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.

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.

The vaccine efficacy of a genetically engineered deletion mutant strain of pseudorabies virus, strain 783, was compared with that of the conventionally attenuated Bartha strain. Strain 783 has deletions in the genes coding for glycoprotein I and thymidine kinase. In experiment 1, which had a 3-month interval between vaccination and challenge exposure, strain 783 protected pigs significantly (P < 0.05) better against virulent virus challenge exposure than did the Bartha strain. The growth of pigs vaccinated with strain 783 was not arrested, whereas that of pigs vaccinated with the Bartha strain was arrested for 7 days. Of 8 pigs given strain 783, 4 were fully protected against challenge exposure; none of the pigs given strain Bartha was fully protected. In experiment 2, which had a 3-week interval between vaccination and challenge exposure, the growth of pigs vaccinated with strain 783 was arrested for 3.5 days, whereas that of pigs vaccinated with the Bartha strain was arrested for 6 days. In experiment 3, pigs with moderate titer of maternal antibodies were vaccinated twice IM or once intranasally with either strain 783 or Bartha and were challenge-exposed 3 months after vaccination. Pigs given strain 783 twice IM were significantly (P < 0.05) better protected than were the other pigs. They had growth arrest of only 6 days, compared with 9 days for pigs of other groups, and shed less virus after challenge exposure. Results of this study indicate that the vaccine based on the deletion mutant strain 783 is more efficacious than is the Bartha strain of pseudorabies virus.

The vaccine efficacy of a genetically engineered deletion mutant strain of pseudorabies virus, strain 783, was compared with that of the conventionally attenuated Bartha strain. Strain 783 has deletions in the genes coding for glycoprotein I and thymidine kinase. In experiment 1, which had a 3-month interval between vaccination and challenge exposure, strain 783 protected pigs significantly (P < 0.05) better against virulent virus challenge exposure than did the Bartha strain. The growth of pigs vaccinated with strain 783 was not arrested, whereas that of pigs vaccinated with the Bartha strain was arrested for 7 days. Of 8 pigs given strain 783, 4 were fully protected against challenge exposure; none of the pigs given strain Bartha was fully protected. In experiment 2, which had a 3-week interval between vaccination and challenge exposure, the growth of pigs vaccinated with strain 783 was arrested for 3.5 days, whereas that of pigs vaccinated with the Bartha strain was arrested for 6 days. In experiment 3, pigs with moderate titer of maternal antibodies were vaccinated twice IM or once intranasally with either strain 783 or Bartha and were challenge-exposed 3 months after vaccination. Pigs given strain 783 twice IM were significantly (P < 0.05) better protected than were the other pigs. They had growth arrest of only 6 days, compared with 9 days for pigs of other groups, and shed less virus after challenge exposure. Results of this study indicate that the vaccine based on the deletion mutant strain 783 is more efficacious than is the Bartha strain of pseudorabies virus.

Two diets similar in caloric density and mineral content, but markedly different in protein content, were used to study the effects of dietary protein on renal function and morphologic and histopathologic changes in dogs that had functional renal tissue reduced by seven-eighths nephrectomy. The effects of moderate protein intake (MPrI = 15% protein; dry-matter basis) and high-protein intake (HPrI = 31% protein; dry-matter basis) were studied for the initial 7 months (period 1 [P1]) after renal mass reduction. Diets were then switched between groups during the following 7 months (period 2 [P2]) to evaluate the effects of increased or decreased protein intake. The HPrI caused significantly (P < 0.05) greater glomerular filtration rate (GFR) and renal growth than did MPrI during P1. Dogs that maintained HPrI during P1 and MPrI during P2 (group 1) had significant (P < 0.05) reduction in GFR during P2. Dogs that maintained MPrI during P1 and HPrI during P2 (group 2) had significant (P < 0.05) improvement in GFR and renal growth during P2. At the end of the study, renal reserve was evaluated in both groups of dogs before and after group 1 was returned to HPrI for 2 weeks. During this 2-week feeding trial, group-1 dogs had marked improvement in renal reserve, relative to group 2, and GFR increased to the terminal P1 values. Results indicate a possible residual benefit from HPrI during the early phase of compensatory renal growth in the form of functional compensatory memory to HPrI. The severity of renal lesions was indistinguishable between dogs of dietary groups during both study phases. Plasma electrolyte concentrations rapidly returned to normal range after renal ablation, but mild azotemia and proteinuria persisted throughout most of the study. High protein intake was not associated with increased degree or progression of proteinuria.

