Effect of steroidal and non-steroidal anti-inflammatory drugs in combination with long-acting oxytetracycline on non-specific immunity of calves suffering from enzootic bronchopneumonia

The aim of this paper was to compare the effect of flumethasone and meloxicam in combination with oxytetracycline on clinical and immunological parameters of calves suffering from enzootic bronchopneumonia. The study was performed on 30 Black-and-White Lowland Breed calves with clinical signs of enzootic bronchopneumonia divided randomly into three equal groups and, respectively, treated with-Group I: oxytetracycline and meloxicam; Group II: oxytetracycline and flumethasone; Group III (control): oxytetracycline only. Treatment of calves with the combination of oxytetracycline and meloxicam (Group I) caused a significantly faster, in comparison to other groups, improvement in the clinical illness index score (CIIS: cough, nasal discharge, dyspnea, depression and anorexia) and a faster normalization of body temperature. A slow decrease in white blood cell (WBC) count, the number of neutrophils, MID (mixed number of monocytes, eosinophils and basophils) and in the individual number of monocytes (CD14/CD45 positive cells) was observed in Groups I and III. In the blood of the calves which received oxytetracycline and flumethasone (Group II), leukocytosis, neutrophilia and monocytosis with concomitant lymphopenia and a low number of T cells (CD2+) was observed. Moreover, the calves treated with flumethasone exhibited a decrease in gamma-globulin concentration, and phagocytic parameters. Both drugs, flumethasone and meloxicam slightly decreased tumor necrosis factor (TNF) but meloxicam slightly increased the levels of interferon (IFN) in sera and in bronchoalveolar lavages (BALs). These results suggest that the combination of meloxicam with an antibiotic in calves suffering from enzootic bronchopneumonia is superior to the antibiotic alone and also to the combination of the antibiotic with flumethasone.     

Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs

OBJECTIVE: To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs. ANIMALS: 8 client-owned dogs with clinical signs of osteoarthritis. PROCEDURES: Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E(2), platelet thromboxane B(2) (TXB(2)), and free serum TXB(2) and 6-keto-prostaglandin F (PGF)-1alpha concentrations. RESULTS: Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and alpha-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E(2) decreased after treatment with carprofen or deracoxib, and platelet TXB(2) production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1alpha did not change significantly after treatment with any of the drugs, although the ratio of free TXB(2) to 6-keto-PGF-1alpha decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.     

Prostaglandins and glutathione peroxidase in bovine mastitis

Prostaglandin (PG) levels in milk and plasma samples from mastitic cows were determined by radioimmunoassay and compared with erythrocyte glutathione peroxidase (GSH-Px) and other relevant parameters in milk and blood. The overall levels of PGE2, PGF2 alpha and thromboxane B2 (TXB2) in milk were two to four times higher than in blood plasma both in healthy and diseased animals (P less than 0.01). In mastitic milk the PG levels were 24 to 55 per cent and in blood plasma 41 to 95 per cent higher than in healthy animals. The changes were significant and largest for the PGF2 alpha values. In milk, the PG concentrations correlated with the markedly elevated cell count (r = 0.49 to 0.57), and TXB2 values also correlated with milk yield. In blood, PGE2 and PGF2 alpha correlated positively with serum albumin, and PGE2 also correlated with glutathione (GSH). PGE2 and PGF2 alpha correlated negatively with GSH-Px and gamma-glutamyl transferase. The substantial decline in GSH-Px in mastitic animals (P less than 0.01) may be related to changes in lipid peroxidation and PG formation. The possible implications of these findings in the treatment of mastitis are discussed.     

