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Biomedical subjects

J R Carlson

Publications and source records attributed to J R Carlson.

At least 127 records · Page 7Linked to original sources
PubMed1985

Reduction of 3-methylindole production and prevention of acute bovine pulmonary edema and emphysema with lasalocid.

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)

Animals↗
PubMed1984

Autoradiographic evidence of 3-methylindole covalent binding to pulmonary epithelial cells in the goat.

3-Methylindole (3MI), the main ruminal fermentation product of L-tryptophan, causes acute pulmonary edema and interstitial emphysema in ruminants. Intravenous infusion of 3MI in goats causes necrosis and sloughing of pneumocytes and bronchial epithelial cells. Previous studies indicate that a reactive metabolite or metabolites of 3MI bind covalently to tissue macromolecules in the lung and this binding is associated with the pneumotoxicity of 3MI. We undertook this autoradiographic study of 3MI covalent binding to test the hypothesis that reactive 3MI metabolite(s) bind to the lung cells susceptible to 3MI-induced injury. We infused goats with [3H]3MI and killed them either 0.5, 2 or 6 h after start of the infusion. Sections of fixed lung were extensively washed, alcohol dehydrated and embedded in plastic. Only covalently bound radioactivity remained. Silver grains were quantitated per area in the developed autoradiographs. There was a 2:1 ratio of binding to the small airway epithelium compared to the interalveolar septa in all the goats. Both ciliated and non-ciliated bronchiolar cells were labeled, as were both types I and II pneumocytes. Normal goat lung slices incubated in vitro with [3H]3MI were labeled in the same pattern. Inclusion of either of the inhibitors of cytochrome P-450, SKF-525-A or piperonyl butoxide significantly reduced this binding to both the pneumocytes and the bronchiolar cells. We consider these results supportive of our hypothesis that 3MI is metabolized to reactive intermediates by the epithelial cells of the lung, where they bind to macromolecules, which may cause cellular damage.

Animals↗
PubMed1984

Ruminal metabolism of plant toxins with emphasis on indolic compounds.

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.

Animals↗
PubMed1984

Electrophilic metabolites of 3-methylindole as toxic intermediates in pulmonary oedema.

[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.

Animal Diseases↗
PubMed1984

In vitro covalent binding of 3-[14C]methylindole metabolites in goat tissues.

Covalent binding of 3-[14C]methylindole (3[14C]MI) in crude microsomal preparations of goat lung, liver, and kidney was measured to determine if a reactive intermediate was formed during the in vitro metabolism of 3-methylindole (3MI). The bound radioactivity was highest in lung compared to liver and kidney. The amount of bound radioactivity per nanomole of cytochrome P-450 was approximately 10 times higher in the lung compared to liver. No detectable bound radioactivity was found when 3-[3H]methyloxindole was used as the substrate. Cofactor requirements and the effects of inhibitors indicate that a mixed function oxidase (MFO) system is involved in formation of a reactive intermediate. Inhibitors and conjugating agents that are known to reduce the severity of 3MI-induced lung injury such as piperonyl butoxide (MFO inhibitor) and glutathione (conjugating agent) significantly decreased the in vitro binding of 3[14C]MI. The results indicate that a reactive intermediate is produced during the metabolism of 3MI by the MFO system. The organ specificity in binding suggests that covalent binding by lung microsomes may be related to the mechanism of 3MI-induced lung injury.

Animals↗
PubMed1984

Improving physician/teacher collaboration.

This paper describes a three-phase project designed to improve physician/teacher collaboration with exceptional school children. In phase 1, the school district's 54 special education personnel completed a 24-item questionnaire designed to identify communication and role-expectancy problems. Phase 2 consisted of a series of workshops in which physicians explained their evaluations and and treatments of exceptional children. In phase 3 a collaboration model linking the school district and a university-based medical center was developed and implemented. Questionnaire data, the collaboration model, and suggestions for other models are presented.

Child↗
PubMed1984

Effect of pH on in vitro ruminal conversion of L-tryptophan to 3-methylindole and indole.