Two diets similar in caloric density and mineral content, but markedly different in protein content, were used to study the effects of dietary protein on renal function and morphologic and histopathologic changes in dogs that had functional renal tissue reduced by seven-eighths nephrectomy. The effects of moderate protein intake (MPrI = 15% protein; dry-matter basis) and high-protein intake (HPrI = 31% protein; dry-matter basis) were studied for the initial 7 months (period 1 [P1]) after renal mass reduction. Diets were then switched between groups during the following 7 months (period 2 [P2]) to evaluate the effects of increased or decreased protein intake. The HPrI caused significantly (P < 0.05) greater glomerular filtration rate (GFR) and renal growth than did MPrI during P1. Dogs that maintained HPrI during P1 and MPrI during P2 (group 1) had significant (P < 0.05) reduction in GFR during P2. Dogs that maintained MPrI during P1 and HPrI during P2 (group 2) had significant (P < 0.05) improvement in GFR and renal growth during P2. At the end of the study, renal reserve was evaluated in both groups of dogs before and after group 1 was returned to HPrI for 2 weeks. During this 2-week feeding trial, group-1 dogs had marked improvement in renal reserve, relative to group 2, and GFR increased to the terminal P1 values. Results indicate a possible residual benefit from HPrI during the early phase of compensatory renal growth in the form of functional compensatory memory to HPrI. The severity of renal lesions was indistinguishable between dogs of dietary groups during both study phases. Plasma electrolyte concentrations rapidly returned to normal range after renal ablation, but mild azotemia and proteinuria persisted throughout most of the study. High protein intake was not associated with increased degree or progression of proteinuria.

The ability of ectopic parathyroid tissue to support calcium homeostasis was evaluated by measuring serum concentrations of calcium, phosphorus, albumin, magnesium, and parathyroid hormone before and for 12 weeks after bilateral thyroparathyroidectomy in 14 cats. During the immediate postoperative period, significant decrease was observed in serum calcium, magnesium, and parathyroid hormone (PTH) concentrations. Serum PTH concentration remained subnormal and did not significantly increase during the 12-week observation period. Despite persistent hypoparathyroidism, serum calcium and magnesium concentrations gradually increased. Ectopic parathyroid tissue is not capable of maintaining normal serum calcium concentration immediately after thyroparathyroidectomy. Serum calcium concentration gradually normalizes after thyroparathyroidectomy, apparently by means of a PTH-independent mechanism.

The ability of ectopic parathyroid tissue to support calcium homeostasis was evaluated by measuring serum concentrations of calcium, phosphorus, albumin, magnesium, and parathyroid hormone before and for 12 weeks after bilateral thyroparathyroidectomy in 14 cats. During the immediate postoperative period, significant decrease was observed in serum calcium, magnesium, and parathyroid hormone (PTH) concentrations. Serum PTH concentration remained subnormal and did not significantly increase during the 12-week observation period. Despite persistent hypoparathyroidism, serum calcium and magnesium concentrations gradually increased. Ectopic parathyroid tissue is not capable of maintaining normal serum calcium concentration immediately after thyroparathyroidectomy. Serum calcium concentration gradually normalizes after thyroparathyroidectomy, apparently by means of a PTH-independent mechanism.

