A series of experiments was conducted to document tumor necrosis factor-alpha (TNF) activity in serum of swine after inoculation with Salmonella spp endotoxin and after oral or respiratory tract challenge exposure with live Salmonella spp. For experiment 1, a potentially lethal dose of S typhimurium endotoxin (25 microgram/kg of body weight) was administered IV, and serum TNF activity was measured. High TNF (approx 700 IU/ml) activity at 1 to 2 hours after administration of the inoculum was associated with death, whereas lower TNF (approx 30 IU/ml) activity was associated with a general prolonged state of shock. For experiment 2, pigs were administered a nonlethal dose (5 microgram/kg, IV) of either S typhimurium or S choleraesuis endotoxin. Difference in the ability to induce porcine serum TNF activity was not observed between strains. During experiment 3, pigs were inoculated with 104 colony-forming units of S typhimurium chi4232 either orally by gelatin capsule (GC) or by intranasal (IN) instillation. A late serum TNF response (17 IU/ml) was measured at 6 weeks after IN inoculation. A serum TNF response was not detected in GC-inoculated pigs. All tissues and feces were test-negative for S typhimurium prior to the 6-week TNF response. Serum TNF activity may be related to clearance of S typhimurium after respiratory tract exposure, but it is not important to or indicative of clearance of orally presented S typhimurium in swine. During experiment 4, pigs were inoculated with 106 colony-forming units of S typhimurium chi4232 similarly as for experiment 3. Challenge exposure with this medium-size dose of inoculum induced a prolonged peak serum TNF response (37 IU/ml) between 2 and 4 weeks after IN inoculation Again, serum TNF activity was not detected in GC-inoculated pigs. Data suggest that clearance of a medium-size dose (106) of inoculum may be influenced by the prolonged higher serum TNF activity. For experiments 5 and 6, pigs were inoculated IN with 103, 106, 108.

A challenge-exposure model was developed for dose-dependent induction of subclinical (moderate) atrophic rhinitis (AR) in conventionally raised Dutch Landrace and Large White pigs, about 4 weeks old. Under favorable climatic and housing conditions, pigs were intranasally challenge-exposed with Pasteurella multocida-derived toxin (Pm-T) 3 days after pretreatment by inoculation with 1% acetic acid. Pigs were challenge-exposed with 1 of the following Pm-T doses: 0 (control), 5, 13, 20, or 40 microgram of Pm-T/ml of phosphate-buffered saline solution (PBSS), 0.5 ml/ nostril/d on 3 consecutive days. Five weeks after challenge exposure, subclinical moderate) AR status was defined as intermediate conchal atrophy (grade 2 for ventral conchae on a 0 to 4 scale and grade 1 or 2 for dorsal conchae on a 0 to 3 scale, respectively) and perceptible difference in change in brachygnathia superior (CBS) between control and challenge-exposed pigs between the beginning and end of the study. All Pm-T-exposed pigs had nasal damage that was dose-dependent. The higher Pm-T doses resulted in higher ventral conchae atrophy and dorsal conchae atrophy scores. The CBS increased with applied Pm-T dose, resulting in significant (P < 0.05) differences between controls (3.88 mm) and the 13-, 20-, and 40-microgram Pm-T-treated groups (7.77, 6.58, and 7.98 mm, respectively). In response to the applied dose, weight gain per week for Pm-T-exposed pigs was lower than that of controls after week 3 (P < 0.01). Difference from controls was 32, 54, 52, and 96 g/d/pig for 5-, 13-, 20-, and 40-microgram Pm-T-treated groups respectively, in the last 2 weeks. For Dutch Landrace and Large White pigs, intranasally administered Pm-T mimicked the pathogenic effect of in vivo infection with toxigenic Pm strains. The optimal model to induce subclinical AR appeared to be 13 microgram of Pm-T/ml (0.5 ml/nostril/d) on 3 consecutive days.

Microscopic examination of the nasal mucosa of clinically normal specific-pathogen-free pigs and of toxicogenic type-D Pasteurella multocida toxin challenge-exposed specific-pathogen-free pigs indicated that the surface epithelium in pigs of both groups was microscopically normal; erosions or appreciable inflammatory changes were not evident. In pigs of both groups and in aU 3 regions of the nasal cavity, the endothelial lining of all blood vessels appeared normal without detectable changes to the walls at postinoculation day 10. Vascular injury in the cartilage or the bone was not discernible in control or challenge-exposed pigs. There were marked differences in the osseous structures of the conchae when the 2 groups were compared. In control pigs, active bone formation and remodeling were observed, and the septal cartilage was normal. In toxin challenge-exposed pigs, there likewise was normal bone formation and remodeling in the vestibular region, and the septal cartilage was normal. In marked contrast, conspicuous changes were observed in the osseous core of the conchae of the respiratory and, sometimes, the olfactory regions. These changes consisted of bone necrosis and resorption by large numbers of osteoclasts with variable replacement by dense mesenchymal stroma, which resulted in conchal atrophy. In the absence of any discernible damage or injury (angiopathy) to the nasal vessels, it appears that the action of the dermonecrotoxin of P multocida serotype D is on the most active osteoblasts and the associated organic matrix of the bone, with subsequent disruption of normal bone formation and remodeling of the nasal conchae.