Three in vitro experiments were conducted to determine the effects of pH on ruminal conversion of L-tryptophan (TRP) to 3-methylindole (3-MI) and indole (IND). Experiment 1 involved 2 closed-system incubations, each with triplicate replications of buffered ruminal fluid at initial pH of 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, and 8.0. Highest molar conversions of TRP to 3-MI were 61.5 +/- 2.7% and 64.3 +/- 0.8% at initial pH treatments of 7.5 and 7.0 (final pH 7.3 and 6.9) for the 2 incubations, respectively. Experiment 2 used duplicate continuous cultures at each of 4 pH treatments. Following a common 5-day pretreatment period, effluent pH averaged 5.6, 6.1, 6.5, and 6.9 for the respective treatments. Data for 4 subsequent 5-day time periods showed production of 3-MI was affected by pH treatment (P less than 0.01), time (P greater than 0.01), and treatment X time (P less than 0.01); conversion of TRP to 3-MI reached 78% at pH 6.9 and decreased to less than 1% at pH 5.6. Production of IND was not related to pH treatment (P greater than 0.10). Total moles of volatile fatty acid (VFA) carbon produced showed a pH treatment X time interaction (P less than 0.01) which reflected a trend toward decreasing VFA production at lower pH and increasing VFA production at higher pH. Experiment 3 consisted of 2 pH treatments with additional continuous culture fermenters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

The spin-trapping of enzymatically and chemically catalyzed free radicals from indolic compounds.

A nitrogen-centered free radical was spin-trapped from superoxide-catalyzed oxidation of indolic compounds, using the spin-trap phenyl-t-butyl-nitrone. The hyperfine splitting constants observed were aN = 13.9 G, a beta N = 3.6 G and a beta H = 2.3 G. Incubation of various indolic compounds with goat lung microsomes showed that only 3-methylindole was able to generate a free radical in the NADPH-dependent microsomal system, as tested by spin-trapping. The splitting constants were the same as those seen with superoxide incubations with 3-methylindole. The study demonstrates the generality of formation of a nitrogen-centered free radical from various indolic compounds. Enzymatic radical formation from 3-methylindole suggests a microsomal-activated free radical mechanism for the specificity of 3-methylindole-induced pulmonary toxicity.

Animals↗
PubMed1983

Effect of glutathione status on covalent binding and pneumotoxicity of 3-methylindole in goats.

A study was conducted to investigate the relationship between glutathione (GSH) status, in-vivo metabolite covalent binding and 3-methylindole (3MI)-induced lung injury in goats. Cysteine or diethylmaleate pretreatments were given to sustain or deplete GSH, respectively, prior to intravenous 14C-3MI administration. Cysteine pretreatment prolonged survival times, decreased (P less than .05) covalent lung injury. Diethylmaleate pretreatment shortened survival times, increased (P less than .05) covalent binding and enhanced lung injury. Covalent binding was higher (P less than .05) in lung compared to liver and kidney. 3-Methylindole alone depleted GSH in 4 hours to 36, 66, and 75% of controls in these tissues, respectively. The relationship between tissue GSH, covalent binding and toxicity supports the hypothesis that 3MI-induced pneumotoxicity results from the formation of activated intermediates and that GSH plays a role in detoxication of these 3MI metabolites.

Animals↗
PubMed1983

Comparative in vitro activities of ten antimicrobial agents against bacterial enteropathogens.

The in vitro susceptibilities of 50 strains of Salmonella spp., 80 strains of Shigella spp., and 50 enterotoxigenic Escherichia coli, 14 Yersinia enterocolitica, 6 Aeromonas hydrophila, 4 Plesiomonas shigelloides, 9 Vibrio parahaemolyticus, and 30 Campylobacter jejuni strains that were recently isolated from worldwide sources were determined for 10 antimicrobial agents. The antimicrobial agents tested included ampicillin, bicozamycin, doxycycline, enoxacin (CI-919), erythromycin, furazolidone, amdinocillin, norfloxacin, trimethoprim, and trimethoprim-sulfamethoxazole. Ampicillin resistance occurred frequently in strains of Salmonella and Shigella spp. and enterotoxigenic E. coli strains. The most active agents against all of the bacteria tested were enoxacin and norfloxacin. Furazolidone and amdinocillin were also highly active against the majority of strains. Trimethoprim and trimethoprim-sulfamethoxazole were inhibitory at low concentrations against all test except C. jejuni isolates. The in vitro results of this study confirm the high prevalence of bacterial resistance to ampicillin. However, this work also identifies four antimicrobial agents, enoxacin, furazolidone, norfloxacin, and amdinocillin, that would be appropriate for further testing in clinical trials.

