2 heifers given an intraruminal dose of 0.1 g of 3MI/kg, clinical signs developed, but they did not die during the 96-hour experiment. The mean plasma concentration of 3 MI became maximal (16.8 mug/ml) at 3 hours and decreased to 1.6 and 0.4 mug/ml at 12 and 36 hours, respectively. At necropsy of the heifers, the lung were large, firm, dark red, and heavier than normal. Diffuse pulmonary edema was the predominant change in cattle which died early, and interstitial emphysema was more severe at later stages of the disease. During the early stages, alveoli were overdistended, and a few more ruptured. Most alveolar spaces were filled with proteinaceous residue, but the alveolar septums were smooth and of normal thickness. At later stages, proliferation of alveolar cells was observed, and alveolar septums were thickened. In 3 cows given 0.06 g of 3MI/kg by jugular infusion, clinical signs appeared in all cows, and 1 cow died of pulmonary edema and emphysema 56 hours after the infusion was started. Severe pulmonary lesions seen in all of the cows given a 3MI infusion were similar to those in the cows given an intraruminal dose of 3MI. The mean plasma concentration of 3MI increased to 10.7 mug/ml at 9 hours after starting the infusion and decreased to 0.5 mug/ml at 18 hours. The results indicate that 3MI, a product of ruminal tryptophan fermentation, can cause pulmonary edema and interstitial emphysema in cattle and support the hypothesis that 3MI is the causative agent in tryptophan-induced pulmonary disease.
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PMID:Pulmonary edema and emphysema in cattle after intraruminal and intravenous administration of 3-methylindole. 116 73

Five Hereford cows were given an intraruminal dose of L-tryptophan (0.35 g/kg of body weight), and 2 cows were used as controls. Of the 5 treated cows, 3 developed clinical signs of interstitial pul monary edema, and emphysema and severe pulmonary lesions were seen at necropsy after 96 hours. Another cow developed moderate clinical signs and pulmonary lesions, and the remaining cow had few clinical signs and mild pulmonary lesions. The severity of clinical signs in each cow was related to the severity of pulmonary lesions at necropsy. The 3-methylindole (3MI) was present in ruminal fluid and plasma within 6 hours after administration of tryptophan, and the concentrations increased to 3.0 and 9.0 mug/ml within 12 to 24 hours. Severity of pulmonary lesions was related to maximal concentration and duration of 3MI in the plasma. At necropsy, gross lesions were characterized by diffuse, pulmonary edema and interstital emphysema; and the lungs were dark red, firm, and heavier than normal. Predominant microscopic changes included accumulation of proteinaceous residue, hypertrophy and hyperplasia of alveolar lining epithelium, thickening of alveolar septums, and emphysematous thickening of interstitial tissues. These changes were similar to previously reported 3MI-induced pulmonary lesions. The presence of 3MI in ruminal fluid and plasma after administration of tryptophan and the relationship between concentration of 3MI and severity of clinical signs indicate that 3MI is the principal metabolite of ruminal fermentation which leads to the development of acute pulmonary edema and emphysema in cattle given tryptophan.
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PMID:Ruminal and plasma concentrations of 3-methylindole associated with tryptophan-induced pulmonary edema and emphysema in cattle. 116 74

Acute bovine pulmonary edema is a naturally occurring lung disease caused by 3-methylindole (3MI), a ruminal fermentation product of tryptophan. Morphological and in vitro studies have suggested that 3MI causes abnormalities in phospholipid synthesis. The present study was designed to investigate the effect of 3MI on the quantity and functional quality of surfactant using the goat as an experimental model. Following intravenous infusion of 3MI, goats were killed at 6-, 18-, and 30-h intervals. The lungs were removed and intracellular surfactant, in the form of lamellar bodies, and extracellular surfactant from alveolar lavage were quantified. 3MI treatment did cause modest changes in the lamellar body phospholipid pools, decreasing the quantity of phosphatidylcholine and the proportion of palmitate in this fraction. The quantity of lavage phospholipids was not significantly affected. There was an increase in the protein content of the lavage, reflecting the presence of edema. The functional quality of the surfactant isolated from the lavage fraction was tested in vitro using a pulsating bubble surfactometer. 3MI infusion decreased the ability of surfactant to lower the surface tension of an air bubble at maximum radius and during compression.
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PMID:The effect of 3-methylindole on the quantity and functional quality of lung surfactant. 321 1

The bioactivation of the pulmonary toxin 3-methylindole has been postulated to proceed via the formation of an imine methide. To test this hypothesis, the toxicity in mice of 3-methylindole has been compared to the toxicity of its perdeuteromethyl analog. Deuteration of the methyl group should slow the rate of production of the corresponding imine methide and diminish the toxicity of deutero-3-methylindole, if C-H bond breakage occurs prior to or during the rate-determining step. In agreement with this hypothesis, deutero-3-methylindole was synthesized and was shown to be significantly less toxic (LD50 735 mg/kg) than 3-methylindole (LD50 578 mg/kg). Both compounds produced the same lesion at the LD50 dose, bronchiolar damage and mild alveolar edema, indicating that deuteration of 3-methylindole did not change the pathologic process. However, at a much lower dose (25 mg/kg), 3-methylindole produced a mild bronchiolar lesion whereas deutero-3-methylindole did not damage lung tissue. Additionally, administration of deutero-3-methylindole caused less pulmonary edema compared to 3-methylindole, as assessed by increased wet lung weights. Finally, the depletion of pulmonary glutathione by deutero-3-methylindole was considerably slower than depletion by 3-methylindole. The electrophilic imine methide has been postulated to be the intermediate which binds with and depletes glutathione. Therefore, the evidence presented here supports the involvement of an imine methide as the primary reactive intermediate in 3-methylindole-mediated pneumotoxicity.
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PMID:Decreased pneumotoxicity of deuterated 3-methylindole: bioactivation requires methyl C-H bond breakage. 362 92

A series of in vitro and in vivo trials was conducted to determine if continuous monensin feeding for up to 56 d would reduce ruminal conversion of L-tryptophan (TRP) to 3-methylindole (3MI). Fourteen mature beef cows were adapted to a maintenance diet for 3 wk. In trial I, the sampling time to optimize 3MI production was determined. Trials II through IV were to determine the duration of efficacy of monensin on reducing 3MI concentrations in vitro and in vivo. During trials II, III and IV one-half of the cows were fed 200 mg monensin X head-1 X d-1 for 21, 36 and 55 d, respectively, while the remaining cows served as controls. All cows were fed the control diet for 21 d between each trial. Volatile fatty acid (VFA) concentrations and in vitro conversion of TRP to 3MI were determined in ruminal fluid samples collected during trials I through IV. On d 28 of trial IV, all cows were given an oral dose of .35 g TRP/kg of body weight to induce acute bovine pulmonary edema and emphysema (ABPE). Ruminal concentrations of 3MI and indole were measured at intervals for 96 h. Results of trial I demonstrated that ruminal fluid collected 15 h postfeeding produced the highest in vitro conversion of TRP to 3MI. Therefore, ruminal fluid samples were collected at that time in trials II, III and IV. In vitro conversion of TRP to 3MI was lower (P less than .01) in samples from monensin-treated cows (12.1%) compared with controls (25.6%). Monensin reduced 3MI production for 55 d, the longest time tested in these experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Duration of inhibition of 3-methylindole production by monensin. 397 43


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