Search PubMed⌕ Search

Biomedical subjects

R G Breeze

Publications and source records attributed to R G Breeze.

At least 37 records · Page 2Linked to original sources
PubMed1984

Role of metabolism in the immediate effects and pneumotoxicity of 3-methylindole in goats.

Rapid infusion of 3-methylindole (3-MI) dissolved in 10% Cremophor EL in water was immediately followed by pulmonary arterial hypertension, systemic arterial hypotension, decreased minute volume and periods of apnoea in goats. Rapid intravenous infusion of Cremophor EL/water alone caused similar immediate effects to those of Cremophor EL plus 3-MI in various dosages. Pretreatment of goats with piperonyl butoxide or phenobarbitone did not significantly alter these immediate cardiopulmonary responses. But pretreatment with piperonyl butoxide prevented clinical signs and pulmonary lesions of 3-MI toxicity, whereas phenobarbitone pretreatment shortened survival time and enhanced pulmonary pathology. Cremophor EL and 3-MI dissolved in Cremophor EL caused severe in vitro haemolysis of caprine and bovine erythrocytes. There was no relationship between the immediate effects of 3-MI and the subsequent development of 3-MI-induced pneumotoxicity and deaths in control goats or in goats pretreated with piperonyl butoxide or phenobarbitone. Induction or inhibition of mixed function oxidase activity had no influence on immediate responses to 3-MI but did change the severity of clinical and pathological responses. It is concluded that there is no apparent relationship between the immediate and the pneumotoxic effects of 3-MI. It is possible that the immediate effects are the result of intravascular haemolysis.

Animals↗
PubMed1984

3-methylindole as a model of equine obstructive lung disease.

3-methylindole was administered orally and intravenously to horses and ponies in order to determine the ability of this chemical to provide a model of equine pulmonary disease. Both routes produced a severe and sometimes fatal pulmonary disease, characterised by bronchiolitis. Clinical signs developed 48 to 72 h after dosing and were most severe between Days 4 and 10 post dosing. Intravenous administration of 3-methylindole produced lung injury more rapidly and at a lower dose rate than the oral route. It is suggested that the respiratory condition induced by this chemical could become a method for standardisation of lung function techniques and interpretation in equine obstructive pulmonary disease.

Animals↗
PubMed1984

Perilla ketone toxicity: a chemical model for the study of equine restrictive lung disease.

Perilla ketone was assessed for its usefulness as a model of equine restrictive pulmonary disease. Three ponies were given 18 mg/kg bodyweight synthetic perilla ketone in dimethyl-sulphoxide. Within 24 h of administration, respiratory rate, peak inspiratory and expiratory flow rates and minute volume were increased. By 48 h there was a significant decrease in tidal volume, and blood pH and base excess were also decreased but not outside normal limits. At necropsy there was congestion and oedema of the lungs. Histologically there was diffuse alveolar injury but no evidence of significant obstruction in bronchial or bronchiolar lumina. It is assumed that perilla ketone toxicity in ponies produces a restrictive disease without a significant obstructive component.

Animals↗
PubMed1984

Arterial blood gas tension and acid base balance during exercise in horses with pharyngeal lymphoid hyperplasia.

Arterial blood gas and acid-base values during maximal exercise over a 1.2 km distance were recorded in four Thoroughbred horses before and after the chemical induction of pharyngeal lymphoid hyperplasia (PLH). Samples were collected after galloping 0.8 km and 1.2 km, immediately upon stopping and 5 mins after exercising. In only one horse was any difference noted in the pre and post PLH induction results. The horse was more hypercapnoeic at the 1.2 km mark and also took much longer to complete the gallop when it had PLH. However, it also had signs of lower respiratory disease. In the other horses, the only changes which could be attributed to PLH were seen immediately upon stopping. It seems that PLH does not inhibit gas exchange during exercise unless the lesions are extremely severe.

Acid-Base Equilibrium↗
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

Greater sensitivity of caprine synovial membrane cells to human interferon-alpha than human or bovine cells.

The sensitivity of caprine synovial membrane cells to the antiviral effects of natural and recombinant DNA-derived human interferons (HuIFN) was compared with that of human foreskin fibroblast (FS7), ovine choroid plexus, and bovine turbinate cells. Caprine cells were found to be more sensitive (P less than 0.01) to natural HuIFN-alpha than human, ovine, and bovine cells. The sensitivity of caprine cells to recombinant DNA-derived HuIFN-alpha was equivalent to that of ovine cells, but greater than human or bovine cells. The sensitivity of caprine cells to natural and recombinant DNA-derived HuIFN-beta was equivalent to human cells, but less than that of ovine cells.

Animals↗
PubMed1984

Pathogenesis of experimental bovine respiratory syncytial virus infection in sheep.