Anti-Bacterial Agents↗
PubMed1983

Effects of mixed-function oxidase inducers and inhibitors on cytochrome P-450 content, gel electrophoresis profiles, and 3-methylindole-induced lung toxicity in goats.

Effects of mixed-function oxidase inducers and inhibitors on cytochrome P-450 content, gel electrophoresis profiles, and 3-methylindole-induced lung injury were studied in goats. In the first experiment, goats were pretreated with phenobarbital (PB), 3-methylindole (3MI), 3-methylcholanthrene (3MC), or SKF 525-A. Liver, lung, and kidney microsomes were used for cytochrome P-450 and gel electrophoresis studies. Although pulmonary cytochrome P-450 was not affected by any of the pretreatments, hepatic cytochrome P-450 significantly increased (P less than 0.05) after PB and 3MC pretreatment. All pretreatment resulted in changes in liver gel profiles in the 43,000 to 68,000 molecular weight region, but only PB and 3MI pretreatment altered gel profiles in the lung. In the second experiment, pretreated goats were infused with 3MI. The relative severity of lung injury in these animals, based on clinical signs, lung lesions, lung weight, and mean survival time was as follows: SKF 525-A pretreated group greater than PB-pretreated group = unpretreated group greater than 3MI-pretreated group greater than or equal to 3MC-pretreated group. The results indicate that changes in 3MI-induced lung injury are accompanied by changes in gel profiles in the molecular weight region of 43,000 to 68,000.

Animals↗
PubMed1982

Concentration of 3-methylindole (3MI) and distribution of radioactivity from 14C-3MI in goat tissues associated with acute pulmonary edema.

3-Methylindole (3MI) can cause acute pulmonary edema in goats. Because of known lipophilic properties and direct effects on biological membranes, the concentration of 3MI and distribution of radioactivity from 14C-3MI in tissues was investigated during development of 3MI-induced APE. Goats were given a 2 hr jugular infusion of 3MI containing 14C-3MI using propylene glycol as the vehicle. Groups of 3 goats were killed at 0, 5, 2 and 4 hr and 2 goats were killed at 8 and 24 hr. Plasma, lung, liver, kidney and other selected tissues were collected. 3MI was rapidly cleared from blood plasma and tissues after infusion, and 81% of the radioactivity was excreted in the urine by 24 hr. Maximum concentrations of unmetabolized 3MI in the tissues ranged from 2.6 to 15 micrograms 3MI/g, including 7.5 micrograms 3MI/g in the lung. The ratios of equivalent radioactivity to unmetabolized eMI indicated rapid metabolism and the presence of metabolites in all tissues studied. The lung contained the highest proportion of metabolites with ratios of radioactivity to unmetabolized 3MI of about 50, 10, 250, 150 and 80 at 0.5, 2, 4, 8 and 24 hr. The data demonstrate that 3MI does not selectively concentrate in the lung and that the concentrations are lower than those usually associated with direct membrane damage. They also indicate that 3MI is rapidly metabolized and that metabolites are present in tissues, especially the lung. These results suggest that direct effects of 3MI on biological membranes are not primarily responsible for lung injury in goats.

Animals↗
PubMed1982

Methicillin-resistant Staphylococcus aureus susceptibility testing with Abbott MS-2 system.

The antimicrobial susceptibilities of 100 methicillin=resistant Staphylococcus aureus strains were concurrently determined by the Abbott MS-2 System and by the standard disk diffusion method. Agreement between the two methods was 94% or greater for all of the antibiotics tested except for methicillin and gentamicin. This study indicates that the Abbott MS-2 cannot be relied upon for detection of methicillin resistance in clinical S. aureus isolates.

Anti-Bacterial Agents↗