Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3-Methylindole (3-MI) is a metabolite of tryptophan that causes acute pulmonary edema and emphysema in ruminants when administered orally or intravenously. Electron paramagnetic resonance (EPR) spin-trapping techniques have been used to investigate the in vitro and in vivo formation of free radicals during 3-MI metabolism by goat lung. Utilizing C-phenyl-N-tert-butyl nitrone (PBN), a nitrogen-centered free radical has been detected from 3-MI in goat lung microsomal incubation. The EPR spectrum of the spin adduct is identical to that observed when 3-MI is irradiated with ultraviolet light. The formation of a nitrogen-centered 3-MI free radical is followed by the appearance of a carbon-centered radical in microsomal preparations. The objective of the present study is to prove that the nitrogen-centered radical generated from the 3-MI incubation system is a 3-MI radical utilizing [14C]-3 MI and the EPR-HPLC technique. The HPLC chromatogram includes three peaks that give EPR signals. These peaks are assigned to nitrogen-, oxygen- and carbon-centered radical adducts. The polarity of the three peaks follows the order: carbon-centered radical adduct > oxygen-centered radical adduct > nitrogen-centered radical adduct. The last has a polarity that is weaker than 3-MI. Only the nitrogen-centered peak and the 3-MI peak possessed radioactivity. The retention time of the nitrogen centered radical is the same as the spin adduct generated by 3-MI irradiation with ultraviolet light. These results demonstrate that the nitrogen-centered radical is a 3-MI-PBN spin adduct, and supports the hypothesis that 3-MI-induced lung damage results from activation of 3-MI to a free radical. Also, in this study the stability of the radical spin adducts and the best conditions to produce the radicals in the incubation system was investigated.
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PMID:Identification of 3-MI-derived N-centered radicals obtained from incubation of 3-MI with microsomal-NADPH system by EPR-HPLC spin trapping. 795 63

The isoprenoid pathway produces three key metabolites--endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator, and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins), and ubiquinone (free radical scavenger). This was assessed in patients with chronic bronchitis emphysema. The pathway was also assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to find the role of hemispheric dominance in the pathogenesis of chronic bronchitis emphysema. All the 15 patients with chronic bronchitis emphysema were right-handed/left hemispheric dominant by the dichotic listening test. In patients with chronic bronchitis emphysema there was elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate levels of RBC membrane in patients with chronic bronchitis emphysema. The same biochemical patterns were obtained in individuals with right hemispheric dominance. Endogenous digoxin by activating the calcineurin signal transduction pathway of T-cell can contribute to immune activation in chronic bronchitis emphysema. Increased free radical generation can also lead to immune activation. Endogenous synthesis of nicotine can contribute to the pathogenesis of the disease. Altered glycoconjugate metabolism and membranogenesis can lead to defective lysosomal stability contributing to the disease process by increased release of lysosomal proteases. The role of an endogenous digoxin and hemispheric dominance in the pathogenesis of chronic bronchitis emphysema and in the regulation of lung structure/function is discussed. The biochemical patterns obtained in chronic bronchitis emphysema is similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with chronic bronchitis emphysema were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Chronic bronchitis emphysema occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function. Hemispheric chemical dominance can play a role in the regulation of lung function and structure.
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PMID:Hypothalamic digoxin, hemispheric chemical dominance, and chronic bronchitis emphysema. 1295 42

Indole and 3-methylindole (skatole) are odor pollutants in livestock waste, and skatole is a major component of boar taint. Skatole causes pulmonary edema and emphysema in ruminants and causes damage to lung Clara cells in animals and humans. A gas chromatographic method that originally used a nitrogen-phosphorus detector to increase sensitivity was modified resulting in an improved flame ionization detection response for indole and skatole of 236% and 207%, respectively. The improved method eliminates the large amount of indole decomposition in the injector. A 10 micro g mL(-1) spike of indole and skatole in water and swine fecal slurries resulted in recovery of 78.5% and 96% in water and 76.1% and 85.8% in fecal slurries, respectively. The effect of the addition of nitroethane and nitroethanol at 21.8 mM in swine fecal slurries was studied on the microbial production of indole and skatole. Nitroethane and nitroethanol decreased the production of skatole in swine fecal slurries at 24 h. The nitroethane effect on l-tryptophan-supplemented fecal slurries after 6 and 24 h incubation resulted in a decrease of 69.0% (P = 0.02) and 23.5% skatole production, respectively, and a decrease of 14.9% indole at 6 h, but an increase in indole production of 81.1% at 24 h.
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PMID:Effect of nitroethane and nitroethanol on the production of indole and 3-methylindole (skatole) from bacteria in swine feces by gas chromatography. 2018 70

The metabolism of 3-methylindole (3MI), a ruminal degradation product of L-tryptophan, results in acute bovine pulmonary edema and emphysema. The effect of feeding an energy or protein supplement containing monensin on ruminal 3MI formation in pastured beef cattle was investigated. A luxuriant pasture of orchard grass was established in a field that was seeded 1 year before the start of the grazing period. This 4-ha pasture was cut, fertilized, divided into 2 equal plots, and then irrigated during a 22-day growth period. All cows were fed a restricted quantity of low-quality alfalfa hay for 33 days before the grazing period. Two experiments were conducted, using 38 cows (30 of the cows were used in experiment I and all 38 cows were used in experiment II). Cows in each experiment were randomly allotted to 2 groups. One group was designated in each experiment as the control group. The control group for experiment I was fed an energy supplement. The control group for experiment II was fed a protein supplement. The 2nd group in each experiment was given the same supplement as the respective control group with 200 mg of monensin added/! kg of feed. Supplements were fed on days - 1, 0, 1, 2, 3, 4, 5, 6, and 7 of each experimental period. Supplements were fed twice daily to provide 1 kg of supplement/cow. Cows were given access to orchard grass pasture on day 0 of each experiment. Ruminal fluid was collected daily for analysis of 3MI, indole, and volatile fatty acids. Ruminal fluid pH was recorded immediately after collection. Ruminal pH of all cows decreased from 7.3 to 6.2 during the first few days of grazing the orchard grass. Ruminal pH then gradually increased toward neutrality by experimental day 10. Significantly (P < 0.01) higher molar percentages of pro-pionate and lower (P < 0.01) molar percentages of acetate and butyrate were observed in the 2 groups fed the supplements with added monensin. These changes in propionate and acetate remained different (P < 0.01) from those of the controls for 10 days (or 3 days after the last monensin feeding). Compared with pregrazing ruminal concentrations of 3MI, the 3MI values were elevated (P < 0.01) by day 1 in all groups, except in the monensin-treated cows of experiment I. In experiment I, 3MI concentrations were highest on experimental days 5 and 10 in control and monensin-treated cows, respectively. In experiment II, 3MI concentrations peaked on day 4 for the control cows and day 6 for the monensin-treated cows. Monensin supplementation reduced (P < 0.05) 3MI formation on days 1 through 5 in experiment I and on days 1 through 3 in experiment II. Formation of 3MI was increased in ruminal fluid of all cows after an abrupt change to the pasture forage, but the rate of 3MI production was slower, and a lower peak concentration of 3MI was reached in cows fed monensin than was observed in the controls. These results indicate that monensin administration in either an energy or protein supplement effectively reduced ruminal 3MI formation in pasture-fed cattle.
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PMID:Effect of energy or protein supplements containing monensin on ruminal 3-methylindole formation in pastured cattle. 2404 4


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