Conventionally reared lambs, seronegative to bovine respiratory syncytial virus (RSV), were inoculated with bovine RSV by an aerosol route. A mild clinical response, characterized by transient fever at postinoculation day (PID) 4, occurred and was accompanied by serous oculonasal secretions in less than 50% of the infected lambs. A decrease in total WBC was observed on PID 6 and 11, with a reduction in the total numbers of lymphocytes. Bovine RSV was recovered from nasal secretions of inoculated lambs from PID 2 to 6. The lambs were euthanatized, and at necropsy, the virus was only isolated from lambs killed between PID 2 and 4. Serum neutralizing antibodies were noticed as early as PID 6 and peaked at PID 13 to 15. Neutralizing antibodies were also detected at low concentration in pulmonary washings. Viral antigen was mainly located in alveolar walls and occasionally in bronchiolar epithelium and alveolar macrophages in lambs killed between PID 2 to 4. Later, specific fluorescence was only present in alveolar walls and was not observed in tissue from lambs killed after PID 22. Budding and free virus-like particles were observed by electron microscopy in type I and type II alveolar epithelial cells. Outstanding macroscopic lesions were not seen. Histologically, mild bronchiolitis and alveolitis were observed.

Aerosols↗
PubMed1984

Interaction of bovine respiratory syncytial virus and Pasteurella haemolytica in the ovine lung.

The potential synergistic effect of bovine respiratory syncytial virus (RSV) and Pasteurella haemolytica in the production of pneumonia after aerosol/intranasal infection of conventionally reared lambs was evaluated. A mild clinical response was observed in lambs given virus and/or bacteria. Gross pulmonary lesions were seen in 3 of 6 lambs given RSV and then P haemolytica 3 or 6 days later, respectively (groups D and E), and in 1 lamb of 5 given virus and bacteria simultaneously (group G). Gross lesions were not seen in control sheep (group A), in lambs given virus or bacteria alone (groups B and C), or in lambs exposed to bacteria and then virus 3 days later (group F). Bovine RSV and P haemolytica were recovered from the lungs of 5 of 7 lambs with macroscopic lesions. Gross pulmonary lesions were cranioventral firm areas of red consolidation. Microscopically, the predominant lesion was a suppurative bronchopneumonia. Bovine RSV was recovered from the nasal cavity of 8 of 27 (30%) lambs given RSV during days 3 to 6 after viral inoculation, including 1 lamb in group B, 2 in groups D, E, and F, and 1 in group G. Pasteurella haemolytica was recovered from the nasal cavity of 9 of 28 (32%) inoculated lambs, including 2 lambs from groups C and E, 3 in group D, and 1 in groups F and G. Viral antigen, as determined by immunofluorescence, was concentrated mainly in individual cells in alveolar walls, some alveolar macrophages, and a few bronchiolar epithelial cells. In vitro alveolar macrophage assays indicated decreased numbers of Fc receptors on those macrophages collected from lambs given RSV 6 days before P haemolytica infection, as compared with that in the other groups. These cellular defects disappeared after 24 hours of culture. Seemingly, bovine RSV does facilitate P haemolytica pulmonary infection in conventional, immuno-competent lambs and provides evidence for decreased Fc receptors on alveolar macrophages.

Aerosols↗
PubMed1984

Bovine pulmonary alveolar macrophages: antemortem recovery and in vitro evaluation of bacterial phagocytosis and killing.

A system was developed to recover pulmonary alveolar macrophages (PAM) from living cattle and to evaluate the function of these cells by measuring bacterial phagocytosis and killing. For the collection of PAM, single-tube and telescoped double-tube pulmonary lavage devices were compared. The total recovery, using these systems, was 70 +/- 10.7% of infused fluid, yielding approximately 87% PAM. The total number of cells per collection was approximately 5 times higher with the single-tube device (6.87 +/- 0.78 x 10(7) cell/ml) than with the telescoped double-tube device (1.3 +/- 0.1 X 10(7) cells/ml). Phagocytosis and intracellular killing of Staphylococcus epidermidis and Staphylococcus aureus by PAM in media suspension and by plastic-adherent PAM were evaluated. In addition, different bacteria-to-macrophage ratios were assessed, as well as the intracellular killing of S epidermidis at periodic intervals. Results showed that over a 3-hour period, similar numbers of both bacteria were phagocytized, but intracellular killing of S epidermidis was more efficient than intracellular killing of S aureus. It also was found (i) that suspended PAM and adherent PAM phagocytized similar numbers of bacteria; (ii) that when the bacteria-to-cell ratio was 10:1, the numbers of phagocytized bacteria and intracellular killing were higher than when the ratio was 1:10; and (iii) that killing of S epidermidis by adherent PAM was directly proportional to incubation time. The time that PAM are in culture affects the phagocytosis and killing of intracellular bacteria, as shown by increased phagocytosis and by intracellular killing of S epidermidis by PAM in suspension for 48 hours or plastic adherent for 60 hours after collection.

