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

A study was conducted to determine the dose of lasalocid that would effectively reduce ruminal conversion of tryptophan (TRP) to 3-methylindole (3MI) and prevent the development of acute bovine pulmonary edema and emphysema (ABPE). After adaptation to a maintenance diet for 3 wk, 20 mature beef cows were randomly divided into four groups of five cows each and fed 0, 200, 400 or 600 mg lasalocid X head-1 X d-1 in .5 kg ground barley for the 12-d experimental period. In vitro conversion of TRP to 3MI and indole by ruminal fluid and volatile fatty acid (VFA) concentrations were determined on d 0, 2, 4, 6 and 12. On d 6, an oral dose of .35 g TRP/kg body weight was given to induce ABPE, and ruminal production of 3MI and indole was determined at intervals thereafter. Formation of 3MI was sharply reduced (P less than .01) both in vitro and in vivo by lasalocid treatment at 200 mg X head-1 X d-1. Further suppression of 3MI production occurred as the lasalocid dose was increased (P less than .05). Linear (P less than .0001) and quadratic (P less than .002) components were determined for the relationship between lasalocid dose and 3MI production. Indole formation was variable, but tended to increase (P less than .05) with increasing lasalocid dose. Cows that received no lasalocid developed moderate to severe clinical signs of ABPE and three cows died of acute lung disease. Lasalocid treatment at all levels prevented ABPE. Lasalocid decreased ruminal acetate and butyrate, and increased propionate concentration (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of 3-methylindole production and prevention of acute bovine pulmonary edema and emphysema with lasalocid. 397 44

Sixteen Holstein cattle allotted into 4 groups (4 cattle/group) were each given a single oral dosage of 0.2 g of 3-methylindole (3MI)/kg of body weight. The groups were killed at 12, 24, 48, and 72 hours, respectively, after 3MI administration. Comparison of clinical signs, pathologic pulmonary lesions, and in vitro pulmonary artery responses to pharmacologic stimuli was made between the 4 treated groups and 8 control Holstein cattle of similar age. Clinical signs of pulmonary distress first appeared 8 to 12 hours after 3MI administration. After 20 hours, clinical signs included dyspnea, moderate depression, and a marked expiratory grunt. A partial remission of these clinical signs was seen between 30 and 45 hours after 3MI administration. After remission, the cattle had clinical signs of severe dyspnea and depression and expiratory grunts were more pronounced. Pathologic pulmonary lesions, including heavy rubbery lungs, dilated interlobular septae, and subplural air bullae characteristic of pulmonary edema and interstitial emphysema were observed. The lungs of treated cattle did not collapse when the thorax was incised at necropsy. In vitro pulmonary artery strips contracted dose dependently to norepinephrine (NE). Group I tissues (12 hours after 3MI administration) responded similarly to control samples. Group II tissues (24 hours after 3MI administration) had a significant inhibition (P less than 0.05) in response to NE stimulation as compared with controls.
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PMID:Impairment of sympathetic pulmonary vasoconstriction by 3-methylindole in cattle. 401 39

In 5 Friesian calves given 3-methylindole (3-MI) (100 mg/kg once a week for 8 weeks, except calf 4, given a 50 mg/kg dose on weeks 3 to 8), pulmonary function (PF) values and arterial blood gas tensions (PaO2 and PaCO2) were measured 24 hours after dosing was done and were correlated with clinical, biochemical, and pathologic changes. Three of the calves (No. 1, 2, and 3) showed acute respiratory distress syndrome 24 hours after the first 3-MI treatment, with a large increase in respiratory frequency, minute viscous work, and PaCO2 and a large decrease in tidal volume, dynamic lung compliance, and PaCO2. They died 36, 38, and 84 hours after dosing. Pulmonary function changes were compatible with the severe pulmonary edema and alveolar damage observed at necropsy. The 2 other calves, after they were given the 1st dose, showed only subacute respiratory distress syndrome with less severe changes in PF values recorded at 24 hours. Furthermore, they became progressively more tolerant to the 2nd, 3rd, and 4th weekly treatments, and showed base-line PF values after the 5th weekly treatment. Pathologic changes were not observed in lung biopsy material from these 2 animals at 2 and at 12 weeks after the 8th (or last) 3-MI treatment.
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PMID:Pathophysiologic study of 3-methylindole-induced pulmonary toxicosis in immature cattle. 403 88

