Changes in serum antioxidant concentrations during infection with caprine lentivirus.

We are currently using caprine arthritis encephalitis virus (CAEV) infection in goats as a model to understand changes in some clinical parameters and host response to infection with human immunodeficiency virus (HIV). The objective of this study was to measure changes in serum antioxidant activities in various age groups of goats infected with CAEV. Serum from CAEV-infected goats had significantly higher catalase activity (105.47 +/- 5.96 kU/l) than serum from healthy control goats (79.92 +/- 17.06 kU/l). Moreover, serum catalase activity increased with increase in the time after infection with CAEV. No change was observed in total superoxide dismutase (SOD) or glutathione peroxidase activity although CuZn SOD levels were elevated in infected goats. There was a positive correlation between serum catalase activity and hydrogen peroxide (H2O2) scavenging activity (r = 0.70, p < 0.05). In order to investigate cell membrane integrity, we determined lactate dehydrogenase (LDH) activity in infected goats. Although there was a transient increase in LDH no correlation was observed between increased serum catalase activity and LDH activity (r = 0.16, p > 0.05). We have earlier observed decreased oxyradical production in CAEV infected goats. This observed increase in serum catalase, a scavenger of endogenous free radicals such as H2O2 may be partly responsible for the observed decrease in oxygen radicals found in vivo.

Pathogenic mechanisms of caprine arthritis-encephalitis virus.

Goats infected with caprine arthritis-encephalitis virus (CAEV) show chronic arthritis and cachexia, which are progressive in nature. The immunopathogenic mechanisms responsible for these progressive clinical symptoms have not been fully elucidated. Various haematological and immunological parameters were evaluated in experimentally-infected goats showing typical signs of CAEV-induced disease. Infected goats showed recurrent lymphocytosis that may be due to constant presentation of antigen by infected cells of a monocyte/macrophage lineage. The serum alkaline phosphatase and gamma-glutamyl transferase concentrations were elevated in infected goats, a characteristic of hepatic and bone disorders. All other serum chemistry parameters were similar between infected and control goats. Importantly, the serum tumour necrosis factor-alpha (TNF-alpha) levels were higher in infected goats. The cachexia seen in infected goats may be at least partly due to altered metabolism as a result of prolonged elevation of serum TNF-alpha levels. Depressed natural killer cell activity was observed in infected goats and may contribute towards the establishment of a persistent infection with CAEV.

Alterations of guinea pig alveolar macrophage oxidative metabolism by nicotine.

The influence of nicotine, a cholinergic agonist, on guinea pig pulmonary alveolar macrophage (PAM) oxidative metabolism was examined. Nicotine caused a concentration-dependent enhancement or inhibition of chemiluminescence response and superoxide anion release by zymosan-stimulated PAM. Thus, at 5 x 10(-10) and 5 x 10(-8) M of nicotine the chemiluminescence response was augmented to 132 and 113%, respectively. At higher concentrations, such as 5 x 10(-7) and 1 x 10(-4) M, however, these responses were inhibited to 83 and 51% of the control, respectively. Similarly, at 5 x 10(-10) and 5 x 10(-9) M nicotine, superoxide anion release was enhanced to 226 and 209% of the control, respectively. Higher concentrations of nicotine, 5 x 10(-5) and 5 x 10(-4) M, inhibited this response to 53 and 58% of the control, respectively. Neither the potentiating nor the inhibitory effect of nicotine was affected by a muscarinic (atropine) or nicotinic (hexamethonium) cholinergic antagonist. None of the drugs examined, by themselves, stimulated PAM oxidative metabolism or influenced oxyradical generation by a cell-free system. This study demonstrates that nicotine, a major component of cigarette smoke, may play a significant role in the pathogenesis of some pulmonary diseases.

Parainfluenza-3 virus-induced enhancement of histamine release from calf lung mast cells--effect of levamisole.