Animals↗
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↗
PubMed1984

Site of 3-methylindole and indole absorption in steers after ruminal administration of L-tryptophan.

To determine the site of 3-methylindole (3MI) and indole absorption in cattle after ruminal administration of L-tryptophan (TRP), 4 Holstein steers were given 0.4 g of TRP/kg of body weight directly into the rumen through ruminal cannulas. Chromium EDTA and ruthenium phenanthroline were added to feedings of orchard grass hay twice a day for measurement of fluid and particulate flow to the duodenum, respectively. Passage of 3MI and indole (products of ruminal fermentation of TRP) to the duodenum was determined by the products of digesta flow rate and concentration in duodenal contents. Ruminal fluid, duodenal contents, and jugular blood were sampled at postdosing hours (PDH) 0, 6, 12, 18, 24, 36, and 72 for analysis of 3MI, indole, and digesta flow markers. Ruminal, duodenal, and jugular plasma concentrations of 3MI and indole peaked at PDH 12 to 24 at 152.4 and 25.9; 15.5 and 1.0; and 8.7 and 2.2 mg/L, respectively. Most 3MI and indole reaching the duodenum were associated with the particulate phase of the digesta. On a molar basis, total passage of 3MI to the duodenum during 72 hours amounted to 1.0% of the TRP dose for 3MI and 0.1% of the TRP dose for indole. Absorption of 3MI and indole in these steers was almost entirely proximal to the duodenum.

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

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↗
PubMed1983

Net absorption of 3-methylindole and indole in cattle after oral administration of L-tryptophan.

The time course and quantity of 3-methylindole (3MI) and indole absorbed after oral administration of L-tryptophan (TRP) was determined in 2 steers. The relationship between the appearance of 3MI and indole in the rumen and blood plasma to absorption of 3MI and indole was also studied. Two Hereford X Angus steers with portal vein, mesenteric vein, and femoral (steer 1) or iliac (steer 2) artery catheters were used. Absorption rates from the portal drained viscera (net absorption) of 3MI and indole were determined by the product of portal and arterial concentration difference and blood flow. Blood flow was determined by primed continuous infusion of p-aminohippuric acid into a mesenteric vein. Three absorption measurements 30 minutes apart were taken at midpoint times of 0, 12, 24, 36, and 48 hours after oral administration of 0.4 g of TRP/kg of body weight. Steer 1 was dosed twice resulting in a total of 45 absorption measurements. Net absorption of 3MI and indole peaked at an average of 1.05 and 0.81 g/hr, respectively. By 48 hours, 29.2% and 15.3% of the TRP dose were accounted for by 3MI and indole absorption, respectively. Closed system in vitro incubations of TRP with ruminal fluid from the same 2 steers resulted in a TRP to 3MI conversion of 23.2% and a TRP to indole conversion of 10.7%. Net absorption of 3MI and indole closely followed and was correlated with concentration of 3MI and indole in ruminal fluid and blood plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1983

Pathologic changes in 3-methylindole-induced equine bronchiolitis.

The pathologic features of bronchiolitis were studied in horses and ponies from 30 minutes to 27 days after an oral dose of 3-methylindole (3MI). From 30 minutes to 3 hours, lesions were limited to nonciliated bronchiolar epithelial (Clara) cells, which lost apical caps and cytoplasmic granules and had dilated smooth endoplasmic reticulum (SER). At 12 hours, necrotic Clara cells were exfoliated; degeneration and necrosis were evident, in bronchiolar ciliated cells. Rare epithelial cells with hyperplastic SER appeared on the denuded basal lamina at 24 hours. Inflammatory cells, epithelia, fibroblastlike cells, collagen, and debris occluded many bronchiolar lumens from 3 to 6 days. Reorganization resulted in a simple columnar bronchiolar epithelium with relatively normal ciliated cells and fewer fibroblastlike cells. However, mature Clara cells were rare at 27 days, and collagenous bands still divided bronchiolar lumens. Thus, 3MI toxicosis is a persistent model of equine bronchiolitis with many morphologic features of the spontaneous disease.

Animals↗
PubMed1982

Isolation and some properties of equine alpha 1-antitrypsin.

1. Equine alpha 1-antitrypsin was isolated from horse plasma by a combination of ammonium sulfate and acidification precipitation followed by ion-exchange chromatography on DEAE-cellulose, molecular sieve chromatography on Sephadex G-200 and affinity chromatography on Cibacron Blue-agarose. 2. The purified protein showed a single precipitin arc on immunoelectrophoresis in agarose but gave two bands on discontinuous polyacrylamide gel electrophoresis (PAGE). 3. Both bands appeared to interact equally with trypsin and were thought to represent two isoinhibitors of equine alpha 1-AT.

Animals↗