Cortical bone screws were implanted into the proximal portion of the right and left radius and ulna of 6 newborn Quarter Horse foals as radiographic markers for measurement of growth. Distance between markers on a lateral radiographic view was measured. Radiographs were taken at 2-week intervals until the horses were 8 weeks old, at 4-week intervals until they were 48 weeks old, and at 12-week intervals until they were 72 weeks old. The proximal radius and ulna grew at similar rates during the 72-week period of evaluation, and growth continued throughout 72 weeks. The proximal radius grew 3.5 cm, and the ulna grew 3.4 cm. Although the rates of growth were similar, growth from the ulnar physis contributed only to the length of the olecranon; growth was not transmitted to the ulnar diaphysis distal to the cubital joint. The proximal radius slid distally in relation to the ulna as growth occurred at the proximal radial physis. These findings suggest that transfixing the ulna to the radius while growth is occurring at the proximal radial physis impedes the natural shifting process, and subluxation of the elbow can result. Severity of subluxation would be inversely related to the age of the horse at the time of transfixation.

Cortical bone screws were implanted into the proximal portion of the right and left radius and ulna of 6 newborn Quarter Horse foals as radiographic markers for measurement of growth. Distance between markers on a lateral radiographic view was measured. Radiographs were taken at 2-week intervals until the horses were 8 weeks old, at 4-week intervals until they were 48 weeks old, and at 12-week intervals until they were 72 weeks old. The proximal radius and ulna grew at similar rates during the 72-week period of evaluation, and growth continued throughout 72 weeks. The proximal radius grew 3.5 cm, and the ulna grew 3.4 cm. Although the rates of growth were similar, growth from the ulnar physis contributed only to the length of the olecranon; growth was not transmitted to the ulnar diaphysis distal to the cubital joint. The proximal radius slid distally in relation to the ulna as growth occurred at the proximal radial physis. These findings suggest that transfixing the ulna to the radius while growth is occurring at the proximal radial physis impedes the natural shifting process, and subluxation of the elbow can result. Severity of subluxation would be inversely related to the age of the horse at the time of transfixation.

A study was conducted to determine whether dietary supplements with alpha-linolenic acid altered the ability of equine peritoneal macrophages to produce tumor necrosis factor (TNF) in response to endotoxin. Peritoneal macrophages were harvested from 6 healthy adult horses before and after the horses were fed a nutritionally balanced ration that contained 8% linseed oil as a source of alpha-linolenic acid. The macrophages were cultured in media containing no additives (control), endotoxin (0.5 to 50 ng/ml), or the calcium ionophore, A23187. Macrophage supernatants were collected after 6 and 24 hours' incubation and stored at -70 C. Tumor necrosis factor activity was estimated by a modified in vitro cytotoxicity bioassay, using the murine fibrosarcoma cell line, WEHI 164 clone 13. The TNF activity after 6 and 24 hours' incubation was greater in culture media of macrophages exposed to endotoxin than in media from control macrophages. For macrophages cultured in media that contained endotoxin, neither the concentration of endotoxin nor incubation time had any effect on TNF activity. Endotoxin-induced macrophage production of TNF, as determined by measurement of TNF activity, was significantly less after horses were fed the alpha-linolenic acid-rich ration for 8 weeks.

A study was conducted to determine whether dietary supplements with alpha-linolenic acid altered the ability of equine peritoneal macrophages to produce tumor necrosis factor (TNF) in response to endotoxin. Peritoneal macrophages were harvested from 6 healthy adult horses before and after the horses were fed a nutritionally balanced ration that contained 8% linseed oil as a source of alpha-linolenic acid. The macrophages were cultured in media containing no additives (control), endotoxin (0.5 to 50 ng/ml), or the calcium ionophore, A23187. Macrophage supernatants were collected after 6 and 24 hours' incubation and stored at -70 C. Tumor necrosis factor activity was estimated by a modified in vitro cytotoxicity bioassay, using the murine fibrosarcoma cell line, WEHI 164 clone 13. The TNF activity after 6 and 24 hours' incubation was greater in culture media of macrophages exposed to endotoxin than in media from control macrophages. For macrophages cultured in media that contained endotoxin, neither the concentration of endotoxin nor incubation time had any effect on TNF activity. Endotoxin-induced macrophage production of TNF, as determined by measurement of TNF activity, was significantly less after horses were fed the alpha-linolenic acid-rich ration for 8 weeks.

To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histologic changes associated with immune complex glomerulonephritis.

To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histologic changes associated with immune complex glomerulonephritis.