Clinically healthy calves were divided into five groups. Group 1 served as control; Group 2 received levamisole (LEV), 3 mg/kg, s.c.; Group 3 was aerosolized with parainfluenza-3 virus (PI-3); Group 4 received LEV and PI-3 and Group 5 was inoculated with Pasteurella haemolytica. They were killed 6 days after virus exposure or 5-6 days after bacterial inoculation. Lung mast cells were prepared by enzymatic treatment. Mast cell histamine (HIST) release was assayed spectrofluorometrically. Total HIST (micrograms/g) in mast cells was as follows (means +/- SEM): control (5.30 +/- 0.26); LEV (5.27 +/- 0.31); PI-3 (6.37 +/- 0.65); LEV + PI-3 (6.21 +/- 0.51); P. haemolytica (7.06 +/- 0.85). Spontaneous HIST release was as follows (% total, means +/- SEM): control (10.38 +/- 1.09), LEV (11.95 +/- 2.13), PI-3v (73.57 +/- 11.97), PI-3v + LEV (19.50 +/- 3.03), and P. haemolytica (70.59 +/- 5.94). Calcium ionophore A23187 (5 X 10(-6) M)-induced release (% total, means +/- SEM) was: 51.53 +/- 3.05, 50.02 +/- 2.70, 83.91 +/- 4.09, 75.21 +/- 4.51 and 70.59 +/- 6.91 for control, LEV, PI-3, LEV + PI-3 and P. haemolytica groups, respectively. Both virus and bacteria increased HIST content of lung mast cells and enhanced ionophore-induced release. Levamisole significantly reduced spontaneous HIST release in virus-infected calves but had no effect on ionophore-induced release. Results suggest a significant role for HIST in pathogenesis of bovine microbial pneumonia and that LEV probably does not modulate non-immunologic release of HIST from bovine lungs.

Beta-adrenergic receptor function and oxygen radical production in bovine pulmonary alveolar macrophages.

Reactive oxygen species production by bovine pulmonary alveolar macrophages was evaluated by a chemiluminescence assay utilizing luminol and opsonized zymosan. Incubation with dobutamine (5 x 10(-8) and 5 x 10(-7) M) or isoproterenol (5 x 10(-8) and 5 x 10(-7) M) prior to zymosan challenge significantly (p less than 0.05) increased the time for chemiluminescence to begin, and significantly decreased the level of maximum chemiluminescence. The agonists' inhibitory effects on maximum chemiluminescence were significantly reduced by pre-incubation with the appropriate antagonist (atenolol at 1 x 10(-6) M for dobutamine; and propranolol at 1 x 10(-6) M for isoproterenol). Salbutamol at 1 x 10(-6) M significantly reduced the level of maximum chemiluminescence only, but did not increase the time for chemiluminescence to begin. This effect was significantly reduced by the presence of the beta 2-antagonist ICI 118,551 at 1 x 10(-6) M. The results reveal the presence of beta 1- and beta 2-adrenoceptors on bovine pulmonary alveolar macrophages, and suggest that these receptors are important in the regulation of reactive oxygen species production by these cells.

Levamisole-induced attenuation of alveolar macrophage dysfunction in respiratory virus-infected calves.

A luminol-amplified chemiluminescence (CL) assay was used to evaluate the effect of levamisole on the metabolic activity of pulmonary alveolar macrophages (PAM) from parainfluenza-3 (PI-3) and infectious bovine rhinotracheitis (IBR) virus-infected calves. Using selective beta-adrenergic agonists and antagonists, beta 1-adrenoceptors were shown to inhibit the PAM reactive oxygen species-dependent CL response. Beta 2 adrenoceptors were apparently not important in the regulation of CL in PAM of control calves. Infection of calves with IBR virus significantly impaired beta 1-receptor function. PI-3 virus infection, in addition to disrupting beta 1-receptors, also unmasked PAM beta 2-receptor activity. Treatment of calves with levamisole, 3 mg/kg, sub-cutaneously, partially reversed the virus-induced impairment of PAM beta 1-receptor function without influencing beta 2-receptor activity. In conclusion, beta-adrenoceptors regulate bovine PAM CL response. Pulmonary viruses impair PAM beta 1-receptor function, an action which can disrupt pulmonary homeostasis. Levamisole partially restores beta-receptor effects on PAM, and may therefore be useful in the management of virus-associated bacterial pneumonia.

Effects of infectious bovine rhinotracheitis virus infection on bovine airway reactivity.

The response of isolated tracheal and bronchial strips to isoproterenol in vitro was studied in eleven male Jersey calves. Clinical, microbiological and pathological evaluations of the calves were carried out. In calves exposed once or twice to infectious bovine rhinotracheitis virus, the relaxation threshold of the trachealis muscle to isoproterenol was significantly (p less than 0.05) impaired (threshold 5.0 X 10(-7) M, single exposure and 1.0 X 10(-7) M, double exposure), when compared with uninfected controls (threshold 1.0 X 10(-8) M). Single infection significantly impaired tracheal relaxation to isoproterenol doses from 1.0 X 10(-7) to 5.0 X 10(-4) M, and double infection significantly impaired tissue responses at drug doses from 1.0 X 10(-7) to 1 X 10(-4) M. Bronchial relaxation threshold was not significantly inhibited (p less than 0.05) in singly infected or doubly infected animals (threshold 5.0 X 10(-8) M and 1.0 X 10(-8) M, respectively), when compared with uninfected controls (threshold 1.0 X 10(-9) M). Single infection significantly impaired bronchial relaxation at isoproterenol doses from 1.0 X 10(-7) M to 5.0 X 10(-6) M while double infection significantly impaired relaxation only at 5.0 X 10(-7) M. The disruption of normal homeostatic bronchodilatory mechanisms may predispose animals infected with infectious bovine rhinotracheitis virus to secondary bacterial infections due to excessive airway constriction and subsequent compromise of lung defenses.