Modulation of arachidonic acid metabolism by bovine alveolar macrophages exposed to interferons and lipopolysaccharide

Stimulation of bovine alveolar macrophages with calcium ionophore A23187 resulted in marked production of leukotriene (LT)B4 and a lesser increase in thromboxane (TX)B2, whereas opsonized zymosan (OPZ) resulted in production of TXB2 and relatively small increases in LTB4 and prostaglandin (PG)F2 alpha. Alveolar macrophages incubated with recombinant bovine interferon-gamma or lipopolysaccharide, and subsequently stimulated with A23187 or OPZ, had altered arachidonic acid metabolism, producing markedly increased amounts of TXB2 and PGF2 alpha, and slightly increased LTB4. Incubation of alveolar macrophages with lipopolysaccharide had a more profound effect on the increased amounts of TXB2 and PGF2 alpha, observed in response to stimulation with A23187 or OPZ, than did incubation with interferon-gamma. Alveolar macrophages incubated with recombinant bovine interferon-alpha 1-1 also produced slightly increased amounts of LTB4 when stimulated with A23187 or OPZ. Altered arachidonic acid metabolism by alveolar macrophages exposed to interferons and lipopolysaccharide may contribute to the development of pulmonary inflammation, such as in the early stages of bacterial pneumonia following viral infections that induce interferon production.     

Release of immunoreactive arachidonate metabolites by equine endometrium in vitro

The ability of equine endometrium to release prostaglandin (PG) F, PGE2, and leukotriene (LT) B4 was studied in vitro, using endometrial tissue from diestrous mares. Because of the high cross-reactivity of the PGF antiserum with PGF1 alpha and with PGF2 alpha, results were quoted as total immunoreactive PGF. Significant concentrations of these arachidonate metabolites were released into tissue culture medium between 1 and 24 hours of incubation. Significantly higher concentrations of PGE, but not of PGE2 or LTB4, were released from endometria of mares with chronic endometritis than from genitally normal mares. Prostaglandin F was released only in low concentrations from the endometrium of a mare with pyometra, but concentrations of PGE2 and LTB4 were similar to those of genitally normal mares.     

A comparative study of the effects of meloxicam and flunixin meglumine (NSAIDs) as adjunctive therapy on interferon and tumor necrosis factor production in calves suffering from enzootic bronchopneumonia

The study was performed on 18 Black-and-White Lowland Breed calves with clinical signs of enzootic bronchopneumonia divided into three groups and respectively treated with oxytetracycline and meloxicam--Group I (9 animals); oxytetracycline and flunixin meglumine--Group II (3 animals); and oxytetracycline only--Group III (6 animals--control). The following observations were recorded before treatment (1st day) and two days later (3rd day): body temperature, the serum level of interferon (IFN) and tumor necrosis factor (TNF) as well as cytokine production by bronchoalveolar lavage (BAL) cells. The treatment of calves with a combination of oxytetracycline and meloxicam (Group I) and especially with oxytetracycline and flunixin meglumine (Group II) caused a significantly faster, in comparison to the control group, normalization of body temperature. Both drugs, meloxicam and especially flunixin meglumine, inhibited excessive TNF production in the organism (measured as the serum level of cytokine). Moreover, BAL cells isolated from calves treated with both NSAIDs were still able, ex vivo, to release TNF, in contrast to the control group (treated only with tetracycline) which lost the ability to produce TNF. The treatment of the calves with meloxicam and flunixin meglumine did not significantly influence the levels of IFN in sera but normalized ex vivo IFN production in BAL cells. These results suggest that the combination of meloxicam with an antibiotic or flunixin meglumine with an antibiotic which does not exert an immunosuppressive influence on the organism of calves suffering from enzootic bronchopneumonia is equally effective in the treatment of calves and superior to the antibiotic alone.     