The morphogenesis of pulmonary lesions and associated edema induced by the pulmonary toxicant 3-methylindole (3-MI) was studied by combined light and transmission electron microscopy. Weanling male CD-1 mice received 3-MI dissolved in corn oil by intraperitoneal injection and were studied at intervals from 2 to 360 hours after treatment. Interstitial edema was observed as early as 2 hours and was associated with focal cytoplasmic swelling and membrane alterations in both capillary endothelial cells and Type I alveolar epithelial cells and with sequestration of neutrophils. Cell swelling, cytoplasmic fragmentation, and necrosis of Type I epithelial cells was most severe at 24-48 hours after treatment. Multifocal hypertrophy and hyperplasia of Type II alveolar epithelial cells was observed at 24-96 hours after treatment. Platelet aggregation and aggregates of fibrin were frequently observed in capillaries and small arteries and veins as early as 4 hours and as late as 48 hours after treatment. In airways, the nonciliated bronchiolar epithelial (Clara) cell was the predominant cell affected. Initial lesions in nonciliated cells consisted of loss of microvilli and secretory granules followed by marked swelling of the endoplasmic reticulum and mitochondria. Necrosis of cells lining airways was most pronounced at 24-48 hours after treatment. By 144 hours after administration, pulmonary repair was complete. It is concluded that the mouse is a useful model of 3-MI-induced pulmonary injury and that damage to both Type I alveolar epithelial cells and capillary endothelial cells is important in the pathogenesis of 3-MI-induced pulmonary edema.
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PMID:Pulmonary lesions induced by 3-methylindole in mice. 405 Sep 71

Microorganisms from rumen converted L-tryptophan and indoleacetic acid to 3-methylindole in vitro. Oral doses of 3-methylindole caused interstitial pulmonary edema and emphysema in cattle and goats. Intravenous infusion of this metabolite also induced pulmonary disease in cattle. These results demonstrate than an end product of ruminal fermentation of tryptophan can induce acute pulmonary disease in cattle and goats.
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PMID:Induction of pulmonary edema and emphysema in cattle and goats with 3-methylindole. 501 84

Ruminal bacteria can perform biochemical transformations on plant constituents that may affect the health of ruminant animals. Reactions carried out by ruminal bacteria on oxalates and some pyrrolizidine alkaloids include decarboxylation, hydrolysis and reduction steps. Prior exposure of ruminal bacteria to these substances increases the rate of detoxification, indicating an adaptive response by the bacteria to these substrates. The formation of toxic substances by ruminal bacteria also occurs and may involve similar reactions. Hydrolysis of cyanogenic glycosides and miserotoxins , reduction of nitrate and S-methylcysteine sulfoxide to nitrite and dimethyl disulfide can result in toxicity in ruminants. Similarly, the deamination and decarboxylation reactions associated with the degradation of tryptophan and tryosine result in the formation of 3-methylindole and p-cresol, which are toxic. Formation of 3-methylindole results from fermentation of tryptophan to indoleacetic acid, with subsequent decarboxylation of indoleacetic acid to 3-methylindole by a Lactobacillus sp. The 3-methylindole causes acute pulmonary edema and emphysema in ruminants as a result of mixed function oxidase metabolism in tissues. The 3-methylindole is also the cause of naturally-occurring acute bovine pulmonary edema and emphysema after abrupt pasture change. Inhibition of ruminal 3-methylindole formation by monensin and other antibiotics lowers ruminal 3-methylindole concentrations and prevents acute lung injury in experimental animals.
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PMID:Ruminal metabolism of plant toxins with emphasis on indolic compounds. 637 6