Reactivity of the bronchial artery to 5-hydroxytryptamine.

The activity of 5-hydroxytryptamine and its antagonism by the selective 5-HT2 serotonergic receptor antagonist, ketanserin, was tested on the bronchial arteries of three domestic species; bovine, equine and ovine. 5-hydroxytryptamine contracted the bronchial artery in the bovine (threshold: 1.0 X 10(-9) M), the equine (threshold: 1.0 X 10(-9) M) and ovine (threshold: 5.0 X 10(-9) M), dose-dependently. Ketanserin on the bronchial artery of the bovine (concentrations: 1.0 X 10(-9) M and 1.0 X 10(-8) M), equine (concentrations: 1.0 X 10(-10) M, 1.0 X 10(-9) M and 1.0 X 10(-8) M) and ovine (concentrations: 1.0 X 10(-10) M, 5.0 X 10(-10) M and 1.0 X 10(-9) M), significantly (p less than 0.05) shifted the concentration response curves to 5-hydroxytryptamine and caused a depression of the maximum at the higher concentrations. The data indicates the presence of 5-HT2 serotonergic receptors in the bronchial artery of these species. The depression may possibly be due to the antagonist's adrenolytic properties.

Effects of tryptamine antagonists on the anaphylactic contractions of the bovine pulmonary smooth muscles.

Calves were sensitized with horse plasma (H.P.), 0.2 ml/kg, i.v., and H.P. (0.2 ml/kg) in Freund's complete adjuvant, s.c. The latter injection was repeated 1 week later and the animals were killed 10 days after the second injection. Spirally cut strips of pulmonary artery and vein and the trachealis muscle from the sensitized calves contracted to 5-hydroxytryptamine (5-HT) and specific antigen (horse plasma). Antigen-induced contractions of the pulmonary smooth muscles were significantly blocked (P less than 0.05) by the 5-HT antagonists, methysergide and ketanserin. The trachea, however, appeared less sensitive to the antagonists than the pulmonary vessels. The results suggest that 5-HT participates in the pulmonary anaphylactic reactions of cattle and that ketanserin may be useful in suppressing bovine pulmonary hypersensitivities.

Tryptaminergic receptors in the bovine pulmonary vasculature: effects of ketanserin.

The vasoconstrictor actions of 5-hydroxytryptamine (5-HT) were investigated in the isolated helical strips of the pulmonary artery and vein of the adult bovine and calf. Agonist-antagonist interactions were studied by pretreating the vessels with methysergide, ketanserin and phentolamine and then establishing the dose-response curves to 5-HT or noradrenaline (NA). Methysergide significantly (p less than 0.05) inhibited 5-HT-induced contractions in the vessels. Ketanserin antagonized the vasoconstrictor actions of 5-HT but inhibition was not dose-related. NA-induced contractions of the vessels from the adult bovine were non-competitively inhibited by ketanserin. Phentolamine (PH) competitively antagonized contractions induced by 5-HT and NE in the tissues. The results suggest that 1. ketanserin is a potent, competitive antagonist of 5-HT but a weak antagonist of NE and 2. 5-HT-induced contractions in the bovine pulmonary vessels are mediated via specific tryptamine receptors (5-HT2) and alpha-adrenergic receptors.

Estrus synchronization and controlled breeding in goats using prostaglandin F(2)alpha.

Estrus synchronization in the goat employing the double injection regimen of 7.5 mg of prostaglandin F(2)alpha (Lutalyse) at each injection, resulted in 64% and 84% synchronization at first and second injections, respectively. Breeding at estrus induced by the second injection resulted in 90% conception. Kidding at the end of the gestation period was spread over a 17-day period. The first and the last does had 141 and 158 days of gestation, respectively. The findings of this study indicate that two injections of prostaglandin F(2)alpha 10 days apart is superior to a single injection for estrus synchronization in the goat. Breeding following the second injection resulted in high conception rate. Due to individual differences in gestational lengths, estrus synchronization with prostaglandin F(2)alpha cannot be depended upon for synchrony of kidding.