Effects of intramuscular meloxicam administration on prostaglandin E2 synthesis in the North American bullfrog (Rana catesbeiana)

Meloxicam is a commonly used nonsteroidal anti-inflammatory drug (NSAID) in veterinary medicine, but its use in amphibians has not been reported in the literature. NSAIDs are known to act by providing anti-inflammatory and analgesic actions by inhibiting the synthesis of prostaglandin E2 (PGE2). The objective of this study was to evaluate whether the intramuscular administration of meloxicam would decrease the circulating serum PGE2 levels in the North American bullfrog (Rana catesbeiana) following tissue trauma induced by a punch biopsy. Eighteen adult North American bullfrogs were randomly assigned to two treatment groups: meloxicam (0.1 mg/kg i.m.) and control (0.9% saline i.m.). Blood was obtained via cardiocentesis immediately prior to administration of the two treatment regimes and serum was frozen. A 4-mm punch biopsy was taken from the right triceps femoris muscle to induce an inflammatory response. Twenty-four hours later, a second blood sample was collected and serum was harvested and frozen. Serum PGE2 concentrations were measured using a commercial PGE2 enzyme assay (EIA) kit. Twenty-four hours following the biopsy, the mean circulating PGE2 levels of animals treated with meloxicam was 57.79 +/- 12.35 pg/ml, which did not differ significantly from animals that were treated with saline (85.63 +/- 17.55 pg/ml, P > or = 0.05). The calculated means of the absolute change between the circulating baseline PGE2 levels and the postinjury circulating PGE2 levels were significantly lower in animals treated with meloxicam (13.11 +/- 17.31 pg/ml) than in control animals treated with saline (46.14 +/- 38.02 pg/ml) (P < or = 0.05). These results suggest that the systemic administration of meloxicam at a dosage of 0.1 mg/kg once daily suppresses circulating serum PGE2 levels postinjury in the North American bullfrog.     

The influence of flunixin on the response to Salmonella typhimurium endotoxin in calves

The effects of intravenous injection of 0.5 microgram/kg body weight of Salmonella typhimurium endotoxin were studied in calves. The injection was followed by ruminal stasis and general dullness. The clinical signs disappeared within 24 hours. The injection was followed by a tremendous increase in the plasma level of 15-ketodihydro-PGF2 alpha, the main metabolite of PGF2 alpha. The injection was also associated with a profound leukopenia and significant decreases in the serum levels of iron, zinc and calcium. In order to study the role of prostaglandin (PG) for the development of endotoxin-induced changes a group of calves was pretreated with flunixin, a potent cyclo-oxygenase inhibitor, at a dose of 2.2 mg/kg body weight. Flunixin inhibited the PG release completely, but did not influence the other responses to endotoxin. The pyrogenic response to endotoxin was very moderate and it was suggested that fever is not the most suitable parameter for monitoring endotoxin effects in calves. The studied blood parameters (15-ketodihydro-PGF2 alpha, iron, zinc, calcium and the number of leukocytes) appeared to be much more sensitive.     

Maintenance of the corpus luteum of early pregnancy in the ewe. III. Differences between pregnant and nonpregnant ewes in luteal responsiveness to prostaglandin F2 alpha

The effects of pregnancy and number of corpora lutea on luteal regression induced with prostaglandin F2 alpha (PGF2 alpha) were examined in 93 ewes. Bred and nonpregnant ewes were assigned randomly to receive a single im injection of PGF2 alpha: 0, 2, 4, 6, 8 or 10 mg/58 kg body weight. Injections were given on d 13 postestrus. The concentration of progesterone in serum 24 h after PGF2 alpha injection was affected by dose (P less than .001). The effect of pregnancy and the interaction of pregnancy with number of corpora lutea on levels of progesterone in serum were significant (P less than .05); therefore, data were partitioned according to pregnancy status and analyzed separately. There was an effect of number of corpora lutea on serum concentration of progesterone in pregnant (P less than .01) but not nonpregnant ewes (P greater than .10). Similar relationships among groups were observed for the concentration of progesterone in luteal tissue. In nonpregnant ewes the minimum dose of PGF2 alpha to produce a significant suppression of progesterone in serum (P less than .05) was 4 mg/58 kg body weight. In pregnant ewes with one or two corpora lutea, the minimum effective doses were 6 and 10 mg/58 kg body weight, respectively. The concentration of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) in serum was related to the dose of PGF2 alpha injected. There were no differences in the concentration of PGFM in serum between pregnant and nonpregnant ewes either before or after injection. Corpora lutea of early pregnancy appear to be resistant to the luteolytic effect of PGF2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravaginal prostaglandin F2 alpha for the treatment of metritis and pyometra in the bitch