In 2 trials, the efficacy of an in-feed preparation of ivermectin was evaluated in 40 pigs naturally infected with endoparasites and Sarcoptes scabiei var suis. Treated pigs (n = 10 in each trial) were fed a ration containing 2 ppm ivermectin for 7 days, followed by consumption of a nonmedicated ration for the remainder of the trial. Control pigs (n = 10 in each trial) were fed a complete, nonmedicated ration for the duration of the trial. Pigs in trial A were monitored for 14 days after treatment; those in trial B were monitored for 35 days after treatment. In trial A, treatment efficacy of ivermectin was 100% against Ascaris suum, Physocephalus sexalatus, Oesophagostomum dentatum, O brevicaudum, Metastrongylus spp; 99.8% against Ascarops strongylina; 90.9% against Trichuris suis; and 13.1% against Macracanthorhynchus hirudinaceus. At the terminus of the trial, statistically significant (P < 0.05) differences were observed between numbers of treated and control pigs infected with A suum, Ascarops strongylina, and Oesophagostomum spp. On posttreatment day 14, S scabiei were not found in any scrapings taken from treated pigs, but were found in scrapings from 3 of 10 control pigs. The number of infested pigs in the treatment group was not statistically different from the number of infested pigs in the control group. In trial B, treatment efficacy was 100% for A suum and Metastrongylus spp; 96.9% for Ascarops strongylina; and 76.9% for M hirudinaceus. At the terminus of the trial, statistically significant (P < 0.05) differences were evident between numbers of treated and control pigs infected with A suum, Ascarops strongylina, and Metastrongylus spp. On posttreatment days 7, 2 1, and 35, S scabiei were not found in scrapings taken from treated pigs. On posttreatment days 7, 2 1, and 35, S scabiei were found in scrapings from 8, 6, and 1 pig, respectively, whereas live mites were not found on scrapings taken from treated pigs on these days. Statistically significant (P < 0.05) differences were evident between the numbers of infested pigs in the treated and control groups on days 7 and 21. Ivermectin fed to swine ad libitum in a complete ration at 2 ppm was shown to be highly effective as an anthelmintic and acaricide.

Live, avirulent Escherichia coli vaccine strains were constructed and tested for efficacy in preventing colibacillosis in 4-week-old pigs. Either or both of 2 plasmids were inserted into avirulent E coli strain G58-1 (0101:NM). These plasmids were pPMC4, which encodes for LTb subunits of heat-labile enterotoxin, and pDHF1, which encodes for K88ac fimbriae. Litter- and weight-matched pigs were removed from sows when they were 10 days old and vaccinated orally with the constructed strains or with G58-1 (negative control vaccine) when they were 2 weeks old and 5 days later. All pigs were challenge-inoculated with virulent E coli strain 3030-2 (0157:K88, LT+, STb+) 2 weeks after the first vaccination. Only 1 pig vaccinated with G58-1/pPMC4/pDHF1 developed diarrhea and none died following challenge inoculation. Seventeen of 31 control pigs developed diarrhea and 11 died. Of 18 pigs vaccinated with G58-1/pDHF1 then challenge-inoculated with the virulent strain, 5 developed diarrhea and 2 died. Fifteen of 18 litter- and weight-matched controls developed diarrhea and 8 died. When compared with G58-1 (negative control), G58-1/pPMC4 afforded no protection to pigs challenge-inoculated with 3030-2.

Seven hybridomas that secreted monoclonal antibodies (MAB) against the peplomer protein and one that secreted MAB against the nucleocapsid protein of Berne virus (proposed family Toroviridae) were isolated. All MAB directed against the peplomer protein neutralized virus infectivity and, with the exception of MAB 6A7, inhibited each other's binding in competition assays. Neutralization of Berne virus infectivity was potentiated when some MAB were used in pairs. The antibodies have been used to localize toroviral proteins in infected cells; use of antipeplomer MAB 6B10 yielded a diffuse intracytoplasmic immunofluorescence, whereas the antinucleocapsid MAB 1F1 detected antigen in the intra- and perinuclear compartments. By use of radioimmune precipitation, protein A of Staphylococcus aureus was found to bind directly to the nucleocapsid polypeptide, without the requirement for specific antibody. Using fluorescein isothiocyanate-conjugated protein A, the intranuclear accumulation of the nucleoprotein of Berne virus was confirmed by results of immunofluorescence.

In vitro effects of a mixture of Escherichia coli heat-stable enterotoxins (STa and STb) on isolated jejunum of 3-week-old male pigs were studied, using everted intestinal sac techniques. Heat-stable enterotoxins increased chloride secretion and chloride absorption in everted intestinal sacs. The increase of secretory flux was greater than that for absorptive flux. Vasoactive intestinal peptide (6 x 10-9M) increased chloride secretion, but had no effect on chloride absorption. Neither vasoactive intestinal peptide nor pilocarpine (10-5M) had additive effect to ST. Secretory effects of ST were not blocked by atropine 2 x 10-5M), clonidine (10-6M), or morphine (4.2 X 10-6M).