3-Methylindole (3MI) is the causative agent in the development of acute bovine pulmonary edema. Microscopic studies revealed a structural disruption in the lamellar bodies of type II cells, indicating an abnormal metabolism of phospholipid in the lung of 3MI treated animals. In the present study, lung slices from 4 goats were used to investigate the changes in phosphatidylcholine metabolism induced by 3MI. Eighteen slices were cut from each healthy lung and divided into control and 3MI groups. After a 4-hr pretreatment with 3MI (.19 or .57 mM) or carrier, the level of incorporation of 14C-choline into phosphatidylcholine, sphingomyelin and their water soluble intermediates was studied. The uptake of 14C-choline and its incorporation into phosphatidylcholine and sphingomyelin was depressed by 3MI treatment. In the water soluble fractions, the radioactivity increased in free choline and CDP-choline, while it decreased in P-choline. This suggests that choline kinase and the P-choline transferases have become relatively more rate limiting and may play a role in the depressed de novo synthesis of phosphatidylcholine induced by 3MI.
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PMID:The effect of 3-methylindole on the uptake and incorporation of 14C-choline into phospholipids in lung tissue slices. 650 17

[methyl-14C]-3-Methylindole (3MI) was incubated with goat-lung microsomes, an NADPH-generating system and glutathione. An adduct between an oxidative metabolite of 3MI and glutathione was formed only when the complete system was employed. The adduct, which was detected by u.v. absorbance and scintillation counting of h.p.l.c. fractions, was purified to homogeneity by reverse-phase h.p.l.c. The ability of 3MI to bind to microsomal protein was reduced to 52% and 46% of controls when 2 mM and 4 mM glutathione, respectively, were included in the incubations. These results suggest the involvement of an electrophilic metabolite as the toxic intermediate in 3MI-mediated pulmonary oedema.
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PMID:Electrophilic metabolites of 3-methylindole as toxic intermediates in pulmonary oedema. 650 69

3-Methylindole (3MI), a ruminal fermentation product of tryptophan, is the causative agent in the development of acute bovine pulmonary edema (ABPE). The disease is dependent on the activation of 3MI by mixed function oxidases (MFO). Electron micrographs have revealed that the lamellar bodies of the type II cells are disrupted in structure and contain neutral lipids (NL) instead of surfactant phospholipids (PL). Goat lung slices were used to investigate the changes in PL metabolism induced by 3MI. Eighteen slices were cut from each lung and divided into control, 3MI (0.57 mM), and indole (0.57 mM) groups. After a 3-hr pretreatment with these compounds, the slices were incubated with [14C]acetate. The lipids were extracted and separated. 3MI inhibited the incorporation of [14C]acetate into all of the PL studied, but had little effect on its incorporation into NL. Indole displays the same effects on membranes as 3MI, but is not activated by the MFO system and does not induce lung injury. Indole pretreatment had little effect on acetate incorporation in any of the lipid fractions. These results indicate that metabolism of 3MI in lung slices is responsible for the depression of PL synthesis in vitro. Increasing the level of unlabeled choline in the medium from 10 microM to 10 microM had no effect on the depression of [14C]acetate incorporation into phosphatidylcholine (PC). This suggests that choline uptake is not limiting the synthesis of PC in the 3MI-treated lung slices.
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PMID:The effect of 3-methylindole on phospholipid synthesis in goat lung tissue slices. 669 67

Available evidence supports the view that acute bovine pulmonary edema and emphysema (ABPE) is related to ruminal production of 3-methylindole (3MI) from L-tryptophan (TRP). Ruminal production of 3MI is a two-step process involving the conversion of TRP to indoleacetic acid (IAA) followed by decarboxylation of IAA and 3MI. Reduction in ruminal 2MI production by the inhibition of either of these processes may prevent the onset of ABPE. A closed-system, in vitro ruminal fermentation technique was used to screen 27 compounds for their ability to reduce the conversion of TRP to 3MI. Several compounds tended to reduce 3MI production at both 25 and 5 micrograms/ml. Desoxysalinomycin, X-206, chloral hydrate, nigericin, lasalocid, monensin, narasin and salinomycin all reduced 3MI production by more than 80% at 5 micrograms/ml without reducing total VFA production. All of these compounds, except chloral hydrate, are polyether antibiotics. At least part of the inhibition due to monensin and narasin occurs at the level of TRP conversion to IAA.
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PMID:Inhibition of ruminal degradation of L-tryptophan to 3-methylindole, in vitro. 741 Feb 74


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