The purpose of this study was to determine whether intravaginal prostaglandin F2 alpha (PGF2 alpha) would be effective for the treatment of metritis or pyometra in the bitch. Seventeen bitches with metritis or pyometra were treated with PGF2 alpha. Prostaglandin F2 alpha (150 micrograms/kg body weight) was administered once or twice daily by infusing 0.3 ml per 10 kg body wt into the vaginal lumen. Bitches were also treated with amoxicillin (15 mg/kg body wt/48 h) and/or gentamicin (4 mg/kg body wt/day) administered as intramuscular (i.m.) injections. Fifteen bitches were treated successfully with intravaginally administered PGF2 alpha for 3 to 12 days and with intramuscularly administered antibiotics for 4 to 12 days. Success of treatment was judged by cessation of vaginal discharge, the absence of fluid in the uterus as determined by ultrasonography, and the overall health status of the animal. As two bitches with pyometra showed clinical deterioration in spite of medical treatment, ovariohysterectomy was performed after the first and the second treatment, respectively. No side effects (salivation, vomiting, diarrhoea, hyperpnoea, ataxia, urination, anxiety, pupillary dilatation followed by contraction) were observed after PGF2 alpha treatment. The disease did not recur during the subsequent oestrous cycles within 12 months after the initial treatment. The results demonstrate that intravaginal administration of PGF2 alpha was effective in 13 dogs (86.6%) with metritis or pyometra, and caused no side effects. Although the study was based on a relatively small number of cases, it is concluded that prostaglandin F2 alpha can be a useful means of treating bitches with metritis or pyometra. However, in severe cases of pyometra ovariohysterectomy is needed.     

Serum glucocorticoids, growth hormone and insulin and plasma glucose in bulls given prostaglandin E2 or F2 alpha 1.

Plasma glucose and serum insulin, growth hormone and glucocorticoid concentrations were determined in five yearling bulls given (im) 5, 15 or 30 mg prostaglandin E2 (PGE2), 30 mg prostaglandin F2 alpha(PGF2 alpha) or saline. Jugular blood was collected at frequent intervals around the time of injection and at .5--hr intervals from 1 to 9 hr after injections. Thirty milligrams PGE2 and 30 mg PGF2 alpha each caused 15- to 20-fold increases in serum glucocorticoids. Glucocorticoids increased with increasing doses of PGE2. Although PGE2 and PGF2 alpha each increased blood growth hormone, this effect was about twofold larger after PGE2. By contrast, PGE2 depressed serum insulin about 50% for 1 hr, then insulin increased about sixfold until 3 to 4 hours. Blood serum insulin increased after PGF2 alpha, but this effect only approached significance (P less than .10). Plasma glucose increased about 10 mg/100 ml after PGE2, but was not affected significantly by PGF2 alpha. Thus, the effects of PGE2 and PGF2 alpha on hormones which control glucose metabolism differ markedly. We speculate that PGE2 caused a twofold increase in growth hormone secretion within 10 to 20 min, that increased growth hormone induced increased blood glucose within 1 to 2 hr and that increased glucose caused increased insulin secretion at 2 to 4 hr, but we cannot rule out a transitory (1 hr) suppressive effect of PGE2 directly on the pancreas.     

Treatment of pyometra in cats, using prostaglandin F2 alpha: 21 cases (1982-1990).

Treatment with prostaglandin F2 alpha (PGF2 alpha) was evaluated in 21 queens with open-cervix pyometra. The PGF2 alpha was administered (0.1 or 0.25 mg/kg of body weight, sc, q 12 to 24 h) for 3 or 5 days. Transient postinjection reactions caused by PGF2 alpha administration included vocalization, panting, restlessness, grooming, tenesmus, salivation, diarrhea, kneading, mydriasis, emesis, urination, and lordosis. Reactions began as quickly as 30 seconds after PGF2 alpha administration and lasted as long as 60 minutes. All queens improved clinically after PGF2 alpha treatment. One month after completion of the initial series, 1 queen required a second series of PGF2 alpha injections before pyometra resolved. Of 21 queens, 20 (95%) resumed normal estrous cycles without further treatment and 17 (81%) delivered normal litter(s). Use of PGF2 alpha is an acceptable treatment for open-cervix pyometra in queens.     

Effects of allergen challenge on plasma concentrations of prostaglandins, thromboxane B2, and histamine in calves infected with bovine respiratory syncytial virus.

To examine the influence of allergen-induced type-1 hypersensitivity on the pathogenesis of bovine respiratory syncytial virus (BRSV) infection, we sensitized calves by aerosol to Micropolyspora faeni (MF) and challenge exposed them during infection with BRSV. The development of MF-specific IgE serum concentrations was confirmed by ELISA. The dynamics of arachidonic acid metabolism and histamine release during a type-1 hypersensitivity reaction in the bovine lung were studied by quantitating the concentrations of prostaglandin (PG)E2, PGF2 alpha, PGI2 as 6-keto-PGF1 alpha, thromboxane (TX) A2 as TXB2, and histamine in plasma of BRSV-infected and/or MF-sensitized/challenge-exposed calves. Four treatment groups were established: (1) BRSV infection only, (2) aerosol sensitization to MF followed by BRSV infection and aerosol challenge exposure to MF, (3) MF aerosol sensitization and challenge exposure without BRSV infection, and (4) aerosol sensitization to MF followed by BRSV infection without MF challenge exposure. Significantly increased concentrations of PGI2 were associated with MF aerosol exposure, particularly when combined with BRSV infection in group 2. After MF challenge exposure, TXB2 concentrations were significantly greater in the virus and MF challenge-exposed group 2. Individual calf data for the change in MF-specific IgE concentration between the first and second MF challenge exposures and the change in PGE2 concentration 30 minutes after the second MF challenge exposure had a highly significant direct correlation. Histamine concentrations were significantly greater in calves infected with BRSV than in uninfected controls regardless of MF exposure. These data further substantiate the thesis that implicates type-1 hypersensitivity as a pathogenic mechanism in BRSV-related disease.     

In vivo effects of meloxicam and aspirin on blood,gastric mucosal,and synovial fluid prostanoid synthesis in dogs

OBJECTIVE: To evaluate in vivo activity in dogs of meloxicam or aspirin, previously shown in vitro to be a selective cyclooxygenase-2 (COX-2) inhibitor (COX-1 sparing drug), or a nonselective COX inhibitor, respectively. ANIMALS: 12 male dogs with unilateral osteoarthritis of the stifle joint. PROCEDURE: Each dog was treated in a crossover design with aspirin or meloxicam for 21 days. Prostaglandin E2 (PGE2) concentrations were measured at days 0 (baseline), 7, and 21 of each treatment period in lipopolysaccharide (LPS)-stimulated blood, synovial fluid collected by arthrocentesis, and endoscopic gastric mucosal biopsy specimens. Thromboxane B2 (TXB2) was evaluated in blood on days 0, 7, and 21 of each treatment period. RESULTS: Aspirin administration significantly suppressed PGE2 concentrations in blood, gastric mucosa, synovial fluid, and suppressed TXB2 concentration in blood at days 7 and 21. Meloxicam administration significantly suppressed PGE2 concentrations in blood and synovial fluid at days 7 and 21, but had no effect on concentrations of TXB2 in blood or PGE2 in gastric mucosa. Suppression of LPS-stimulated PGE2 concentrations in blood and synovial fluid by aspirin and meloxicam administration is consistent with activity against the COX-2 isoenzyme. Suppression of concentrations of PGE2 in the gastric mucosa and TXB2 in blood by aspirin administration is consistent with activity against COX-1. Meloxicam, in contrast, had a minimal effect on functions mediated by COX-1. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam acts in vivo in dogs as a COX-1 sparing drug on target tissues by sparing gastric PGE2 synthesis while retaining antiprostaglandin effects within inflamed joints.     

Arachidonic acid metabolites in carrageenin-induced equine inflammatory exudate

The presence of cyclooxygenase products of arachidonic acid metabolism in carrageenin-induced inflammatory exudate was investigated in ponies using two models. In the first model, an inflammatory response was stimulated by injecting carrageenin into subcutaneously implanted polypropylene tissue cages and exudates were collected at five predetermined times between 3 and 48 h. In the second model, exudates were harvested at 6, 12 and 24 h from carrageenin-impregnated polyester sponges which had also been inserted beneath the skin. Prostaglandin (PG) E2, thromboxane (TX) B2 and the stable breakdown-product of prostacyclin (PGI2), 6-keto-PGF1 alpha, in exudates were measured by radio-immunoassay (RIA); PGE2-like and PGF2 alpha-like activities were bioassayed following an acid-lipid extraction technique which provided a recovery rate of 78%. Agreement between RIA and bioassay was within acceptable limits. In Model 1, using RIA, mean PGE2 concentration reached 197 ng X ml-1 at 12 h decreasing to less than 12 ng X ml-1 at 24 h. Mean TXB2 and 6-keto-PGF1 alpha levels were highest at 48 h (22.3 and 34.2 ng X ml-1, respectively) after considerable fluctuations and with wide standard errors prior to this time. In the sponge model, however, PGE2 levels were surprisingly low for each group (mean 12.8 ng X ml-1 at 12 h) and TXB2 and 6-keto-PGF1 alpha were similarly lower (means of 3.3 and 8.1 ng X ml-1 respectively at 12 h). Mean total leucocyte counts and total protein concentrations were increased in both models after carrageenin stimulus. PGF2 alpha was not detected in measurable quantities in any exudate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arachidonic acid metabolites in milk of cows during acute coliform mastitis

Concentrations of prostaglandin F2 alpha (PGF2 alpha) and thromboxane B2 (TXB2) were evaluated in the milk of cows with naturally occurring (n = 3) and experimentally induced (n = 5) acute coliform mastitis. These arachidonic acid metabolites were measured by radioimmunoassay in unextracted milk. Experimental infections were induced by inoculating 600 to 1,200 colony-forming units of Escherichia coli into 1 mammary quarter per experimental cow. In the experimental cows, milk was collected before inoculation and at 12, 24, 36, 48, 60, and 72 hours after inoculation. Somatic cell concentrations, bovine serum albumin, and concentrations of PGF2 alpha and TXB2 were determined in milk collected at each sampling. Mild-to-moderate increases in milk PGF2 alpha and TXB2 concentrations were observed in cows with naturally occurring mastitis. the increases corresponded to the clinical severity and course of mastitis. In the experimental cows, increases in milk PGF2 alpha and TXB2 concentrations were observed, but the increases were not significant, using a statistical model that included factors of treatment, cows, hours after inoculation, cows-by-treatment and hours-by-treatment interactions, and random error (residual). Results of the present study indicated a large biological variability in milk arachidonic acid metabolite concentrations in cows with acute coliform mastitis, and that arachidonic acid metabolites may be important in the pathophysiologic process of acute coliform mastitis.     

Influence of arachidonic acid metabolites in vitro and in uterine washings on migration of equine neutrophils under agarose

The influence of arachidonic acid metabolites on migration of equine neutrophils under agarose was investigated. Leukotriene B4 (LTB4) was chemotactic at concentrations between 0.1 and 1000 ng ml-1 and prostaglandin E2 (PGE2) at 1 and 10 ng ml-1 but not at higher or lower concentrations. Prostaglandin F2 alpha (PGF2 alpha) was not chemotactic for equine neutrophils at any concentration. Random migration was significantly inhibited (P less than 0.05) by suspension of neutrophils in LTB4 (0.1 to 1000 ng ml-1) and PGF2 alpha (0.1 ng ml-1) but not at high concentrations. There was a significant positive correlation between random migration of neutrophils suspended in uterine washings from persistently endometritic mares and concentrations of endogenous PGF (P less than 0.002) and PGE2 (P less than 0.05) in washings. Thus certain metabolites of arachidonic acid affect migration of equine neutrophils and may play a significant role in recruitment of neutrophils to sites of inflammation in the horse.     

Pathophysiology of experimental bovine endotoxicosis: endotoxin induced synthesis of prostaglandins and thromboxane and the modulatory effect of some non-steroidal anti-inflammatory drugs.

Endotoxin-induced synthesis of thromboxane A2 (TXA2), prostacyclin (PGI2) and prostaglandin E2 (PGE2) was studied in 3 cows after intravenous E. coli endotoxin (055:B5-0.025 mg/kg b.w.) administration. Blood sampling and monitoring of clinical signs were performed from 2 h prior to until 6 h after endotoxin challenge. Blood samples were analyzed for stable hydrolysis products of TXA2 (TXB2), PGI2 (6-keto PGF) and PGE2 (bicyclic PGE2), biochemical and haematological parameters. In a similar experimental design the efficacy of the non-steroidal anti-inflammatory drugs (NSAID) flunixin meglumine (FM) and phenylbutazone (PB) in suppressing eicosanoid synthesis and clinical signs in response to endotoxin challenge was investigated. Two groups of cows, each comprising 2 animals, were treated with FM and PB prior to endotoxin challenge. It was observed that plasma concentrations of TXB2, 6-keto PGF and bicyclic PGE2 increased rapidly after endotoxin challenge. Concentrations were significantly elevated for hours and were correlated to the severity of clinical signs of endotoxicosis. Pretreatment with NSAID suppressed mediator production and alleviated clinical signs. The experiments suggest a certain pathophysiological role of TXA2, PGI2 and PGE2 for the early systemic ill-effects of bovine endotoxicosis.     

Changes in the levels of eicosanoids in cats naturally and experimentally infected with Dirofilaria immitis

Feline heartworm (Dirofilaria immitis) infection is a severe, life-threatening disease. The eicosanoids are lipid mediators derived from the metabolism of the arachidonic acid, involved in the regulation of the immune response and of inflammatory reactions. In this study, naturally infected cats showed significant higher levels of prostaglandin E(2) (PGE2), thromboxane B(2) (TXB(2)) and leukotriene B(4) (LTB4) than uninfected cats. Changes in the levels of eicosanoids during the infection were observed in experimentally infected cats. PGE2 increased significantly during the first 60 days post-infection, then progressively decreased until day 180 post-infection. At this time, PGE2 values are still significantly higher than those observed before the infection. TxB2 and LTB4 increased progressively from the beginning of infection and reached their maximum levels 180 days post-infection. In experimentally infected, ivermectin-treated cats, 15 days after treatment (45 days after infection) both PGE2 and LTB4 levels were similar to those observed in experimentally infected, untreated cats. No significant differences of PGE2 levels were found before the infection and at the end of the experiment (165 days post-treatment, 195 days post-infection). Increased levels of LTB4 were found 15 days post-treatment, afterward they progressively decreased. These data show that D. immitis infection influences the production of intravascular eicosanoids in cats. The high levels of PGE2 observed in the early phase of infection could be related to the survival of the worms, while those of TxB2 and LTB4 detected at the end of the study could mediate the inflammatory reactions and thrombi formation during the feline dirofilariosis.     

Prevention of pregnancy in the dog with a combination of prostaglandin F2 alpha and bromocriptine

Fifteen mated bitches were given prostaglandin F2 alpha (PGF2 alpha) [250 micrograms/kg body weight] and bromocriptine (10 micrograms/kg BW) twice daily from days 6 to 10 of diestrus. Progesterone concentrations declined during treatment. None of the bitches whelped. Daily treatment with PGF2 alpha and bromocriptine for 5 d appears to induce luteolysis and prevent early pregnancy.